var title_f6_2_6176="Contents: Pulmonary infections";

var content_f6_2_6176=[" <script type=\"text/javascript\">",

" $$.inlineInitCustomer(",
" false);",
" var quirksmode = document.compatMode == \"CSS1Compat\";",
" if (quirksmode) {",
" $(\"html\").addClass(\"ie-standards\");",
" }",
" </script>",
" <div id=\"message-wrap\">",
" <div id=\"message-bg\">",
" </div>",
" <iframe id=\"message-bk\">",
" </iframe>",
" <dl id=\"message-container\">",
" <dt id=\"message-title\">",
" </dt>",
" <dd id=\"message-body\">",
" </dd>",
" <dd id=\"message-controls\">",
" </dd>",
" </dl>",
" </div>",
" <div id=\"topPanel\">",
" <div id=\"header\">",
" <div id=\"header_container\">",
" <h2 id=\"logo\">",
" <a href=\"./toc\">",
" Wolters Kluwer Health UpToDate",
" </a>",
" </h2>",
" <div id=\"header_right\">",
" <div id=\"searchpanel\">",
" <a href=\"/login\" id=\"loginbutton\">",
" Log in",
" </a>",
" <div id=\"cmsSearchBox\">",
" <div class=\"header-search\">",
" <form action=\"./search\" id=\"cmssearch\" method=\"get\"
name=\"SearchForm\">",
" <div class=\"header-search-left\">",
" <input autocomplete=\"off\" class=\"searchfield\" id=\"cmsTxtBox\"
name=\"search\" placeholder=\"Search UpToDate\" type=\"text\"/>",
" </div>",
" <div class=\"header-search-right\">",
" <input alt=\"Search\" id=\"cmsSearchSubmit\"
src=\"/sites/all/themes/uptodate/images/search_button.png\" type=\"image\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" </form>",
" </div>",
" </div>",
" <div id=\"cms_lang_dropdown\">",
" <form accept-charset=\"UTF-8\" action=\"/\" id=\"lang-dropdown-form\"
method=\"post\">",
" <div class=\"form-item form-type-select form-item-lang-dropdown-
select\">",
" <select class=\"lang-dropdown-select-element form-select\" id=\"edit-
lang-dropdown-select\" name=\"lang_dropdown_select\" style=\"width:100px\">",
" <option selected=\"selected\" value=\"en\">",
" English",
" </option>",
" <option value=\"ja\">",
" ���������������������������",
" </option>",
" </select>",
" </div>",
" <input name=\"lang_dropdown_type\" type=\"hidden\" value=\"language\">",
" <input name=\"en\" type=\"hidden\" value=\"/\">",
" <input name=\"ja\" type=\"hidden\" value=\"/ja\">",
" <noscript>",
" <div>",
" <input class=\"form-submit\" id=\"edit-submit\" name=\"op\"
type=\"submit\" value=\"Go\"/>",
" </div>",
" </noscript>",
" <input name=\"form_build_id\" type=\"hidden\" value=\"form-
on4lUWpxHun_wp6revUkjCG6rK2IBuCGME9Cw0HXeok\">",
" <input name=\"form_id\" type=\"hidden\"
value=\"lang_dropdown_form\">",
" </input>",
" </input>",
" </input>",
" </input>",
" </input>",
" </form>",
" </div>",
" <div class=\"clear\">",
" </div>",
" </div>",
" <ul id=\"utility\">",
" <li class=\"first\">",
" <a href=\"/home/about-us\">",
" About Us",
" </a>",
" </li>",
" <li>",
" <a href=\"/home/news-events\">",
" News &amp; Events",
" </a>",
" </li>",
" <li>",
" <a href=\"/home/contact-us\">",
" Contact Us",
" </a>",
" </li>",
" <li class=\"last\">",
" <a href=\"/help\">",
" Help",
" </a>",
" </li>",
" </ul>",
" </div>",
" <div class=\"clear\">",
" </div>",
" </div>",
" <div id=\"nav\">",
" <ul>",
" <li id=\"productTab\">",
" <a href=\"/home/product\">",
" Product",
" <span>",
" </span>",
" </a>",
" </li>",
" <li id=\"editoralTab\">",
" <a href=\"/home/editorial\">",
" Editorial",
" <span>",
" </span>",
" </a>",
" </li>",
" <li id=\"whyUptodateTab\">",
" <a href=\"/home/why-uptodate\">",
" Why UpToDate",
" <span>",
" </span>",
" </a>",
" </li>",
" <li id=\"supscriptionOptionsTab\">",
" <a href=\"/home/subscription-options\">",
" Subscription Options",
" <span>",
" </span>",
" </a>",
" </li>",
" <li>",
" <a href=\"/store\">",
" Subscribe",
" <span>",
" </span>",
" </a>",
" </li>",
" <li id=\"wkhcsTab\">",
" <a href=\"/home/wolters-kluwer-health-clinical-solutions\">",
" Wolters Kluwer Health Clinical Solutions",
" <span>",
" </span>",
" </a>",
" </li>",
" </ul>",
" <div class=\"clear\">",
" </div>",
" </div>",
" <div id=\"greyBar\">",
" <div id=\"greyBarTitle\">",
" <span class=\"emphasis\">",
" <a href=\"UTD.htm?3/3/3134\">",
" Contents",
" </a>",
" </span>",
" <img src=\"./../images/space_arrows.myextg\">",
" <a href=\"UTD.htm?8/24/8590\">",
" Pulmonary, Critical Care, and Sleep Medicine",
" </a>",
" <img src=\"./../images/space_arrows.myextg\">",
" Pulmonary infections",
" </img>",
" </img>",
" </div>",
" <div id=\"greyBarButtons\">",
" <div id=\"printGB\">",
" <a class=\"icontxt\" href=\"?view=print\">",
" <img align=\"middle\" alt=\"Print this page\" border=\"0\" height=\"20\"
src=\"./../images/icn_print.myextg\" width=\"24\"/>",
" </a>",
" <a class=\"icontxt\" href=\"?view=print\" title=\"Print this page\">",
" Print",
" </a>",
" </div>",
" </div>",
" </div>",
" <!-- menuMessage.jsp -->",
" <!-- /menuMessage.jsp -->",
" </div>",
" <!-- header -->",
" </div>",
" <!-- topPanel -->",
" <div id=\"leftPanel\">",
" <ul>",
" <li>",
" <a href=\"UTD.htm?3/45/3806\">",
" Specialties",
" </a>",
" </li>",
" <li>",
" <a href=\"UTD.htm?18/22/18798\">",
" Patient Information",
" </a>",
" </li>",
" <li>",
" <a href=\"UTD.htm?3/13/3294\">",
" What's New",
" </a>",
" </li>",
" <li>",
" <a href=\"UTD.htm?0/37/606\">",
" Calculators",
" </a>",
" </li>",
" <li>",
" <a href=\"UTD.htm?0/40/654\">",
" Authors and Editors",
" </a>",
" </li>",
" </ul>",
" </div>",
" <!-- leftPanel -->",
" <div id=\"rightPanel\">",
" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/wk_utd-rgb.myextg\" width=\"220px\">",
" </img>",
" </div>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" <br>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a href=\"#\" id=\"printHeaderPrint\" rel=\"\" title=\"Click here to
print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <div class=\"toctable\" border=\"0\" cellpadding=\"0\" cellspacing=\"0\"
id=\"tocTable\" width=\"100%\">",
" <trs>",
" <tds>",
" <h1>",
" Contents:",
" Pulmonary infections",
" </h1>",
" </tds>",
" </trs>",
" <trs>",
" <tds>",
" </tds>",
" </trs>",
" <trs>",
" <tds valign=\"top\">",
" <div class=\"toctable\" border=\"0\" cellpadding=\"0\" cellspacing=\"0\"
width=\"100%\">",
" <trs>",
" <tds>",
" <strong>",
" Atypical pneumonia",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?37/19/38199\">",
" Clinical manifestations and diagnosis of Legionella infection",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?31/58/32680\">",
" Epidemiology and pathogenesis of Legionella infection",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?3/5/3162\">",
" Mycoplasma pneumoniae infection in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?7/6/7270\">",
" Pneumonia caused by Chlamydophila (Chlamydia) pneumoniae in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?8/14/8425\">",
" Psittacosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?32/15/33015\">",
" Treatment and prevention of Legionella infection",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Bronchitis",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?28/38/29289\">",
" Acute bronchitis in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?7/43/7866\">",
" Management of infection in acute exacerbations of chronic obstructive
pulmonary disease",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Community-acquired pneumonia",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?28/33/29210\">",
" Antibiotic studies for the treatment of community-acquired pneumonia in
adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?37/36/38473\">",
" Community-acquired pneumonia in adults: Risk stratification and the
decision to admit",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?25/26/26026\">",
" Diagnostic approach to community-acquired pneumonia in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?30/49/31514\">",
" Epidemiology, pathogenesis, and microbiology of community-acquired
pneumonia in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?22/38/23143\">",
" Microbiology and pathogenesis of Streptococcus pneumoniae",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?23/24/23945\">",
" Nonresolving pneumonia",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?13/4/13386\">",
" Pneumococcal pneumonia in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?21/12/21705\">",
" Pneumococcal vaccination in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?1/48/1801\">",
" Prognosis of community-acquired pneumonia in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?0/5/81\">",
" Resistance of Streptococcus pneumoniae to beta-lactam antibiotics",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?3/18/3369\">",
" Resistance of Streptococcus pneumoniae to the fluoroquinolones,
doxycycline, and trimethoprim-sulfamethoxazole",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?19/15/19704\">",
" Resistance of Streptococcus pneumoniae to the macrolides, azalides,
lincosamines, and ketolides",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?24/24/24969\">",
" Treatment of community-acquired pneumonia in adults in the outpatient
setting",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?40/1/40986\">",
" Treatment of community-acquired pneumonia in adults who require
hospitalization",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Fungal infections",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?38/5/38998\">",
" Amphotericin B nephrotoxicity",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?1/26/1449\">",
" Diagnosis and treatment of histoplasmosis in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?21/23/21881\">",
" Diagnosis and treatment of pulmonary histoplasmosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?38/63/39924\">",
" Epidemiology and clinical manifestations of histoplasmosis in HIV-
infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?33/51/34616\">",
" Epidemiology and clinical manifestations of invasive aspergillosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?38/51/39734\">",
" Management of pulmonary sequelae and complications of
coccidioidomycosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?41/24/42376\">",
" Pathogenesis and clinical features of pulmonary histoplasmosis",
" </a>",
" </li>",
" </ul>",
" <strong>",
" General",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?12/10/12458\">",
" Clinical manifestations and diagnosis of bronchiectasis in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?17/7/17524\">",
" Clinical microbiology review: Respiratory tract infections",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?24/9/24729\">",
" Lung abscess",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?23/24/23945\">",
" Nonresolving pneumonia",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?27/27/28089\">",
" Parapneumonic effusion and empyema in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?1/48/1800\">",
" Postoperative mediastinitis after cardiac surgery",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?37/5/37978\">",
" Pulmonary complications of primary immunodeficiencies",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?13/43/14005\">",
" Renal disease in tuberculosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?17/11/17591\">",
" Sputum cultures for the evaluation of bacterial pneumonia",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?37/11/38073\">",
" Treatment of bronchiectasis in adults",
" </a>",
" </li>",
" </ul>",
" <strong>",
" HIV infection",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?19/43/20154\">",
" Approach to the HIV-infected patient with pulmonary symptoms",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?15/5/15449\">",
" Bacterial pulmonary infections in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?7/25/7577\">",
" Clinical presentation and diagnosis of Pneumocystis infection in HIV-
infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?18/41/19093\">",
" Cytomegalovirus infection as a cause of pulmonary disease in HIV-
infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?11/46/12009\">",
" Diagnosis of latent tuberculosis infection in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?38/63/39924\">",
" Epidemiology and clinical manifestations of histoplasmosis in HIV-
infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?1/10/1194\">",
" Epidemiology, clinical manifestations, and diagnosis of tuberculosis in
HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?35/29/36310\">",
" Parasitic pulmonary infections in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?2/52/2889\">",
" Prophylaxis against Pneumocystis infection in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?26/60/27593\">",
" Treatment of Pneumocystis infection in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?4/12/4298\">",
" Treatment of latent tuberculosis infection in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?21/47/22261\">",
" Tuberculous pleural effusions in HIV-infected patients",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Influenza",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?38/60/39880\">",
" Antiviral drug resistance among seasonal influenza viruses",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?34/31/35320\">",
" Avian influenza vaccines",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?22/4/22599\">",
" Clinical manifestations and diagnosis of avian influenza",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?36/27/37305\">",
" Clinical manifestations and diagnosis of pandemic H1N1 influenza
('swine influenza')",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?18/1/18456\">",
" Clinical manifestations of seasonal influenza in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?5/25/5528\">",
" Diagnosis of seasonal influenza in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?14/58/15272\">",
" Epidemiology of influenza",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?31/2/31786\">",
" Epidemiology of pandemic H1N1 influenza ('swine influenza')",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?13/48/14090\">",
" Epidemiology, transmission, and pathogenesis of avian influenza",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?2/34/2599\">",
" Infection control measures to prevent seasonal influenza in healthcare
settings",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?19/11/19640\">",
" Pharmacology of antiviral drugs for influenza",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?43/13/44249\">",
" Prevention of seasonal influenza in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?36/8/37002\">",
" Seasonal influenza vaccination in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?38/7/39032\">",
" Treatment and prevention of avian influenza",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?37/21/38234\">",
" Treatment and prevention of pandemic H1N1 influenza ('swine
influenza')",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?21/46/22250\">",
" Treatment of seasonal influenza in adults",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Nosocomial pneumonia",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?30/18/31017\">",
" Aspiration pneumonia in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?23/30/24040\">",
" Clinical presentation and diagnosis of ventilator-associated
pneumonia",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?26/32/27145\">",
" Epidemiology and pathogenesis of Pseudomonas aeruginosa infection",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?11/57/12183\">",
" Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-
acquired, ventilator-associated, and healthcare-associated pneumonia in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?30/48/31494\">",
" Pseudomonas aeruginosa pneumonia",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?13/7/13433\">",
" Risk factors and prevention of hospital-acquired, ventilator-
associated, and healthcare-associated pneumonia in adults",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?6/34/6695\">",
" The ventilator circuit and ventilator-associated pneumonia",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?35/63/36858\">",
" Treatment of hospital-acquired, ventilator-associated, and healthcare-
associated pneumonia in adults",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Other respiratory viruses",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?0/38/617\">",
" Parainfluenza viruses in adults",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Parasitic infections",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?35/24/36229\">",
" Cutaneous larva migrans (creeping eruption)",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?15/38/15977\">",
" Epidemiology, pathogenesis, and clinical features of schistosomiasis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?41/28/42437\">",
" Hookworm infection",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?35/29/36310\">",
" Parasitic pulmonary infections in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?11/25/11668\">",
" Pulmonary manifestations of ascariasis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?16/34/16935\">",
" Toxocariasis: visceral and ocular larva migrans",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?14/54/15207\">",
" Trichinellosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?2/30/2532\">",
" Tropical filarial pulmonary eosinophilia",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Pneumocystis jiroveci (P. carinii)",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?7/25/7577\">",
" Clinical presentation and diagnosis of Pneumocystis infection in HIV-
infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?22/8/22665\">",
" Epidemiology, clinical manifestations, and diagnosis of Pneumocystis
pneumonia in non-HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?2/52/2889\">",
" Prophylaxis against Pneumocystis infection in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?9/4/9289\">",
" Treatment and prevention of Pneumocystis pneumonia in non-HIV-infected
patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?26/60/27593\">",
" Treatment of Pneumocystis infection in HIV-infected patients",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Severe acute respiratory syndrome (SARS)",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?17/21/17753\">",
" Severe acute respiratory syndrome (SARS)",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Tuberculosis",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?38/47/39673\">",
" Clinical manifestations and evaluation of pulmonary tuberculosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?11/46/12009\">",
" Diagnosis of latent tuberculosis infection in HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?18/13/18649\">",
" Epidemiology of tuberculosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?1/10/1194\">",
" Epidemiology, clinical manifestations, and diagnosis of tuberculosis in
HIV-infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?4/12/4298\">",
" Treatment of latent tuberculosis infection in HIV-infected patients",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Viral infections",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?18/41/19093\">",
" Cytomegalovirus infection as a cause of pulmonary disease in HIV-
infected patients",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?6/56/7050\">",
" Respiratory syncytial virus infection: Clinical features and
diagnosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?15/17/15640\">",
" Respiratory syncytial virus infection: Prevention",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?37/27/38327\">",
" Respiratory syncytial virus infection: Treatment",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?17/21/17753\">",
" Severe acute respiratory syndrome (SARS)",
" </a>",
" </li>",
" </ul>",
" </tds>",
" </trs>",
" </div>",
" </tds>",
" </trs>",
" <trs>",
" <tds>",
" <img height=\"10\" src=\"./../images/spacer.myextg\" width=\"1\"/>",
" </tds>",
" </trs>",
" </div>",
" <div id=\"footer\">",
" <div id=\"footerNav\">",
" <ul>",
" <li>",
" <a href=\"file://www.wolterskluwerhealth.com/\" rel=\"nofollow\"
target=\"_blank\">",
" Wolters Kluwer Health",
" </a>",
" </li>",
" <li>",
" <a href=\"file://www.factsandcomparisons.com/\" rel=\"nofollow\"
target=\"_blank\">",
" Facts &amp; Comparisons&reg;",
" </a>",
" </li>",
" <li>",
" <a href=\"file://www.medispan.com\" rel=\"nofollow\" target=\"_blank\">",
" Medi-Span&reg;",
" </a>",
" </li>",
" <li>",
" <a href=\"file://www.provationordersets.com\" rel=\"nofollow\"
target=\"_blank\">",
" ProVation&reg; Order Sets",
" </a>",
" </li>",
" <li>",
" <a href=\"file://www.provationmedical.com\" rel=\"nofollow\"
target=\"_blank\">",
" ProVation&reg; Medical",
" </a>",
" </li>",
" <li>",
" <a href=\"file://pharmacyonesource.com/\" rel=\"nofollow\"
target=\"_blank\">",
" Pharmacy OneSource&reg;",
" </a>",
" </li>",
" <li>",
" <a href=\"file://www.medicom.com.cn/\" rel=\"nofollow\" target=\"_blank\">",
" Medicom",
" </a>",
" </li>",
" <li>",
" <a href=\"file://www.lexi.com/\" rel=\"nofollow\" target=\"_blank\">",
" Lexicomp",
" </a>",
" </li>",
" <li class=\"last\">",
" <a href=\"/home/privacy-policy\">",
" Privacy Policy",
" </a>",
" </li>",
" </ul>",
" </div>",
" <div id=\"footerLogo\">",
" <a href=\"./toc\">",
" Wolters Kluwer Health | UpToDate",
" </a>",
" </div>",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.3 - C21.34",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"sfInfo\">",
" <a href=\"/home/terms-use\">",
" Terms of Use",
" </a>",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" UpToDate Marketing Professional",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0605-95.154.198.148-93821F3066-14]",
" <br/>",
" </span>",
" </div>",
" </div>",
" </div>",
" <!-- rightPanel -->",
"</body>"].join("\n");
var script_f6_2_6176=[""].join("\n");
var outline_f6_2_6176=null;
var title_f6_2_6177="3D ultrasound of displaced IUD";
var content_f6_2_6177=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=OBGYN
%2F62490&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=OBGYN
%2F62490&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Three-dimensional ultrasound of displaced IUD",
" </div>",
" <div class=\"cntnt\" style=\"width: 413px; height: 444px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCAG8AZ
0DASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwDg5dSESbYgB2pIdUc4Oeaxr7JuAF45qykYSMZ614/JGx9B7SVzZGsykH
5jmq1zdPJGSxODVGFCzZFOv8+TtHWpUEnoNzk1qYt5cHzuCakhlZtoGeaI7Jpm4GaurbLbJluorobWxzpSb
uWraAIu+Q802ef5vlJqr9oeT5R0qeOPAyeRWdras1T6IsW1zKnKMfzqVru4fIZj+dUwnPBxVmDGPmNS0tyk
3sQMly7ZyasRJcthcnFXQ6hOAKfbzojcioc32LUfMSG1uYVDh2x9a2LTXGtFCl23fWoVu1mXbj8KqtpZnfc
DWLal8Zqrr4TdXX7ifhM1ciupHAMjEH61mW9mtui+3U1YDjsa55W+ybRutzWjuZMAbjj61qWUrpglj+dczH
IwbINXor51G0jis5X6FWTO0guhEu4yHP1pt3qXyZ3n864x76YtkE4rMv8AU353ybRSjGcmS4xW5015q21iV
c5+tUv+EmaP5Q5J+tcPdakCTiQmqEl2B8wfJrrjRb3MXUij0b/hKWVctIc/Wqd140wpUOfzrza5vnY4VjVC
eZmONxraOGvuzKVdLZHeXvjqdQVVz+dYM/jC7dyfNbH1rlJXycZzUZ4FdEcPBGEsTPodNJ4ovGziRufeqc2
tXkgJMr/nWPE3PNPdie3FWqUV0Jdab6izanOX5ZiaE1GUnkmq8mDwRzUQyD7VpyrsY88r7mzDfuozk1o2eq
PkfMR+Nc8jjaAaHZkHyniodNM1jVaO/s9TTH7xsmpLi8ikGU6159FeuvBNW11JgvBrB4bW6N1itLM6hpwrZ
zzWjZXxjUbDya4cak7dami1kxH6UpUG1YccQkd6dSvGGFziq0kd5eDDFq5638ThVAIFbNj4ljYLlQKwlSnD
ZG8asJdShf6PfAkqrGsuXTrtf9ajV6LZ63ZyKBIV5q8/2G4j3AKaSxE46NCdCMtmePTQXEZ4U4pIbh43wxI
Nek39rZkHCqK5TU7KIbjGAa3p11PRoxnQcNUypFqUiDG44qddR3t8xNZIgZW5qZUPYVo4xIU5G0t7EuDuOa
guNQLqQjmsh0bPNNiyOtJU1uP2sti59ukU4yTTZLvevNJvjK4AGahMZL8DiqSRLkyEyEt3xSsglUqTUrRH0
pWiIXIqrk2ZjXViUYntVBwQcCuikVmU7hxWXNb5bIrWEu5hOHY6C4XE3TkGlRHklHPFWL2ExztnjmpLOMtm
ubm0udfLrYmSERpgfepYdOlumHBqaEgNyMmt2ykWOMHgGuec3HY3jBS3KlvoqwoCcZ71Vv7KJs8Diti4usq
SDWaYnkLOfu1lCUm7tmkoxtZI5q5jSJiFH5UyJ9y4FTargOQtUoJlU8V3LVHG9HYvBDt3d6kVehxxRC4Izn
ipFOWwOlQ2y0hSxb5VFX7ay3IGc4qewst4DEdatz2sgXavSsJVFeyNow6sgghRcDv61djcxdDn2qnFDKPlI
Oa0bSzc/M9Yza6s0iuxGZmI+Y8UqNvI2DPrUeo4QbVODVO2vktQd3JNCjdXQ27PU6GG3OwMaWWSONTvIFc/
LrzKvB+QVzuq+IWkJAanTw85PUU68Io6bUdajgBCkVx+pa000hA6Vh3GoPK5yxNV1kLnNehSw0Yann1MU56
I1DdM2KZ5rucdKpq7Z4zxTmkYituUy5i6gHUvUVxIqgjOTVYuQOaiPzAkmhRE5AGJYnNLIxxxTFIAzQ0mRx
VkXJIZQoy3WpPPDLVJjSZ96OUXM0TvJkcdaRAxB5piEA5NO39eeKdguTAALyeRTDIc4zkVCWPJzTQ4J9qLB
zEkhB6VF5jhuhxSk96Tce5piHrOy/wmnFg/J4NRZOKTJJ60WC5IW54FPjnlU8Eio1YCnqwJ7UgRchv5o+dx
rTtteuEwN5x9axAygdM0Bs9AcVnKClujWNSUdmdZFrfmDDvzTZb0HJ3ZrmFPPQ08yueM8Vn7FLY19vJ7m0b
uLGWYCmfbIw3y81gSlm65pUf5eDg1fskR7ZnRJdRN94gGpo1jk6Ec1zsKlmGTV9WZFG01EoW2LjUvubsNgH
xgVbGksgzjcKzdM1MxsBKa6m01GKRQAQK5ajnE6qahIw5dPbGQCPaq7W2MfN+FdTM8RjOMEmsaeHc3FKFRv
ccqaWxklFIZSKZ/Z+UU461fNufMH1rVFhIYYyOnNaOpykRp8xk6u3m3RC9M0RnYoQdqnuAMsw5JpbaHK7z1
qbpIpr3ggBD7jVl5Xc4zxTGAFU5JmX5U5qbczHexqRBmZRurVlCLbYX72Oa5+xEjyDrW+U2wc5yaxqKzRrT
d0cdqcWZGFY8kRjOTnFdTdwKZWZjWRfbAp6Zrspz6HJUh1KlszE8E1q2ciAjcawDKTkLSCRsgA1pKHMZxnY
76z1CKJcFhgVfj1S3Y9RXnMbP13HFXUkZl4Y1zSwy3OiOIZ6Cl9bkg/Lmpbm+j8rC9favP45jCMs5qO51tl
XCGs/qt3oafWUlqdHf3Ac9axpniGSW5rAutWmkBwazZbx2yCxrrp4dpHLUxCZu3tyuCFbisG7bJ4PNVzI57
mnKCTzXTGHKcs6nMCqO/WpVG1TimhR3oDFeDVEonV/l5pGuAvTrVR2Yk+lMzjrRyhzFh5zIeKaQx5qIE9qT
Jp2JuSHcKQ8fWmj6mkNMBSfWmnmg+tNzigRIG4waDz0pme/ag+poC4400MAcUwvg01mJ6CnYVyckCkJBFQk
tipFUkc0WC4/PFAPpTcYo4pAOQ8nPSpQg65qADnrTw+KGhpku4K2BU6SpwDWeSQcilEmOvWk4jUrGiZQOB0
pwIPNZ6znv2pwnyeTS5SuctMRUZU5yKjWRc9advyaLBe4+JmVsitKGQumO9ZYfI5qzbsRipkrlQdjQCZA9a
sxySRYwTmoLZiMBqtbVZs54rFnRE0ba9cgZNTtdEA1nRnaMirMWZV6VhKK3NlJl2zlWaVd3XNdhEsYtos4z
zXGW8JjcEiuutlL2kRB45rnq7o6aW2pzc9i0YzIcU+0H5Vo+IiFkYDnnpVHT4g/LPgelHNeN2JpKVkOlhD5
KjiqaxCJzkZNdFBHEUxuFUb2IbuF5qY1NbDlDqWdGtPPkGF4rU1t7extMEgtiq2kXUcERB+Vq5bxhqhmm2K
eBURg6lS3QqU1ThcxtR1EtK2w8VkXErOTyaeVzkkVFty3PAr1YRS2PMlJy3Et4GIyTSyIVOfSrSHAAA/GkK
gjk0+YXLoQRSYqylwIxnNU2G1jVeZtx4P4U+W4uZot3F5uzg5qlI2eTUPOehpJAzcZq1FIzcmxrsTwOBUeM
DjmnleMUgQ+tWjMRQakH5GlBAHqaOvQUhjT7HmhuBS4zyKaQTTAQjIBzQcACnBTjnilCUBYPKyOKZtPSrKA
9KR1yOKVx2K5XFIVyKl2knpS7PWncViqc9KYQQasMmT1qNkIFO5LQxV4xQR60E84pQPU5piExRtp44PSn7D
2FK47EYXFOpdhHWkIPUigBjKTSYNToSf4akVQeq0r2Ha5UIbHSl9qu+WCOlRtB3o5g5SuTTCA3NT+X1z1pm
w+lMViLgHGaNhFSCI7gaeyg9+aLisQhQDkmpFak8o9zSFSvagNiZCKniPOc1UB/CpEbb1pNFpm1YyK/U5NX
Ex5mM8ViWsgVhg1rQSgsMisJKx0QldGh5fy9eKms5NsgBohAdaR4isg2mue99GdCXVHS2EYlAyOtdPbWTLb
R46HNc74fRjtzXcwKVtYhn1rik/esdidoo89upGvbxlX160r2ckQODip9IRROWf1q3rMy+Xhabm1JRQct1z
Mg0pQB+9OaszjzJNwHArKsi3GfWugtIhMorOp7ruVDVWMG9V4UZwSK5e5iM8pdz+Ndn4hQRxFe1cNf3O0FV
7V14duSujmr2W5UumRG2iqzEkgYqIsXcsTUqyDGe9dtrHDe5YjzgA0rAA4NMRix5pxBZhipLK04C59aqjaf
rV67iyuT1rOkAU81pHUynoxcY4FMIK9akjwx4qVoA4x3qr2JtcpNyOOtKFIXmnNA6npUkdtLJzjiquibMr7
TjOcUoyOlXhZEr81MNp5ZzS5kPkZVVDjilVDnJqXY3YcUpViPei4WE2jgk8U4IpOBURR+BUifuzyDSGiVVw
aRwAKVRJKPkFJ5EwU7qQyF8jp0poGR1qXYzfKaUQqp96dxWK7KB0FMYZ7VceMDpUZGOo4ppiaKbID2puwjJ
q3vUjABzTCjHmquTYhQMT0NWUGOvWnwDs1WvIUjctQ5FRiVPKLcnpR5Y6HFXI9oPzUpgRxlTS5iuUomMDoa
dj3qdrZsHFNWE45ouHKxFQ9aSTge9TiF1AK0Nbs5zSuPlKGMDPU0uBjmroswOTSNak9BVcyJ5GZ5bBximMv
ORWqmms46VUu7WSBuelNSTYnBpXZX5PWo2zUgPX1phbrVEMjLYHNPDBlFNIDA0wcEDtTJLMDYNaVvPgAHrW
PG2HOatwvk5qJK5pCVjo7S9AGD1q7DL5kgrn4XDLnuKv2UxVwD1rmlBHXCZ3uhSYYY6V1stwfJiwcDniuH0
G4Xcoc81089wpSPPvXnTVpHoR1ijkoLn96CDwp5qzdXazEAdBXO+f+/MSnnODWvFC0cak85raUEncyjNvQs
xSJuA7Vv2csccOc9q5kptOakjuH2HkgCspw5jSM+Ul8Q3JmRsdulec6pKfMPrXaXs5kBXFcTrKFZzkd67cL
Hl0OPFO+pWjfCk1LC27pVNX5xVmEgHHSuxo4kzThxt96fnH1qK3kG3kU2R8n0rGxvfQSecnIrOl5Y+9WHPJ
qrKwBAzzWkVYym7gpK8Vet33EYrMfIbOas2shRunFVJaCi7M3baFHOWAq3JFFGmQKzLeY5BBq4WLgDtXNJO
50xasV5jvOFHFQsMHDdKvrEBzQ8CEZJp8yBxuZ0hXGMcVXKheTWhLGBxUBi3sAKtMzaEsoBcSAGuhh8PB4w
zAVDpdr5S7tua2YnlZdqk4rmq1Hf3TopU1b3kZT6attwgBNRmzWQHI5rWaN9x3cg0+G1VfmZuKj2jNPZo5a
702bJ8pM/hVH7FdKcSJivR7do0YBo1I9aS+s4Jl3DC+mKaxTTs0S8KnqmeerakcEc01oRu2kV1EmnjecVTm
0p25UVsqyZk6LRzzW4X7oqAoxzkVr3duYevWqaKWbpWsZXVzGULaFaKPHLdKmX5TxnFWo7cscEVo2OmmRsA
ZFKU0tyo029EYzIW7UsVnOzZjBNdhFoIfBIxV1NI8lcY5rB4mK0RssM3ucdHbuBhh81aNrpRmUFlxXTW+kr
vDyrxWpFbxqBtUYrCpirbG8MN3OVXQ/kBAFUpdLeKU5X5a7eS0LtlTgelRzRqV2Oo+tZxxLLdBHFmxjJxUv
8AZmxQVGRWzLaKkm5ea0YoVlg6YrSVZolUUzipYpEJCLxWTqSsVO4V3F9aAKQBiuZvbU4Yda6KVRMwq07Kx
yDqQfl6UxsnqOK0rmBom3FeKicRMvPBrtUjgcSjzSj6VKQCfakIxVXJsR7efepIww6dKAM8DrVmBQPlJpNj
SH2UhVsHpV6EkSg9qotHtO4dat2ZDONxxWUu5rDsdHp07IeTxWrLqcgVAD0rmFcx/dORUhu8qOa5ZUlJ3Oy
FWysXNFt2u79pMcZrsGt18sDsKx9JUWtluAwcc1pafcCfKtXLWbbutkdFJKKs+pTu129OafFGDARV65s2UE
9RVJYpAflOB6VKkmimrMz7iER5PeuS19RuJxXbXw2rz1rlNYVSpz1rroS1uctdaWOUGVbrV2D5jyKpSDEhH
pV+14UZrvlsedDctLkD0o5ceg9akZlCcioGkOCAcCslqbvQSTaowOT61TmXnOKnLc0x+cirWhm9SsvzH0qa
M9jxSBMD3qQYA6U2yUi3bvjrxVtZWPArNhkG7BrRjZcZx0rKSN4Ml8xxgZq3GMx5Y8+lUlO85FSl+x4qGjR
MbLw1T6XatPcD+7mq7KWkGOa6PQrfau5jioqS5YlU480jdisoIbZd2M4qAxISfLYCrLQtMACeKDZ7RhT9a8
9S7s77dkUXXC9c1D5UjjA6Vea2Oemav2MIBwy8U3UUVclQuZEVvKQckjFTwRPuw/QVr3EKjkED2qoAQ2Rya
hVOYvksVruyLqDHwazH8yF9jZrdaVkY5B+tQXMaSrnjdVQm1oyZRT2MG6sxKpZhmsV7R1m+VeM9K6vhDg80
Q2oeYNjArojVcVqYypcxl6dpMkpDOpArqLDS1VRt61s6daReWoyK37LTrcDdxXFUxLkdEaUYLU5qGybzMBe
BVxrMsnMeT9K6lYbaIYABNCS2wblQKwbbL5+yOPXTZ3OGUhfpV2301YgAwzXTeZDuHzrg9qlZLdlBXBNDbZ
PPbocxJZrt+VKy7rT3LbsECu3dI1HSq0gicYMdJNrUrnucS2nqEyTzUX2fYMI2a6yeyRs4XiqT6csbbu1Wq
j6jsnsc5cWvmW78fMBXmOtXklreMjZGDXtklusilUwpNeeeL/DPmyPIpG6u3B1oqVpHNiqcnH3Tgbq985Mg
5qgWOckVcvNLmtSTgsPaqcgccMpFezG1tDx581/eJYmQ1LPGNgIqhkocirCz5X5hTaEpdxu0g5FSbzkEHml
X5hnt6UIoJzmgC5byh0w3WpFVl5AqpjGCtXY7kBMNyaya7GsX3Hm4IXBGKR5QQuDiq07ZOR0qpJKQRTUQc7
HpVzMqReWv0pNMlMb5I4PSs5W8yds+tacZMarwMGvOlGyseind3N9L9BDtfk1nyTh5wqd/Sq0qHAIJq9o8K
tIGIyB61z8sYJyNuZydiK+s2eLcRXA6+xikK54r1nVHjS1OMcCvJPE7eZOxX1rpwUnJ6nPjEox0MEje+RVi
P5eBVaNiPrUobjmvTZ5aJmmJ4zTWk45qBzzSckUWHckMv92nI2TzTY1BFSKoBoYIXvzSMOxp6jninKR0xzU
lWIc8gr2q5bybhzVeQAHgUQsd3ND1BOzN20j3jAqw1ruX5uKg0ltrgnpWneyA8Jwa5ZNqVjrik43KkMQSQA
V1GnxoY1rnobZiNx6VuaRuOOelYVtVub0lZnRwLGYsYOaVod2AoNSWM6r8rKK1EKMvQZrzJScWdySaMn7OF
XH8VRszKeBzWyYBnpzSraKxyQM0lU7jsYEqtMDnO4VBA3kSfveT2rpWtEY/KOaydS0+ZSWVc46VcKiejJcb
aoq3BEq57Vnu4Qkc1fhik2nzRim+QrvjFaxaWhDTZmFc8gGrUT7E569quS24VfkAqWzsvPByOlN1E1diUHc
S0vNiZyavpqzgAKTiqF1pzxn5c1XEUqcbTWfLGWpd5LQ2n1KcLlTVeTVJyPesyVrlFG1cioUnlc4kXA70Kk
rCcy3PqdwDndx9akt/FRgG1ic1m3QDDAzWe9oWbIHStlTg1qZylJbHXp4meQblNSL4lYjDEZrk4VCLhqgni
lMmY84qfYRuHOzuV17ePmYYqvc65GAQWGK5GRJVi3KTx1rndQv50YjJqoYVSejFOvyrY9CfXYVUnzFrA1fX
FlQhHHNeb3uoTbz87fnWa99O7n5mrup4FLU4qmO6WOovL51Yk7SKypnE33gMmqcckrAE8j3q0u04NdagonK
5uZSnj2tntSKFqzP8/Iqr9081oncyasyaMEcDvTvKOMirFrbhwDnmrEsARfl5NQ5amihdFKIno1KYyflXqa
RlYE54NWbRN33+tDdtQSvoIV2w4PasqZsPx0reuIwIqxp0IbgcU4MVRWPQ9KiEj5Pc1qzogx6isi0ysh2ng
VpQqXbLnivLqb3PVhtYmVs44q7aHZ8x49qZHECu7HNMuSycA/hWLalojVaakepXLSKwz8tcJr6gZYV192eP
UVzXiCArAXI4rrw9os5cR7yORjO4nIqXI6Cq0bHecdKsZ9q9JnmJiqATzTmUZHpTIzzzzUkvQCp6jFUelTQ
Lk4NQxAgH3qxArZxSZaJjHu4Wk8rC5xzVu3Co2TzT5JElbAAWsuY15TOKA5J7VBvAbirt0AEOOKpFBjI5NW
nczkrG5pEg4JrUZPMkDfw1zenSlXANdJBukQAGueorO500ndWLisCAvQVqWq7UASqunWuZBnkV0L26pb5Re
QOlcNWaWh204t6ktgAxVf4q6CCBY1BJ5xXO6Or/AGgFvyrrI13Y3DiuKrozoi9CEJvOBVu3swV4Ymp4oQRw
MVp2VngbjWaVyZTsVYbQRrnYD9aiubJZlJIwK2wgHFQziOEbmYfSnYyU3c4zULBYVYrzXPhgr+9djq9xHJn
aABXE6pIEYlOtaUtXY2b0ux8spzxWppcykYPFc9bM8o3Nx7VvaZGABxzV1IpKwQbbNdlQrnrVRypb7oqywK
r7VVYjPpXOjQayIw5AFV3gjB3BB9KuxiNuAQTUVwuDx0oT6BuZGoSRNwFAIqjGC6kAVoXtqGywFZmZImIAI
rrp2a0MZ76iPblTuampMFfAHFWg2YstzVUkFvuYHrWid9yHpsWZyiwFjjpXnnia+jEjLHjNdNrd8Y4io6Yr
zvUpPOuCe9dmEpa3Zx4urpZFdUa4OWq7BaIDjHNR28bYFXkBUAjr612yl2OGEerGvBsHTioGAC1cDkt83I9
KdKiNHuC8+lSnbc05exks2CRTPJ53E8VfWEOeeKZJFtyOoq+YzcSKNtgyjE1ZhuMn5uagEe0ZHSmBwrg4pN
XGm0aJVJDkVaitwAD0xVa1kjfB4HtWgzqU4PaspN7G0UnqV7ghl6dBWTKBuq3cOwfGarSDOMVcVYibudjBI
BJkdCea0o5csoHArGhGxiKuQPmRRXFOJ3RkdXbhTHVK9bMnyjFWbQYh3H0qlPJsZixrjiveOmT0KUi/Md/I
rC8SNutioPHpWrcXIJJ61zetz7xgGu2jF81zkrSXK0coi4dvSpc5Xil2kuadtA4r0rnmJDoh8w4qw0WQPWo
Yqv2kTOwIHFRJ2NIq+gyOAgDjmrUce3BNSdJNuDmpXUouWrJyuaqNgZV25A5NV/JYNnBxVizVpZMdq0ZIGJ
CkDFQ5crsaKPNqYskRYYNMW3CkcVszwqmAaiARxtA5
FCmJwMvy9jhlFbemyksAOnrVKSEhsL0qS3k+zkKRxSl7yHD3WdvpAGQB1PetponIAU8VzegTYAYdK620lV1
yw4rya94yPTpaolsrYQgMcE1s2OZX/wBn0qtDCJEBWtnRrUl8kYHvXLq3qXNpItxRAAYFXowxHGcU50VAAC
M0/wA9Y4if1q0jlcrkWwoCzuMVzuqXWZSA2RUuqX7/ADKG4Nc8skkrtg9Klu+xvThbVheyAD2NYN9ErNkCt
O4Zmbac4qjd4AwvWtKasXLVFWJQuABxW9YAALisVASMDrWvpucAHrTq6oIaGlKrFOtVJbdivvWmyBotx61W
LkA56VgnYrcw3aSFzsyKhmlmK8sau30mSdoqixyp3da6I66tEsFncJgnNV2cMfmGakAJzjpTGeOFgXq0uxL
BUGcnhTWdrN7DbQnawz7UajfggiM8VxmuT5JBY5+tdNGjzPU561VRWhV1bUnuCVSs6K1LHexx9algUMM1bi
i3/Kfwr0laCsjznebuyC3jDPgdBVyVEAwvFM+yyQNnsaGUs3JqW7lJWRCVGcUgJ3YNSSqVX5TzUW9c8g01q
J6E8cHmEBSBT76zaKLdjPvUEU21xjrWkb4SQGOUZ4qXzJlJRaOeikySvSkYKrEtzmppYf3+VHBNWHsC8e4V
rzJGPK2UM7BuSpop3IzmoWjZCQaVUxzTdmJXRHczPuznpT4ZN6ZNQXIpsTFVwKq2hN3c7Z3BY881NbPscE1
Xsbd55zkcZrSmiWM4PauCTS0PRim9S/8Abj5e1TWVqN4w4XJqSL5mps8anjHWs4xUWXJtoyluTg7qxNSm3u
QtdDc2oSJj361yd2xWYhuK7KVm7o46zaVmRkYFIMDrSn7mTUOSD6iuhHMzRtEU8npWzavHCK5+BycAdavh2
XbkcVlONzanKxthVYb0AJprREn5hwabpcqseTwK0ZJY+SuDXM207HSkmrle38uAY71OshkPHT1qtxIeakEm
xdoFS0UmS3EKGIknmqMcIU8Hr1qx5hwS35VC0oVgexpxvsJ23JJYyI/k5qtsJ5YVsQRefb7hVWWAg7SOaIz
6Dcepr+HyqR5boK6K1vndtqhdtcrZQlAFDda1bWJ0IwxrjrQjJts6qUmlY7jS5d5WutspF8sDpx2rz7SpBC
u52wT0restUOcdq4H7rNZx5kdHIFBOGNUb27EUZUHNVZ7wOuUbmsi6uSD8xzRe+wow7kUvmTSMWzjPFLGgj
OT+NPSZDgdzVspuj6VJtcy7yaMg8YrBuZgZSErprm3WSMgDB9awJrQrIQBn3rak4oiV2QI8gIyBitOwmBYZ
4rLmUxiprNvmXBq5xTRMXZnWxFWi6mqspwTilgb90Mc0jnPWuY1RlzsEc5FUbt9x4GK1blUx1GazJ2I42DF
bQsyZFfeUXIrK1WUOvXBrSZgGIasXV5Y4jksK6qS94wqPQyrm6WCMljzXJX8zXdySPWtTU71ZmKrVS2twz7
q9OnHlV2eZVlzuyGRKY1AGc1r2NtIcMBVrT9PMrAla2VtBAQR0Has6lZbI1p0XuZ1xZs8XI5FZstnKgJAzX
UPPEy7ScGhY7fg7gc9qxjVa3NnSTOHmWQHgGljTenI+auyurGCQEgAcVzV5CLeYqvSt4VVMwnScNSO3tVkU
k9RSLCN+2tC0KrGOlPithJISO9Dn3BQ7GXNAYucVHFd7OG6Vs31nJHGcrkYrCuIiM/LVQakiZpxY6dBMpKi
s6dTG9aljIqrtfrUGolNp24rSLs7GcldXMmcqw96ag+UU1iMnNN3+lbWOe56otv8AZFJxgmqMr72Oa2NYcF
CRwaw4/m+teVB3V2exU0dkaGnQh26cVJd22xh6Vf0C3BXc2MVPqcShDj8qxdT37Gih7tznruIGAk+lef6mC
LpuO9ej3g3QnPAArz3Vh/pbD3rvwr1ODFrRFQMSuKj5qbbhfembT1rsOIs6XjzwW6Vo3siucRjGKzbUYHFW
VILAfnWclrc1g7KxYt5CgAXqaurIVXrk1SjAB4HSrNuPNcDFZyNY3JopjuqwkuT61FJD5b8EYqEuEyAc1Fk
zS7RbluYyMcZHaiGMTnJPArPWMu+RVkM6cKCMUcttgUr7m/YNs+UfdqzMkbDORmsmynYICan3mRxt71zSjq
dEZaFy2VnlAUV1OnWBYK0nAHr3qlomlyeWJGrf3COL5zgiuKtUu7ROmnC2rGTRxxjIwfaqYuTvwp2+1Vb6+
y3y5xWetw3mlmPFTCk2rstzR1ltN8uWbFR7kll+8DWNHM8v3DxV+yKKPmPzVm4cupSlcuhkU8DJHSrEdwdu
3PNZ+fnyBU4kRR6GoaKJpJSBz1qjM68kmlmdmBOazJZSz4qoQuJysJN+8JpbNSrjio2cAcmpLZyW4rd7GfU
6CFh5QxQ7/LnFMtRmP3qO5YquPSuW12akEpPJ21VuHVYyTRPfKiYbrWXcXBmUqM1vCDe5nKSWxRur8CQgDN
c3rUryv35qzqFyttKQ/WqTXSzHpmvTpQ5dUcFSfNoZsFoS5LLWhDb4YY4q3aw+YemKuJahGBYjFaSqERpl/
TMQQbmGar3N6WlIx8tWTKhh2IOazZlKvkjiuaKTd2dDdlZEr7H56Go1LBsKM0u5WAxTCWXJWrSIuOuJ3jXJ
6VlzyLP1HNW5Zd6kNVVIwW6YNaQVjOTuV7Z2WTaw4rptJthKQwOcVnLZgpuwM1Y0y4e0nw2dmelTUfMvdKp
rlepo6ztjjAP5Vz8sUcynbgn0re1fZcxB1cD2rNtbdApKkbqzpO0S6ivI5i4jMcuCMD1qjdttHJzWzrLjcV
xzXOXTknFehT11OCr7uhXc9T1qNeRzxSM2enao91b2OW563rExlmMcfrioI7R4kDNVoxj7YWb1q7OBLGQg6
CvH5uVJI9xx5m2xNPufKh64NJNdmaTg/L3rGmkeInbS2k7FTu60vZfaF7ToWtTlHkFR3FcHfx5nJrrr+QNE
xrkr05c114dWOXEu5X4PA60NESMimKduSOtSB/l56V1bHIPhGwZFSRrl8jrUUUmTirkURzkVLdi4q5IijBA
61ctysKZz81QxxknmmyoenasnqarQSad5XAU8VMYdij170tna8irhtjIR6Ck5JaFKLepFBGeOOKtugCe1WI
oQAFUU+4g2xnb1NYud2aqGhVRlKbV60lvK0VwM/dzUEbPA7ZHWp0IkXLU2hJna6fraRwBfQVUvtYEknJJHt
XOg7IsZqSLOPlBP1rl9hFO50+1k1Y2o54phzSTBCQF6VzlxdtBJt5yangvzxk8mr9k1qifap6M6i0by1wOl
WY2Cnc2Saz9PlSWPGeauqWWuWS1OiL0LiTlvuikdmY89KgiuVVCMc0skjlQxGBWfLZl30HXExVDtNZwlLHr
SzzevSqgfcx21tCFkZykSkln56VdtiFIxVDeeAatwEkDFEloKL1N6BnCAqabNl85NRWzkR4700S4kOa5eV3
N7ox9Ti+YkcVUikESNuPNa2rgOvyda5TVJvIQ7zg12UlzqxzVHyu5kawgurrg96s2mm+XEG4rPgdZp92STm
t+3YFADXbNuKSRyQSk2xkACPgip2iZ/u8CrUUCuo21abTnMIZelc8pq50KDsZFtG8cnzEGtFYYpl+frUD2k
kfJBzTwrAZH40pO+qBK2hQuYBFIdv3aVQhXA60XAZ5B6UqxgN9a06EW1KsluZH+WrEdgdm5hzV2CEcEVelO
yHkYFTKo9kUoLdmakQWOs65bcxGcGrM82CwHSsq4feTtNXCLbImxrSSqSrNkdqltpmUHPWq6Pg4PWnvIFUm
tmuhkn1M7UyXck1z9ycMcda1NQuV3EZrCmkLOa6qcbI4qslcidsH3qMk0p5akfINbnOz1gXXmSkL1JrqLOz
2WIkbvXK6ZbbboFx3rsLq6WKxC56CvBr7qMT6Cl1bOT1khJiAKzhNj6Vcud11cHaCRQ+nMsecV0RaikmYSu
3dFC6fMRx0rmbxiZePWugvv3cZTNYTR/OSa6qWhy1tdCpIPlHaog2OM1ekZdhBFZrnLHHWt46nPLQlV8NkV
r2l0pQA9awRU8bFWHOM0SjcITsb4kwwIp+/e3vVO3fbHk81ZtSNxNYNWOhO5PvMTVp6ZcIxy1ZLqzZzTbYS
RybVyQTUSipI0jJxZ1UjpGQy8k1ZjKyKCwrEUSFQTmnrcOgxmuZwOhTNC5hiLcgVGbYBcqM1lC6kkn2kkV0
NkVSIFznilJOCCLUmUIIC83z8D0rUCxLgADNNASV8qQKY0yRNhsGobci0kihqttv+ZVHFZkLKH2txW3d3Bk
hIVOMVyF95sc27kDNdFFOSszCq1F3R1unP5Tg5rVa8RFyWritM1E7grmuk8yKSMMeaxqUrPU1p1LrQvwTB3
3A5FT3F0dgGOlZ0TKF+XgVYH3cj5qycVe5qpaCCTcDuquZAHJXpUzkbemDVZhjkdKpCY95N3fBrQ09sMozz
WRznNX7BsyLg0prQIvU6yML5HTms2dx5mDxV6J2Nvjb2rNuF3PkmuOCszpbI7l8oSOledeLrorIVBrtb+4C
AgN+FeYeJ52kvdvbNeng4e8efjKlo2LuhPuOT0rrrcxsowea5vw9EEiBK5rol2Lgj5a0r6yIoK0S1EzJJx0
rbtb7ZGAwzWXabXXpmpZIWYEKcVxTSlozri2tUaM11FMhAUZrOEahiWPFV47ebzAoJrTk0+SOAOxJyKVow0
uVrLWxmTRqGytVLpmUD5cVckXrzWfezEAA9q2hqZS0LGnyZPzGp7+b9zjNYT3YTocGoJNRJGH5rT2TbuZ+0
SViyxDI2DWYJcSMrcelTs/ylkORVTcHc7zg1vFWMZMuHZ5eR1qlNLuUio7idYwQGzWebr5jWkYMzlNFK8z5
pz0qjIuSTWhcMJKpMM5rpicclqQdKHXpTgpOfams2ODVEHsRwkykdM1ZuWMicnqKyIrjdcbc8g1qy/NEAOt
eLJWaPei73KloqxzYrX+TyzuGeKzo4gDvbtUUl4FOKmUeZ6AnyrUxtdhHmMV4Fc9KR0rotWlEinNc3MME13
UdtThrblGd+SKqH73vViY5JNVGbvXZE45DxwM0/JyDUI+Zh6VNjGBQSjUtmDRc1LbbvNGOlULYkcCtCNwgz
61jJHRF3Ls8h3gDpVmFxGynGaynugOB1qOS6kTnNRyX0NedLU66GSNo8kjNVX2iTJNc5FezHoTV+1nMp+c/
Ws/ZOJaqqRpgxmX5RzWgC7IFTJFYqIRIWU8Vt6TOqMGkrKorK6NYO7syyqNCAx6elVLuQM3Aq3qd4HGEFZq
ygMC3UVnBN6s0k0tEadmqvD83H1rH1mOI5VRzV3zi6YXiqc8LEbmNVDSV2TPVWOcnxbuMdfWug02TfGvNYO
qR7iTGelS6LdFW2Me9dM480bnLCXLKx2CRlgMGrKP5YxnNV7Z8xjBp0mQa4Wr7netrkj/AD81Ax7Zp4bCfN
UQkQk8UITAAj71WbBtsqmqbzHdU9kN8y05LTUE9Ttrdg1rn2rFnkPmuM1o2mfsxHbFZVzxI5PSuOEdWdMnc
5nxDci2R2J5rgHY3d3uY963PG95iQoDXO6W5eVfrXuUIcsOY8XEVOapynZaMBGqqRxWxcLGwG2qmmwhrXd0
4pu2QPhTXLL3pHXH3YluK7NvwKuw3xfGKxjC5b953p+427YqXBMpTaOlidiQQRmtqGdpLfZIMjFcRFqEisM
Vswaw/kgNXLVot7HRTqoXUQkUh44Nc/eEykha17ycXKk5rLQDzOelb0lZamVR3ZmGPs45prQK/QVq3sKsmR
1qjI6xLz1rojK+xg423KRJgypPBrKv3ZDlWqa8uS7nFVZgHjz3roiras5pyvoiqJsj5jk0hA25Bqs4wxxQJ
Noraxz83cVmwKajAnmo5G9Kj3HNVYi5PKNuSpqmxyac0h596aKpKxLdz0O0lJ1A4PGa6sEFB9K4LSLgmcE+
tdat6m0AEV5VeDuexRmmi5OcQkCucu2kBZh0FbYlDJjOafJDE1qwIGTWcHybmko82xyUk5kRs5yKosm9WJ6
it68sdkbFBXPyloywrsg09jjqJrczJzhiKqSYxVu65bIqtIMriupHHIbFk/QVOuDVeI44qyi8U2KJdtVVuD
Vh4wo68VTi+UZzRJc/LjNZNNs2TSRYhXdIW7YqvKSWIPTNEcxVCPWomJZqaQm9DWtFSOHc2KjmfD7kNUzKy
ptBzmmK7A81PL1K5+hvWUzNj9a14ZVVc5rm7Ofyzn1qw1yTxmsZwuzeFSyN6a6Vhz2qESRuc55FYjTNmm+a
QetJUrFOrc2zchCMHpUNxeFs88ms0EnnNPcAJnPNHIhc7ZXmZuQOaqRuY5hjrUplKHnrUDkFvet0jnkzstI
uSY13V0caxvDvY1w+kznaFreNyVhK7jyK4K1N30PQpVPd1Jr5hu+Q8VUWRl61DGz7+eRU5Hcii1tAvfUcZQ
xqzZ/LKpqo6DbkcVJYuXuFUnpSa0Gnqd7pqZtdzdCK5/XrlLfzNp5rct5Qlnt9q4XxVOyrK3auWhDmmdFWX
LG55v4kuzc3zgnvTtET94v1rOuiZrxiOea39GjCEZHNe9L3YWPAhedS529gFFqAOuKQP5cnSotDYyyBTWtq
cEcaAnANeXJ2lZnrxV43RV8xSQSKp6hIJH+WnC5XbsGDUUgUnk4qoqzJk7ofbkM6+tahRBGOxxWLAXilzj5
fWn3c7HBDYolG70BSstS7hgxweKik+QnPAqC3vMgA4zRf73hJT0oUXezBtWuiOe7CJgHNZN1cFh81VfMkDk
PUMkmTzXTGnY5pVLjZjn8agLlQQehp0kgCH1qozMTmt0jnkxJcZOKruRjFSNzzUEh5rRGTYw0mecUueaaw5
qiBnG7mnnjpTO9DvzTEdVIrWgVgMZ70+yv2eU5PFbGoWiy6enHIWuejsniJNccWpLU75RlB6bHUafdh2AJr
fVAyD0rz6zmkSYda7HTr3fCA55rmrU7ao6aNTm0Zcu4wqYOMVyOrWZDMy9K692EqENWXdwgqwPSopS5WXVh
zI4KdSpINVXB9a29TgAc4FZFzGQuRXpQlc8ucbMhjX5xzV4EADis+JsHmrQfp6VUiYsnf7uegqu5BPFI0wO
QTxTcg8ihIGyRM9M8VOgwM1Eg4zViJAOpzUspDFGTluKVsZFSPHxuxkU1FZnHynFIqxMCAg45q5BbOyZIP1
qGKHe446VvW8e2DkVlOVjaELmK6FG9aQDcDxitCRPMf5RimfZSoJ60uYfKUiSMAUkjkAAnmrgix/DSGEHqv
NF0HKzKuVx82aqq25xmr15GUfB6VQAw/BraOxhLRmzZErhga1PPOBmsWzfAx61q243D1rCa1Oim9C9FOAoB
FSGUsMYqqsZzVhDg8isWkbpskXJHJqazQrOrD1qMOMYAq/pkJlkArOTsi4q7OptV32oz6VxXjVkW3kUHmu/
jgMFllvSvOPGRysh2kisMNZzNsRpTZ5ejhbk59a6TSN0jA9q5SU4uienNddoLjygK9urtc8PDu8rHSWLGFw
wODV26ne5XBJrFW7WNsNzWjbXkb8Y4rz5xd72PSjJWsRIgR8FqZeZB4NGoMFOUqOznErYkGapfzCb6FR7mU
cEmmvKzR5DEmr17HGVO0YNZLgq2BWkbMyldEf2qQE4JBFXLPU3yVk6VnOp3ZqeAxk84zVyimiIyae5YuWTc
TgVmTMNxxU94M8KazySDg1UFoROWokjHpTN3GMUE5Oe1NLADJrUybGvwDzVY98mnyPnpUZqkQ2MGaUtx0xQ
2c8VGfemQG7ORTCPegkZpCaok7e31kSxrGx6VK1wj8DFcdby7ZBzWjHNluG5rmdJLY7Y121qdLBah/mGKlZ
mhXPSqdnfLHbgMeaLu5EmMGsOV31N+ZW0Ny0vN4UE1bkKMnrXMQM6uu3Nb1mrMhLZ6VjOCjqbQm5aGNq0Y3
E1hTxgqSK6jUYMqTzXO3CFGI7V00noc1aOpjSRlTTWkOMGr0kYYGqYQByDXSnc5GrDVAOKmX2pTHgcdKapG
cCgNiUH5angBK5qtjNXLVQTjNS9io7luI5XB6VMjKoIxURAVeOtPiGRk1kzdFq3XcwNbtuvmR7AO1Y1qpJG
OldHZ7Y4845Irmqux00kU/s6qpPpSAbjjFTy4ySaEUEjaKi5pYgMG0FsVTflulbjFVjIIqk8AcEr1ojPuKU
exialCWjyRk1gSRbGzXYPExQ7q5m9j/AHxzxXVSl0OWtHqJatgCtvTmBNc+GC8A81q6VJzgdadRaE0nrY34
wSwGKS7+RRirNspK5IqlfZLVyLVnY9ETWp+Xmuh0HiUHtXPWy4UZ6V1ehR/LuUVjXehrR3NrUrr/AEXbjtX
B+JoybCRyO1dhfvvwrD8K53xbGq6Q+3rissPaMkka1leLPD7og3TfWui0N/lVcGuZuSRdNn1rtPC0SNGrdT
XvVnaJ8/h1eZ0enaOt0u5v1qG4gS0mMY61f/tIW67BxWTdTefcBs968+PM3rsepLlS03HSgsOaiCNGNwrTj
jDxjPWq93HsT5etNS6EuPUzprtTwQc1QldzINhq7JAGUnvUFvDiT5ulbKyMZJtlmztjMhMgqjeW4jl+U10V
sQkXy45rI1NF3E85NTCTcipwSiUVYYyearXDLuwKlRSTiklty3StluYO7RQZsVC7buMVYliKNyKiYCtUYsg
I5oqTb1poHFMkZjJqCTrVk1HKKaE0VycCoyfepHHNRMOaozZOvLCrkOdwINUrf5j1q/CyrwTUyNIlxj8gwx
zTreV965qGNwWq7DGGxjisnobrXY3bN1ZVyBmun05VaLBxXH2hEZGTW1bXpTABriqxb2O6lJLc1J7MSMVAz
XM65YmAnIrorO8JmyelZHi66B6daii5KaRdVRcGzkHBTNUZc7iauSSAjmqUn3+ehr0onlyLERzGQaasWOaW
EgcHpVjAIGDkUNjSuRBe9TRKQcinonOSOKkRT0FS2UkSR/Mw3dKsWyM8xUdKqEEdKks7hllxUNaaGieuptQ
xmKUZ6VvxFTADWJaP5r4JzitMyKsQUGuOpqdlPQY7gtgVdt4G25UZrPmIQZXmtCwuCkWetRK9tC42vqP+yS
kksvWqV1BLEc4IFbUN8smFYDNQahluQMrWcZSTsy5RTWhh5fGNvFY2oQo8h7Gul8ouGwMcVzd7GyzM3YV1U
ndnNVWhgXMZjk71p+HzuuVyeKrXwBXPepdBbbOK6pawOSCtM7tlIjBUVQnwRz1q/bEyJjNQXEPJFedF2ep6
UldEVvlyFFdjo8RjgHrXMaciq4J9a7TSow8QYHgVhiJ2NaEbmZeSEXGD1zVHxOgOjOX44rU1CESXOR2NZXi
sN/ZTKOeKmk05RsXP4ZHgepKftrY6Zrr/AAdMuApNcxqibLl8jvWj4ddllBU4r36i5oHztF8tU7m7tDKdy9
KSK0YKOOa0NNmVoQHOatNGMZUV5rm1oeuoJ6lCJDECWrPupN8pGcCtzaNvzc1m3NoSxYDAohJX1FOLtoZ2/
BwRxTjDuGUq4tmHODVgWghA5rRzRCg2Q2MRxg0s2mNMx461YDhR8vWrltdFRhqycpLVGiinozlLzS5reTIU
4qGNcfertZpoZUbzCM4rk7uMeYwU4Ga2p1HPRmNSmoaoybsK2cVn4PPFak0J5Aqv9nJB4rpi7I5ZRbZRI9q
RR83tVlo8dRiogOau5nYZPHxlaqSdK0nH7s1myckjvVRJmiEDINQsOanxxgVE3WrMmQJKU4qwk2cVUpQSCK
qxCbRpwy4Yc1sWtwOOa5xXq1DPg8VlKNzaE7HU+YpUHPNSQ3QU8niucS6boTTvtJyMHisvZnQqx2EWoCP5s
8Vi61qH2qbA6VmfbTtwSarvMWbrSjSSdxzruSsTNjrmogdxJNMLGkzyK2sYNk4YdKswMOhqoq9+1OBwcg4q
WNOxpKcCpIiRniqUM4yM1oRsCRWbVjaLuOK/KTi
o0iw2R1NWpGAjqOD5pFA5qUy2tS5pqukvzHg1ssgCgk1neUyspFaMaFsBq55u+p0wVlYl8kPHgGooXaBtp5
FXdm1Rioo4w781kpdzWxJDOm8EjFbHySQriqkVlE6+9R3EhtsIp5rKVpPQ0V4rUlkXCHy+M1yWtkwq2e9dU
0oWHcx5rkfFL+YMr0rbDr3rGNd+7cwZJPNX6Vc0Yfvxj1rLjkwCO9XdEn2XyI3Qmu+S91nnwl7yPRbFQYBj
g06SEnmrttaqtorqRyKh3ZYjtXkc13oevy2Woy1jTPIrfsbjyU2/w1iKhDArWjCreX6Gs6q5tzSGhYLebcH
Aqj4mX/iXv7CtPT0CgtJ2rI8UziS0dU445qafxpIc/hZ4drZDXT465qTQWxOFzimavHi8f61DYsYrhWPTNf
R2vCx81e1S56Xp4IC5HBraSNhHu6isHSLtJ4UVSAa7G1VHtduRuxXj1pOL1PcopSWhlR7HbBYA1Y8uMISxB
FY97DNFdNtPGas23mMmGzScdLpjUulhjhS5MfHtSmNmHNV7ndGxKA0sd6AnzVdnbQi6vqXLazDtg1oT2EcE
QJ5NZtveAnINTzXhkGCeKykp3NE42MjVZVXIQVhNIzEjvW3eRmUnisqSLY/NdlOyRy1LtkAicsCaYwIYmtS
NMqCKoX5CAjvVp3djNxsrmZcdTVTo3NWGbkk1Wc85roRzSEkfA4qk/DVakGagZatGctSFuO1MZc1MVJFRkG
qRm0Z5pB1pe9KBVmQ4GpY2wRUS08DJ4pDRYL8ilD5qLtSx9aVi7k2c8U/pSKvFKo45qSkPXk4NTRR7sk9qr
5INXbVgcAmpZcdRQhAGelNMe5varciALkGmJGWHFTcvlIFiAatPTk8w4NVnhZVBxVuwO0+9TJ6FwVmaNxZj
ysg807RreISnzTVSWeQE+lR/aGXkdTWNm1Y3vFO5vXbKr/J0FTWsyyEAH5qwIZpJm28mrEayW8m8k1m6elj
RVLu50DM4YBvu1OrIMEdayotTjdQHOKfHcRuflesnBmymuhsicnAjqreM+8E9afDdRpCenSs6S+RpCCeM1E
Yu+xUpKxYnJePOa5rWZNwIrflOY9yniub1jCgnPNdFFanPWehzznbISKt2DYu42PrWc7Zkq3p5L3CgdjXdJ
aHnxep7NoxNxp49hVQh1nKkUvh5ytkoP3sVbEbNNuZa8N+7JnvLWKJ7a3+XJGatGMqKs2UYZAO9TtCGyK5Z
VNdTdQ0K1upIx61h+KrUpauy9a6VIXiBYjpXPeKJjJaOq8nFaUZPnViKi91njGpxM1wxPrVIIQw4ranjZrp
gw4zTnsogNxbmvoFOysfPOnd3HaTKIyp3Gu70i78xAN1ecxrtkxniuk0u68lB81c9eHMjrw9Tldjq7wEnPF
Mtp9v3gMVmpfecACan84LHx1rj5GlZnZzpu6NCdYJYye9YF0IxIQvSpfMc5OcCqsuHY4rSnHlM5yuSQYByp
4qVnkc4QdKgt/vgHpXRWy2yxclc4onLlCEeYzowfJJkwDWHfnMpI7VoaxeIkhVDxWHc3GeB1rSlF7mdWS2L
AvfLjxWNd3JeRjUk0hxzVRhuPNdMIpanLObehGZSWx6UhYE8VKtu7chaYYyhxitNDKzI+W4xUvlZXmprePd
UkqFTgCk5dClHqVZIgFHFQtADitAR7yBRJBg0KQclzkhSgUnSlBroOIctO6UwHFKTmkMkRsg0+M/NVdSQ1T
xn5hQNM0lVTEDUVAY+WBSxgmszYTFTRDa1Kqj0p4Ge3Sk2UkWIzv4zxVu2jAIqrbjHNaMC4GcVlJm0Fckfa
4xgCqL5gkyDV5gCvHFZt0x3damBU9B5uCeCOtS20ZlYVWt8SDkVuaZbDcDmnN8qCCcmXdPgjjRmYAECqN/c
BiVBq/esqIVDAHFY6RCR85zWEFf3mbz091Fby5hztJFTRzOhAwQK14VXYFI4qO8tU2/KOavnvoyPZtapjoZ
i8W3NRtbbgSH5qGMGEDcOKm39CpxU2tsVe+4qiZIipJ2iud1aVncgHpW/dXRWEjNcrduTITmtaS1uY1pWVk
VXXmtDQY99+npmqJBIzitnQYtsqsOua2m7RZhTV5I9MsU2Imz0rWXOB8tZmhyCRQCOa2pAYlzivBqv3rHvw
2uS2LHf6Vf+ZHBxmsVtRihGcDNW7XVY5yFBGa5pQk9bGqktrmpdPm3OBzXn3iO8MZdelelxWpmtyx6YryH4
kP8AZbhgveunBxUp2MMTPlg2cTqFwfPLLUUdyzDL9KqbjK3WkclQRXvKOljwXN3uXRMpcYrV0+I3R2q2K5k
PtNdH4YmLzgCpqKyujSlK8rM2YdOmiPDE1a8mWPBbOK218uKNWkIzTpjDNDwRXnOq29T0lSS2OfuJQiYzis
9ZmDHjIq/qNsWY7Tmqap5fDjNbxtYxle5UuLx1yBxVQ31wB8sjVZvlVjwMVSaBguVbIraKVjnk5XATu7EyE
k0u7jJ60xI2cgYwauR2pbAI5qm0iUmyqBv61Klvkjir/wBlwBhSKsRWxZT61DmaKmQ2aRgENWff248wlTxV
u7Btj71Ukl3J0oje90ErWsyK3AAwOtOuA4GcE0+zjyenWt1NKeSDcfSiU1F6ijByWhmaZCJhll6VNcWnzdO
K0NOsnSTbjvWvNpkjBCFP5VjKqlI6IUW4niWaKTpQK9Q8QcDzS5po6UtACip4hUC9anj4pMpFmM84q3CvHH
WqUfBq3A/PNZs1iWFGRipkjOPamRYq4CqpzWbZtFDY0IH0rUskMkYrMjcZGK2rJtqZ4wRWU2b01qVriMpkV
RlhBH1rTuWLE1TkGBRFhJFSFfKJq7FfeUuc8iqTtuNVLgNnC96vl5tzPmcdiW7vnllLE0R6gY0wODVeG1kY
7iOKjvUMRGRVqMdjNyluacersv3jWjYX5uJBkZrkxhwCOtdF4dZEcb+lRUgkrmlKpJyszdvEHknI+lZEkwj
XGava1fxhQqEVzM0+8nB61lSg2tTWrNJ6Etzds/Q1Rcb25p3uadXSlbY5W29xFXpW9oycjHWsuCPcua6Dwz
bGS6UHpmsqsrRZtRj7yO68PQgJuPWuhAEilWHFULO2W3UYrWiYG3OBzXg1ZXdz3IRsrHD+IV8mY7DxTfDjq
9wM54NR+Kml88gCjwuD5wz1rst+6uct/wB7Y9TtrtVsgvtXlHxPs2lzMvSu6851UKa5zxYRLZurc8VhhnyT
TRrXhzQaZ4hGzLKR71NKpIz3pdQjEV02OmaYGyOtfQ76nz1raMgkHFXdE1A2dyGPQGquMk0wrtNDSkrMSbi
7o7mTWftYUKTirttLJsAXJrhrC58lwSeK9G8L3dnKoM3WuKtD2a0R6NCp7V6shXzC+W4q9DYeeMsK0LyKGW
YGDG2r8BjSMJxk1xSqu10dsaWupw2vacY8GMViAsgwa9G1u0HkFiODXDXkChyVrqoVeaOpy16XLK6HWcaSK
G6NW/Y2UbruYfNXN2m5ZQvauuhkSOyBB+bFKs2th0UnuUrmNUcgCmwlRxjmmNN5smacpROSeamztZl9TO1q
Ald1Y8a7l245roL5zKmB0qpZ28fnZ71tCVo6mE4XloWvD2mG5vEVx8ua9LbRoltVWMA4FcrpksNthiRuroL
PWD/EflrzsTKc3dHfQjGCsyrFp4iuhle9dH/Z6vBGQPWqkTC8cMMdeK620gQWUW7rzWKk5PU0l7q0PjCjPa
k70DrX1B8qKKWk7UUAOQVZXoKrp1qwMY60mVEkj+97VPggVWjPzVdjwRzUM0iPikIIyasNKzYC9KrZUAmp7
FgT81Q+5pHsTRFj0rVtJGCfN0qKFEJ7VcdNsQIXisZu+h0wi1qNds0xwpHNPjXzB0pJI8HmoLM+RSCcUyZA
Yww61PKwGQagVwXAJrVGLJdMuAZAjDipNcgRlyoFTmGKGJZVA3elVNQ1COWLbgA1K1ldFPSNpGAibHxV5Lj
ygMHFVC+STim43e9dDV9zlTtsTTzNK/3iaapwcUkcXfvUwQHtzS2HqxpGADmpI/mYYpjLheTT7YZbApMa3N
e3i/d9K6vwvbESqwHQ9awtMg37d1dnpEXlKNveuDETsmj0sPDVM6i3ImIQ9qkvZUsrdiWHSq9nGwywNYniw
TPbnDEV5kIKUrXPQlLljc5rWdYie4bJzzS6HqSpcAjpXLX6lXJYUukSM90qoe9ev7CPJY8r275z177V50AZ
euK53W5HMTbulbek27fYlLdxWJ4h+TIxXn0klOyPRqt8lzzfWLcFiwrFb5TjNdjqkStAWAwa5CUfMfWvapS
ujwq8eVjQ2e9IWzTGBHNN3GtrGFySNtsgzXSaVeBMAHFcyuCRmrtsxRxionFSRpSk4s9CsNRAxlq0rO4ae4
GD3rjtPfeATW3pt35VyuOlefUppXsepTq3tc6LxBcMlltPpXDJIXlOea6rxHdxyWY2kFiK5C14LE9aWHjaA
YiV5l0juBV61YyJgsazUYnitayhAUE1c9ETDVkdynlrxUdpDJKw64qTUGJ4FWNCUyuFzzUt2jcpK8rD5oAE
245rKmt3jkJXNd//AGUnlhnIyapXumLyVWueGIV7G06DZx8LTpIN2cV0tl80QZjgVQnspDNlQdoqVJDGNrc
AVpN8y0IgnF6m9Z3n2eRMNxmvR9LuI5dOhYtyc14rNefOu08A12Ok6uyWEYLdK5p03HU3jLn0Pmr6UuKKMV
9EfMiUZ4pcUhFADo+tTZwagU8jFWOopMaFQjdVmNu+aqKDmp0I6UmWmWC2adE+01WzRvORU2K5jXjuCm0k9
K6/SlS8s19TXnu8lOa7PwVdByI2PSuavG0bo7MNO8uVl6/tTajKg1hXN5jIIwa7fWFDQkjFeda3IFlIHWsq
D59zbEr2exBLOzydaRnIOR1FVoclhirDHjFddrHDe+oPdysuNxxVRjnrVjb6VXmxnimkhSb6jM4NOjbnPeo
yaVRVEXLSyYbmnebgmqozmpFGTSsUmSMxkGAKv2cIRlPWq0RUYVa2NOg3EcVnN2RrTjdm9pcG4KRXXaemxF
BrF0iEDaMV1FrD8gzXk4ietj2KELIuQOUTmqepILpCpOa0IwrJtNI1qijce9cKmou51ON0ea61orMxC96PD
vhqWK4ErdM5rvrq2hzzyafZWjs48rGK7PrcuSxy/VY8/MXLSHFsB0wK5XxOg3cda7OaJoYTv9K4zXSWfI5F
Y0JXlc1qr3TjNUjxbE4rirrCyGvRdXVTZsQOa84vhiZvrXt4Z3R4uLVmQlie9NI70AZNOIxXUcQ08c1PayZ
YA1A3NJGxVx6UPUE7M6/T8IgJNXIpAW+Tg1h2VwGjANXopduSnWuWUdTvhPQs3rucZeoomwvvTH+cZbqach
AACjmklpYd9S7YRb3yelbMZCriqul2skyggcVfuY1iTB61zTld2OmEbK5VkgM2SDxUWnTixu8ueAaje6ePI
TpWXcNJMxIPNXGN1Z7EyklqtzuBrwmYAMOK0ItRR0GcGvKjPNat941oWOtlcByeKznhFb3S4YzW0j1WKKGS
AuQADXK628Mch2EEVh3fiqfyPLjbArJOoSTklsnNTSw0ou7HVxUXojTEuZck8VqJf+XEqhuK5Tz2Lc1K05w
vNdLp3MI1bbHCjrTlpp7U5RXoHkAaMVKI8ijZikOxEM54qZc03FTRAEc0MaQxiKQNjpSy8Go1oAshhilwDT
Ix604nkUii1GuUIq/4fuTbXoBOOaq2gzGTRgpMGWs5K6aZtH3WpI9GnufNtCoOTiuA1lcTHPrW1a6gyQc9c
YrA1OQyyFjWFGHKzoxFRTiiK2b5TinF+uar2hZpQq1tf2cxty5Hat5NJ6nPBOS0M5DhTzVeU80MSkhU0xjz
VJENhjjNL9KQNxSA/NTEPJ/Onx5PSmEZORVuxiMkgAFS9EUldl3SrIzOODXX2Fh5ZXaOaTQ9PMaKwXOa6aw
gxKAFzXnV6/Y9ShQstS7pWngRA45rWWPYu0daltk2RjIxTnTPNeROo5M9OMbIrCFwcilnWQxknoKtA4UCqm
oXDJAVUZNSm2ymkkYc9w7TbAea6bw+D5WX61ytrbyy3JkcYGa6yyVkjG0dK2r2SsjKndu5JrBdo2C9K4+aF
pGYHrXbTkvEQR2rmLlNlwc8A1NCVtB1InG63FshYEGvOdTTExIFew6/aK1uWHSvKtdQLK2K9rBz5keRjYWM
fGBmm7uac5+UVXJO72r0DzGycdOKMZOajD46U8MKALdrJt4rSjnwOayIThhV6Ns4rOSNoM1YXLjjvWrptn5
jgsOlRaBZCYjufSuvisBaw72AHFcVWqouyPQo0nJXZUN99kQKgAHSsue6aaQk9DVXW7z98QmMCo9NuI5GHm
kCpjTsuYcql3ylxof3ZbFZc+UcmumPlvGAhHSsy6sCzZwacJ9wnDTQ525cnJIrNLHzM9K6e5swsZytY7WoZ
66YTRyTg7jYIjOARW5Y2aJFlhzVK0URcVeWfYPas5tvRGlOKWrKt1EFJIFZ7lia2JWEo7VRmUKQBTixTXY4
qnLSGlziu080nQ0p5qMN6UpNIu4hODil3YprGkHNArjmfNSQgNUHFOQlTwaAT1L7Q7VyDVdsA07ziVxUeSx
zUottdC9BLhcVIXGM96pICOafkk9aTRSkXRc4XFQTuG71Cc0hPakkNyLelhUmDN0rr7aeK4j8tSMYriEJHQ
1atriSBwyscVnUhzamtKpyaGlrOkFXMkY4rn5Y2U4IxXWR6kJogslZeoxo5ygopya0kOrCL96JhHIqWIdM0
9489sU+GIs2BWzZzqLuIcswVR1rr/DelMSrsuQaq6BojSzKzrkE16PY6eltAOg4rhxOIUVyo9DC4dyfNIWz
tlSMAVo2qqjg4pbOBX/iFTfZmz8vNeROd3ZnrRjY0o5ldACvNDqcDB4qvbxuGAYHmr7QMFyORXK7Jmy1RAS
oXaRzVOeEu3qKszRsnJpkTZ9xVR01Qnrows7QA56CtCPb91arQtlsE4FTZVDlTmok29xpLoLczJEvJ59KyJ
wJ3JK4q7cxmU5qt9mkI+9irhZaidzNvbbdGyk5GK8s8X2AikYrXrVypRSM5rhfFlp5yM1elg6jUjhxcOaB5
VJkE1DV6+i8uRl61RIr3U7nz0lZi5FKDg02imSXYRnkVfiOB06VlwPt61finULzWckbQaOk0XUTaHf6VNq/
iae4UohKjpxXLvcHHynAqITbmGax9jFvmaOj28lHlTL4eSVtzsacrNGQVJqONhgc0+Z1UcGq8iV3Og0m/wD
mUSHit9ZoZ/uMMivO4Loq2K1be8aD5g3WuepRu7o6aVeyszotT2qvasN9pb5TUc+otcKQagg3E04QcVqE6i
k9CZs7sLzUoVyvzA1NBHt5PNWRC03IGAKHIFG5mKzK2KdKpbBApbmJklx0FXV2CJMgE02+qEl0Z51jrSd6k
PSm9q7TzBF606kHNO7UAIeabzTjTT0pgJk08cmmL1p6cUASqtWFQDFQJU6cmpZaJAvoKDGcZAqSM81Jn5qi
5pYrYIHNNZauAAjpTSg9KLhylZDinhsdKc8a4JplAEglbt0qRJiRg1GnWpVUDnFJjVxp+c4xzWzommvLKvG
aoRIpI4r0LwRDGRyoP1rCvU5I3R04elzzsyzplnLbSJ8hx9K6o2wuLcbBhsd62rSzgMIJjGalSCNHwqCvHm
3N3PXjaKsjl4oJYG2kE1p2ayoN7KSK7C1061kALRAmrSWNup2iIY96iUHISqpHGPdAHIQ5qU3bNHkKa7NdI
smGTCM1SuNPtonISMYqfYoarnKIZJ22uODVuPTnxlBXS2lhbFwfLFb9vYW2P9UKJUb7B7ex5w+nzehqA2lx
E4GDg16jNZW4H+qWo5LC2I5iWmqLJ+seR54beQpjHNU5rW6OdtelJp9sXH7oUXNjboPliFJUWh/WL9DyebT
rkglga5/VtNkeF94zxXrl+iYwI1Arj9d2xxttRelaRbgwTU9D5w8Q27W926kEc1lDkV3PjONHnYlRnPauKl
AXOK+goy5oJnz+IhyTaID1pppxPNIa2OccrYqQOO1Q0UDuWPNyOKIyS1RKKlj60ik7mhECQMVZMBK1Ut3Ix
Wgjll5rFm8UmVTDtOe9PySMVMetTWsSO/IpNlKPYrIH6AEmt3RbCa4YZQgfStfRLC3eRd0YNehWOn2sUGUi
UHFcdfE8uiR3UMLf3mziJNMWJBxzUYt5E5x8tdjLaQtISVqlqEaJEQqDpXKqzeh2Oglqef6q+GPFZgvWUAC
tzWY13niuauVAfivRp2aPMq3i9D//2Q==);\">",
" </div>",
" <div class=\"lgnd\">",
" Three-dimensional (3D) reconstructed ultrasound images can be helpful in
assessing intrauterine contraceptive device (IUD) position. This 3D image shows the
shaft of the IUD in the expected location. The right cross bar is slightly low,
deviated downward.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Deborah Levine, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6177=[""].join("\n");
var outline_f6_2_6177=null;
var title_f6_2_6178="Patient information: CPR for adults (The Basics)";
var content_f6_2_6178=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"11\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div>",
" &nbsp;",
" </div>",
" <div id=\"basicsTopicMinWidth\">",
" <div id=\"basicsTopicRight\">",
" <div id=\"placeholder\">",
" <div id=\"basics-graphics\">",
" <span class=\"basics-box-top\">",
" </span>",
" <h4>",
" <img src=\"file://www.uptodate.com/images/basics-graphics-title.png\"/>",
" <span class=\"openRelatedGraphics\" id=\"PI/16340\" rel=\"graphic_box\">",
" <a href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </span>",
" </h4>",
" <ul>",
" <li>",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?25/30/26086\">",
" CPR position",
" </a>",
" </li>",
" </ul>",
" <a href=\"#\" id=\"basics-seeall\">",
" See All Graphics",
" </a>",
" </div>",
" <script type=\"text/javascript\">",
" if ($(\"#basics-graphics li\").length &lt;= 4) {",
" $(\"#basics-seeall\").remove();",
" } else {",
" $(\"#basics-graphics li:gt(3)\").addClass(\"hidden\");",
" $(\"#basics-seeall\").click(function(){",
" $(\"#basics-graphics
li.hidden\").removeClass(\"hidden\");",
" $(this).remove();",
" return false;",
" });",
" }",
" </script>",
" <div class=\"ieSpacer\">",
" </div>",
" <div id=\"basics-more\">",
" <h4>",
" <img src=\"file://www.uptodate.com/images/basics-more-title.png\"/>",
" </h4>",
" <dl>",
" <dt class=\"basics\">",
" The Basics",
" </dt>",
" <dd>",
" <a href=\"UTD.htm?9/53/10068\">",
" Patient information: Heart attack (The Basics)",
" </a>",
" </dd>",
" <dd>",
" <a href=\"UTD.htm?33/39/34419\">",
" Patient information: Sudden cardiac arrest (The Basics)",
" </a>",
" </dd>",
" </dl>",
" <div id=\"tooltipper\">",
" </div>",
" </div>",
" </div>",
" </div>",
" <div id=\"basicsTopicLeft\">",
" <div id=\"topicTitle\">",
" Patient information: CPR for adults (The Basics)",
" </div>",
" <span class=\"view\">",
" View in",
" <a class=\"lang\" href=\"./es-419/cpr-for-adults-the-basics?
source=topic_page\">",
" Spanish",
" </a>",
" </span>",
" <a class=\"contributor contributor_credentials\" href=\"./authors-and-
editors/patient-information\">",
" Written by the doctors and editors at UpToDate",
" </a>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H29400952\">",
" <span class=\"h1\">",
" What is CPR?",
" </span>",
" &nbsp;&mdash;&nbsp;CPR stands for &ldquo;cardiopulmonary
resuscitation.&rdquo; It is a way to get blood and oxygen moving throughout the
body of someone whose heart has stopped working.",
" <br/>",
" </p>",
" <p>",
" CPR can save a person&rsquo;s life. It can keep the brain and other organs
from being damaged by lack of oxygen. It is something you do until the heart can be
shocked back into action or until it becomes clear the person cannot be saved.",
" </p>",
" <p>",
" The instructions for doing CPR on adults are different from the instructions
for doing CPR on children. This article is about doing CPR on adults.",
" </p>",
" <p class=\"headingAnchor\" id=\"H29400959\">",
" <span class=\"h1\">",
" How do I know if a person needs CPR?",
" </span>",
" &nbsp;&mdash;&nbsp;If you come across an adult who is passed out, tap the
person forcefully and ask, &ldquo;Are you OK?&rdquo; If the person does not
respond, is not breathing, or is breathing abnormally (gasping),",
" <strong>",
" call 9-1-1",
" </strong>",
" . Then start CPR. &nbsp;",
" </p>",
" <p>",
" The person who is passed out and needs CPR is often called the
&ldquo;victim.&rdquo; The person who does CPR is often called the
&ldquo;rescuer.&rdquo; &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H29400966\">",
" <span class=\"h1\">",
" What if I don&rsquo;t know how to do CPR?",
" </span>",
" &nbsp;&mdash;&nbsp;You can do CPR even if you have never done it before and
have never been trained. All you have to do is press HARD AND FAST on the center of
the victim&rsquo;s chest. It doesn&rsquo;t matter if you don&rsquo;t know what you
are doing.",
" </p>",
" <p>",
" Pressing on the chest for CPR is called doing &ldquo;compressions.&rdquo; To
do compressions, make sure the victim is on a flat, solid surface. Then kneel over
the victim, stack your hands on top of one another with both palms facing down, and
lock your fingers together. Holding your arms straight, press on the center of the
victim&rsquo;s chest with the heel of your bottom hand (",
" <a class=\"graphic graphic_picture graphicRef73357 \" href=\"UTD.htm?
25/30/26086\">",
" picture 1",
" </a>",
" ). Use your body weight, rather than the strength of your arms, to press on
the chest. Pushing like this squeezes the victim&rsquo;s heart and gets blood
moving again. &nbsp;",
" </p>",
" <p>",
" Make sure the victim&rsquo;s chest drops down at least 2 inches under your
weight with each push. Between compressions, lift all pressure off the
victim&rsquo;s chest so that his or her chest goes back to where it was. Keep
pushing hard and fast on the center of the chest. The goal is to do at least 100
compressions a minute. &nbsp;",
" </p>",
" <p>",
" Keep doing compressions until an ambulance comes or someone who is trained
in healthcare takes over. Do not worry about breathing for the victim or doing
anything besides compressions. &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H29400973\">",
" <span class=\"h1\">",
" Does everyone do CPR the same way?",
" </span>",
" &nbsp;&mdash;&nbsp;No. People trained in healthcare do CPR differently than
other people. People trained in healthcare check a person&rsquo;s pulse before
starting CPR. Then they follow 3 main steps, which are easy to remember based on
the letters C-A-B:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" &ldquo;C&rdquo; stands for, &ldquo;Do chest",
" <strong>",
" compressions&rdquo;",
" </strong>",
" &mdash; For this part, the rescuer does 30 compressions as described
above.",
" </li>",
" <li>",
" &ldquo;A&rdquo; stands for, &ldquo;Check the",
" <strong>",
" airway&rdquo;",
" </strong>",
" &mdash; For this part, the rescuer checks the position of the
victim&rsquo;s head and jaw to make sure the victim can breathe. If needed, the
rescuer might move the victim&rsquo;s head or jaw to get the airway open. &nbsp;",
" </li>",
" <li>",
" &ldquo;B&rdquo; stands for, &ldquo;Do rescue",
" <strong>",
" breathing&rdquo;",
" </strong>",
" &mdash; For this part, the rescuer holds the victim&rsquo;s nose shut and
forms a seal over his or her mouth. Then the rescuer breathes into the
victim&rsquo;s mouth to get some new air&mdash;with more oxygen&mdash;into his or
her lungs. The rescuer gives 2 breaths this way and then switches back and forth
between compressions and rescue breathing until an ambulance comes or someone else
takes over.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H29400980\">",
" <span class=\"h1\">",
" Have the guidelines on how to do CPR changed?",
" </span>",
" &nbsp;&mdash;&nbsp;Yes. The American Heart Association (AHA) changed the
guidelines about how to do CPR in 2010. It used to be that all rescuers were
expected to check a victim&rsquo;s airway and give rescue breaths if the victim was
not breathing. Now people who do not know CPR are advised to do &ldquo;hands-
only&rdquo; CPR, meaning they do only chest compressions and do not worry about the
airway or rescue breathing.",
" </p>",
" <p>",
" People are sometimes afraid to do CPR, especially if they must do rescue
breathing. Hands-only CPR is easier to do, and experts hope that people will be
more comfortable doing it. The most important thing to do for someone whose heart
has stopped is to get blood moving again. That&rsquo;s why compressions are so
important and why it is better to do just compressions than to do nothing at all.
&nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H29401062\">",
" <span class=\"h1\">",
" More on this topic",
" </span>",
" </p>",
" <p>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?9/53/10068?
source=see_link\">",
" Patient information: Heart attack (The Basics)",
" </a>",
" <br/>",
" <a class=\"medical medical_basics\" href=\"UTD.htm?33/39/34419?
source=see_link\">",
" Patient information: Sudden cardiac arrest (The Basics)",
" </a>",
" </p>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" <a class=\"policy policy_editorialpolicy\" href=\"/home/editorial-
policy\">",
" peer review process",
" </a>",
" is complete.",
" </span>",
" </div>",
" <div id=\"topicRetrievedDate\">",
" <span class=\"emphasis\">",
" This topic retrieved from UpToDate on:",
" </span>",
" Apr 20, 2013.",
" </div>",
" <div class=\"patTopicTool\" id=\"patTopicToolBottom\">",
" <a class=\"toolbutton findicon findInPageLink\" href=\"#\" title=\"Find in
Topic\">",
" Find",
" </a>",
" <a class=\"toolbutton printicon\" href=\"UTD.htm?6/2/6178?view=print\"
title=\"Print This Topic\">",
" Print",
" </a>",
" <a class=\"toolbutton emailicon etacLink\" href=\"#\" title=\"Email This
Topic\">",
" Email",
" </a>",
" </div>",
" <div id=\"disclaimer\">",
" The content on the UpToDate website is not intended nor recommended as a
substitute for medical advice, diagnosis, or treatment. Always seek the advice of
your own physician or other qualified health care professional regarding any
medical questions or conditions.",
"The use of UpToDate content is governed by the",
" <a class=\"legal legal_termsofuse\" href=\"/home/terms-use\"
target=\"_blank\">",
" UpToDate Terms of Use",
" </a>",
" . &copy;2013 UpToDate, Inc. All rights reserved.",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 16340 Version 2.0",
" </div>",
" </div>",
" <!-- basicsTopicLeft -->",
" </div>",
" <!-- basicsTopicMinWidth -->",
" </div>",
" <!-- topicContent -->",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [1105-183.1.191.153-3399DFF423-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6178=[""].join("\n");
var outline_f6_2_6178=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H29400952\">",
" What is CPR?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H29400959\">",
" How do I know if a person needs CPR?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H29400966\">",
" What if I don&rsquo;t know how to do CPR?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H29400973\">",
" Does everyone do CPR the same way?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H29400980\">",
" Have the guidelines on how to do CPR changed?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H29401062\">",
" More on this topic",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"PI/16340\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li>",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?25/30/26086\">",
" CPR position",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_basics\" href=\"UTD.htm?9/53/10068?
source=related_link\">",
" Patient information: Heart attack (The Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_basics\" href=\"UTD.htm?33/39/34419?
source=related_link\">",
" Patient information: Sudden cardiac arrest (The Basics)",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_2_6179="MRI MTS T2";
var content_f6_2_6179=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=NEURO
%2F77659&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=NEURO
%2F77659&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" T2-weighted MR image showing mild left sided mesial temporal sclerosis in a
round hippocampal variant",
" </div>",
" <div class=\"cntnt\" style=\"width: 360px; height: 378px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCAF6AW
gDASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwD5ft4tqedIGxzswOprX0W3+1XEO8kQ9Gz61Fp0MtxqSRJkRqxyq8gV6L
p1ppdxZslvMm+3G64Z12hRQBnxW9vZRNd3dyIrdMqCP4/avPNantbjUppbGNooGOVU/wA60fGGuHWL8LEAl
nAPLiRehx/F+Nc/QAUU4KSCR0HvTaACrml2MuoXaQQo7M3HyjpS6Vptzql7Fa2cTSSOwXgZxmvsj4H/AAes
vD1rDqmpw/aLt8FEdep/woA87+HXwC1ae/064u5IbeOIrPMZF3CRf7or660+xttPtUtrKBIYEGFRBgVzXiX
xxonhvfFc3sL3faFCPlHvjpXKW/xhtJLiNfs6GNm25DEfjQB6rMpbYAAQGBNSYrI0rxDp+pKvkTqHb+Emte
gCGR4rZZZppAqcElugrkdQ+JXhyxmCTXTYJwSFJ/Sofi3cXFt4dd7dGI6EjtXyRq9+81yzSOSegA6CgD2D4
ufEfTtamgg01HltVXBdhtO4mvF9VkSa4kliBXIxsJyKrfaEICqSFzzjnJqK4meHkKGBPOfSgCnaXW2fAX90
pKkk8/WtSe7HlMY2OzgEDvWGuxldjyXfg0sbuipul4Un5B0P1oAtPulJkU7vl6H0q9paM1xAgJUSHacVDZW
zTxl9+CTiuw8OWdrFcQSOA7qQwHrQB7XaaN4lsvgYYvBkoi1lmMoywzs5yAT36VR+Ctpq0PjO5PiW4STVrr
T4Zp17nsM+/Feg/C/WBe6V9neMRqgyBWHpdxDb/GQW+V3y6crqcc4DsKAPUmjjX59iAoDg46V4X8e75r/Sz
GF/1LB/SvbNYZ106ZozhgtfO/xFuWnWQXDbsIRjPrQB4DdsUVnO0SZzuB7U+xuCZvNIVjt/i4pNTSMSuioM
cg5NZir5b4GC33QR6UAdbol/c2F5FcQOY2iPmDHI9q+wvhZ4vTxd4eErkfbbfCTjHU44NfFmmT7o9u3CqME
5r1z4E+Ik0DxLMs7sLGSJjK3OeBkcd6APqa6njtbeSeY7Y41LMfavA/HXxYuftDxaa3lhchSB/OtD4i/EkX
vhIPZJJa/aZGSISZUugON2CK+bb+4kmmLb3KsclifSgD0ZvjH4hDr5NybeRBtbPIP1FemfDf4zPql3FZeIU
iVmGBPGpGT9K+Vnmd2eVVYszbeeldL4QmlXVLQoNzBx8p7HNAH2H47+Hnh3x1ZY1S1UT7f3V3D8sie+e/41
8lfGX4I6p4Kt0u9Oh+36fuYtcRn5lHXDL/UV9m+EZJZNEh8/744rXmijnieKZFkjcbWRhkMPQigD8r6SvrD
49fAfRbWyufEPhudNMO7dJbP/AKpif7pJ+Wvli+s7ixnMN3E8Ug5wwxkeo9RQBBg4z2ptKDjNJQB0XhzxRc
aS6JKi3NqOPLbt9K6uSwtb6GS7hcS27jch7qfSvMq1/D+tz6POSoElu/EkTdCPb0NAEupacY2MsCSIOep71
lFNykDh04I9a9Fkgt9TsI7iAhYHGcK2drehrjdR002pmMpw2cjNAGNSVdlT7TH5saYcDLAdx6iqVACjrRSU
UAeieGLGRrnaqeWx+/Iw+6O5zWJ4t1a2LPp2khltkYiSUN/rj6/StzxvqJ0fTl0eB1e6mTNzIvYf3a86oAK
kjjL7sdFG45qSG3Zm+YHYOpHamzOAvlxtlB39aAIq1dB0K71m4RLdDsLbd3v6Cl8OaDeeILtrawCGRQCdzY
6mvsv4I/CC18MaZDqetqDdAeYiZ4QY6n3oAyPgp8LItNgiubm1VZSQ5dwcqB/Wuv8Aiz46/wCEd0Oex8OOD
qDLtE2eEHfFQ+PPiAImlSxytuoMZ/2vf2rwjxRqD3MjTOzMHORzwBQByt9cMzve3Ukkt1IxLFzyal0+9dZV
DysE7EVl67uYEBfmUcZqayBjhjAIGRzQB7N4W1lrfy3WZ8uAAB617z4T8Sw31rGk8paVsAE18v8AhyaPyY8
Egr2ru9L1lLK4jWGQhu3FAHu3i7STrWhXFpG2JGXKehNfE+t2b2V9cWtypDxSsChGCMV9b+DPFZudtrekA/
wn2rh/2gvAaXED+J9OG2aNdtynZgf4vrQB8xXKtbPI64wwB+tV0mN0n73coHpVvUw8SbiUfbwBWVFNIj/Pt
Qk9PY0ASEiFkDOzJnIAHertqnmmVSu3A6471SuiY5Yyx+bcMYrX01XaQkoVDcEZ60AaGmxbVYhFX5ep7+9a
OkXGyRgWO7HYVWii+VMHB5IPpRBHKZPLyUUDccdSKAPYvhzrjwPDaozGeX5VAPQHua7qCxFp8b9NBAYNoh+
Y9c72zXlnw4sja3BuIAWbgkt1H0r1ZVZ/jPoEqtlP7EO7nuWagDv9ebZpUo3EAjGe9fPXjWB2E0pQOjDbnu
K+kp4lnheJ+jDBrw74kaSLSSaDkqwLoR2oA+btZtyJ3ABUk5II7VgyOEYiMEnoDXY+Io2juWVcZOAd3UD1r
mNVgW3bEQyO5oAsWBAcor7SyElq6TwxqT6frFncQ5IUgnd3xXFRPhkKAgqPu+tatvfMsyqozgflmgD0D4m+
K38Sar5w2JFFEsapxgYHNeX3MztISGHY7P8ACpNQvGZhux+dU49txco8KuVBwd3egC7ZW7ToSxzufKr617P
8JPCjT3KTXcHzh/lB9K4/wJojz6lCcfuSchsZ/SvqnwDogtY0ndSDjIxxQB2On24trSOIDGBzTrm5htU3zy
Ki+pqYnAJPavFvjb4vSyQ2cMoWUrnFAHb614n8N6hHNpWseXJaT/u3WXBVvrVXxN8MvCHi/wAOw2Nzp1u0M
ceLa5i4eP0IYcn6GvkK/wDEM9zdOzylZGOCD2969v8AgD8QpEvBoGqyFopeYWI+4fT8aAPC/i58Fdf8ATSX
SIdR0UnK3cKn5B6OO316V5VjjNfqVqMH2qymhKJIsi7SjjKsPQ18d/GH4SWttqt5faFY3EL5LtY5AVvUq39
KAPniipbiGS3neGdDHKhwynqDUVAGpoOrS6Vdq4y8BIMkR6N/9evWk8N2fjPTjd6C0UgUb3hY4fOORXiNa/
hrX73w9qK3enybHHDDswoAsXdrLpt/NFJ+72NgA9vase7jCSZTGxumO1en+JdKsNe0RdZ0663eawadSOY2N
ebzKsd28TKSBw2R79aAKNFSzRmN8dj0PqKKAC4nluZnlndpJHOWZjkmowCTgDJpVUs2B1qV2aKPyuBzkkUA
OmmKxCFMBQPmI7mm2dtLeXUVtboXllYKqjuTUKgsQFBJPQCvqH9nb4QXSXEOt6xHGGO10RhnYvX8zQB2X7P
Xweh8P2Eesa1Fm+mUERsOnOc11Pxl8dR6Og0iycG5YbpirfdHYV0fxK8Xr4U0gG2VWupPlQdl/CvknW9TuN
S1K4ur2aSa5dyzN7HtQBoX2sSTplnYs/UZrDu5hJIEZWKt/Fu4zUZdXUFGb5+ApPSqyzvvKSKrKM8NxzQBT
1LfLHIeWAGMA9qj09SyDkhRx16Uy6dkZCUJyT0OBUVi3lnATLhjuAPTNAHdaFcJGUkjbD4wR2xXZ222a1jl
VcMuACe9ea6MVSVGP3WNepWCRGzgdgRGeCKANPSLiSCeNVcsGB5zyK9T8Tagbn4U6rJIBJItttIY9yQK8du
JYoJQqPwenPStDWfEb/8ACvdTtMkrLsAJ74NAHg+uF0ikyAPm5+lYUIYS5kIbc3BPYYrU1x3MbeaV3M+7r0
qhbhv3nlIGcrgfSgB0zmWdRguQRhsVt6aux3Y5IyB9KwYC7XAR+CnUdK67w9AZrsREYXAJXv8AWgDsrLRTd
jda/d28nHI4zUltosYkUvIVB4PHIJ7Gt7w9ew2WpTWNziFpFDRMf4jirN1pkv2wzbGRHOCQOue9AG/8P7CK
0l8yDLqjZkDj7wHNbng7xLpPi34m22o6SjxiGwktmRxtIKuc8VZ8C6fKt5bDDOqODvI4I9Kh1m3n03426U9
jYpDaz2+HljXbu65HFAHpeoaraafdWVvdSBJbt/LiHqa4/wCI+kfaw8iYGU5J7fSm3UMmo6vpOparMgjtrp
2RWXaEAPFS+MPEulGIbbhZEA+ZlOcUAfM3i7TzBduWBdge4riruEMJM5zwxY9q9b8Wapo9/LNskKsQRuK15
dqPlQykCTzARwexoA5kAKQd2c5GfxpRKx+dd3tx1FMmh3uwOV53DFMeeUKGCEqSUBHagBJTunVDtbeo5I6V
r6XCzzo6rkk7VAFZeFWNfvYXqR1rqPDLol/BFjGSPvDgUAe4fCTQf9GjuGyfn2nI5r6F0y3W2tUABBxnBry
LwXYBNOSWC/JYndtHQGujPia4tLtINRcHeD5Uw4IPoaAOv8QavDp2nTTs/wB1Sfx9K+NviZr8ur69dXG5do
O0D2r1D4m+Jy+kTwCZsu33Q3INfP8Aq0+/lhyx785oApPIDcO5BL44xyMmus8FX72+qQzKzC4DYBHbFcejA
vkYXj16102iMolVo0IPUe9AH2v4F15da0aJnP8ApMagOPX3rT1vSLPV7cR3sYOw7lccFT9a8d+FmrtFGghc
mVjll7fSvaI0knZJZm2pj/VDofrQB4X8XvgBZ+JrKTUdDdbXW4lYkBfkufQEdj718Z6hZXGnXs1pfQvBcws
UeNxgqRX6l14d+0F8GbfxpZXGtaQNmvwJkKqgCdQPun1NAHw5RU11bzWlzLb3UTxTxMUdHGCpHUEVDQB0ng
3UVhuJLC7lZbS6G3AOAH/hP51c8UaXIAkykeYhweeo7VyFdLo2tQyQraargxr92U9foaAMO4kZyfObPPA6E
UVu+ItIKSLc2i5jkG5SOjD2ooAxLYm3jaSRflcYXPeqhJJJPJqzqEyyz/u2zGvC8YrU8DeHLvxZ4osdIsUL
STyAMQM7V7k0AesfszfC0+L9WbWtWgzo1o4A3dJXHOBX21BBFbRLHAixxqMBVGABXlGq+I9I+EPhaw8P6Xa
rNfJEGEQOBuPVm78mvLZPjX4qkuXkluLaMc/uY4+PpmgDovjRNNJeks26EEgH3Oa8NuPmz5ZwV/i7Gu91Lx
oNaQvqUWxmG7g5XNcbqTWpDeWQpJ44oAwJHcuxJwCPvDt71KZtsnJLBeBx1461HuHm+WzbgG7Uydo0UhJN+
4Z565oAhumaTI3nYBuHHSq0EjxTLKwVt3HB/nQssqqMqcPxk84qvKhMoBwVxnjjFAHU6POZDuwo25wCccV6
t4fnW+tFicKSqgqQec14tYXYjEUTgEgYH0Nd14R1hdOuozckNEMAMOtAHReIikF4nmMBuB+XPSuV13WpLiI
QQlvsqcAE960viBexXNzHLaOpLruLdvpXBXt60eIkjDM3JBPSgDN1ZmuLmM+XnHXJ60zmGMuSRk/w1C0im4
L/AD5U/Mc8CpXkz1VmIGQPXNAF7TkWe5Mm77vRiOtdloaBGMzHa20qGA61y2hwqVCniLOQPeuvtUVFR1X5O
gXPbvQB29jbW+uRQw3kMjSDaqyoOVNdR4x/4SfwZ4XW9gsP7ZjBUKgjJZR2zivObPxjJo6kacigg9JBnBrU
j+Lvi+TciXUKwbSuPKB/LNAH0H8Mr2bVfClrf3mmtp11Ny8L9QcCulms4JrmCeWNWlhzsY9Rmvkq08f+KLW
9a4TV5xg7nRvu/TFfTHw88TL4r8NQagVVJwTHMi9A49PbkUAeNftEeLLuDV49Jsi0ccaDcRxkmvEZ9Wnjws
tw7Pu4APAFe0ftK6DNFrdtqyxlradNrNjgOOxr5/uLCSYNsdQADyOoNAF975pjIAw2ngk+lZ1/eQ70VWGMA
KP61nNZX7Ha52qRuwOtVjG8LqZULZ6kdhQBelTYV8uVWEmeMVTDOp2F9nOMCrgkEkXlRqFT7yseuarXYwE8
zPz5Y7RypoAqyzmM7QxIY8n3rZ0q7kMsZBKunfHasadY1dSCxUtkcdeO9a+jSK05Uj5n+UUAfQHw+1aQ2kc
WSyk5PpWj4x1JQIow+JBIMZ78VwXgK+ePdbPPHDGvJyMs3sKva9IsrzT3MwdV+WPB6UAch4t1J72R93GOc1
wmpzs4BjZt2eAO9b2pTB9yFs5OBz2rltTbGIeUYHg+1AF2C3ygeQLzxk9RXa+HLHzZdsR6DLMfr0rhdPJaQ
KJBgDjPeu10nUkhjjRSwz1OOR6UAe4+C5LDQWiurl94QBTGnOB6/Wup1L4s20LhLG3AjHeQ818/Xeu/ZLby
Ip9z9m71zN9rV1OzOsufUNxxQB9Q2fxktGnVJoAQSAdp6e9eg6L4o0rV0U21yoZuiscGvhuy1KRWcPzu5Jz
yPpXQ6R4mvNOZWjlfZnjnlaAPTP2oPhGurW8vi3w/ADexqPtkEa8yrn749x3r5BniMMzRsRuU4OK+4/hl8W
LfUZ10vXJI13LsR26H2NfP/wC0x8Nz4O8XPqmmxj+w9VczRbB8sLnlk+ncfWgDx4qnlHB/eA9OxFQ1JEAXA
JwKSWNo3IYYNAHX+FNZjktRpl6NzdIGIzg+lFcjBI0M0ciHDIwYfUUUAR19nfsofDxvDnh6bxRqseL3UIx5
KsMGOIZP5mvm74JeDZfG3xE0zT/L3WccguLonoIlOSPx6fjX6JRW8UVslvEirAiBFQdAuMYoA+KviFq82r+
MNUu7o73MzhBngAEgAGuIu7zy2wik7hg8dDXp/wAW/Ct3oXi+9iFuxtJW86GQAhdp5xn1rzi5t/MZ90Y+Xk
Y6igDL/tUrFjlgGwAeMGo7jUnuzl3wMdCccirEVhHchkkQ7t2ST2GKjGnAAqilsHn5e1AFaWV5jHswCTxtP
WpCfmDkFlUc81dTRCxwFBVl+Ug9KpJYT28bOcKMknNAD47tAVymXHRgaYsZO4sgJZuueRVMyZZWbZz2Awat
QsS7PuV48Drxg0ASLBJ5hBycHjHpV+zvVBaM5BUdScgGs+3dXLpuIJOBT7kbFGwgMV7D86ANqa7V4VXduQr
kEmsW4ZmkZgBzxxVKLeDu3McVaPmJGuE+QjOetADIkyTGMDOOtWVR1nG9hICcZFIsiyL+9Dc/dKjFEaRmVF
O5Rv8AzNAG1ocqeVgQjcGIYZrWvb5RD5cfDqAcrXHG5uLZpCGCoxwUH86a2rK8gjJY9gMdaAN6a5LCR3bcv
XHeo4rpZGjTL+Z0wvb3NYa3XzttHIODntXV6RY28ccU8cgLOMtmgCW3MwI3ESEnAyeSK+pPgDptxYeDpZLi
Py1uZzJGvsABn9K8D8Np4fGsW66/NMYchmWFPQ9M17J47sfFPi6w0NPhZrUGnaNH8tyqtscD0PGSMdqAIfi
78QoVM2hwWcNxE4Id5RnJH92vCNlnMCDE0Cswww5ArrvijpU2majHDJfJNdKuyQqQ3Tua88+1JDMYblsIRk
EHg0Aa194cugBPagXMOOZIuq+mRWBLpgcEN80oPI6VvaXqd1p10slnOWGc7VPDD0Iq1rt5Zam4vYLc2s7/A
H0Xpn1oA86l3QzurHoSNpWq80jFFEZOSMsQOK1vEWI5d7PkjmsmUkASqOGP3fegCPe8lqCoCPnGalhZ42jA
K71PXFOiBdzvCqGG7jtUqsFyrhz7quaAN2z1Ex+Xtdd3PzA9Kt3WuGWBoSS8YPH4965e6VBP+4clcdFHOfe
mRuY2ZJW+dxnbmgCbUpNrctuLD5CKyWLM2ZNx/hGaszHeEd5NgXjaORULIZ3z9yJfQdaAI0WQYddvHDEVoQ
awY3QYYBM44+9WcXKoAWHlZH3e5oXY4ZsAGMYyT0oA0474yfffLcnnsag+1CZlMpO09UU8mqAKvhQctt5Ip
Xj+5HGeGH8I5BHrQBqveI20IrI45G7nIq5b3nmpgkKw/hxyawPKlO5PnbuOOnvVm0edXVnAYjgY5NAG5a3P
kSCaM5yc8dRX0Z4WSP4p/CTUfD2rsZ9Qt4SLWRuuQMxt+BAFfN9pE6qZghUk817/APs4Jdtqu5SBGuQzf3h
g8YoA+Rb60n0+
+ntLuNormBzHIjDBVgcEVNLtuYPM+668YAr6C/a8+H39lazH4u0+ELaXziO5CjhZccMfrg186QStC4YcjuD
0NAEfeipJ9plJTgHnHpRQB9w/sq+Bo/DfgWPWLqP/AImWrDzCSOUi/hX+te2sQBljgDkk1XQWumWKRqEgto
lCqvQADtXjnxk+Islvpklho0hhmZuZPUUAegeJdQ8Kajmx1m7tXZTgKxyQfrXl/iH4TaReeZdaJcx5PzDa/
B+orwS+1S8bM9y7lz/ETXQ+F/GWo2FxEpu228DaaANPVPhnqFnMrqRjO4Y9ahtvCl6iLJLbkAkgkDg129n4
5jnhxetvjxzg85rZ0C903UJhDb6qsO/pDcdB+NAHAw+ERLbedcR+Vg7s4xt9K5jXNBmafFnazTwfxSBeAK+
oLPwY15Gxu72CW2foluflb6mrtz4OjFv9ntEiSPYVz6cUAfEuraQ8L8IEI6bl5xWE1rIU2yZwPm4717/4y8
Ja1qHiPUrKw0GdrKwhDG7H3ZG9BXkmo6ZJEWWYeXIvykHgj60AY37swx4VexOOtOCfOyBW5OeTTri3XYzeW
wkBC8dKRV2SRkg9CGGaAIUswJFcMcEnPNXIgVh/eADGce5qDLj5YtpAHG6idmG1VIYDP3eaAG5LOmwZZeD/
AI0/Y/mgnkA7uO9XLGOMKjgYyvzDvmp5olQKdyiRex6mgDIaAh9xViCOAx6c1SliRA7qodyeAeBW5JDhMsd
5buTjFVFhidSHK4/h96AMxYzuKEkMy5C+hq/Y399Z27CRGK8dRU2mSxJfZugCMYB9u1dnbW1leWy+SY3YqS
y55U9qAMrStTa8dkMblwMjaOK9q+H+uTWPw+8R/YnePUoow25eqjjOK4Dw34Svr2/jhsIlU5+Z2OFArsLPw
9q2g+OLi1mltxohtgkkqyD9+zDlQKAPKtSumhaWa5meR5CWLE5JzzXKajqjMB5qZUHKEda9O8V+GZ9J1Apc
orQ84I7r2Fche6PZLHhyqOckHPagDEttVu4gHiwSRwG6jNX5NdeBAksY3Y7etYMkEiMyoxYK3ykHqKnnIOz
zcELzz1oAlu3N9M8vJIAAB6UyNHe3
IaLYVPQnrU0KLCpXdlZBux3q08qGAGQ57D1oAoC1wcJkvjoO9XbWbbA6hMyZ+U5pykFlaMgEdPXFHkJI7FF
KYOFY96AKksymNgq7c8yY/i5qIoFIYLkdCc4xz3qy/wAk5DYZQMjtUwRZIQXKlUxgnrmgCjLHCsfzKVk+8C
OhrPWRhM4bc6MeAO1XpHNy5ESjYvy59qfbxiYboVKqpx70AVYbEPM+9v3bc5Hr6Veh0hQOAfMPUEdRXSaDo
qmNWXY7Zy27k12FvZ28Kny4QWU45XrQB54mhSZQwwjLdDjGKeNKlEhJgO/G0kDivSWjiyC0O1sbSOuDUEk5
hRQ9q6sc8hcg0Aeb3WnzpH5m19xIyOgxVeK1khcmIALk9a9Ijsri+Xe8BiVMYXGc1f0TwDd6teOLaHKMcZx
zmgDiNIsJ7xhCImc9selfUnwY8Ox6Fo8Nxdskdzck7EbhiPanfD/4W2mieXdakRNOF4j7L9a1PEnw5t9c8Z
6X4gfVb63Nht8u0iOIiQc8igDQ+KXh2HxV4D1fSprU3LSwkxIv3vMHKke+a/N/UrK406/ns7yJoriByjoww
VIr9RjcQBwrTRhj2LDNfHP7Yvg9NK8VWPiCyiC22ooY5to4Eq/4g/pQB88k7gBg7vWimjrxRQB+jHxIvmgt
2U7ggTOe2a+ZfF1/JdSsknDlsLt7ivpT4m2uyNLoz5jciJ4ifu56EV86+LbQi8JjAI7UAef3hlJy3Knjk+l
LFKuyMylixPPtU9+sYneORCMrms2CUI5VSNuOc84NAGlHctHhlZiRnAJ7VajupmcPHIytjkg1hxTu4kVVyP
UjkGrlvNst1Dtk5z+PpQB6F4U8c6toxH2a+lUjpGT1Fe0eHvjDDdabuvoVE6jlhwCfpXyulwu5sIdxPQnFX
rfUWWJgrFX6bQc8UAfR118aliciOyg2dwc1wvjG68JeLlN0qrp+pOMll/1Z+orx5rt2VWRxtOckn0pkN8RG
2WACk5U/zoAt6lYlEuE38AEgqeDjpisVCLqQYUBlGGHTt3pb7UW+VEBZmHaqyOYwT1YcsWoAsOjKkfRM8be
+KdahUXzVyxXIK45FRpKCBIuXB4IxU8M6xB9vQnk+lAE6ruiDxnAb0GPzqvM02SwxuGBnOa1rWHbah1ZnUd
cD1r0D4X+BH8W6kyIiRQRASSSsvTnp9aAPKvKnkdFTeVx0qGa1ZZFkKAFOK+7dL+HnhnT4VRNKgkcDBkkGW
NQar8M/CepA+dpEMbf3ovlNAHwksSuo3qcjIL9BTVaRHY2spUbsYVsEivqvxD+zvpl0zvo+oPaseiSLkCvP
tW+AHiSzybXyLoKcDbwW96APJ4tQ1CBwLe+ukIHzBZTzUF1fajPMjPc3cpz1eQ/Ka7nVfhp4n05l87SZFAX
5igJzXLXmnXFs2x1k3qMMm3oaAK0l7fso8+6nddo4eQmqNxIGbM7swAx611uj+CfEWtFPsGmXEvy8HYefau
10T4B+KNSZDeJDp8RPzGRufyHNAHjZtf3cbJ2+UZOOKQRZnCqQ57rj+VfUuifs46XBMkmranLcBR/q4xgH8
TXpugfDfwpoar9j0e2Zx/HKu8/rQB8QWnhTV72Y/Z9OupsdAqsRWhdeGdUtHH2uylt1UYwyEAmvvqC3hgXb
BFHEvoihR+lV9V0yz1a0e21CBJ4WHRh09x6UAfnvd2Msci7lZGU4BHpVsSOY5Y2U5XoTxXs/xr+HX/CLk6n
ppd9Nmb5gRkxnsPpXkV6iJErjlnHLMOBQBjXEU3lv8qMWwOetCrN5TFkATrwORUpumCBJmLknh1GMH0oivY
PkR0DSgnqe/agCilsY1bYrGUfN+FaumQF1yynZgHCnoaZcXk7FvkRN/wB4p1IrT0WQSXcYVtyqNzrjFAHVe
FLcR6a0rx/vBIcluMDPFSXupuZgsR+bO0gVJZxvbKs7LutpDtkLHAUHpV0y6ZZuyzWhluhyRngj1FADLK1v
L+bbEWD8dBXe6B4D1C6AaU4QYyZDgVwp8WywriyMdu7d415H1NY2qeN9WeJkNzO5P3sSEUAe46j4e0DS7uy
j1bV7dbSMF50RxuZh0HHai5+L3hLw9CbXQrNpCP7o2g/U9a+Zb3U7mdt1zM0j7i3B6Cqqz+fKHPBHrzQB9I
H4/wAbn5NMVfZnJNcv44+M+o65pptdOjFlGw+eSJzuP49q8Ya9DLtiIJBwSRiq15qY3LGcEn5cJ2oA2Brl+
su9b+5Wfdnd5rZ/OvRotan+I/wv1vw1qO651K1T7ZZSOMtlOo/KvG7aCaVGNwfLB/PAr2D9nWwluPGwmdGa
1WF0ckcEHAxQB8xkFWIIwQcGiux+L+hjw58S9f01F2xR3LPGMY+VvmGPzooA9U8VePNV1WQ+dNIBvLcH72K
w77XpdRCGZlV/un2Fc5NI4XDguw4znFZ7x3LO6kt/ug9KAL+qSFyzmXaPugdyKzG2+QNhO7dyD6VMHcqQ0Q
dkPVuuKX9y/O0ow64PU0AKRIwUggMOSQeT9ah+0yOxJXk9qkkyq5TDZ4HHOKikJEeCF4I5HUUAJ57scSErj
gjuamVmYYUhMHGc9aa7Dy8nDseM+tI0yJGDKi8qelAEqzmF2wA0fHFLcXMDuZPLUrjkVC84RMwKhyuckfpS
CVZQpOBkEHAoARVMwLJGyfNwc9BTnCNuILZA4OaihiaKJtp5J70SwkM4IIckGgAlkDr5QZsgbsD1qe2I2DO
ApGSPWmCNQQpAOOtR3BaH/VqPKYbiR2NAHUaNdO9hJEVVXAGfXFfR37NGo21xYanboR9oGxyfVRkfzNfLOg
SnEkhYkdct2Fdt8P8Axc/hTxLBf2mY4Cdssechl70AfbhHI5paxfDHiOx8Q2EVzZSAlhkoeoraoAKKKKAEZ
QykMAQeoNefap4N0y78d2zPaRm3eLz5FA4LLwP6V6FVZk/4mSPj/lkwz+IoAmhijgjCQxrGg6KowKfRRQAU
UUUAFH4UUUAc38R7KO/8EavDMqsvkFxkdCOQf0r4p8QTqtpIu4AkA4r6p+N/jC20rw9caVDMv2y6Gxv9he9
fHniVh5aylt6lipFAFW4f90UDg7wPbj1FMSHG1nXy5B1Y81BZbWtmUknkj3NWRCnJUlzjnccYoAmlC+V94E
44PvVjR7pom8zCqyjoT1NVoWDDayjnpUGoW0R+ZHaIZyy+9AHbQa7Nf2z214qiJyMqDgEYq7FZ3M8amKZbi
NOFkU4dB6EdxXntvdXFsMAAqSGBrb03U3wxjchgeHoA19btJonJjJXuVHGa52TL4JkZHVua62z1qK6UxXa5
f7vm4zgVmXulNGzyITIj/dx3FAGIvmMWKou1lxuJ61EHMOS5IxzuHAq2VRFXhlyflGKjuC7W7xyKpCng+lA
FC8ndoV2KqryTjqeaWxtBI4PO8+3tVHymMqZ52g/St3TL8W8waRYxgYBoA6jw/wCGrq9lijkxFbHJMh9a+h
/hc+g+Go3to5I/NYgtIevpxXz5beI55rchmVkCcACtnwv4xFhcbpUDxkgZIOQRQBH+2P4eW08W6Vrtt80Oo
2+x3znLJ0/Q0V3Xx5t4PFXwhj1CxjVo7fFyspPKnOHX+VFAHjs2j3UTyJPEwK8EEY6Vm3YjhWMbR5hyCCel
fQPxPstSu5Z7jR9IH2B/uzy4TOPQV4LrcDRuwmQCQYDUAZtxtA4fcrDG8dqpsimBtnyhfXrVlYh5gY8R5A2
+h9aSW0YRCRiOCR7NQBW8pScByowCcGopQ6sjMDtz1Jq6/wC6GGjDkYyR61Slkl3Lt+Y7sfd7UAOVgiKpk+
83BPpUgGWOW+XoO9VvKAaTfJnHRcU5SFjI25x3PagBcKhBY5HY1G/MqESH5+SBSyRO0ZYFQOgHtU1rCzDDs
ME4+YYxQBPGpC4YhgPepJ/LUfKxYnkZNVpbQQXCo08exu6nrSXkpEA8hlCr8uSOo+tAFmNS0UhOMD25zVWV
vkIBxIVzgdhSrK3kBcn5cHeO9JnC/KAeevrQBLbHaqCNhzjkmtOKQSoVH3QeTj+VZaPHHv3IB0Hy9RV4AKg
dn2huQi8mgD0L4feLr3wzfwzif/R0bBj3dvpX154e1aDW9Ht7+1YGOVc8HODXwMHWKQbc54BIOQa+sv2c7p
p/B00bHhJflB7CgD1iiiigAqozD+1kXcdwhJx7bhVuqDRt/bqSAjb9nZT/AN9CgC/RRRQAUUUUAIzBFLMQF
HUntXlPxN+KEGiwSWullJLjBBfP8qzvjV49fTDcaRY3BjnfCHHbua+aru4nuZpZZZszZJ+Zic0AW/FmvXGu
am95fOWcerZ61zN+PNh2uNwPQirLxhzlmyAOcfxHNU5JMyOqMAqdvSgChCrQAqXwR94GrVoqyPlQCMDIPem
Mc5Lndu7+tNgkcLhspjkEUAWSGztUqrjoQOmDRO/2oZkVWYjHBx0rR0e1trtktSQl1J9xmPBz61m3lo9rqE
ltKpJjYr0469aAK8Sh32mU5zhu4oaO4jcAnzF6krxx2qN/LR51VvmHQCq00jopkUZ2jAweaANm0u3VjJIxU
AcZHNbmla5NEwLOJIm+8vt6e1claXCzshuAzJj6EfSrT26puktJXK9ArcE0AdvfXVi9jvWMI7H7mM8VyeoO
DtKMNmCcA81EJgSdxzx0PriqwcPLnbtTtnpQBFJK5I2IAcdc80+K4EoC7A0h/OpWhEj/ALvBYDG7PAoERwz
L8pQ5L0AXraRVYhSUPTGfSrsEqZOzJK8Yz1rNFud8XlyIGfsTz9auW0bLAS+1ipxkfSgD134Ya1BqPhnWPC
V+VkhvIJfKVzyJMZwPxFFee+FL5tP8SWNxjbh1YkencUUAfX/huxbXrS11bV/mDDdFAfuqPevG/jpa6XqOp
pJYKkTp8jBFwG/KvTtS8Xxad4YjtrXaJgvlAg9BjrivBdXvJLwnLFn3E7gOtAHnzW4gvJF3K+PbpUchUISc
kDoOxFamo20kNw7yADPfFY16yRR5dlYdOOKAKKmWbYI4wMH5RmrTabMWLSP8mcsqcVa8OQCV3U52jP7xj39
BXUyeGLq7s1uYZBBE2UCkbi2OpoA4wWm3awRBGc4B64qzb28W4syfKta15pbRuEhTzFAwCB3rb0nwdqOoQz
mC3ZmEe4ooOTx2oA5+HT9zxpFGHJOVG3rU1zZmMhZosuoO5cYK17N8GdC0qTQ7jWdVtWW4s3MQgnPRh3rkv
HWoabfalM9raJDJk7mU8GgDx29t1gd1ILryVLdKzg37nYxIwCQuK6DW1YxM6hWXd3rCBb5/l4xyfSgCS23L
sI6Dg/Wp8bWD4UR5IwetQqrFASwbnkgVNNIGuFBClSDwB2oAC67ZEVVUk9elV4cIMZJ74HOKhldvMdHXKnn
AH9akDbEUx5AC4I60AbltC0yiZFUIT29a+mP2cNRAsp7J/lfJz7ntXy7aXssC+bboHhUjKN0zXXeDPH934f
v/AD7cMrZBZe2KAPuWkBBJA6jrXJ/DnxrY+M9FS5tpFF0g/fRZGQfXHpXW4AJOKACseTUY18WRacXHmtaGY
L3xuxn9KfrOvafo0tumoTeUZ87SenHrXzzo/wARJNW/aGimhkK2DE2YB6GMZA/U5oA+m6TIz1GaWopFORtO
3v04oAlqO4fy4JH5+VSePpUMLsJX3bjnse1Jq13FY6dcXFwyiNEJOeh4oA+Pvi/ffa/GV95hfnH1rgjJjIk
XnoK7X4gLHqXiG4ubUqRI2dw7Vw2pSLFLgZWVjyccAUAOdo0jO0DdjHvVAxqxBf7vc03eyzctvjJ4PvSshk
V93CYyDQBG0buzGTgkcMPSo4wjld+4EEfNmpp1yEQMxJwMetQiLbIFcYbPAzQA9pPJYPls5OGqZNVuGVEkh
SdXJPz1HdIZYipYKucjjNSaWm6dVchCB8px1oADBPLI8hso0Ukk4amyaadhVVDODXc6XpP9oSGKJ95J+cqP
ugd6jvdHS3YRbsMOdw9fegDz06dPG+ON57HtUkasIyjFwfT3rrrvRpy4l2mRGP31Gazn01WRw+4OoLA9KAM
uBUn2qrIuBk5ODTF8yNwp2uo9B2quzNA5jkUlxnapHOPrQqzTzlonZFIxigCcybYiVGBnNVWaWRNsQfk46V
fi08gI3mO6dwBWlZ2TNEI484U45FAGRa2d1Jc87Bt4GeSKu/ZLiOf90wyxya6CC0jSQuW+XGPl9qstbxvJ5
iHjG0bh96gDEsDOt5GH3E7jjPTqKK9K+HXgK417V7Np28m1Vt5J5DD0ooA2TcSX8UAmDqso6gdqo6lYm1iL
RRlh0AUdK9i8H+Cjp1lHba0UDwgeW4Awax/jCjW9ipsLZI0jBDso6+9AHgGsNs4lUqOvJ71yt4DcAq4Xlt2
SOgrX1u5ee5bcd27I57D6Vl2ifO5eX5BwrEdaAJtJP2XbG5G0tuIXua9I8K3f2i3McrGMjO31xXny6csMyy
dieTiuk006nEsbaPb+fcu3GTwKAPX9E8IQXCQtIqouMlzxnNegWraT4O0uS/uyFwh8vnLPgV574B0HVEmt7
3xLqMk0cR82WFc7Isc4964f4p+KX1vxBcQWpIswSqjOOKALL+Lze6ZqkjSMv2m4ZsAAfL2wK4LzUMpZWy46
7ulQ2hS3cpu3YGV3HFSXTQJECjKXxkgDpQBja3Iu8Bm464HQ1hRqzqzSqeDgZOK0dVJkZvLUEMQM5xg1Q8v
yYSihmOOrdR9KAJLFirlFU7R6etOu4Stt9p2sp3YU57VJosnllneMMVXAVj1Jo1SaGf51V0jIwI8cA0AZSz
JIzIxyVGBg/wA6nRUVF+YkhsE+xFQxRxqhYqpB4POMVIJEBEexh2VVGaAJIj5gEkStsXqP/rVddpgi5K5PU
AYOPeoYy6EomSSc5PFELFrrDoxbuc9KANjQNYvdGvkvdMvZrW4Vso0T4Ix6ivX7H9obX4bQRXthaXEwXHno
pGT6kZxXiIm2qrxRjzclSfWnSThYlfAC5wV7igD0jWvi1rWt39rcXqWzFMqiGIYCnqPrXIx29zpGvafr0UR
8iSRnRweFYHJU1lWse9XYk8DgGtx/EWrXHhuHwpp+l/abJ3a6kucZYNjBI9BxQB9S6X8S7LVNGsH0+VPtEq
qJM8hWx0rvzdxw2Uc13IqBlBOeM59q+N/gDeXtrrzSzxmXT1Yo7SDKhweMeprqviB8Q7rUtbure3lZvKcqj
IflwKAPa/GvxN0nwqkb3EMs4fIDRc8CvBviZ8U7nxTAYoJHgsCOIlOPzrzfWtYvJldLx5XYn7gOcViRSHy3
aQFsnAA6/jQB0p1o6faBNPdBKVDByobA/GufmnmmuHknfcWySWAHWkiGX3SL8q84qG6cyOxcbYhzgd6AK8h
IGxccHjjrQEO1dz7YepG7k0vmxqqqxGWOcDNU2UCcrzIHzgt6UAaEWx5GERIAB55zTN7NLGWYjH3sjmnxjb
ZAxE4HzMPU9KhVpPN+dSOMluMUAWUASU73+Vl4DLxUduBFLlpBvVieB1HpUbzeaJAHbajDkHIPtTgr+cGkV
VQnGM9KAO20vULixkWW2fDMucLV25vhdszPgOf4xXKWWbedvmJU424Na0LOGLHPl45+ntQB6L8LHjudUSwv
mQxPlV3YGCelZfxR0mDTNUmgiVUOeeDgkVzlhPJaSLJE+2QsGGOorb8dX7at5Nw/O6ICTPUMKAPMdQIuL1E
VixYgZXj8K37W1iSPMcZATljms5kMd3Gdp2gDPHpXS6TA93N5FvCGkfIIWgCvp1rCrO+35iw2k9AMU+dlQy
yKVhJOeO9bF3plxp6fvIlifrhj1rmruFnuSrtgKpIweooAZIXLFwSyJk5zirmm3RijJdwB1AxmsxIsIG5C9
8jvWzoely3l1FEpBcnJA7igD2b4e/2sdDN7o1ml1eQLuELHarLRXpGj6Vd+Gfh8g0iHzdQ2CQgAZJNFAHjm
kfG+/laKLUbdZFPBcnHeu9k1e28V6a8cbAusZKp2cH+tfIb3yH5EL7yflOeldb4T8aX2jXKtDL+62jdu5BN
AFzxro/2HVpwiOI84U9wepFP8OeGJ9Zu0gWRIozzuccL7mvctEj8MeMvDb6rcqv2tR+
+jzzkD7wFeIeLfE8q3s9lpZW3tkyhK/eZRxyaAPQn0fwFo8cUWo63dT3GNrmKMYz7V3vgy08CXCwrpOp/Ox
wElGGJr5Lef7QqFWJbkFs5qawvp4bmNoHMbL3U45oA+0vijbx6Z8PNVazGxljAznk5OK+R7i7me6kdVy2CO
R1r3PwJ4pm1zwW+la0ZLlJIzEXc7m5PHNeVeJdBfRNSlhLkIzEIN2ePegDnriRNqZR1lAAPFR3dxGLd2WMl
lUbSavT7HgIPPHXvms5oim1Q5JJOA3pQBk3ZUSKmwo7AOT71XvFlKlpNm4DqD1qbUJWF8hk+9nAwMmq+oFj
cKYmYI3YjvQBCh222eo3DODzmo7iSTCJIRsfOE70sRZWeNiCw5GOMVHkPehpTlx0OKAJ5AtuoXaQ0gHHUYq
SGOTzS7bSVGQVPWt/TtIF1d+ZkvGkIfa/UNXPXUwt9QYnuSAtAE8yOJFdAMsc8N7Upb93I4wBkAc9T3qCYi
dQiuF47VDAdkjIpJdcZLdDQBcjOITtd+H6YHIp90V8iPYQPTPrRCiOxBY5xwo9TUN5GI2jDKCQegNAFqzLT
KVLkc/eAroLG8msrwG0kdCU2Pjo69xXO25YIqx8FzuJPtW5YR/L5kjDOcY9KAPQNesl8MQaVqWgXP7u7sgy
2JGVicjlie55rzSUSwuzysplc7j710N/qE/kQwmTcY/lVR3HpXNajK3nEsMq3BXqRQBmqXa9aSVic857Yqx
OUAG1CFbJDDuarSzOjKFif3+lK4MoEuPLx0G7OaAGLMTG4OQzDAI9KRm2Rkbd2QMZPH41BHPm7MaZOWzyKk
lhDSffbhSCB0oAqtcBYiseWcHORTRchWJkAGB90UsqRqsalWUA59M028tJYJgJFDRsB8ynOPrQBJb3MQQLI
2xMducin3lxvUKgAXs+MZrMT5L3Y5BUAgN61vQWS3NqocnbtypPYigDPswiXTJIwCseo+lXZA5jXCngjPzY
zVdVihvAhb733jjpV2VQpWRCGHI59qAOisLWO5A8r/AFe3+I8g+lWo4vkJQkYJGGPFZ+jSZnEaZVSMFq6tL
W3NqohCBgDuOevNAGXaQu8wMaHJwMenvXe/8ITcaz4caW3cG4hUsU7yD2rG0R7e2vo/MAZSQMbq9qRI7ewj
+xbTHJHlZEbGOOaAPmubRLwSvatBMr7wF+Q5PPSvWPBXhi28NOl7rM8cN0y5hRuw9xXXz+No7LwVJcRi2kv
o3MKSsikj8cda+b/Euuanqt7Nc3V1NLcMfmJbG32FAHpet2+gXd1dy6prhuLnzMxRbNqKPSueu9P0yS7Upc
xbFG0AA4xXJ6fLFMqNLEhIYBt3evRNJ1bQdKti/wBgt55wMrvyVzQBgw6Cl1OFUyuwJKiNMZFek+CNJsdJv
YZ7yKJpQAF8yTGDXnPiP4gahKFhshDbKxwBbxhc/jXIXms3115fnzSEkk8NQB9ceI9R8W6lYTw+HP7NiLKQ
JA+8qPpRXypofibV/D16lxpt5cQyggkhzg+2DRQByN/D5UxZVQKwwemfrUEM6xIoaQhVPDD+L2q3qEgjl8t
kHBPvxVGS13o27CjOV9DQB1Gia5NYTM9u8qLIAGZT/D71najIl1cNKpClmPBOe9YUcskMrpI2PMAwo9am8y
USLgYG3HBzzigC5BG0dw8rtIqtwFxw1WLSGNnQRbQrMTtb9aq28sk67M5wQy1dtRhUlG52yCV9KAPefA+j3
8ek4tVMQniwjAdDjrV7wb8ImsYdSudTum1DUrpiyjdlYx7H1qz8JfEtrq0MNi7lbpRtXccBjnpXceIdes/C
ltNqOtSG2tLeLf8AL8xkbPQUAeJ634D1G0mnk2r5EYLE+1cm8MUeFCq
5UEA16H4y+KkPi7w6sWhxeTFK26SQ8HA7Yry0o2RIh3MfU0AYOpkm+aMZ2F+T6Uy8lSKDiQFs4JIwB+NW9S
t8R5AVmzk7T1rM1D7giYDYRnnnmgDP8wpHLs2tk8YqLTstIqqdxPr29quSwotpktkDI6YxUenhVhUg5O4ZN
AHosbnRdD+0zxeXNcLtVT1Ix1rgJ1E7SSKPm3bvatO5vmvrWM3MjSLHhUB64rNCrvbYTyScEYGKABkVIOFJ
bpmqqlxKHcs5ye3SrccrBSrxtk88npUeUKuQh6c80ATQyeZPg/ICM5NXY4PtjoY3AIG0A9z61kmMsqOr43D
hT6Vbt5JIVAjY56n5aANJYTGm+RQhQd6u2OZLgShyTtGfeqOmM968n2jcRjGR61r6ZCkXlK5AB56ZoAm1aH
yPmHIKgkDsaxJY9yeazFVHIOOvtXSajJ5lxtf93GOpx14rFnUyxGLccfwntxQBz927G6jwBsbsx71FeFMrG
o245+WrV1DGtyMNuduuei1DcxIu0R43Dp70AQQhVuRLjBXuKdNtLyNln3cDimwM0blHALyEkD0p0hJiY4y3
v2oAjUbUZn+TngHvSXCq7KSu1R1GaltXDwS7sttx1HWq93K7EsBsOM+tAFaa22KGUZKklAT15rX068VpJLS
V22svyjbwp+tZVvNDEN10xkCsOAMHB71Yc+RdxvDhwSMfTHegC3f6e1vEGlUh2PXOantYUlVfMdsrzxTb+9
NxGjyH/dApdOmZ9xVlKD5eetAHQfZ/tGLiz4ZV3FOhI71eEglt/KQlMAHJPNHhzRbnV54rO0QvK3AG/AI+t
amoaLcaZeSWs0apIhBwWyD+NAFAsVdIAvB+bPrXrfwxhn1rw9qumGV8bdyN/dyMcV5rZ2ovtSiUuEBIUnsK
9C+GPxB8OJ4jPhDTluE1GaTykupAAhcZ49aAOBv/AAHrvgmK50/UryS6gu3EkeOenfFcVe2jRF41VlccnA6
mvqLx1ZgagDrEoeaKLEcaHjB714p4lis7WBpFG0u52nq2aAPPbWRodzzxlVH+1+uKvXGpKqx+Qdq9cetZl6
TLK4ALg87jxiqRgkmkj2seBgDvmgC/Pfr8yruaVegByagt7kNcqBkYHT3p9taosZllIMjfLjHJNSw2YLkoC
rjjPegC3HKs0q/J8w657GirUEQVd5YBs/h9aKAMLVzi4i8mTLH72B1+lWrGEXzcKWdRyPf6Vn6wWS4iJVVA
AIbtWnpNzHCRKhGT1AHNAEd5phMpLpggYGFqgLCVDksVQjJA/pXoS3ulXkCC53wPjDFRwT70sWg6ZMoaPUo
jLncqyKQPzoA86O+3aN1BjwcFcdquWN6EuwMKFfg4710Wq6Sy3DtIibcZBz1+hrmrrTJYZDcR5ZgOVzQB09
hfS6XqMFzZ3HlkMDwa92hm0r4seH9L0/V5WS5WXynWM8snrivmOwvfKkzIu0Zy6kc4rp/D+pzWF/balpUrK
YiWjKnBU0Adh408PWPhPWp9EsbdorWBsRkkksPU/WuTu0bcVUiOM9K6rXvEjeJ557y+kb7WUVEGM9OvNc5e
eVJAW3MH27CccE0AY80DpDI0zEQZHzIOo9qx9R2lYhGW25PXqRWhPcGC2K3DurYKEA4GO1VZlk2xKEyvGWx
2oAyb5mljECkjHOMdak0KKV7rBj+VQG9utXI0XzcyleM/MOeKsztb2dqEt7tJWlG5hGpBU+hoAtS20TI0qK
qKGxhaypVjEDBUYuejZqwl4WARQc8Ar6mp0t1AkMkezAyfrQBkTH5Am7GSAQTTPKZlkcHAHQetXJ1RQoVEy
CcEjvUE7KsYcqSTxt64NAEMTJ5SGRRuAypz0qR5VxtV9oCgnBp8dvF5bbj+8Y8MvQVXusZRBIscqjByeDQB
u6RdL5cq5POApHf3r0j4c6TFeXN3eXMQkW2iBVT0ye9eN2s4gTGQSDndmvSvhj4rhstSEd2pENwNjuTigD0
O80e31+Ce3NnFDNHE7RyLxyvPNeS35gRHJQ7gMAeh9a9x8Q65Y6NpdzcWrxSTSRmNQOeCOtfN+rX73d7I4c
oPboAKAKOoSr5xaA4XvnrTISQytKN6hRz6UxVhuXLggqPmGfUVOrx7STtBHYCgCk/nOGYMqAHcuOpqS0fB5
Odxzt9RUU6w7DGdzbeeOtQWcTRuHIAVT8vc0AaroCyr5bIAc4HQilkhBHfcvPPpU0VyRJsYYGOuOlWra3e4
lVt4WMnBycDFAHMXdvI0oeIEKeDgU+CNo4gjb8qSMn9K9c8Nx+ErG1u474rNcOMD5SSD7VxN9Ev2iREiVoC
xIY9cUAZEcBawj+6pBwd3JNWbCJFO0R4jPG7dwasbwwEZIVQvULmtC1lt4LK43QbnZQIy3bHegC/pF1d2Uy
zWc0sbD5QyHBq/dNdzXInu7mSWVxhiWziqunajZ/YHYrsun4VdvAz3q1bHzIWEg6HKkUAWLGJjdwR24LTEg
DJ6kmvRfHHhrwj4C1601nSLFl8UlFmKtMWihcgZbb61g+GL/wAPaBINRuXlvL6MAxQKmFRvUmuX17VH1PUL
29uSzyTMXODQBf1zxRqWqXEl5dXTSTsACR29h7Vx2t6hI00bNMHUjDKfWpJL5Y7Z47dwSzbsnsKyg6JOS8Y
KnnHHJoArwrJ5+ZWOxgcjpU4gWCcSEln7HPSpQouYiSq8HgelMgthzmQcHgelABbtunVFcIM+mcVLNFc296
kq3AK8jBSprK2LXIZ1A9cDr7Vv21kJmZo8EkYCmgDEj3uvlyHaRyDRVu6gJlVm4ZRhsryPpRQBzUyrIyNIw
POAMe9PQFGeQEbs8Cr0tv8Auc9Hzx9KWK33jc4JY8HigCjbuyyu+1Tu/vVfS4GxAwYuDye1XrXRJ5UeU27M
meB+FNNrsULswDxgjNAE9peF2+ZmZVHOR2PGK07zTYZ7VXt2B5+YGsizsSzjYzEq33cYrelsru0tJLhYd4i
Cu47AGgDjdY0uNv3kLZkTqAKybae4tZWSP92QenavS9W0d4rQXMCZhdA5I5689K4nXLELE87MMAfw8UAPi1
YrnzYVLMdqkHvST6q7R7FI2dwKwbKUshEhbJPPFTRlVkDbt6+hGOKALqeXcEfaATEG+UH1qG7vpJle3hTam
D+QqG5ugZHjiIMfVdppLZZmyqKzSNwoAzQBJbRrdMijcilgobGQK0PENjZadqSQafctcCNR+827dx71peG/
C19cRyXF4whReAmcH64rQufDxHkiRGbcM57/AEoA46VyxBBYEnrVy3l+9HvWQDpuNbmreGntbNbhFfZhjnH
C47GuPAaNvO3bUP3c0AbpWOSOXeFGe47Gsq4GHUyEsGU444qWGQtncxaMgZXpzTZ/3iqCSu0/KF9KAG2qsV
kVDgk7ueMYqlqas8pLEb85+Y1poDl5EUsinH4VQvAMkyr97kZGcUAZtrzcmNwenB7CtCwdlfCMQ2cjnjiqT
NkCMHknjAqe1hPnAAnK87vUUAdXrmoXUtlbqj7EUZPeuWuLllLE4z/Ew/izWxrEks1oEi+VBGAD61zhBA2H
DOxGPYd6AFVntWJjzhjx3rUDbrcEt94Y5HNZ8QywV/nAOK1gEiVkAySM89qAKEsPluMYJwOQamt4yRu37um
QPWnvHlV+YBjx061es7cpGJFxkdW9qAJVg3RLIwJ2/eBqWRwsY8kbmABKscUkjvwFOVbofWq+pw3A0l763y
ywsFkbtgnigCq0kyqxVTkngZ7/AFratYX1Gz2RbTf7gWHqPSuw8NeC59V8KwauIMsznzYwMDaO4q5/wgiLa
yXek32LmPBZGxn6UAeXv5ltOYJg8Kg4YH1rUEe+Ly1kB7KQPX1qxrthO07yMhkIGWYVznmyeaJSdpAx1oAs
TTfZZyGJJACN7kd60YNZMaoNw2E8jFZch+0Hcy7z1NNvvJDjyIwoAxjPegDpJNYiWLekQMh4z0qlc6s0y71
XaB1J4rDGfNAYHJ6ZPSp1YFwLiPdGeCu7rQA7e0v71WG84JHSpBakt+/wzkcCksSZrhUCKoB4U9q6u100SM
NxU7RkjoTQBgW0TQkqh2qeeOasYRT5bEmQ9wK25rEIRhHpF09JJMsCcUAVLZGjA3FgepYDqK6Xw/pqanMFW
RkkBDAjrVe104ySKhYheuSOOtdFY3NroKtP8plOdsQPJ98+lAHUaloGlJYfaPENrBMioCbhZNrEdvl9aK8o
1nWrnXb0vdu3AwpDYAHpiigDa1PQNJVwFuJOOCSmKozaHp11pNzHBqSQ3agGJXX72DTJ5ZJBuE4ywzgN0qs
dSt41Af8AeyKOirk0AdR4b1UWkcMd5Yyl1XDPuBRscZFXNeh0e7BaNEtZcbht5yT7Vw8NyzK88TGDZ91Cx+
b8KjvNQaRUd1O9Vyy55BoA2ALKNPMe6VihAPy9MVX1LVhLDNaWDzRxOMu7Ht6CuZe4L8KSFPzNVSa9EFwNp
Zht5UnpmgDuo/Gc9vYNa/ZoXhxsBK5I461wviG7V90eV/eMCVqpPqLSqFEqpzgEDrWaySNO8srh84UH+tAD
o4WZlMWWGc8dMetakGlS6lMFiL7VO0lR1FVYZCFyoBP3Rj0zXb6cv2GzXYSJXXeWXjigDDj0K2tcJMikZyy
j72B/KtzSdRjtDtsdPhWFUPzg5Y89D6U+O1+0RJcSf6iRslV5J+pqVmt41CRkRp32gZwKANyDxFpJij+1WU
0bkfPI4LAflUzavpV1dReVfwvlwuIlORXKxar5bH7PEZIxySwyK0rHX001jOmkaXHedUkaPcee+OmaAPaNb
8Kvd/DG9s9FiWbULwgxs/BHHc9q8Y8V/CLxNZ+ELfU5bAefCCtxGpBKgfxV0Fj8XvE+n5V7mCZH6o8SgD2G
K7zwT8bbC8ZdP8Qwxort5ZkByvPYg9RQB8qiQEDf8rAYOB1Iq3YybAG3Ftx79q9k+Onwog0qIa54bdXsZn3
eSnOzPceorxFWeOURShg6jkFcUAaskW23AUuAxJOOetUdSteAY2YqRx61Naz74CJRnJ7NyKfmUyqqjeOmSO
AKAOfMEvnkqFYYztY4PFaUCgBXwVccbR6VoG0jaQtkEk8DHX2qPy2jTcAOuOnagCXVbf8AdRbAxIXkVjeWF
mYKqggZbPrW/czNJEiscru+VlquYI9jMQG5wWHUGgDAggkaZmPToPb3rYWIFxkDOMZHXipVt44HDZBDDjPN
NjjJcuvVuAB60ANkEcxw/KngHvUhIWIouduPvd+KZJBJblnVGIHY1XeX5MDO0rnbjnPoKALelb7u5W1RG85
vlUEfezXukHwuuIfATafMsaTzlZ39Rg5xXPfDTw5c+H9Q0HULmyF1c377wskZZYYwOC3oa9r8SeNdDS1Nqb
62hv8A7si+YG2k9hQB5B4T8cS+GDHod3YyTWcbEEo2GbJqbVdctbvUzciy8oY+ZQfmx2zUevixu9RElssUh
bG5l6Z+tQLpqO5IyNvJwaANTw/BBqOoN8vmLINpVR0H0pPFfwVu7iH7foqNJGxJaNcZHtirPgQ7vE9mqMEX
zADxjPNe2eOvG+j+BtPEt+26ZwTHbxkbn/woA+Vrf4ZeIZbZmSwuoyn3gU6e9cnd6Y8E0sFzF82c5xyK9J8
Y/G7xNrkjQ6cY9OtHbasMI3Ow92P9K81uH1e7aSSWUyu2Tk/qDQBkT2ghJdDk9cjniq8zAKrMGP6CrDeaN4
5DjoM8EUkDJNG0cpbd64zzQBBa3PluJ4xnnIz0yK3bTXY/MjM+5H7kdK594PIVhvEiqcY6c1TSO58yTCEgg
EAUAd/Fr6RMXkmVkycZ7VYi1xoZFZUVm6jv1HpXnzwXDx7jblAnVeeasJHdxI5Bk3AfKoBoA72XxDJcFHkl
CLjgdB+FYl9rVt5rMkrzkdMHpWFaaZcysRKrsDzt5rSg0dYmjKyByTzgcD2oAiaSe8l8yHMURG0g0V21t4f
lFqJjGcHo+3A7UUAZcl9FGcxwpk5zxWBcawyyGKEjOfudKoXV7MZT8u3jbg981TazlvWCHAcc4HUUAajau6
RO7OVIwdp68VINVMrGVmIZlGR2P1rMOjSxIHMuX6HI60x41aURuoRscFe+KALMmpMu8blII4xVG7uZTveID
PHSofJ+Yr8zBeT24phDQsFReMkbe4z0oAcDKYyzFgvYY7mrsbNHErPnDKRkjgGq8aTR8Shgrn16VZnk3Q+X
G5AA6ntQBZ00ossfmgSIB6nk16fPJpkugWF7DJEs0KmG4iz8xGcqwH415UWJjXG1hjANHmFFIdmDDDBgeDi
gDuxeWCkgzRrH1A3YqC41XTkI/eKS3Xb0ArnLXSI7mKO6mXJY/drVk0K1YKDEwcUAMuPEERuBHEi7VHTGMi
qEmoXFyNx+VyeFHpWxHokbRh2iY44JHpSSaNDGPMUnkbVBFAHMiS6MZLgs6kk89qWzmkhvN7Oc4+UYq3d6T
cM3mRHaR8p+lV7eCX5QeXBxnPagDs9atfF3jex03TtLupJRp0JYQiXaSvUn3rM8aaXd2+nWF8bOeEFPLlMq
FMsD6Gup8FXElhrthIkRlkBwQrYLgj7oNes+I9M1f4heA7m41zSJtKvLWcpbW0hDF0A+9mgD5etjtZCB8p5
yB0NbU9psTzjny3AK7f1rAvYbjTdUktp1kjdX2FcdK6ZZNtjEGYFSDtI/hoAz4m2SZZm5yCo9Kk5RYkA3A5
IJ5x9arsyS3Cuowo4Jx1q0sjbTgJsJxmgBGUSNGFA3KOmMCopQ8YVY+hbLcVPtkiTcXGT/AKv0I9aq3Um8Z
ALSK2OOmO9ADlTMhDEEMMgntUixvFDuyvmJ0x0rOlukE2I3IUnnjNaVv5MlmwicmYH5gehoAzrkzKgDuzF+
SAe9avg2yDNe6vdQPNbaXGbgRlSfMk/gX86w7qMyTKEG9if73Q16r4J0qKDwnO98kpR2GyNW4kIGefagCO2
+OmreIfDV9pd1bxWdwMIk0C7cR9NpPrXDf2naRTpwW2HLEjJJ+tVL+2A1CVIodkZcsFHv1qsdHlMoZW2xE8
A0AdlY3sLnNtIEOQXVjiugtxPMch1CZ67uCK4VLQQWjPgvMAcbjwfSqiXN5PIsSsVhJwcHnms6dWNS/L00O
3GYCrg1D2ys5K9uqXS/r2O31bxIdKYJpc2b8cmdOimuXvNW1DWbv7RrNy95cjq8rZwPQVbWzVE27cgjGTVW
6CpcDcmFVQfrWhxE9tbRrMjLH87DKYPetYWvk2PniIgPlQPcc1n29wuwOFJK/dHsa6nWbyOfRrHYCjqGLCg
Dg9XtFk2yhVBzgisG+tfs5bygQzcls8D2rpdQZpFUBt2WL5YVCLdpLciRQWfk4NAHL2yxtN5bMS4OeOmfeu
606K2KqJY0wygsQP61xeoWzWt4wjBBYZBq3pWryr+4bGABkt1xQB6ZB4UkuI99tc2zROQCryDK+nFS3Xg7U
4w8YiDls7SmD/kVzllqed209sVr2XiW6t54SkrljwoLdQRigAi8OXELqLlGRWGSwB/Kul0rSNJ0o/aL2NLh
wAyAnp+FZU/ieSYBJwQO3PBNYuq6hJLIhi5VeD7UAd9qXiW3W3YWiQ7RyEI4WivLJJZWKpltzdhRQBipaxm
SQcFuOcZPWrcNmPmc7NynBwecVu3+mJbwi4i5ikUFMd/WsIeXEZGkwC6kDmgC7cwqbNRtQEZOQa5p1jeZmZ
PmA4JFbdw8K2hAYPuX7uawjcYt5FgB3bSxJ9aAM+eUOGREAdW+8pPIpfsgliEoOFLdG6tWhZWryOjXCeYpA
46c1Xv4QJPLBI5yiDt60AQSMTtj2PlenORTVVyu1iXwevar9vbK5YJhdvqcVJLaeVBEBuIJLNzQBmKGFzsU
rhehHrU8q7Iy86kkDacD1qC5h+zT7ypCPgj0xWtHYm7BMIDKRnZ3oAmstXQ2qQNsTYMA55rdjujsjIk3yZy
D2rjbjQpjLuwyEHp2+lX4tPvEX77r3A7LQB2MWqyRSxw7Y3R25yOlWpLqGRTB5aEqTlhXGQ29/b7vLkVi34
81pLc7oWyGBHXae9AG1eWpKAxg7jj7orOTT4RdgEnA5LGq9le3kzAWty6c4G9c10MksWl6eZbya3ur5z+6t
oxmSRvp6UAR/wBrL4ckj1F0SURn/R4gPmd+2PavU9P1jxf4msdA1O/vbjSrgMwmtUjBjlTPy9eQaxPh/wCB
5W1GHxD41/fX6j9xCeIrcdsKO9ek39oNRiuIjPJBM0e63mXjafUUAfPXxzsvsPjK4mjjKiXBGOm7HOa41ZW
e3K4AO0Ec12PxRe6kl8vVplubuL5TKoxu9+K89O91BDD0x7elAF6CYoNn8Oe4/lU4nzmNuJCM4zjiqCMCzY
XKLxjPQ04ecpWRFw+OpPOKANAy7Y4wi7h0IzkioJLjMj/Jt2ocr61U3ySP5nJbuAaRsvPG/wB7dyAKAHeav
ksQAucHHpSwz/KzW4ChxwQc5qtcxytOCgODwfWn25Pk7AnzH7u3tQBr6JAt3e26DG5jkqTg5r6c8BaE/wDZ
K3OqeTNGqFIoSuFjGOvua+V9EdoNVilGGVe4yMGvpz4Ra1NcbbO5EksbjcTnP4UAS6N4M8PpcebdWwuHklJ
cMMBQT2rE+LfgUaFo0t7oypcaLJOJH8xgWtW6BUH9059/613OsxzC5uLxB5Tbs7Seo7DFY2iySeM/GVnp8u
W0fR3FzOh5WW4/gX6D/EVz4nWHInq9D18ltTxSxE4pwp+877WW3zbsl526Hh1noeoala3Fxa2wkt7Ujz2Y4
259uvasfS7ZHvCkG1mYnKnOetfUHxC+F8uoTy6t4NvW0vWS3mTRElobj2K9B+FeaeCLvw9D4nl03x9praHr
yqd2fljmPYqenNPDUPYU1AnOszeaYuWJateyS3tZf53M+fwrfjT1lgtjcbQCXVcgVyN7auZmSSLY4OCMdq9
W8YeK57TEOnzGGBeBsxtI7c157qOr3F3Ksl15cgwQflAJNbnlGRHZSLGgjjLEt8qkc1a1R4Y7ZPnV5iNr7S
eORxip7XUxaP5ihVkTkBhnNVtQvf7TlMiIinAG0AAH3oAw53Etz5Y2hVGRWgFVLYSyBGUelYRtlk1CWVWYA
nAweOK07+R4beJNpHcqR1FAGHrcPnXMRh4GABg1RTTF3N5kjKSc5ArVitpJLkSt8q4+Udq2LSzDCQeWDgZz
/hQBgxrKp+UbwBjIqSSZkmRjksBwFz8tTasy6ahjkQx7/mjPrXIf2tIY9gkYSOeST1oA7yzuWu0j5TJIIye
a05gft0FqqM0rRknAzjnvXn+l6kbeVpZZ9iQfOEJByR2qG38c6xaS3M9pMsdzcn945QNwOgGelAHf36vb2+
yUKsyHGR1orzDUPE2o6hua6lDSMMFlGM0UAe4WMa33gkbGQSwNs+Zuq+1cNqyGJVO0yMnQegq58HdUXWZrj
w5cymGS85ilJ4DDpWjqOlSWeq3FjqCyeapIDNxnHHHtQBxwO9Fd0KqTnFWbeDbKvmsvXKrjoKuPb/ZnaKSM
tkYXNLfGMY6q4j5OOTQA2+kjtojlwqDkEeprIt4zPItw7naG6GoruWS9aOLdkMeAByAKvpF9mjGMsuMZz0o
Au+YkKZzlXz/DVRyZoIyihmGeScYq0UEsMZ3cgflVScs2CgxzjC9/egCK4TzYEDEM4yMHsKZp9wbeYKwKBR
jJ96vIhZAxXJHv1JqO6tfOBMgA2nAx3oA0rfVlLhZdrDpn0xVtLyKYTAEBCc7s1habZLIu9gBubAHpWi1gk
TxsytgnoDgGgCy0kUx2qhXZ8u6o5rY+aiMyqFXzCQwAIpsrpbhIzueSVvljQZOa7a08BC50qHWfE92lpaJx
9niOJJB/d9qAOT8PafeeINUFhoEW+TAzOThEz3zXpOmaBpfhC8RNy3+tuuJ7hjkRt/s1yumavaw6kbLQ4Tp
9qgONhyxA9TWrptx9r1BEAaR92Q5bOT70AemeG4
2E6qwaeU/xM2eKl+IHiGCzjsIUjDSjePlbGR6U2DVLLw3ojy3alb7y+54I9B71474p8QPqN7JcOGQ42qhPC
igDnPGE4v75pSwRgPu5zXJHgN5ZXzTwQRwK072YyTFwy9eFNY5clw2Qfm4BoAk8opKmBwR1HQ+tP81TIOCG
6fUUMGCld67VGTnqM+lMmiJKN1QjrjBoAlkm3ksFKHPGOmBUOVMYLhsgdfXPenFyzMFAGMDmq4YhnV2IwTg
9elAEySNuIVgeMbqdC23bliCfTp+dRKNyKuAJRzuXvTzDKUOR8ucNQBdXaW2r+6zyzZr1X4U+KV0vV41kYm
JiAzHuK8gL+W2zBYAjJNaCzGGMyRyv5pOFA4AHrQB9afEfXLWHw7b3ungTXt+RHbqvOXPAH9ayPBkbeF4Et
ZCBc5Mksuc73bqT/L8K8z8E+K9Lkm09tVnYLp8Hl20T5OZXPzyH8OB9BXq2oWhmME9uyyROoYMrZzWMIuU3
N9NF+r+f5Hp4ipCjhoYam7uVpSa7/Zj/ANurfzbXQ9G0nWortFWQgMOnuar+LvCWh+MtPaz1u0jn2rlZgAH
Q+oNcDpN/NDes24KEU9e30ra0XxS8E0jzMGUnauT1rY8w8F8bfDjxJ4L1r7PYyPqulTDdETnMYz0PvXLS3b
b2t7mGS2ug3KTArkexr7Cl1aG6uRb3EccsRHzjGT+FUtX+HPhnxHaMl7b+a/VJlwskefcUAfIrQyxsGSYIz
HPzDIp3lSx7x8rs4Hzg4xXpHj/4M+IvDMFxe+Gpxq+nIQ32Z1PnKO/PevK11hUmEF/bvZ3C8GKVdtAGtC0c
MMARDIT/AKwt0XNXNYjigtI5A6y7Rwe/0xWE+qWvIRwoJPOc1yviDXJ+Qk54+4w6GgDek1mJMndkqdpUcVG
NQu53Eu1jEBwF5xXnct3LLNJIzYaT72Ohqe21G80+Qi3uGXHBAOQaAO1v9QW5tXS8Ijiddqs56GuBus+e6l
gwU4BHSprzULi8ULM+VHOAKp0AFFFFABRRRQBYsbuewvIbq0kMc8Lh0deoIr3rQfFsfjzUvDiXaobu3BS8O
ME543e9fPtS208ttMs1vI8UqnKuhwRQB7z8SdMbRvEU9ucpF/yzBGMqecj864S9Vi2UcgBR8w71z974lv8A
V7m3e8meWYAIzu/Ye5rYtry2VEje6jdgBhQcnrQAkUe28b/ZUsT3P0q0sgVGJX5R0B96ry6iPN2w7XGMk+l
VHnQzHErEjnGOMUAbigCJW4U7duAaFMc8ZEQyx4x6VSWR1jbI3FsBFH8WfQVp2Gl3QIUQyb8BmO04HtmgAs
7dkjPyscDJx2qLyTMihi2Vbdx2rpra70HSTjxBeMC/At7X55GPpge9aWhfD7xN4pfdotjNYaRnP229AiYJ6
4PJoA5e1MEaZmAwvIJ4rs7LQLrxBpsP2Owaytbcb57+4JXcv+yD1NbGt+G9I+G+kpMT/a2tSsdk0g3IecZF
ZviPxNqmu6Baz3KPDbovlsiA7d3+RQBtXGn6HpHhh7jwyjXmopJ+9upFDbB7CvOJr25v5JHv5JXYOdysxCn
3xWl4Q1S3tobtZrp7dpEK7ADyc+tZl1ZSJcyOlwJWlHC7skCgCTSLkgSIpQF+S2Og7V6H4btF0ywF9NJGkg
G5dwByK4DSvs+kWxvNQXepz5SfxsR6+1YmseKbrUiVbKIpwB6DtQB1XjDxhPqUrpcYkyeGXgY+lcRd3UrEs
Zevr2NU5ZHZVZsFxnHFMDGN45JVyT95aAHXDhwWyrSE/fxxULMVwFUrnI6ZA96sKsP7xmbAJyoHao5cRnzP
vA9TnBzQAmxQAIwPM+6T1zS3SkBG3EA8AA4xTpSNiNGCDJznrTmQ+YBtDcc0AVHDFXLD5Sfp0poiLBmEmC2
OQc4rRXSp3smuFULbxEqWZsA5qsiKowqtlgMCgBsAcyYU8juRUzPL5RKKVB5Kn+dSPFLIAqgKhz060sEbkY
jAHOSrd6AIAfPAaZMSjnI6EUySMs27dg/wrUwCIWjEfBJJYDApixlYMNhiTjJoAjZRCyMsjZ6HvXpPw1+IU
2j6nb22rStPpmdjgjJTPevOj8pxtGOOi9aa6fPvEYCdCcc5oA+ttWsrdIhfac/2qzmUFGQ5HuM1j28ZHzM2
2OEFiSa8+
+BvjJdKu20fUedPkPO7na3tXq/iyNfIEunxq8HBPTkUAZGnarKlw1zdSsFkB8vPGK9N8F38cWkyXN5MfmI+
YnrXh1jBJqGotJcKpgXjnotamp+IlaaLT7Ti3iGDt4A9TQB9Ax6paSQtKsw2Dqa5zxp8O/C/jeyZNb0yGR2
X5biL5JV9ww/rmvKLfxJlIrS0kZ2XgDaea9a8F3222aO7k2OQMIT0oA+MfjL8Kta+Hd+xglku9DkJMM68sg
9H9PrXlDOzfeYn6mv0a+Kmnw6jojwyopLKeSOtfBPj7QW0LXJI9pWKQllGOnNAHM0U5WZDlGKn2OKGdnPzs
W+pzQA2iiigAooooAKKKKACiiigApyOyHKkg+optFAEyXMqsSHPPX3qxbag0DMdgbPYnpVKtrQPD91q1wqq
u2PuTQBVTVrtb+O6D5lT7gxwPwr0TwppvjHx5c+R9raytTgvJsK5HsB1rv8AwJ8Ibe5lt2S0EkmN25znmvo
fwb4DsPDNkTKVLqNzEHgDvQBzHwy+DHhfwtbJqN3F/amo43tdXY3Y47KelZvxd+IllceG7rSdAnAn3bJRGc
YT2xXReNfifo2hQi2sylzHKuGaM5256ivnPxSbeHxK13ooZre5AciXpg9s0AW2tZdQ8HwzfbpLqa1c/uTks
oNYljrNzYwNYXEu61kPzA9FPvVJdWuNLvLkiVrZXPAjOQTVwC21ZWYiLz2j3SL03N60AQahbPprrPHmWGUb
jtGcirLtaz20N5HmNsY2g4496j0m9mtQ1jfFPJ6BSM8e1Y9+IEmmW3OI2HGT/KgCHVruS8l4kYKGKgMeOtV
GVkcK6n5hjHvSscsoAyEwWJ9ajkctKzOSUJwD6UAOlVDEGZmXI6CkMatGDvJGO/WmlVbIZzgc1JEwRMkHy/
73oaAC3QOwyCrdOelXLiBMKx27TgY9MVEHRwfLckA8GnKp8wKxbyxnOfWgCHztqAum8IT09KUzMcOmcbsYP
cU26LJu8rC84we9AyIl3Kc/eBHQ0AW2kkl0podzKhbJH9agtwqw4kBYryGNW4BLJbSy4JjQASYPTNVZXJlJ
IJQjGBQA4BTNnzGVcdOgqWMragMoLgnvyRmqYVsKSvynn5varMO55PMGN+MbDQA6XCYgjXgnO4881QRHmkk
3HaEGMf1qdg6gmQMOcDmluSqKMEb2OD7UAVVjkdw27twtIjknawIbJIOeMVKrgk5PzqOARwfWhZApVuAoGM
UAWNIuXhvEcfMCegr6X8G6omseFlt5W/eAZwOScGvl6NjEyFjhn4VVHWvTvAHi6HQ1LXM2J14WADJYntQBt
+ItYW2M1rbjyFyQ2T8zGud00XEz7g23PWRj2r6A0rw5Y+I9JXUfEOkWO58EFMq3tnBrF1v4eae12kMWbaCR
cIIzkA9s0AcBpF3a2JX7KTNcMNxc9FrstB1m5+3o7MZGf5cp0NRP8LdT08otqnmZONwwa6nwt4LvbKWFLmM
p82SaAOtv7ea50MNO6u5XoOSBXyr8ZPDhuJZGZHOCdrAdK+zY4kEHlAHbjByK4/xN4HtNYjkjaMYJyCOtAH
543elXUEhURMy5wCB1qi6NGxV1KsOxGK+4oPgbY2939quLjzIwciID9K8j+O3w0sdPSe80yNknjAO3PBFAH
zvRSkEEg9RSUAFFFFABRRRQAUUUUAFaOhaa+ralDaIcNIcD3rOrf8DXCQeKdOaZmVPMC5XqKAPZPD3woCBC
1t85A+8uc16H4X+EzW91HK6hIicnAFdv4IuIP7NhdIhI0nyguc5r0C1RBDHlVj6ltozQBRtLe38O6M8zRKy
QJksBya8s+IHxUXYsVhzHJGUkBB4B4r0W+1618yCwELzteOYTGpzgep9K8l+Jfw7nS5E1ruSIncEC5AHpQB
5FeaVcTW76jaOl3bMxLIDyPTIq7pnie5m0prGaG1uooztMbAb0X2NVLzSNU0O5liErrGScqTgHPtWFLFL9t
LWzCMjhinegDZRLB4mFo5S4Y4KTdFHtWff6RNZQuYLlMY3MVbrTZbW8uJGWO4TJGSAtbegeC7q6dPt80iwO
Od38X0oAyNG0y41B0eZg0EI+/wCprL1kJLduoP3fusor1DxXZQeH7fT7CxYqyxncic4z6+9eWazcmG7ZDES
q8sfegCvmWKDMyhmYZDe1RwTswYyAAAZyBxUU8uXXZyvBPOeKUyBWYRhCOvTpQBMshdC2wBRj7vJNCbQoZg
3XmNjjmiKPEhdDubGSBxinKDIFRyPqBnPtQBPaWhkmJUkE+p4qW4jLP5RAjYfNgHriiEeZKEAYRr91Rwfqa
tXKOoLblKMMEdwDQBVWKR2UksMcnPeoZcOygnBGcYq5bOgYsGbavy7M55PcVLLaG7YEKVZTgg9qAK8Amlgu
VhJJCfwjqKrQhkmJlbIC9D24rpNEhVBJE4YBhyQO1Z2pWojkdlKxo3QDkmgClAMRkOVPGF57UFwsnKjjoR6
VHCWaORoiobGd2P0pPNWVA0gZecDHUmgCV13265k4B5z1FVpoGXopwoBznirZQTph42RiMlu1RWaS3sotbW
MyMxxtXJJHrQBTdjLGjAbmBPB6VGjFnYn5snJU1rT6ebS+Nu/31XBGOBTVthLIIrbBYnIOKAM7yH8xFLEAH
dnuK1lg2pJeR7d54Yj7wx3plw3kTMI13gDBbHJ9qu6fbSSW7qsixLIACX7UAdb4F8can4fZI2mlubWXhkkY
tg19FfDbXBrdvcXE/wC8tymWLLnyyOvNfN1rdeH/AA9YrJJIl9es+SnUYxzV8/FO+ns5rLRbT7LZSDawztG
Me1AH1P4Y1yDVjKumhp7GIlRcluCfSt6SSOMBpHVQTgFjjmvlz4YeM7/w/pktvCwfYpcRk8HPNVPHvxI1nU
18qS4MaxDerRnbyT6CgD6xHPSivkPwr8Vdet9kCXE1wEGAWbp716l4Q+MxubpbPXLNUJO1Jo26n3FAHtLAM
MEV458Z9LDaXcHllUZGTzXpOl+JdP1BmVJAjD+8RzXJ/FWEHT55Jz8hX5cN/SgD4E8Qw+Rq9wmMYY/jWbXU
+PLWOHVJGRweT2681y1ABRRRQAUUUUAFFFFABWhoE/2bWrKY4+WVTz9altdLe+02S5teXhOJE9vWl0TT3ur
lCofHUHtmgD7G8C6tCdBfYUaeNfMXnBHbI/Om6R8VP7NtLpLzfOWlO1uD8teC6Jrd7o+oQO53wOmwgHitDW
okhuFuYDtglTzCp7UAejSeLdU0LXBrS2r3Nhc5MRI+6K2D8ZrO8gaK9txEc55HIPpXKaD8RrSHw3Fpd9bRy
pwuQuSvvUT2ejarbSMy+XLI/wAjIOPxoA7K0/4R3xOk39qxqpKlg68HrWX4u8FeGNOghl0iaW4wCGVevtmk
0Lw2osGjkkJwDt2da6DS9EitPkBknlKKCiDOKAOB07R3EjR22nbXPBcDNdvpemR6OHn1Vl8y2iDRxueAT7f
jXb6Xp935Y/s/TjGeoeYcbq5nxhaaVpv2iTxHdpPdSKS+WACnsAO9AHjnxH1JY9T+V991IN78YXPYZ+leaT
DzhLIzgdS6nqT7Vv8Ai+7tb6+ZVvovJXA4UkkDpg1zdwbWMFVuHYE5GVxQARFGkQKm0YGQe1EsEhmbygsag
5LGlt1VWdmcNIxBU+oqSFnd1XKkycFc8jmgAs4XZPO65z81bGj20N3OkLkxh+jAdDS2mn6hN5cVtb741JDB
nAH1robfQ5dOMM897ZxqpyFzuP6UAR+IPBep6YIZJF3QkbsjqVrBcNLK4eBwrDCnGK9ubXL3UdINk9xplwM
Y3E4dRWRNoBtI45Lm0O3IwduR9aAPL7OxcyhzCQ6naq/1rSls5re+ha5Vvsspw2z1rqtTgjt7eSaJl8wY5Q
ZxWn4c0EaxEkcsmLnAcL2JoAyLHT0fZJtMaMpXLfeNZeqaOZEMxDnJ6Driva9M8Nos1uZSPPOflZeAcYNRa
l4NuFvNlrtc8K2R0+lAHzvd6c8YdYwqgj6GsyKB/lXa3mE9K9J8a6dHp149rKC7kffI4FZvhzSQ5UPEGlzx
j07UAYdjp1xevFEiSGVmxhuAK9t8H+FNL8LeFJNQ1WOGPUJSFjCHc5B7CsDRtImEu2S3KRBjuc9gK47xl45
kt7R9P0ybPznErjJAB4xQBD4v8OarJqc14tsUt5TuXfIAfx9Kxo9Nmty8l5c20KryBG4Y/pWdnULuM3d3cy
zbgB34/Csu5tmtpFkYSCKU/KfWgC9fXAaRvsYYupzvbgH6UTvJHsNyzZPOFOatWMAMbHcjY64PNQXrGJV8l
hvc4QE0AOt/9JcQn94w6npgGr1rHHD5iuhCKNqkHiqekxGKE+YQJGJ3YPetK2tzIuZVMduOcL1agDR0y6+z
CWdUYidQgA/hAqrrJSNpZM8SDMfOcY65qwZESJ327YnGFDdcVlXUy3LMHi2pjCn6UAQafIqSxzw72xjcG46
12ulJb3UVw4JVkHJ/u1xunwma8ed3kCoMovtW1Ddyv9p8pdisgHy9OlAHeaL4mmsrsfZJQ0IIRtwrrvGGsL
f6ES7iSULgHPFeHxXLRxhg+wtwSO9aF/re3TzDFIduz5/8aAPJ/HM5m1yTJzjsOg5rnat6rN5+oTPu3DcQD
7VUoAKKKKACiiigAopx6mkoAtafqFzp8jNayFdwwy9Qw9639D1NA8awoFcH7p/XFctV3RONWtMf89V/nQB7
PpOiT6uqCJSwdc5Ud63IvBGtW/mRSWk1xGSAGCk8elanwnJCzAcAS8e1eyCaVbpUWRwvoGOKAPGLb4YTSzp
NM81uCASqjn6Yrs/D3w0NpCql7iYAk5uGwBXrluiGeIlVJwDnFcL8Vrq4i+1iOeVAMcK5FAGlDoWl2Nu02o
3iIsf8KEANXP3/AMWPCvh4SLYQid14KjHJ9c14VqF7dS3rRyXM7pn7rSEj8q5+9UDoAOvSgD1zxF+0DqN+j
2OkWMdqXXCzFuQPUV4p4p1W/wBQnmuL68muJpD8zSMTj6CorYA3OSBkE4PpzV3VFBs7okDPH86AOegtVmgL
nczcAL2p0NnFLHJhGZlPG41oWPCjHHNT2AA1I4A6mgDJlh8jMkTMxUDIxxTbUu6crskyTk1uTgeRccD75rL
tuUUnrigCKOe6tyVhmkbPJAJrorNJb22RZHIx1YHOT6Gs1vl2beMsc4ras/ljTHGW7UAFrpssU5ZJ5jzgFS
etd54V8bXNtcppusBr6JGCFWPIA9PWuX08kGXBPAJqhYMf7VhbJ3Fxz3oA908R2um33hia50a3RiV3cD07V
m/DoLPf2syMcjG6PGMEVp/DIloNWjYkxjaQp6Dj0qb4ZRoPEV4oRQvmnjHvQB6hcxf8e7W1vyrZJIznNZ2q
3pt9XaNm2kclgvHPauhR2GpqgYhP7oPFUNeRftbHaM5HOKAPDfHdtLNr7xzRRvHIMhiuDVjw/Fptt5TGNzI
mF3AZzV34kEmZCSSRms/wLzcJnn5hQBf+KOtwaF4NaKxYpqN3wpPZT1OK+f59PL2McjFSS2SwGcV6D8c3Y6
4AWJAgGOenNcjZEnTUUkldw47UAU0dvswgjBBzlmzxUl6VktAhYFUGQ2Ohp8oxIcelQxgeVKMcY6UAULO4M
OnSSc5lYbQB1xTTCZZlZ14HTPrSXPy28IXgZPAq5YcvBnn5z1oA0YEWQom1Ae59fer08STQmIuyIvQrVF+F
fHHApWYizOCRzQBWuLie/uBbQACONtpftj3puqShplgtvlXjefUU+x+Syuivykjkjis+Ak6xJknpQBs2ULy
R/u5AvG1WqxdMun2Tokgdz1I61Ug+W4KrwuRwKZrSgbcADLc+9AFYBwoMzM0ZPyZ7Gqeo3LLHISeNhBGe9W
05eBT9307VkamM2E+fegDh5W3yMcAZPamU6koASilpaAG0U4dRRQB//9k=);\">",
" </div>",
" <div class=\"lgnd\">",
" Note the decreased volume and abnormal increased T2 signal of the hippocampus
(arrow) and atrophy of the left temporal lobe, including the white matter.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6179=[""].join("\n");
var outline_f6_2_6179=null;
var title_f6_2_6180="TR beta molecule";
var content_f6_2_6180=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=PEDS
%2F77294&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
%2F77294&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 597px\">",
" <div class=\"ttl\">",
" Location of mutations in the TR",
" _{",
" &beta;",
"}",
" molecule causing RTH",
" </div>",
" <div class=\"cntnt\" style=\"width: 577px; height: 499px; background-image:
url(data:image/gif;base64,R0lGODlhQQLzAfcAAP///8+2nXx8fnlMeUxJSvXy9QcnrQYpvOLY4v/48
q2srAQu2XBwcPLy8sWyxTAwMP/r2Ovl6//Ysv/y5eUnJ6+WfIuMjv/V1QAKNAAenCAgIFoXGG1sbf/FjAAY
d2dlZdra2qiMqJCQkD6Kcv+4cgASWR9qUWBgYJ6cnf/SpYJZguWZTba1tpVylUQpQxAQEEA+P15dX7y8vLy
lvP+lTFdVV5JRU3R0djAsLZqcnlRRUjk1Nk9NTwsJCjo6OsvLyysqKkhGRx0bHP8AACMfIFpXWMnIyDEuL5
GPkAAAAOjo6AAz/
+Tk5IxmjEBAQMDAwDEtLtbW1pGPj5EPEHZzdICAgFpXV4SBgj87PMgHCJ+dnru6umhlZkCzjH/MssjHx9nN
2cDm2f+zZj+yjP/mzf+yZv/MmbKZsgCZZr/l2P/lzNjM2LN1dv+ZM2YzZtDQ0PDw8MxOT4DMs+Dg4EBmszA
dHhEpj0wZGqCgoHUTFD4bHICZzMDN5j47O1BQULCwsPEBArOZs/Hx8Qgux/Dz+XVzcyAgLawLDKyrqxokV9
DZ7IOBgePj47q5uVBzudUFBuMDBE2agqCz2dXV1e/49cyaaODm8/+sWZ4NDmcVFoBngjBZrM/r4roJCrDA3
/9/f5Cm09/y6xwiSYMREmCAvx4hO3CNxp/YxdDs4xUmcy+sggIx8ZKUlg8qnfD59qCAoJ9/nwQw4xglZYOE
hs+/z0+4lV+/nwADD2/FqK/fzxMngf/fv/+/v/8/PyomJ//AwP+AgAAv72C/oAAGH/+/fzCsg/
+/gODz7I/SvBCfcB+lebDf0KDZxiBNpv/fwFC5lqaIigApz3DGqYWDhCCmedDA0M/Oz6CSlJDTvG5Abg+fb
79hYv9AQKqAfD88Pf+fQHObkP+fn4mGh8PCwmVhZFZTVDo3OEk8SdYXF6qpqf+goImHiHFXcl2DeIKCgt6R
RZ+fn0NnW7+mjI2BkDIvL+/v7xeIYiOVcJ9rOeTXytaIPJmXmJqYmainpxBAn3p4eCH5BAAAAAAALAAAAAB
BAvMBAAj/AAEIHEiwoMGDCBMqXMiwocOHECNKnEixosWLGDNq3Mixo8ePIEOKHEmypMmTKFOqXMmypcuXMG
PKnEmzps2bOHPq3Mmzp8+fQIMKHUq0qNGjSJMqXcq0qdOnUKNKnUq1qtWrWLNq3cq1q9evYMOKHUu2rNmza
NOqXcu2rdu3cOPKnUu37sg3Tpy8scu3r9+vJ5IkOfG3sOHDT18IfoG4sePHPv8k8eMnyR/ImDNrbhkYD57B
m0OLHs0RjuAHDwTDIc26teuFnzXk1ZAEz+vbuFtXtg3gs5/cwINjfvJkNQA4xIUrX868eeEGTFbOEbHXufX
DVJAcvDKQ+0LvDcET/xQv0XsUBRKNaJ94vuITwRoYXL5Ov26UK0UGMkGiJQoBI1EAEAV0AhGoABIKQPdfdP
uhJ2ADRhAUIBNMaKFFAw38NyGCAgVoBIT8RQeAegr4ZwQTBEahXoQANBggQeohsd6B0UGnwIXq1agFElsAk
GKDAu2nhYgIvSfYYn7gYVx9TLJFBRMKoMdEEVtsoQUWHOZHgEBUBKiAEVpQYQSWJxYBJndYXLGeQPkhQWWY
TGCpwJQxAlCEmkxsYcQWW27BhRE3kqkeAFAgYQQBFFKpQH4D+WmEmgBcoYURRTBBqZUEKMBni3pS8aV2RYj
pKZ2aKmTkkag+UEV1TbZKVgP5wf8KgBY9sjlQfld8yKgCVBSRH6O02sooQW2y+KtAYcp4rECPFgEFAFw0cC
uzoApkaLB2EhTtiNUCYOWg2WbbgBZcEGBotzkSsAWRRaLq7pEaEObqvF8pgIWvUOzHYrjZRuEperxGt6yhw
hpUbMEA8GcEgOEyQUCAy9rKbbjnGkssteGuuB6j+VGB47kZa7ffnaa+i2q8fyxJ78pZFSGtt0hEEW0DUVQq
LaMEbGuht/lh4aPMAnLB77QEZ2uzzBhGyCjQUfi8Y4tx+jgoo4YaITSlBPGXsHZcBNg1uBxDO6CMU1PLxIR
CJ3Rqqquy7PZWDawZKc9/1qydd1us10CvCnD/t2iPW4QqLXlzlygQd3Z7y0UR6IHnJhJUWBsqlFS2553hjw
/rIxVcaIHe3lQK6KB3iHPReYmNdzhnr1S83O6RSc7x9uy0J/SpFjQ9Ed98tffuO7Ic/i788MQXb/zxyCefP
BiBNO/889BHL/301DcPxkBhyKH99tx37/334IevfRguSWDG+einr/767LfvvhkTKC9/RIE0ccb9+Oev//78
9+9/E4EYiBzG4IUCGvCACEygAhfIwDHIoSJdQIMEJUi+iIiBGO/LoAYzSAMyzO+DDQnEGVpyhgAKRA5eaIk
XHkiRLqRhIGOoIETEoAaWlMGDtTOZDnfIwx76kIcneMJr/0RIQhMCAIUqZOFEXAhDGT6EhjbEIe2SoIQqWv
GKWMyiFrfIxS528Qc3eMEDlMQaIrKkhAJMIUtWCMEXCiSGEoHiSm7YOypakQUosEYVQcCCcXjxj4AMZBZF4
IMXMEB2ojGjQAqwBgQIxAEcYaQjB4LGE6pRIJRIAycEcgqOZHKTA2FjC90IADhasIYDgYAaEgAANcQvJHTM
oRXTgQIQ4KCKQZgGBzggyF76kosyqMFkeJcZRTrAfrBQAQCawBBmOkQFZ2jBCAVSySNe8hQEtIUqSsmQMTx
EFV6whS1CqUSJMPGNTnSIHBNQhg6Y4RLmQ2VCygCRCZCAILGcohVjwP8CEAQBizr4pUAHukd3CEEDIlCZY8
yIgBYMpADLBMAaIvBIibagCQ5YwwDOsAYAnMF+AIjAGhwASYM406NGRCIAOFGLgVCCm2kIBScBkIZajOEUa
VCGF17oBQICIBRpOEUnDeJNgXihC+JLKjVIacoZopIEEBhIAsxQQwkIxJVTLQMx1EADM1gVAiSAKgAkMAH4
pbIM9BxIPmdnRyXoYBoiQMEVQRBQgtr1l/Ao5AlY1RgznoEWBWEmRwXCzCYUgJERUMFEZwDJM2S0CbSY5EA
c0ALJVlOlXshFQby50zeWkhKZDIUqYoqMTnoBp2PIBSgJQomiAqCnDIxtAZXB1HT/NkSOlygIVQGQVqqm4K
sQuIQaolqGBEyAnmVIwSoLklaBrPVtbdUBC5TAgekqga5+vKt2e/mDD7zACbxBjF87ShDBkpeZLYDFDCjqz
Ca4F5prmGZBEOCAEFAypWrsLEE460Zv1sIWyJBpUcdAYHCm4ZKsHcNqC1iRMdQ2jqhsrkB221s1qOESZtgF
b69KA7R+Y8MHkfBz3Rbd6U5jGkqwhg6yu90WBxIEIjhoFRTaFzPSwr7l9eh5BULfAUQUAC2AqEDim5CTXla
NucDFZl/bX4Fw4hTK4CYAavFSgRzYIKFQMEFgK1sG0raJEBbIJVg5EApPuIYJUAMJUpBWCHQA/58IEbEU2W
pFHci1utYwhwhY0E8X+xmQfxBmEAujSGmOtLAAcAAs1hACZoZgDbRw6AAaGemR0oLIBEHADNYwAyPjdyC12
Ck2uXkKW6QBF97ERRpy0VLacoLVQc3FlQkSCmUgIw1pqPJRkyq+pYL5lFctwy7U0IEU7PYSu5CAcJNN7F2Q
QAI1LAO03yxhgaRZuGqdM3TrnA4+p/jEJ9bjn8f9xTCO0S+KBAAtzrDeRD/yDBGA5LpnAFEEnMGR9l6vSAt
SAAc4liBHJkguvBBgAAz1FF4IRScHjoyXcsILm3x4gIFakFAcUKavLWdEzllK2zJEjgCYgLE17MqQe9WVIv
/f7VQ1nADzadiqBSnr+bJdxzpbl9w496UIgGBIRNIl3SkJ+Bo1DhGON/WJ8kzJiFnW1jzm/Om+DOZkhDgXo
KNE6CsR5RIfDOw5apvEf2QBEcZO9rKb/exoT7va1872trv97XCPu9znTne0u0C+KjmDC8YuBBMgOCVyMIGv
Bk/4whu+CPZgajwOz/jB6yPpKFn6ytrKRRZYASpS4MEHiCCAznv+86APvehHT/rSj54HUnjJ/UjIDs+P4O8
okcMIqmB60t+Dqe2ofejfAfmTSJ5elN+i5TEfAwEQIQfIT77yl8/85jv/
+dB3fgxS75KP+u/62M8+/pqgieRHgoBdDr//
+BHYhUhEH/r3mKAEwXF+5q8AgxuMv/zN0MGae3H4T5FC8Y/f/v77///KN30vEV/4kw3soAkImIAKuIAM2IA
OuIDzkHzgEAkUWIEWeIEYmIEauIEUyH4A+IHQVwkiOIIkWIImeIIomIKVgA/5YH9dhH9OoX/GB4I0WIPJJ4
AzYQUCYIM82IM+
+INAGITRBwP7Qmf3d3n5t39CuIQBSH0yoYNMGIVSOIVUWINE6IKVh4QxqIRV+IM4+IQ72IVMCHqs8HyeZwH
INwvQVwM5wApoKIZwmHxXKEtHWBCC8AWCgBQyyH8/qIb+54f+94UxAYVxGIQxEANHcIhv2HyJGAMw/3ADOc
AB0AcDOWABYViIYjiH+lSHAyEIiyAIBMAIAsEIiDAUe6h8NQADMFADb1gDMYB8bIh8McADzUeJyccBgFiLO
RCL7SeICbEIAwGMk1CKHkGImAiEtjiJyHcDH7CLu8gDMLADaMgBOwADvpADsyCJQRAEqgiL1ciLx9iDmmiE
L6iFAIAIqWcFk3COUOCEQHGKcoh8AgADaqiKaJiMq5iLyAcDAhADaGgBZTgL/RiGFhADHECJauiGHOCP8hg
DN7CIvogQWnh5giCKk8AIUkCMgmAhXzCKGfkQxhiO4nh+vqCK0pgDlAgDaHgDMcAKtkiJ/ZgDO1CGNSAALL
mPIv/pg+O4bZwoEFKwCFLghF/gjj8BjziJfBZAi/yolMi3S0nJfL7AATewAzlQfDngC8UnjRbwiAeJkjkgA
EcglVR5A0EgAK54g0QpkV+wllsylABgBYXwBYVQilaACI3QBwDACFYwlGkpkZeYkzaYjMo3C6ooiba4lV5p
iwP5il4Zk7ZYfFbplYAZmEXIk+VIEEEJAFLQCALhlkJhlJKJk5TIA/O4j2UIA254iDv4mAMpmcX3AZCYmF/
JmJQYBGUYk7LYlwZhBUEpBXjplkg4lJMAjG85K4UQlOaoECE5mSCYjIfIA/qYjFSZkg05C7TYmK/Imh8gia
HJnB+4kyTmA+L/OZ7kKZ47YI6Z+QXBqZs7AZrJ+JSUuJXxWZIwEJas0Hn3KIutyZqRSZ24SZ2ziZYNMZEAA
JydKQWeeXlSoAVruY4D+pfeCYCCmQPMuHyNCAPNCKCOWQM1cI2OqZ+skIjcGKHNWZluQxwomqIpug/oCYyN
UAgHaopceJTzmJ85wAPX6JDI55LLN5OsQJVWyZoCEARf6Z+0WZXNeIgCyhAEaqAFKgWgWJF4OQkfIAh36BD
LSaL9l4scYJvLd4ZpiI07+oYCwAoJiYZ+CJBtKABPqaX/B57GYwQt+gVakIeIYAVWQJzvOKO7qIqsCItISY
ng2JLKt41BoIa46IyRqIaO/8gBbMiG2QiorACNZ5mbDaGnwliKxDmMANAIcLklnfoBdYmlEOqmH1ihUViNO
6CPpjqJJhqn6MmeQQGaEWoBNzCkgBiRFtEIX4AIMDoRWdqqvSgApCms3gmnxSOnBIEIxKiHfBqhrKCaTcgR
jbCgeQispWqs0WeJi6itOYmsxKOsSTiD3mqpOZit5ZqurQquwyOuW0iu5aqrLRGs6lqvJMquwuOuTUGrxiq
vLEGv9hqwgImvv6OvTMGvwuqvKwGwAtuwmEiwvmOwS4GwraqwKsGwDpuxVNh5ENs7RtAHvRmyIjuyJFuyJn
uyKJuyImsFR7ADRKCKMBuzMjuzNFuzNv97szZ7BLypsjzbsybbB9WIs0I7tERbtEZ7tEibtEq7tDR7BEfgC
69aPPshI1RbtVZ7tVibtVq7tVzbtV77tWAbtmI7tl1LAGNXBGSbtmq7tmxLtZOyMHAbt3I7t3Rbt3Z7t3ib
t3qrHv/hOiBEPPuBBVjCLn+7EFhTuFVxIitxAsR0Eg2wKFAgJogLEYdLO2NSBJmyEu1hMBUBLoTTEEUjEYZ
DEbAjAj4nEkZABVCQKX47uQ1RubMDLqAaOK0zK27SI5YSJQmDtgKxKH/CBL3CHaCDu4DiIC0SIVEiOGNCMI
9zvLrLOgEiM4zzOFDSIrwSOrubKwQBOmbCM7WrKWj/KzO1qwVFwAU9org7wrtxMzkK8S4PwAB8BQB44QQMY
BGBKwQvQAR5sb/827/9uxL+G8D+G14ggQcCfMD1mxSw+zaDIiv+MiKRgwUoQgAQUjmekzAlEjlnwwXR0SNd
IzaX8iITwzizMiQLcsEIEsItEjQAgCgjwiu6MiI2syVPcyDaEiFiwjRC071coB07UyNbQjBYECFdc8FRQLg
FsUMvwLirYSROQBEKwAVEQAVA8EM7tBJW7C5VMBJVkMWC8cQKrDkMfC8PkzAEMHgUszAb4yvmkiFXkCDkGz
MhAy4DUTYjzCZsDDKbM3h0DDYTYzQYMy0JsyIIQzCD4ibOMshp/3woPLIQP+QHkpEEYPwQ/rK6CQIATuDF7
4LFmpwEWywSXezFk3wUC+w2g+Ips1IrEnMFKrIe2wIjSCA0efIwjPItcnPHuPzKf7wzdnIfdbwxf/wr0kLH
LWwtYFIrAxMh6gE02UIwVBMhENI57avETOzEDlEhWAAFrEwQmdzJR8LJmvzJIRHKWTzKRlHKLAMuo0IlVgI
AWLAFi/LHjqIpUTApfUMrVsMEkkIplnLLdjwoQxwF86wnMyIm+GEnX9IfZjIlwQwAMNzDBOExfFImZ5LG3O
IwYPIszmzM8PwoqnwQJvO+fGXNC+EnRGC+B9HN3pwE4OzF4gwS5GzF5lwU6P+8MpYyEBdSIXJMABYiLTfdI
SHyuBwSBTIiIjRyvAVx0w5y00QdvSHy0w6NBNU7LnKcN4+L1A7duwiCOwMxLl/CIMHjIIp70yuCHoor1hSy
I1E7EKgSOweBHE8QvxJyBat7IQnxBiqa13qdoiux135NHKf7EXPw13ot10RR08MjxklxH0jgwjOBMhUxLgQ
QuSLsuiDBBM+iPJW9FAvTukZh0lxgvJY9EkQw2rmhz4I7JKZtEqW92qzxuJPdJa59Eq0925uxBVRABCRs27
TN25gRuIPr2yhR28L9HJArucU93Mn9F6kLBYzj2ctN2tFdF8B9BUg83SRB3NjdFosyxR//vd29Dd5rUcmsK
94r8R/mbRbYrM3Xnd4l0b3uHRZRfNLfHd8oAd/2vRX3UdfQnd8mgd/
+XRWSrc2bHeApAeAGDhWgLdoJvhII3uBKoc9QgAWqDeEu8eAWThSwTdkZDhMY3uE/gdu6zeAgzhIfXuI5gd
rBjeIevtYsPhOP6yzI/eIwASk0fhPN/dw3LhMysuMzAdxS7eMz0eNC7hLdTQX1XeQuQeRKjhLkfckngQeM2
+QJweRULhLYnCbtzcWwgweB3eRWfuUeMd8o3RIxfRptYxBrgyovTRQr3eYkseYrPeflrBFhLuYZQd52/RJn
jipLnDID8QQ9QA8C0Ag/0A8n//ACcC4USWB2vuALOLAD3hAE5UAOVCAOKMACb1AIiy4STzDTNfHpdn7LeB7
ZWjDZ2ywTfW4yvCHoMMAPc9AAX/APQtDpQNHoZffokd4HlG7pmK7pnJ4Soq4Tw44Rd17qEQHaSc7n1AzoAi
HoO7AOX8BHHKDoSIHrZKfrkt7rl57pm27rIFHsOCHuFnHsyM4Q+03hW87s7iLSByHnggHuPvHmwk7n9i7KG
hE45/4QGy7bOkHOfmC6pY7Y+94ouR3aPiHlzo7sBH/uKh7kBS8UDS/m/e7iRYG9n1sQGd8TiIwlc2MQvNIh
in0YE9/kOQ7lT0EAoJofKNIhWt0jI98Tvv/MLAISJAgSIEiABQFCBT4DGSXv40C+7kqBtuhxMNmiJnYsFBj
tOiyvKG0SML2CGT//4jHu3VehJbJSNBEzNEGRukWABUWfyrZiKFzwJDFfGFNf4k/e31GRHwdi9Ft/9j/RAD
4D94OMNXLvF2lv4Vlu3VyBM/mxM/r+JyPC9T9xHtFhNdmi+FgTunnfF3uf4PON5F+BN8LLN5dPMvjhKwWuE
+t7J4MjOW7i0CK88X/RANrN4nrO9vNzO6yR+h0+4Klu2jtC4psB+xCu7BHvFbgf4Om+57vfFb0f3wPu78H/
FcNv3iKO8McvFsmP3Spe4c3v/PZd8dNvFs8v3Kk74qz/f/3C3/22HfTenxYnPttVP+Pjjxblb9rNXd7pvxb
rP7l9L/TvPxbx/7eTv+z1r/4WDxAABA4kWNDgQYQJFS5k2NDhQ4gRJTqMQgUKAS0NJm7k2NHjR5AhRY4kWd
LkSYhFjKBk2dLlS4kNtGCBciUKTJw5de7k2dNnT5U/hQ4lCmALFyJcthRl2tTpU6hREQaVWtVqwyhXoGDJe
NXrV7BhxRqkOtZsUZkEoFC5edbtW7hxURZZqvONE7xO/DyR63ULlaQK+g4mXNjwQSRIdj5J8sLJgyRJ5hxm
yuQKFq5MKG/m3Bls4sVJnAiE/MYzzwYK1LI93dr165+gdTLWUIVB/5ITsF8aAVxEgUbdwYUPFyk7J+PIkTW
YJi6SCRLMSDQ3p17dukLjOBmPBiAiiZ/rG1MXWbsy/Hn01LPDZPzgyRM/uNM75H3x93z8+V2vf4k8+YPJ9E
OIACyumE5ABBMkjD+X4HjvPeYUFCiKIsir8EIMM9RwQw479PBDEEMUcUQSSzTxRBRTVHFFFlt08UUYL8SsL
QmHMoKAL3LUcUcee+SxEB4EEHJIIos08kgkk1RySSabdPJJKKOUckoqq7TySiyz1HLLIncw7yp1uOHmgpfm
YAAvEeBACA4R8DoBD5yMsKKgcD75BABe7CRzoXAoQKebHAIVdFBCCzX0UEQTVf90UUYbddRQaNhg45pt4oj
jUUahsZQNTAe9RlJoOnW0G0kV1TQOTi3dRlRWBT2V00ovbZXQSCddVNVZF2XD0lBh+NIqYIYYgheX3nghiQ
cg48sgOCBzoor44pyToF6EBeATYX9hCNshOM31W3DD/TYOYXctlwJhxQ2UDWFlFZXdIdxVN1B0h1AU3kuFp
WBeRvHNoV5xye12UX35HVRgTn39KtghtG0pPhEEemMOPJ594QU4vQNPoGV3m3agaoe4VlhiF+LWW4NTVhlc
hBEGWF1/WY3Z4JcR9bfglQ31t+ZxyyV4iH1VRjgHhb1i2GGWIiuoiiQYeEKDJOBwIoknHHz/T9qCQh552G1
9zvlrsBtt+dx0YW631Zn55Vnns3EOe92z1551aEXdNnjooq862iWlCWKar7+nfi85rKm1ltuSFTr5bcYbF3
TsbuXONW1MKVdX8kFvBtrxnctm2etE7eYX71+r2rulqSMGYOK/AbjtDe9yA6Bvj7M+nOSuB3Z8d7AhZwNzt
M+WWXiaPT9U86AZ79zecOkOfXOhfc4b2GxdQi5Zqpk+4bYHAGhWNKaTKBzk27k2GXTe07+7XJeNB9dyR+EP
F3i4481BdLCXDxj9Q/FXl/SFVa9YJ0ATHJjmByecQE3ea1MC4QQTOdlOZIjLHcrUd8H9dat9zBOX/PpF/zy
1ua9QyONc3ETYKuchyn8ZTFjppHI6nbSOKBE03ARxdz7dYVCHPdMg2TgYLg/qCoTzol8OSNg4/TWPf4ZaoR
IHNj3TCVAnFYuQUGhIPhuaT3FL3GEXH+W7InYqiPca4uVOmLm2QU95JvxhrlLYPzWu74kujAoMh3NFgWiNg
ji0oBf9KDb2+XBeY0wUIVtVxCOu0X5hdNQbmRjH0UmPjlCxo3DwCAA93nCLOfxjJxUFxjMGz37DG2Xx2jjC
NCbvbUn8HCfhqMpIzjGADVPI1AAgw4nY0iFvWBZjq
rAQXErkkpnUYkIW50lkIgqUp5xcGePnzPmFsn75gmT+2MjCn//Bcl4ANJoUD2LLOVSNI7psiC4dFKCEBDMi
wyxf4ozJxWQmc5mDhOYHSxlCZqLRfk1UGSt52MdHavN/kpwl0ghym4uJj4oASGB8luM67pzJeyc4FoB0WYW
KmgYO8XkBAwCAh2M5AQ93gdNdGuPRjx4Lanz5A9Q0AKcnQEY0CWFnFt2JkGPGU6eBmqfZ7lm5en4Lkaks4S
KliSlHFoqf/yTaJJ9Sye7gJqbia91J4wMeXdryBEkQAXyeYEvviOAPL+hefP7AtK5CrQqD+yVZn7DVP7wBW
W+lmlxPMFU4vEADT/iD7A5S063d9CA53Wk8e9rBoJLxp2bMp6ASucprOhH/oEqt5kBl2U1aFmRqarJlVbkz
06yKD1kEseXU8HKs2X12NLr0JW0ek4QqMO0Pt8wespywUshowAmzRQhg97jJyRb2j4cFYmILadxDHvWxYfO
nG+E5qKU697J686ZANstQqlIttQIBbdSwCwCyCgQOUhOfWR8E3u7B4TvfBYAv5bqX98xBtrR9gnfW+h44zE
EEFE1CFQniW02+05XC7SRx34fc4yFYVEPdZ2Vz1ty5PVdQ0Y3wdK0SpjEZBA/fYQBqPcvd0WxVAzJ13Xeqs
Fdb/iEJtWGABkrMALMCID4M+IMvAQCZE0CrCnNA1ompNoeLMaAK7nlBjh/wAnQWBMDF/0RIn/5EYMMGMnJH
FaOCUblYcTGYmgJ9cGRbGVzoOliyTZVLFRJIwI86wTROQCmbJ+oEEUj0owhUoJzfiiaBtMkPvH0DAuMqUga
6yTR/0MuZTGMmvDCATYKm6cc8IoUYQPmCAqhBDjhgAUOxghWBgoYNbHANx2maUZ9iQ6hSRiowS7pVtQK1yl
iBaUxBsUY9MQIUrHBrXOda17vWNT2AAANgB1vYwyZ2sY19bGQnW9nLZnaxieALGPhiB8EmAgx2cO0jBNsX9
HBCs72d7B1A+9vjJne5zX1udKf73EeAdrab7QunzhonDTBCve19b3znG9/ruNg69P1vgAdc4AMneP/BDQ5w
LVzE3hixdxGogAXAbKHel7E3ESr+bwUgwQhaQIIWNk4AI2Q8MYkROVfqDQWP17sIVzACFojw8iKAvAgvJ4L
Gt+ByIqD84Dsn+FGKoBSeB13oQxe4xRvO8nzP5N8313lSVIJvLRCBCka4gsMlbgTgyBsqW+j4gQCgAC5wQQ
taoFGOq+BXJtR7IFGwd9YfwgSOCwYADbjCy7FQFwDgWyCpQULVDbT2xNDIJQlXzEDKwvSVG17uRqg5x4mQd
bq/HAp9IEIfrFAe39A85y8nwOWpIBAqaGEgWIgCEoiACAA0AgorJ8AkBBH1KBBAFrFYhS6g4PaQ/KUIok9I
FKD/kIcpZAIKgodL6ZFwEwVQYeoCyTgRDlT14xvE+QbZAhS4AJzHQ+FXCkB5AwighylsYPhalwoX9DAK4be
FCwRYxObXAgAgjxfJANCKFfpAgJvTnCZypw8UCiGF+6M7AmAEAPgC7YsCLCCAl7M/LFAALLACKVCLDxg/JI
CCRVgEKCi8k2gAJKgQ0vsvLPCNgbiI2xsI3ks4yYOCnGuLK1CLRQAAKygEgRAEAiCPi7g8RBAECxSIyxMMs
JsQKAAAKICCLxAIRHg5QRgIKYCCUlgCJ1yCROA9kdAKLUAEAiCAhCiCKRCWIZgCLugLLaiDPMiDOiCAPtCC
JbwCLuiDCCQC/8GwiAuEAv4TCC6YQybgAijAOwAgAgDowIHQipWggkzgQkwoAvKDCi24A0AQlkMIQgXoA0E
4Qx1sOQXYHoFggBNAAgJIQgAoBCJIOERIuFrzuoWAAtTjwbrjRABABC7AAilQvUkQCCkgAhkUiA/4Py7wvV
gEgEkYP5Pwvg9oBETog88TiIRbhAjEQiHUgqWgN3urvkkggg+IxE/Egrk7PWUkAlX8gpdrPyvkxT4YCCtYB
ENkAj4EAC34PCKwgiIUiHUkCG7UhSdcAjvQQJBgAiggQIEggDkkCCJYRGEBhHMsvjp4BGF5hDpoR0a4iC+4
v0JYPSjgxF70Oi34QmOsCf/cO8cG9D4CmA4syAIuHIKBPESmKIJOCMk7MAIkkIKGFIhFQAIFMAfJEAgeM4d
GUMJCQIQP4EEFuAJ7VAgjCMeBaAQiUEaBMMBw/AAp3ENVXEhBqLkXHIiXPAkt+BgdvAlz3EUAIAAqQAouWA
kjqIMNGEs9kEEiKMJZ3MO8IwCddEeCYISXm8VGmJMvMEoINMStXIk6FEICkAKBIEptVEImnEdZWMqP0IKdV
MKfHAgigAQuhISRdAskGIWQHAW/5EErjEoarEWBKISlxEcAoBAsoKNzZLpi3EeD5MLIJMmhMEmUVMlFqEtb
ZMYe8CsAOIEe+BIpkAItqMWXZJC/Esr/v5w5fQSAJcRCK7hJxmxKIuhFJIhKl1zMkBA7grACsHQ0RKiDQyA
CTKgDidsALjyEnWxOAGg/tdxD1UvCMxTMymM/8iRCHuyDKxCIK5jP6TO9FzTArRjAVdQ+AkiFVVgFOyhBkb
gRgpjKg6CCPODCTDjNt5jMyrxMGHxIgphLgvDMgsACpJBOtzQKNywIQSREa2RNpkhEgGxEADBH1fsCRIACJ
iiHmRwIHiMHE2y9iIxEB+xHhcCCU6TBvsOR17M4IqzKgYhGCS2EDyAAm4CCXexF4isO6MzLtSQILVhQIhiC
QwA58BQWyIzGD+jFaqRPMySARmi/2HxILXC4FLSC/5z7gA8IQIHYApAzygokAq6oT8B4uWZECiIogif1iAY
wRYHoxUnyPj3IAz0gANw7iygoyIOsA+U8wsqDRyYd1OkjCK34U8YUCHzEPe+7gynIA18k0aL4vlDNQ+YbQs
4rgiIzCIoKxiV8wDG9CKPECij4AADES+iw05XgvodMzoSrPylg0z7ViAosBAzU0QKFT3QswUA9xV4EySsVS
SPYUmEZBc1TwVHd1Qq5AipYubQzRLCjAgUkgrp7uaWUuvkUCNNTQC5QQ/8DQEV1Cd/rvA8FSo1bkDoYhVGo
A6SwArVIvtMbiA+giUV4SGVdzYIYSBE0iIzrClJligZwOZQjCP9624K6E0shmE/TezkheIGinDoOvBDqjAi
ZQIK6aADAYNNipDou6MDlYzzNe7kU5dOXTQxSDAnuM8MPBEJ7hYJHyII7GIIs0D5r7ULAYEbTy7qRSwwuyB
C1IAgq+AArCMHeIIiZqwsFGFhBuLxPFEcOJQlnXFQl+9a/GwyVjL60o4LC29r/q9oGKD0lRQiF9ceBUA2DO
FmIjdihmNhM6ITu1NEiyINFhIQ7yLgt5MIN+JWmJbmOaMEkpMF1/StHU8ug3E3M7YN424i0/TnH3bt6e447
OIQNMFyNA78pSN0NML1NZUzM3c0+
+D8A9MS1y0eipLqXy7qoGwgCMIRpecr/IByIL8BLOUADOfgJBaiDKcgCUc1ZtxA5rEvTAhkIc4QOGjFH563
b1p07FyUI3wO+9OPbobiCQTzIx7PYf+TCTigCJEhcYVlcf3zdQsDLjcjHgVjIRlvYvKtc6ywJJIBAzJ1fhD
hXc03RxtW4gRzJyGRHHkxLgSgCv7y8Vow46mXf0DSEBSiFU6TZoSRe4/0JKABJYZkCB30L85uCfn3ARviAe
z3PgtiC7F2IkaSCyQUALeRCLxRfoSgCEX7fX2GCOgjJLGBf9x0C+N3eAqTfiYhM7b0kPryk/iWJlYRHJbbY
CryP52hcxkPiBW5HCCxNKBDG03u5WnNQ0CgCO1iC/wOARAP8Wh4svOI93p5oVCGu4rNQAD0AyEcgAgKUAhY
21pobOcFwxpzV3g4FQn8EyCEQSB3+CS44hJDUA+ILYRx+2SI+4kNO4o7AiBrNX7uF4s2diCkWXjtOUQKoAz
24A0U1AtRVXdbN5C5u4HP8VgzBjAoJXnaFyVJYBSdMhAl0wHWUV+CI459IX2FZX7mggktGy2FdCSJI3dTNA
5WAgjvYgBbO5IOITH5kTMfkUkNu5JbYAkcdgjyoVearA0zIgikYPiTYAGieAj34lZEc3o5gPJacRady4v0t
iCgeiVE+ylLmAuDbwjz4yqOdglfOO7utTi92YLKQu57tw8tIBP87qGhZ+Fq64Dg9JGafGNyAvIOwDYsrWGb
jBEBnFmK1gOQhQEh5luGCqMiBUFAGLWFwzom624BE/VMjeFoq0Iy0bVqvm+dShogo4GlNFYha07UnxpEdAT
n/lVBNlj5ASN1FtriDTuiF5RGMyBECoN2DgFiUHQgkYNuRw8MPZduD4OieaIAiEMs6qOG3CMvU3E607IMRn
VZhyQIiGFouHAV7/ObIbIBLNVREndea7om0O2qJWEdcq0GYcEa9oxANUeyN+OeoXtip3kKBrNaQRGg+fI7d
A44PiVqIyA6MkAJDZBC19gm2c163uII6yATh+1e7bgu8JloiuOqFTojVROv/P0wK1z7sllBZFczFg2CCmbP
Tm+hYzfuVfKPshdgQ6O4J5qa5gB5ocjbozja9WvPMCQzugTCCKt5V/GO+Wu7ZRwSASVSAUl5tvoU7LOYNDb
ztLMCCcQaEw91tujWIlhsI80O/URVumCCATICEqSZQgiAAwh0CTHDR9g1JTC6Js2zqUIaKuOVUKBDLDcCCt
JvZmrNTKVwEiyyI6oa5P7wDkDyEOlgJJMiDLHhxoaU68mhHRBjRtP5gn0Buu5vuB53vmV055T0EVdZfhVDY
u0NHRWREXBZwl2DlkMwDw3RyLsyDxLjkCt+IBb5yg2gCNwCDnvjWgeDIvZW+kcRfg/hn/26k38YMzy98cMU
V71KAgtetObJ1b51Q8EVscPAGC8nGEMHIjtWsuwyUPoWIOj1k189zTS5MSSZ/CS0o3xH+SS24ajf3YZTI8o
3gci/fCd/rg0GeuTsoYJnVvI5VxUmwcYJA8z6dkCDmwiHuQysvglSoaDtIBPatuhuXY56QcmGhcrkwAhSHc
V8H9IL47/DVb+
+9wtgjAMEzR7Y+yUXX8kbnCF4n55+MgjxmUI6z8kvnZ2knCE3nCQhuBCxg6zxAccNVAM7GYdMrglr0UcSQ0
DTn5vBM7VgfhCesRwBAikMHADvHiUnf7l/XbePw8L0+0SV34TDXCg2swCvIOrEzUf8ln/aXUHDH1HOyQHdR
5UAXh3FGPwlMn4hw14ktgEQYrDtA2ACQXN91j/THM8PLKwKyVXX6vYI7MMgs8M4+7PgXT8kiwHcnrEcjMIR
WQHWB+HeYwHZFzgTDPIuW70LFKHghJgJoF5aPx+bqKwJSRG5UNQprLALwE9V+p/iSUFmY+1MOpIme/rrJvv
TXNelM73KdmFhoJYIgTt8hfnrPRmojOGqaT3UVPHK2v5CLoJBWGATET4UOTONS6MdnQANm+Iki0HgEj2uCn
+
+pr/ohuHqFLwLBZ9cDuTmtB4DR/LquI/uoSDt8I9uQOGDpiPtNxwnTyzUV1OsR1m5258MtqJD/r0SIEl916
qVlZQ2KqsOQuuNlAzD6LkCDMPiJtF+LPQcLYIdx5o16zHf1g594/d4Ct9uCorTYv/NW1H8KrSjK5daDsRzL
FT+JUW9u2NcJtoO6OiACdR6+6Rd20+M+RPgCUQQIAAIHEhRopAhBJlCmZOmk5woAI0gmIsFChQkALQSIEDA
CAIuBJamoFOyCJkzBlCpXsmw50IhHlzJn0qzZMkqRnDoVAJg4kMiQoEOy5NQzJQ+ULQWJsGwAhUgpJCoVNr
Bp9SrWrFq3cu3aksudR4AwQYmCZIrQIRtiei1oxEpBK2ytNnEDpu3VBiQNEilyEQBOnTkVEMHyZaBGmQcJ/
1LJIxQSkQZINkypPEWPxFIHVrUyZERBqVhEMBI0iRLvVSNQ9Ogpi/q11cCCefoUSMTyUYRainCZa5slFyKy
FhCJorIIT9jKlzNvjppJHUBCp1A5m3bt8rdxfdese5erIoKELM2kQkQqgAZMBzaA6d4IEyLrfypGOLBIlus
S0QpdC2XBEgG2wsVHpexV2knOtaTQIUEdAgVpCjpnxB1ZWJhFHlLV1tN5FCmg2h0bEJEcfSptQYQhqyxhBw
EqGYEFGW2IISGNNdqoFRhuNLGSERukRZR1/XHXlnYEyZWVdzOZQgcdm/CREh0E8bGHTFr08UVxEdlnUB0be
LmBHkgQAf8FIwN9gUV9BHGBiVCA1GEWf0FtoIUhAQY4CEKERTiQaTcSpIVjQuWhhZ/K9ZjWFBqi9xt7UDQ4
xCN1zLXeHCJU8YdAJ7YSoB0jqkREjDMWOiqpfua441TRTVddnGoN6VWRAx2JVZIumSKJQISEZ8keuAIQJQB
T7kFlS6pNAoAULS72ko/TiXkFAWUyQsCiLC3LZX6A5IFQkHIaQUQsdhqAUBRcVFVSgqN2O0SipeJ1qLM9LV
pEXzoRcEdao1TL1BMvlODBMCcIVEQiSxA3omw6gSqjuw07rNypwN0ByRCYFIeEHl9uIGl2cBn5qky1trRJQ
ZbQwQcopvwKgCeO8GH/CrErKYTIQNReG1GzQSXK1BVE9EEERGkSpMBqfVW17lpXiBLuIIYgQUApokBBokB9
jrqFHtINAYgeSj28Fbw6K/rThVlYnDO7+wLwQgYBBoOBCAAoZIAoOCgryiB5DyJfqF/7/TdWEa+kl3wdyf0
eTOfCppoVjTcOBcguicwSsAOB4olAUUbpCCHBxqxSFFA0MlAhRdwcdtrrtVeTAi0W1IAWxgkkpny1e9RzYQ
pgkUqAC3iG4GmjFnFHJ53csSXgVlFYdoby/vQjFnU8EhQgd1BNxBMY2LmEAU4IpIXPkEdUsJ18M5w8+umnJ
DhNElE00Z6otYe4EYrTZZdMJBO0/8eTK2su0JRcsgUoHOsLEFIAgZiFKNrVrnYyCc6eeraxIthvYGxpgFKM
UIrt2eFAALAaqZCQE0KpzyYJG4zzbPOjIlyhDlM4xB1c95Psbc8AMKgZFOxjBPIFyHyiKiEQAcc+lSggJ3+
ZDG4wwxwFvG8ikWvJ5FYCClJ0zhOeUIQjAIDFle0BFAAYlkygxYikpJBLGgsTETxWopZAgQAk7MnEtpYHkl
xBMG0cCBcgtMPtHQB5IAwiIFmyIaAIhSgRoQIXqPYbtrkNbgKJgnxIs8fyLeyHgbwkqYZYkCsQLwujgBDSn
riVIhRCCqaUghWqZZMoAuANKWkZHUxBHk/Qgf+KAFAZIUjhCFD4yiVFgEICN5Qe+sVHjYyyFhYQWLNOtIkp
RcBE2daDBFGkogjxCVeAZFGtP/qJfrLDZE0GWTZM6GaEKWHKH/wFMO8JZCMQMkgp7CDPTlUSnPY0lY5kRgS
KBSUPVwglc4pwmIFIQZXdwd8c/lAFJyQhCaipQhWeAIfXUXB2Bj2nMQEwn5Vc4QrxGQgWpicUZ+ZnpADYgi
EWsIpSaOEKpTDAIGSBBftx80ZE0Njx7lkQJjQRCR7ZEL0EcwWwHAKGHtSoQOYAUUzNjgii0IV9eNrEeuq0q
s7RpAILWQSALkegBCkoktxwjhc0tKxJYKdXGNpQDZxABE//SIkwT4icNC7FJVjwCAG8xoU4ZQEKAMBPWooD
hQPc6YA5uUIFa2ojQgbFkFaNiFEss4GxrfGkWaNe1wiyUYJAkggAEsUbl9K3x5L2NVh9ZB0QxQWuKserBL3
oTOpyDrOWFa1dUSttH+DK+3jNIBW6UIboqtkF+bUnewndKLJwiDrwBLAjRUIpVBQgUQRtJYqtEWOHgjydoq
5dGxLT+4rQqnaVaKFOOMFEzWMHTkXGfR6iamnj25XTDiwP0smCpBhou4AOVCBgpZUbyAED2p4VL2rVgB8iy
oAH+IEgpiNId8UEBcc1brMF2cJx0SQQJlCBNzFxblCcybslHOAIFURX//AKlV3HWjXCZbyNZfJAhED1M7RM
8QMGDHCAEhwBDgrZ1CoMQQQtICER86wmfOWr5MDlc3D0ao0iJVQELXyhyl8oBGxDhr9W4mHBBaaJylqChxP
U4wkiYAADIjrR+8wlwkSgnyjZMxAm1JEKH26gfNIDhVbE4nctuS6NVrzde7p4kNBzlIPe+ZM33CIYdnIknV
YhCyigCQnrvRO9RrvkTduEvuz5pn7lE+es1FEwyAnrdwryBkUQ4kmEAAUoOgcASfCvc+GZ9R7IMx5akyfBf
5gDSx6cVbFZOCVbwIJ8ELthI8gudHnIwhTq0Fs2P9Kp1WUJoCV00y/l9LGFXpSgB/94hzuQUbMi0J6dPOCO
gYmiD1PryaWXgKckc7reLfH0IVmIEdaqj5UCaQbMfuUJSWQRZnw42cpMAYqDW4IPzZCEJ/QnE8MNO3UuMYI
hCBsLURDoCoZIhCEouNdCatjBbGndiVOSbQV5k7TfwjNlNbrC9AhzhugOkAeqUO0+2MfSdpq3pu0tdJV4Wg
EuxBAoW4UdIPp7ZVqkw7Ca4XT+
+U8gnlg4sSrnks2+vIFicgkX4r0KIlBBFCqSNBWgINIQp0TYG57JyoduI0NrVTWscc1wNVCCAGUgCcDW85t
nlwq9tSLT55M74gXiaSiUlF2s0k8Qmw4sPpCCD5af+pP+57n/ADpdJpuV6vu+5ctBbC8RRCBsgMZeBGZSz8
Km6ykSogy8UtELz6Sd33v2DW6cYgHRQ3jQnpjyBoYOQwNMBUBwiguAIgqV3okXOn2jkFqt8jt9kh/IJmb5K
1a7bGWOCM/3Oa/1lnA9spWZbLHVFG/REEG6PUTCHbS2rbYbgQvxlKcuiDBtladLeI0fQvphkhF0yZeESRl9
y3s0RloMynAJBB6IwN+dFIqIQpY53/PVm6cRgdYMQSds1bNdyB2Mmrs0XZhpESnEkhY5ggo+CS6dIOYogq+
U4Na5BdrsjEtAUiuswiBQV9iJC5pIkB5UVEGYzjVxyqChGO39XwBe0rcN/wR4UYR4LdBwvYEGYAAG3AIDAN
4BEIdxMJ9gWOAFbpqnFUGgVE/smVoRfFO/bVlNWB4t4YVC0OACLaFBBAcWSEXoDJ4dGILXSERomVxPFEyfq
aFKxF1zgBgAulwNxhyMVYaMXdbWZBZ9aEDbLEEsDAMemIcsBIgutAgSDJ7e+FAYyp2nNUARdEkdQIQX6gQh
os8AuAECWIUiDAt5EMl2udlMMAGzzVmH2ZlAtNAG3AEWtOKDNcARHMBIyIQhBpQSKqIU0l1j5QTxGM92Yc8
wbE8G+MGJkN4SiMKI+BwlBd0ochq+AQZ8zM4HWkgIBpEbuIHD3AzOzGEYEUEilAIBNP8AE72PAigAJE5ByV
Hb8hkCFKQcEpLKM0WTM8YLNGpXT5jTUtCQuHgPwazImPBUvC2BKI6jveGbVGnB0SidCJZKO77jLRKgl6CRS
4AGNlVTEaTCkeXEowSFHhCi220V3PVfoZSaYLicSYIJI86cCPlFBREBHLxANDyazilE/kGBhlxkRmokOTaZ
i0BBHkzBBtxj9aHPSGKFImxCk9wa2GwX7rnHR7VEEYSEnRgCFnCjvOUE6wXFOgLi291kikGl/BDTi60QWHR
CFmTCPQ4XHtyCB2QABjyAIHxPGg1kIM4TPYmjXcaXp2EBmwRFJjyekLCjO2KFrBHC+GGFFhxVRCD/DiSN3v
Z4I1viCRJkQiEppsnBWeQs42PaBOhRxE/tHrdBgarIiY0JxB88wAswwJoJBLIlh3tRBBjGZlXRV3ysUFYmz
1ZqhSWQQlfUnEbhFL24BBVsYmERwGlSEAFswCGMAnPRXxF8XCKcpyGA5uw1TEgCkRGYn1XGHAK6BxUs4nD1
ixUmAR4gxpiQn2Mip1XRl3owJ54FHhA9p2bSAVhqBXUKGh0qhCwMQmcUUSsQHkLADhdcwZBERhHKG2taF06
SCh0KoH1uyHzChBbgi1Doi2YVZSVGwy28lUKgyP5p1n8CqE6NYRneARLoIuIQ5N8gqFVw5oIyqEE5qEw0QB
31/wYA6ORhAYY7XVuJFNl0ZVnVhOiojCgTlqhtesnxYEGgHMJoaNYf
3NwS5NxfEYEulNjRNNG33CiO2pOnRQEW3EEeBKFkZMyXcMyBZuZVdGWRasU/ndMK0WE+0iboEAEmAMIj3AF
oqg4UDIIB/COI1mWWylcTqpBW4QQR6AEW7B8R4IGZ5hz4RNcSyAKBEAFjJoKYwGmcYlI5bgESyE5zAo6Q1o
QkMAmTdEUR1CiSmqVLyhOrqgQVxImbxM98gIaf/RmWqhimcunzaJXcDFUrEsEc3MJRLsHb4IGYoF7+fQsHt
erhvWpySuVM1GqQ+intcUcj5gYdFgFb2sFFIeLSVf8WARwh/1mqs8ZX19XOT2oVYeSBeB4VUzCAYBLmA7QT
7+zNmxFBuB4nuQZSORYEuvrNrRaK2zlhExEGaXLKRRVrm9QBsnJW/FSqw2jpYy1kFiCbSHHNpAjEE5yAH+w
nXxxAKeSQRj2sq0ZsEE0sQVTs11ysn2QsS7xrvF4UJLEJJNxBAg3Xob4Ps+qrn6BsIPUUbYAbbsiYfa7RE7
wVQXicuxmHw9qJvEIszwKRzzohZViGEvXpSvCBrHFFq8nEMLpFgX6dWVZo3qQCbL3ImChbXYEPYxqClBaku
1AtILXr/H1Xh0wEFahmvNBHvwzDMLzAbqVH7+3F3Zrt2apP2hr/RE+VrHOq60B4gnR25Vfekq7KoEuQAuaQ
X0rgYks46alhxXqARGEB6Qc169QqmaCVEVLNGRG0rB5czxww0hJkwAtEINHEDwGQBud2Lvp8blVdrP5sptY
pgnQOBK/sQXi82h68LgBI3EpYmOxO51Mw5acYRIp04x/m68n6LlCqzdDUQVXqAcGKwN7ZSQnEjZ4pWlONaf
RKrxCZq0yEmoGW0K16wucAQHQSBOdIieVlnyV4AuX5SvjCrhw6C+IKUhw16pHehy5MqjLyrk3Jr7QKk4VJF
btWgQdsD5oiH4psiVOAHEIMMAH7DRioQAjYBNA+zK1S3UAQ6UDQWsnsAR00/wPcgoIjbAKxcF75xu4idvBK
MB7JnZPwLiu2mfBioXA0Au9m6cVTcAEhEsEfDIOjaeswYMqJGMLGkRAVmJ7vvGkbXEIOY9IrqEAB+DBIYmZ
KCDEAEHGudOYmYA7/kEKscR4UDwQqLANgUGpE/JaFBJdXZFci1pUT4mtBJAMaHEP8yleBXqj9bBYBZAIkAM
IUfChSwUCOGQAGeI9TnJ7B6JEhPBX3IFuMtIEE3DEgvUI7xmI49bHbFoQkeJEWbcKCZnBBbMJ4uMz3EQIYA
QAvFQQqcPIywCNgoCHHdgUWvOUhQPJGNYDuDgQaoMHDULFKOEIvKUL/6GpnsgTBwcagVv/Wey7gbgJAFcAA
DPivQpDP3nBBEYhC+3YjU0hAG+gyL5eQL7uBA1jFDzvMrXKmQOSqrgby9hYELZGC92LRLvkKHcQtAFQzGhS
DK2DzWMJEWXLFFtTBIUDCcvkqVpTzOa/EEyyY17YEAw+EIjRD1q1Ew9Viq4GlMrfEE7DVHwTnQCQAGUBAtQ
HwRmkB5IrNFJ7AeV0unYSLN96rU82TLEQGABjDQe9yQiePA7RjQzt0OmZBXCow6QpEr+CFETMyJ5O0lsRuT
6KkVwzQmNRo8M4ZXxeETH+yQLyBCOBWEtw0S0RwIBcysThJLRKERjsClQzLkuRKFrnEE5jVAzDATY//VhFI
QSEcyEbVs6DsS794wAF4gOXehyzYwc8wwWxORJZ8dViP9d/kiBvMAFasYk604uiuxB6AtFZAM0GINF3X9QY
Tm1eYYsbgKRYTxBbIEEsEdsNY65iRFYGdAERt93YTxPUqKOdFNutaAq1FCSEwsNQJBPlyN3efAIE1lBOIQA
AwzBb0gSAIgvj0dTvlAcWQRfAdQSUmb8JuWOFcG7gRBFi3wQTYtt+8witkhY+
+xzgDcVs7h0kcd08U7vluxeNST2U+N3t4dUtQ9+GOmQa8dxJoN3tDFEEAyx5I9gn2j3pLySZIwsERQjMsnM
Rp3YpDlHu/92bLA8NgAc0gi+uE/7F59EUZJ8H2LIFDCQQX9N6HfouGbVYHiDWDp6yeegmfsvWD14grCIMr/
KxBbbhW7NNjKF9ltdMTkXipzEel+AF2NxRir4T+NBzKkIIlYO/
+YA5nvsyMBzpRmxVb4cGahQoSQMEpSYGnWNj8lCwRvACA9M4LZIp83CFBEICQEQo6Z3kQPXTDlHVuZwUqFE
MXFIMnC4QcDAQzFEMxSENLUKeZZ4UGNhOID8Q8T7c5CzZBvMFCHbZM6LmUUAnqKihBWIJXnuCv0IEjpPcDY
/YL+IEIXO5AhAqRNRGnuwUUhIinaBYDYICjvU0WxnIi/CNhEEErDGSnezpWIIAKNIEKxP+iA7w7qgiEA5z1
VoB6qJs1Vow5ACzDqqMCNXQBnwiENKDCSojJX0LYXeMtVzzTdAyahW2BJguEm4toS8ABUq/EFuHF93GFpml
oAwqEUzxKpEwKHPjBLVyhH0xUcGwiBZI8FBiCLpxqz7A7jewxABTAjuh8CHzHvAfCdApzEC00vltFGAgDwl
eNQITBqgOA0xNrR6TdXJw0fKw7Z1HlISBFtaaEerjExV9qV0yzVxRzV4xWfEj3Rm2BigYFi5aXEzAAsLWxi
hAHRvRM+7IfS6TAQDgDCYgKBPy9M+D8VUTAlxdANbzCHiNAE4CB0HOFvjuML2cDMFuFHCh9wUP900f/fUFo
xLk07wx6BU9tlegWG8WtRNgTvkB4thT0AYlslAJs7W/4wTB4QAlYrlPUPEVyQXwQASjGVPoZwzcIhDMYQwI
kgECIwQQkAAksuOrPBM8DcwQEguIzfgE4/nSubWW0bSC1QDak2lUQPNOHNKz/OzbM2USQCKcqeTab2jZ3BZ
35xYYSq5Wmvur3jWoIggGdy0YBBJM6j4YMAXRHAQCFAIiIwBBsyZIMLwBoIRJrAREiCY0U8fiRSJSFC1OYE
aNQzAQyEwBA6KDQWYqRM2nWtHkTZ06dO3n29DmzQBMEM8EECqSiiYoBDn7SNIIEalQmTalWtVkgQlNUxwAw
E7aw/wvYY66ecQWgAMoiKX2oAIgChQgBAkSgRDFyJ0veLHmQELE68m2eLFPqbKHpl6aCIjjRoPn7GHJkyTj
JtDmJBZFCK0gULh55pc6UQ3cIzCQCw0DEiBieACiSSFQfLCO1JFSIeKQEYwBOAqBhzMwlZ2TMKCQ+GXly5V
URqBiqEEwBAK+YQg8E+WlUqFOXd7ca5lkXOa4AoOpyXiGq8MsUMiEySaGgPgq4ENGi0CIVIxsKFpzSNzIup
ugvi9lMq4kJLhhzzLsGHZysMjGQgOKLChEhgjunqODCtpGIcCI11VgDgAkoTDRioQagwKKB22j6xgwzaCiu
twTEOA4AHB/ckf9HqxxoAsgmAPixieoUQsBIq5DYYIomp9ADxR6lfMwIK0ZChAsscGOoiP36G+K/La2CgqD
+xGSIqsamXCgKAoogYKooPmrxCrk4WxNCy7j46KP7amrACCNaNE2KhyKaaKG+PFOIClkSufNMMiS9hAwASE
igpd166wACPD39dE0kBuxvgyhBPdUmI0pbSAsq5hIkPiK65K+/MCMropP+ADnzzJ3UxHPQLTgrokVhARh0V
VSrirAntDbYAIoOXXRiGA9KeOEPhRrAAgpTozAEIyim6hUlhSC4RIxLAZDgkkteUhbeeCET9ctS5a2puaSG
QiBI6UJQQYUQkFMxMwDkU6D/rw8YYeQDIpDwslYA570DkILyWHQhv9p8M8MorujsI5F+9dQIKkTSggsm9Gt
PgY/v9YlZmxoQqT0iyswCQw8VwqMKEeZY6AqNTC3CjohSUZDcl5Veet5RC7KXaQCkk1rIJqSr5rqpQwADOb
Q+WASKthqYS6O4AC27bIkhC3oDPYg97FiFjHXLo85mGhlPJEwGQNgriqDZiCvujJoyy2qS00QsDEMijy/z8
NNFAOB44meFjCDCEF1Y5NuQAwYZ5AAiLiec9NJ/opdUUwmP4BUAZmiBda4XeiUr5JjQAgmaj9XCIy0GrSnp
poSVVmfL926gCCY8KwIJLbjD29PFPGtA/8FEVTd9oZhnwqIQhS5kAolRvhxlcDQZSAKDW5yAY1siWlkikY+
p4NOjoLG/H/
+ZkNDj2WfruH5pQRkK1kIglIU4oHXKsctCioC2sgEqUBF0T2SQxz+3/U5buNFbFJAnEs9swQhb2Bz0ehSFq
SigLQRA0RbaYpixZSh/2luIqkayiIfpoWIG+Z+HqoCBBSwhGCU4gQKIkIiIDEJ0Ngle/pj4MsXQT3dME6BC
hCS1FigEgQrEQh8IEC3XEMEKYbQCXIxQh/61TW1/oUImCgKITLRlJB2ZSZew4BEouEwhDwMACXlkhD0hoUU
qYx6disAFAN5Phvix0kKkwBkq6AETmP/QAxwz9oAQATEJ29JFRBJBBEoyIUNLbOIolbUkJz3pkPJqznMAoA
KuVaN1rxBYclTkp0ZgqIEjsYLoaOWfNFqFCJDoDySgMBM5mvAslHSN3I71Nj6S8l6JdAsUYKUZP6GQCsRji
AaioZolJAEAl1tAKzSSoSJQUpTQVGeonDYEqDGNSEACAOuaEAjpBKlIk1FAsgBQCCTkciG7hJgv06kTIuTQ
IGKSox8H+RmF+I0LNHvmOpUlTQBwgQCN+MIHNmcELckKgwzxgwdUcwCKAIAKojAEWxayBUMYIkoFpehMG4S
6p6WSplRBwiJG0kiAaoaXX7IVZIqAiVphLJxI5cn/RHPqKWkCqoFEUJwRSmRUQOSBnwx5wws8cIAM3AIP2o
JCF3+HBQPYwTMybepaI2NTd+KUrTx5SzUBQADFbEmgvQTTL6sSmEPkoS7GVKqvGBTXU0nTCFAQYxgd1rj+Q
Elnc3hAEl7QGqA5LFFGXEIpEqJWw37WJ259J2h/4qpGNMIKpWngYsmoh1NugK9VAR/zYJhHuBCAC0gAIWFJ
+ynELjJjAqqX6vzih1tgYBgPgEN7yCjWQUTkAEdogGd7W92a9MWBcLVuTXjX0Kg6EHzaeRh1bTIhupTvLOI
CFMKKoKU6Nk9QNGHqdpfzW9NogY1t1EMUidBDiCyhBE7oDBFK/7EqKhgiEQnuZGzp22AH07I+ROACBhM0Ev
EigYhtvYMwH3GHwb3FMIcT1p7ock6JFvbBDbKvh1SUh0d0GKlEsKRqggFOi5RiFaLgTAR5PLoU/xhBPY4vk
GmyrUIsrBAE+B0ViBBihpzyYuSlCRSyQCAD1RW9OGHCU56HYiInZ8UZIxEVVgRI02jgAN5MQomI8NyM1FbM
X/7y/s64QzkvRAHABYAVbHM5qWbsS1n46V+I8KUh4AbONwHl3bx858iEOXI4IcIJSqCaDGhARbI4ooSV6Gg
gi1a7DkaCFHp6pwbOBVKBHrRVsJCrghziyg0IGl0SgoSP0lqEGsGCqebr6f+fIFaxi/UL9TQyYdPM4QUlyI
AHkpAtLYBrFaXwZKd9/WBQ+zrPukwIEa3ACBO1qNAEWnVVtlCHQ0DiEIUBGgEYAYAvQOFNcmn3uzXygV2GR
CG9rjZPnmoEIj4sUNvKAyQggVUM+gUOInACAyrnmkToog85A96+Rd3O0crZyIIQRCFYpKL3AEAK0w53QQQt
ZZpsoYFFcDJD2u09IjDi5QtpWMHyk+9Gd0cRfCBETSQxEkvwYaYWvSgBrqwAvW5AWkkrERT6kOU4U3y71/a
18oo9lb4Em2xRIMIZ7zBu223pC6XZEhH64CHP6PsxhKCDKfawiZ7PhA4j4cMeqGKKn5j/AugOsmhiBUEAP7
n1Pzr7w2Q1UAXafPsmJof6KOncPzsv3j0O1EiXeqx1yWxhLlgoHxTgg5+XU2ghEa8mzM9+8+Q4QhEL2fke6
EB3AMQdAKx3hOsVIglL7MESinAE6hXCerwD4O2sdz0ohD8TUzQj7yo2HE387m4otMjo9Ur6H26RgSUcAAOG
V0h9IDfxxVs3O9pJNJGRp+uVzwSCPJ4gZMp9iCFkwcOJgkIjGGGRNxVi/gBAxG2/0Ii5+Ant/mITZgIUQAE
ACvD1DpDuJIH2Xg8UdI4OCMES4o74gI/uKNAAERD5AID3RmIPks87pEkLyk4hPuBjBA4QrmpzMsYJ/6wvIh
bgpLZAI/DI+76vtxrPf0LNwQigEGDllqIojsyof/SAwX6iCNyvIIhpJPZJwlDkCuBCI+yKbDSCkgLQKmBvI
bAw7rZQIeZuJGCPD5qBDujAHxIQALyQCxUiDT9wJthQ75YvRZhOjOZiKqhOwmqLCF6gm1QDnDyuFWAq8Wyw
uqTO0aKABBVCCpQpjvRqqB6DTL6EuhAGw0bCCqtiE3ZuIRxh5wjBERIwAs+wAWFPEewuC3cODTlwEzsR9tx
wIVgxBOFQW4SMqmIRCG+jBVVjAcCpPjStFVYQbgSRtAjxzqpkJL5gsMKJEYvQJ45wmNRK8mTF5h6ED+jAE/
jAFP9AwRNIgQ9IwRMSUBK0cfa+MAslwRqBDxwvEACycRu7cRVBUBFIARQs4Q17Yycs4g7qQMlMg/pSYwEwg
AHcwxBWISIMwenQBBhBSxjlrEToqhBocBGFShl7otxyBRLuwCFzgi6ErfRq4gmq4AEELDIsgfi6ERTz7u0k
ARRybiTeDgAIgQFJkgFREvi60A3fjg/kcSEY0BWtogpewA/woOGMAxZxotzKBKsO5A80gLK07wpwbAnsgC6
o7SANKyHlzLQYQQrEJVWSUfFGItegoCATT8+gcY8K6w1EwA+SQC2TACSVZhTbDic/pQrWMgk0gAH+YLmEji
a4AAkLYr+Kp8j/oMAOMsI+pHIq2cqUnASyqs3WoCCibsIIXMtJYKsrIwOMzM7m8OAElJIu1bLwqgA0Q7MKL
OtU+EDnemQORFM0naAz1/IBumEob6IIqix1APPkiCA2ruwXD5Otwk8q9o0+OETLLszHsGN+rmD8xBIzwwAN
qEEzObMzP1M1R7PBUnM6q4A1W1MDTqACYtMmriC/huARiODgAAAPlFIDwmoh6qMPzs82eRM+1YkK+gAREIG
lUuXC1u8xFCA09kIre+IyM2YxmDMsFOIs/eAF1rItH4QTCYEQTNM0JXAPJpQlc6JBe2Qu19IPROANhJIec0
JFMiEL0g29GuIWUsMAwKql/9xE0uLTRaFpC/qgmuQjlRKzSaCkMgGAympFETFS8gYUDQp0JjryI3uE925vQ
unANLWRD1KPJ3QPQx+AOmdCL4tsfrjAPYkAzUpKA5hr11r0RZtIBJZLJ96gQx1tp2qoIEGtMqOgDlRtGemn
CD6GQJXFEkhhJtQOFHluDDvx9caQJEkhLn3LO6mCCJLAm75pwJoMTMMUf+YAQRnuJp7ACbDF07SgexaiELr
PwiyuOAkNoTrhGH+iTlEFFCoUAH6PDzZhDJ1U7hwh7yzBE2BPJg+rUD9DmaKgejxkS6GrS2/MAJ4vEB2Vie
bgBJLgBIISAP6gUquATB3NPb5AIb5A4v9ogk1vxbEOIix9olRPxRUtwU8XAkpbcRNY7yY3gRRYjyZRpUoV4
i3g6C20yUTT7ABuQQTY7Ll0YVd3k1jzx1h9sjXOMz2hDi3kwovKy1NzFHnMqA4usiq6FVT2gCTVcFBbMlwB
YABjb+5IEvY8oQGd6lYBI2zideJEIEE1QAQqggg2aQkMIIlqsF+ZCA568gUG9vsgKKT0h38c71P/ogGOM2c
ftjGYAVVGcSE8diFAIV3pwFVfzxRIYRNMs1wdAfZMoWnx5Fw6QALkCi606TbmIDs14EwJQNOiDbNgNmabSF
kXL1BqETAuzPIgIzCmIBMCKzKEoTHY41Q+EQAUARP/FSLn/nYhbtISdu7n+rYlsdBTIOAb2mA3emLLEu8BS
gAiJuJntG4QdAHx0DZtOzdexqYPrKAP3qYmyuiMiDBHi8BppmBfHwNvkwEVTkURLjEyCGETrnZKGLcNLgFT
boJ6FGKf6uYs3gSPiGAYvKkEtA8JDGGswjJHPRd6J4MLMlUQrMBhkREic/SgdOV5FeIZ0AB2HVV3eRcnkMd
ABuUKUGRV0vc2MMCbPED7tmVFGjV66/dTiICuvG0rs9cyhSkJuxcAXKEYwDd2XXR8e/cmqADlUoSFWiS3lG
dQjPe/AIzU3PVgDdN+7+UNPvIBzhQA3oABFIIBHkBKq21LBIFc/wZqr3KUChxrCN4oOQQ4fA34G8gXJ7Jpm
dpDb1oEdzYkgmEAAw4gFq7lWcMJIzN4acgUDkDyDZwAJMn0Aaqt+RCxdWeIKymIAPQgD/QgH2PYLF50AhD4
JuCtCOAtjnLHZbbAT4hgZjXgBWJgbY8YiZnGWCXHCcB2IeYAD0LY196iEBAB/9w2nCSzSShTn4rAa5WDGYo
BPQDgPM4DFVCBkYvhi0ErAUhAIdhFDMQAUyRADNyFKjwjvrKJCeAEAK7ANroSgOcYOZb4DVwZANryCRhA+6
bOb5AgOcNLO3q2Kn5266bNQcgDAKQhDBx5JIR5GeSgt2yEBhSid53BDCYAk/8BwAwq5Sdc5on6bE86BOEYw
An8IFt8YpVZOTJg+Qk0wIlfgI8VYkp9LVCSc1gf4wooxiAs8kFcYRmEgTzEAxu+OAyEoYBByxic4UPXRQLI
4F10ZDmIoB40oAQM4KvUkyfGmZz/YoM9eCFAMlvg4AHiGMiiYIt26XpBhk/sBzKgwH+HQAkd5BjkQJ8BYBn
CYBmoQZhdOqANyxi29kMhgJMBwF1Moji8gwgYoAQEcgmiIQmKWI4rWlnwwImdeCT42Jv9gDQdjQcVghHmI/
H0IgswweuaYuQKgqJrIgyUeSHkoJjBgrS+YZPZ2lx62lzIIAWcoUFOI81EpKqXmqn3WjL/3uJKRjWsSy4yC
MCoCgITsko5woA8hIFo2cMVusAVtqIrvqK6esOTERhTyKCglYMI/MAFI2IYMFqv+Zq0rYKGFsIYE0/VcvRy
pmAwXtY7mOE8iHaYu+AZYhc8xEOYe+tdOmCTxeAlPLkDxHihqW8PSyCKAbS0l/svQK8ERzqwv7opGGpvmHt
N/OJ8kKuDxdm6u9sn0EIKGoGjgvY2uNqru1cS4dm7OXtZlfIFanmi11u+c6JkisB3cEJOTfoxxoZJRmEj5v
tBiID6rA/74NugAHxKsIJwWEleuusKyDue/2JJCKSYEFyob/EFTyq+LdxBECAQmsANriNqQLwJZoDB/0HFt
Daqi51C8iKSJ3DlS+5ABzkcrPVQzbibxpMjAl4nG9zAx0OccED8x7OBOmoHT+YqoDjVivmXqPpyCBYzxyfj
Qz47F3E8yh8DDF5hAH6cy91gAPAJzMNczMeczMu8zHu8y318AELAyHtEC/SskfY3YnJUAeh5CDBBN68cMgT
8RJegH9d5J8YawItCyLv8FcAA0RNd0Red0Rvd0R8d0hVdBdJ8AF6hGqZmSk5bIWxIzglKMqigDvLgDuxWzy
2zvZfyJwTdwgugGv7lx0WcaYQ8G1rAAdrcU7Cggm9p/FS4EeVWC7YAwksdrB9D1XM8AhAoSZQmBExcXkCa6
aDAPf9nCC/0gi+elwn8ZmWE3dQJTdu9e25uQk7oJ8PkFgoEgzCivdutHKXMDCfkJJXTfbnb5NnRPcKtQrhI
Ls/hXd2VBwqUvD3IjN2Lfb35xcwL3uAPHuELfpbwBAt4CgB0vbwkj5ep4hHNRN+r4kw6AgukpQEmhApgSOC
9GwxUYA1K3uRPHuVTXuVXnuVb3uVbfgaqaE0wT00RdrhS19US6uIN1SYUoI5QRAvgDc5CvrvBQObXaQ2OXk
oU4ANKzeZTJ0eRwM4vZueH/SZsTVVSieit2+hpKuk9Bcmt6elv6nnZ5oKqPtWJHe13outn6us9JcU/YMX1J
2EnQ1j8fe3pl+f/8x4n2p6i3t5T/mlOIZxxuFrGn5cLzIiLg53vnw7jG/8m/P4naOEMZiArFv4qbB0nKH8G
ML0nAH9NZNFtn4hP4vYxpD6HqB7y6fd3AQAJ3ASRT9lODmT1aULyewIWzmANfgQAlJ4m1uAMeiIE1mAGYKE
pQH9KwGixWHTDH4MAcn5Xaj+ezTePVAdZaF/6F+L2d4IWML/3h+Q5BAYWksIBYOHLEYBfAgYAEKD4vd+Kjt
/3e0RMUttaJT5HsYA2xTr7a1CBAaIIAABIqCCJMhAAEwVXEg4k4jCixIkUK1q8iDGjxo0cO3r8CKaJxzNrI
ookObDJmhADC6w5M7BFAQAh/xCskSkxxIAIHteI/Ag0IkSHXwRKRDJliNIhG4wMDTqQSp6lh7BAvYo1q9at
XDEOpaIAgFEjZAkYGWjkChKhXdu6fQu3a8iRtEwCQAlAJCwVsGzCBJCtiWC/FCO06PkzbsWnA4tORLqUqdO
sTKBkOjSKyBbFnDt7/vxwIJQiRUY7NLI2IZKzCRmDfg07tsa5HREcbpn3bsncA32+TOnwN0UViGUDcO34aN
KlTV0HbaClyBUmxqtbvx7a4dgGAKic3dyAAPXW2Mubj0u744wmZ/bmXqPiTAuVLdo7iBAfgQP2LdYIT3iTf
H9x5JNxyBkVEWTMTXZegw4+6JBrDQGgAP9pmwFwRRFcsEYehB5+iFF6HbmEwEAlAhBBSSWmyBOKu7nEUwEt
OsTiRwXKRoQVOupIAIIOIZFHFkJmcQeDWGkBBRFETAhik05K5FxHUT5J5XkiVknRjbGRxSVZCElUIWliRjF
lR1vUkcUQkNzBJJZuNlimRQ0oQEUDRBz0Zp7WXalnb4lhGedGRRyyFCSB9omoYoc6xER0RBCgRQNGUIEFFl
RcmGimb/HZp5YeRiGmmAosihEUaS5FqqaqYrVoFFdgAQUXCnAXURRIEECErOOtyitQnNLS4hlNwDJTR2vMC
NWxDv0ZkacQGnHHkFnkgUSqFnGByVKPQNFrt22V2cD/FlRAgcUVmFq0EBeP4ultuxbx6UA2JZ3hAABrwBKR
TcWiWKJLA0VQrEv7KpvvGgOvWCwCCPyU4r72MvugERtENkW1WTmFCSSd1JGaux4D5Vyj6kL6pUfiknvpxyp
fuTBKif2JQAhnqOBfEyG00EIIIZxUUjb1DVBAAfzVm1DMMxtscwgzoAQLLCFkA8AMsMwcHMQOSkyxxRePHJ
bKXnPkWmmy0oqVq7ie+/WqIi5cAErtreHAAPlKTdJfP/HMG0kOEM0sAnTvnRBJEeCbW38SORvxxEtVbG3aj
mvlWsltMUH245qKaLOwsPBEC71/ykfL0sLdrVveL+32eQuhn4GX/26jo7gXTn42Ca201DZeEZJKtml578f5
DnxQa/sHywz7OjBgXjN1/npuLg9EUucACL3s8mdIP73gPxFXbAi7PdwkqKEWMWpWZ6a5Ju/Bf437QGFyITk
ADYwLRZ3rq201XirYHBEt+9fXPLz9BCU7a8KJBuK/JtSHJvtD3rz4IrcQ7I8lALKak9onkUEVCoP36xNjQE
UEKFyBOw24QpKwcCEkQKERX5ACFCRHgA8wghGFIAB3tlCEXHGog1XilJ4Q5yAmdIksdsqKqSLDQR6+6SmV0
YIgJkEALnSHAIwAACKgcBYiTCIhUqBCQhTQB4dYQQFIQsQkkLRDJTbJh3kCYv+DkKCHDchxA3UwElSwpS1u
qVFlT6HCIhIiCChsgQiC4OKGCEAUBCFBCg6Rggq/kJDo7PFJbHyTG8+jIKU052JEyNjGOjbJdj2lCJBMiBW
QYIVE2qmQA0EEghSQSlNqgTGCSGIoPVNJN13SPJmUjC0TYgSu3dJjffzjQAI5SFYCQApS5MIHCvkFQSakAV
goRCFdaKcqDqQRiBymh3KJpV2Wp5ebzIoCsEAELHTNm916Cpm0AABGfEAgVyDAFmeJkAaoqw9QgKdDQEiEI
iCknlWM5jrZ2SBwVkmc2CGnHYOihTp0YggbOyhCNcUYI+CKCPYjSJLM4pAGxM8iV1ASFED/eVHzgCEwgmmp
S18K05jKdKY0rSlN99ckJGxgCjydgh4eChQsnGoIWbBKSlX1FEkNkQlIaKpTUVoRslAnCkM0wkiPWp0CgGG
rXO2qV78K1rCKdaxkLesBPYSapyKBCb88TmSG0FasYucpRoDCjqzQh2pJYa97PRQTCNAHK4iwCAS4a4/kil
hViS9U5cOKUJdS1MQiiq6xHIgjXXOoIhTimLgqZWN8JNnQYql2Q7pdViKapizUwZ+idRNlG6m1DlWkMg5pB
BE8C4DktHa3TsLa4mJ7FRWmk7W8pdJruQjc31kkCmFMyBdum8jiShetilMK46YLvONaNrmHgoJnPwBd/
+eCFrvkrY5vrZvcoESBCxYqb5Po2ge+SuGURJCvFA6lAChIoREfIBdudeveAMOGtEIybdmIMIUsHKIOFhWw
eZjoVIOsRq1NzcikioCEBuRQSRwer4M/DJfFiqqtXFgOUfUI4gdLpAEvBIqIxzc+9aV4xnFp6xFRRePyOIc
KjwKKRr8AZCDjSgtB/oIkc4zkrCi1S2zNShEmqhRAxDXJQYmcSRts4coOxArh/SyVv+zjOsxxA3pI70cUUI
dHDAEQd/AimGMTNiJ8oBFQqJxGjKBlAHD5vx5+s58nct4hXDcrKtQDR+38Z84wZlREqOIpPYLniOw5uomuN
KCrK2gzu/8YCWiztKKmiU4C7BW8u7pznictXk+rGi2YHjRWuCBmPdhw1Z8eCBPUxWEl9TmqBCjyF4Zc5CPT
utKBdjVUkHAHQCglD7seNqscogAKZ5gjL4axmGTsbCobQQ89ncIGNN0RAkB5zVPOdoQ445RcKymN5qYyU9U
K1I88Fsft5kq5KRJpMbK73n9uq1SoYlR+Z8U5Rmg2pE+9b4GDua2VuUxmOq3wjxDc4B3JtykTHvEkxxU60i
l1xkEmkYJzxeJbxvjHaRxX3S3p5FCZ+MgRzvI3t/V8amJTzCUecopzxAjxlW8fTH7zAEuKCAoAOkY0qBRDB
V1KOefKu9Xq8aU7OAr/UaTQSaFyY6Xcu90ul/rSkdQxqhch6hrBo1K25XWNdL0tRTB62nmrTyyw24QQxwjG
NMaxt3ul6W5pu94FzAQscAHRA9mCNCEtzL9bJGRYdrLbFS/Zxk9TflDFCFUf//atW8TvkJduo9g1kAyNLyE
lxTwAYE3mWXceSiGVIkF6RL4vSj4jnF99a0eVh1HUwc1iwYS0hsLWHmsE2coeArNtz5aBaNioq4mIAghQeU
GZHvmTZKua1/zTgRRhqHDVPhHqQHSNiHspUqa+bC9llIKwC1SogUrtzS9XBbQ6NdtHIgAGeYdHhJDwEpm31
uGvXGAhFmhRFlZVBJISfQAoYFuQ/wlZo33cBxHolCaZkYAO8W9KURUAOBSjURo+klY9QgDqpIA0Zn1Rpgdd
UwS+NyR3oiRydAdKQnYR0XCYoRkaGBHb0R0c0n4jSGNolgc+xXuiJyYEkCTqlisZwXHToYAS4j7tlRBRMHs
r5nq3QhphUSEEgG08qETv9njUVHdauHhwsXwD0Xy2NoXTB4Zpk1Y7dHldohrplIZgAxfoR4YGgRBpgRYVGI
e9QwXcNgW7lxBFcAdjBnxFqId7aATnZAT8BxUCOBYFCABYiAQYtodKZAR1UHyAUAdfUn/0xmN5UAd1NhFiJ
x4UAntNiIV/xwRbUE+PQgWOInirwYgcwYGmAf9MqUFVWvCFlfg4SDAKkTEK9AeBAOAUeiBoHDURtLIFa0Er
V3AW3eSMUmcEWsAFsIJhi1grdIIrsYiN7ocW3OEd8kOMOseLXgMkkUEtD2h/OTQKWbAxRJBwk/Il4WI/XLB
WB8hyq5gh6QQWV4VvWkAF2/iKaIghTVgEF1IhI1SOHcQEaXZ2RDAenah1jKZufVYQX8JU9qMFBTF4ERcFAI
lOGLYFs3hnAIkrBDCQCzldo5IJmRB+2veDPUV0TlU/ThWDA3iLrlJ4xDVs4TKJ/KgF/qgV0xiQrqgFBKmSa
rQQClBq0aZWwHSEFBEF1EEnxAiOTFmKVxCFfkZNAWUuJDn/OUawBSYpfEmJWO92UEIoJgmBTvCIb+w1bWHS
NcEUe+a2Q0yQIdNxYUqIQxqCGqTRUQQRauiEBTkkQlFABaSRYUVgCImwcmhhloiFZqMwBXegein4ewMxS4b
WTdRXV4vQCIUABfr1Bf1VRkZGBKJwAIMgC7N2BaIwCHbgXYxABE4ERUSwCF/ATVCQCquwBLEgClsZmaHEYk
O1Af4kkd3HYkQACRtQm+aHBazlXQlRCOE1CYbgm0uwBIkAT0QQC0tgCJBUCMYEAIvwAYAEBQugnUtwAOQ4n
GoELZHRCUaRnBBRUklhKKKIfE/xBc3VGE+hBYmwnktgBwdhCNo5FFbg/1kKKkaDsJ6D4J7vyUPbFhmHQJ8Q
GHyDSEePaXuENBCMAAXKZFva9AWiMKC6sBbeCZ7iSZ6FwEgJ0QcHsJ524HoSelRYQCjYh4IqKCS5YoQwiHx
U8EwAEEibFU99QABUFE9EkAraaQAQiSGisAB20GuT8JyMIFiQJAiFgAWG0Aqx2WI2elRRAAV3AIpBCGNQyZ
O2p2GBNRqAxWUNUVJ9wFE5VAregCkulE4ntFGvCAV0eoB0SQU3Kaa3FC5BKX77p4BUFQXrlSQdIykJwQRCW
RFRAJaFyk4KwF6RghGjAn5Z+HfrpSQ8JgWT0Ah5FRRptRBqJZyYukd9eAidsAGduf9huSY/SfII4Eeoacdi
UiAIjBBfCWGlKzaJGMZ/VBBf1QkFLrpX1aluSOmqXxMFmMgcKDiMJfWLhxBQ1KcF57lluAVSDkEAsjAIg5A
InQltfcBKz+VZXyCg65kI0BqtKqMFDfhb6ogqwUeZU7BuyLdIpoQIgEQElaMApTCgpdBpXEBcDNoY76qd8T
qvtxSfSxGM+Kp1tZprAdd5WmCkAEBnkMQIKJkgdjCgBSoRXBCwCdFrzuWw2ymvEesuLJajucoa9VlVXHKpN
9ergrClsDKqdqYFsjCg3Akm6vqfRAZkATq0Lwuz7RIFWBBHULBORRCTPKV5CgdQHVkRLNYK2tn/CvoZEeOy
CNU5PgTQmImAtobAtLFhbW3rtm8Lt3Ert3NLt3Vrt3eLt2+rKkQEbRQWh8J1Uk75VLvytIZgCFgglKihBeN
RikuGs0t0s5EruZNLuZVruZeLuZmruZvLuZF7ta/xbpwamUgCSb9GBMy6Vz8ng7uaIGUJHZP1d5/7GXX1g7
NKNtXyrGCIBY3gXF2mZxwSJteGEcsptaH3nHoiuwuXKFiQLUqRCbznUGCIWbhlBRyCBKlQroPQChTHYx+AT
U5hCERAqSCSvF9WvorBVpGRBYpkYpIBhgSQsrnlu9WrGiSrnRB6EelWRX3wKkTQClSKvLGLKHaivuwbGU0B
/4aGF7B0Nr/Wa79LgL+bJ2dAtghK8q6icIgQcr4alyhUG2V30DHRm8AniUOoKwWqS4YPHMFS2Zbq9p3bCbZ
VssFINsMhhgVmqgf4SIY71VPZx4uCa5OqkQh2QMSpYHBOKWEq1LWtAKSuJcCZsozxk1aDC4ZqWYVRxapIiA
XdpAWGsACGwL95EidWbLfj62A1DBdbwF4KeYtQB4ZFgLRAVggZzBEldXV69igxLMObx6PS4sd/LCRF8hpPU
AVzgBV4UAUaMQdP8AYXAQdP8ARw8Bpo7BYRhQmdkAmqRxA8zFM+zIOkBFsjRwR98FwIURl3vESbx31vxcpv
hcAU4QRJcP8CAxHLTkARb+AEeFARTsAAA4EHTtDIV8EAtuzIsZwESaABFcEAx3zMs/wZlNwVdnJ9Q5AJTCL
Cn4xbjlQRQFyGW4tOkCQF3WQEWJCzDxInydnK6ey+sJwELwAHb3DMtrzIkjzPIiDLTwAAcyACVVAFjQzPDx
DJ8wwAcIDIfzAQjzwHf1AF+JzP+4wHhpwQb4DPizwHiAzRCRHLfvAEePAAACDRcFAFugwAVZAED2DIf+DMn
gHNI4dp66sa7fvK2BzKFFEEqUDEdpAIejgqRvpcEiZhrQonqqzOQ73OExHLLyACJ/ACSWDLJI3PTs3MSTDS
GuAES/0ExpwEhJzVcPD/AC8Qy7P8BO3MzJD8AlT9AomM0VJN0kvdzpI8EHOAzBERyw/wAEnQyxqQBBc9yYg
SBcZIFTV6zSMIyshVEUXgoNppshdRWERKp6Jw07qQTmbsIOe8ykR9wBgXywygAS+wzE2d1SOd1WGN1nPwBk
mdBInM1APh1HiQBLp8Ankd1rNsz/x8z3Og17EM2rrsB589EGFNzGk9EJsNAMcMAL/My6Cx0lxBAFMxBLmKK
YGtgIR1V6hK04dNoIdITYhQwVBgCC9sB2W5x4Vd2ZatSZid18js26D91KF92gPx2n7w2qhNzE7t1Oot2gAg
2nCA1SJNy2r92fU9EPCczA6B2wCA/9t4vciv/dudkdxb8bRxdCc/EkdzVEdg2IZccpOGPaMZXFdKgphNGgv
hu7awQdnk3coxLRG4LQJ/kN4kfQJXzd4MIMklXdztTeMgndV/0N6x/MjtLdp/YNCsveC4Xd8A3t8azdEGLt
Vv8AIdTdJOsMip/cyawreMUlXl3HkKsJVF8KXlmgp0rC5hwWKDkApR6cSFraFjpuZrTuHmnRDpPQdsXdeRz
NYA8NpincjGrNX4fOetjd8+ftr2fMwvEMz9rd6HHtF1fczJjNWEPhDLzMwpzeCaQlVYDoYVdhFW3KqRSoal
0MRnLpWdW+UTIdEJ8cjB/MhwINCn3tuR/AQQDf/J+RzJbz3rA/3qtm7Ii8zQDlHqAi3QESHRwRzLv37QkOz
WU44of1UHL5iWabqHsvIZ6ETH5lxcBa5jibLcZ1cHmIKZK1iJ76cY42zp59HgvFLqKtYnfV2hNVqf3z7iGj
Hu5P7EehJoLm2x3beH4D5MDT4HCz3S/O0RhKzXGxHSEYHImVLuWCHNS1HNgTiM+f7uFyFSsGsc933cQGHkF
4HLIn3xwJ0oCY8VSFAHh5AFmQC23d6j7u4ZIudBsoHIJJ3IjCzrFV3Isk7Pta7QItDvvE3IOv/W+xzM9vzi
+B3M/S4CdX3Q+2zQA43IIlDoHgLyWBEmbBx6zh6H4YpuEUr/7bDx2nRt457N1u5c5J9d105A1fWt4C/wAqR
d1nWty1E93LbM5F691B7d9nYNB5tt9guuwZmiVB534WRRiTPM8gH8GnBty/ed2iSt21k99hvd3gCg0FkN1x
pN0qZtyBqQzPcd93b+2bj92iy+2b79B28w8FvfJ3U1iC+pfWnunIP/GQBJ8aBx34rv2eu95+pt5E4d1lTtB
Llc4LjN+akd/FJdy79vy5Auy+81wFAwsxV+71Hfb5+B6YYPGohf4/J96PR9z7H8BDo+y/3u1HBQ0oYs0ctM
5x0d1jLe+a8dyUi/zCLA9G+AB+9c9+SLKFtwB8DYMQBRJMsQgkOIAECY/1DhQoYNHT6EGFHiRIoVLV7EmJH
hQY0YkSDpGFLkQo4jLzJIkuRFkioAkjgBUCXJk5gz56xM8mAmAJQp/cikiQdnEhFwdKp8AwAOTpcwb6Zcqd
RJSqRUk+AxmfVhSa1dJyrYUHDIFJAIBYrl6lXtWrZt3SZM6/bjW7px6SJ88wTOkzkAniSdoxdAYDhK9RJGu
JcmYoRP+CbMq3Bv0r+J+UZGGJimYcF3Rdr1nJVJnUcEAd1RkPBsQdChXb+GnbW1WipaYnedfVv3bra5eVO8
UmfKoTsEFBa5s0H5Bt+/nT+nGwVL6CJGoGtsfl37dpLcMRqhwiW1wihGzJ/3nl79SP8jRahbXx8xe3z6sOf
Xx59ff8X27/d3/y/A1+6jjwoqmICoAS2wQFBAB5/rzzMC4BOQwAcvvMjC9ZigAgouKEyIiSugKGILDE+8Lc
K73HtQQxRfbMjF9RpAAgsCxgOPCCqigLFHHzGU8ccXg4xPAQKwGBGJBoVksqsGuCDvCoSuIIAAKUV6EiEkC
CiiiNSotDI/IptskUwmliQzTSyLmA6hKLpEqIEpQcSoATa1BFFOAK6gU70x1fzvT0AHFZKKLVi0kwkWEzow
JENZRIIKJHhUqNH6BCX00h6j4JIABI3sUk4jw8y01EpTc89OHhcFQAEqHEUVofMmTMhVMU1NE1P/6PTcAiR
eQWLxCkpxzZTEIkg0AosuobjS1pCMJVEhI8pyFj9dieXuWujAG7ZVBaaVtSxsS2UVABapuNIkFo2Qkwrr0N
1P23Ghk9e5SId9swFwAdh3XkLTndKsLr0cqdkuTTR34PHom02Bjx6GOGKJP0LT3wGZZDFfAKK4cgvbLAY5Z
IRmKyIVO05GOWWVVS6lT5Hfqne3KD59VYEi9DSXiScrfrnnUkkeZAmhhya66KITcRkhPKrY7I8qsGpor74c
qqymzUKaaqInTnDCiSqm1ijrhP5I4o/PejSCiyKQkPOKgaWMQm2Efab7Z4iKCNpovY1G+qGpHlBqJZgaeoK
l/4deyqyzkDCDCA+VGGBAg5Y6EhshPzQYKea6N+f84ofw3jv0oft2aKqZHEccDyeSUv0NnTSASSif4EDphd
VbBwAPDXJK6g0nGNDJCThoX0kDqBFiIPbfd2dgoZWSUgr6hI4ynqffX3gB6tqjysxwpfx4HHkn/vBD+hh7P
AY6VFzp/DcyJPBqAjPIOBFo0UUnvaGpnDjhgf2tttoJXtISPODhCSgRgeMkNwegvCEJfniCBl7glyRITici
EAFLnpBAhWRNJl57XkIKB5O8PEYhJ3jCHyQIgKmcoHYAyCAKdZIQmUwNfE4jCgtzsjqIaM41rmCGMKiBBuh
0AQ1dkEMY2v/nGgikgARtaIMYvEIGKLaBBCmAgIPsd7+95Y8hU0Gd42ACFKsVbnJv8ANOWoI4q5ERKGakYB
XI9pITFCYhHtwJGRuDONNNjoZHSYIOEZK1qRSmchrwQ0LYyMdASsSHdFmGNIqBBkpSsoiVREMynoENVCxxL
ROQgDG+UUUoSrErVCRlG75hDAlMIF53yxsX+ZY0Qb4AgoiTidne6L0XaCAvhmMjUDJoNpT8siVm3EsVdJLI
OwbSjTtJyEr6IhM/wpAlcCBkI7NpyEYW7ngvABwcHihIRwZIDkbEJCa7sE52ttOd74RnPOX5zmSks5LUEEY
nPTmSCTwxlf8EaEAFOtD/Kn4jBfohmclWttCVtcxvjaRg7FRiur/kpHnYq8JUWoLRNwDlJg+oAjjjGEdlVg
ElzWsmAPWotMdpVCEZ9AMDoiK2rDkuptw7wQQTctIbklM+ATpGEIdozzAU1ahHRWpSlbpUpiZ1kulMhjCYk
b59ZiUBzjAGDVJpSq2gkpRXzOIrH+KwiZVVYjzb6eAA4DuUZpQBIuBhRhPpO685ASt/6NoccPcGrjGgML7D
CmD52jURLCR5ueMh7hSyta59zbD845r1xIeQjJ4gsuJEaULg6gezSbacD0IFNp5RT0s+B51o2KQ+q8oWUJJ
glFzNCiov0QH6aXG1bMkg2M6GojCc/xM60kjibZnojPg5IwH1E65aGJe55DbXuZ555HMzEl2vSGOe18Vudr
W73S6otrkQEEN4xTte8pbXvOdFb3rVq94OXIe60rXIe7XSBWSkwb73xW9+9btf/vbXv//lryqU+FwyXEINB
0ZwghW8YAY32MEPhrCDUwDb38h3sVzzw/EYslKFsNFnFjZJF9JwojEM2LlkKAOK1EBh3oA4dylxwu4ewpiF
eLhnLhaJiEls4uaiWMUs3o2LQwiAzuLFCSKA3F7BN86cgM+XCnnD7nhnPfK9wXfhAwD1sDKHJT/AfLfSj44
xVGLp+vhEK3YvbEZItYkygIwS/MMfAPc48DETL/9Ms6kO/fcGcG6tbABAoQoneMMDftla+xHzhchM4BSfGc
i6AfGaCee9XWa2KQixMRxOIGWYiK1wsNNJS5RJFZ5MtJoIRfSIL8IJL3iBEwDAhUReTRFWeyEUGFn0iRt9k
QmkwAy7AIAEwvqQYVPElRhBM71gs5QkQK/II7WaA1Hal0WqFQA9ZSReHugYvmSwCtgMJBzwELkcBirVFzlF
LdKQC1ukYQwSeTdFkJGLXIzh1hbJdY93XREIlGEXau
iAr9UQkX1HJAESKDhFkv0cF8vkJTIWIaV3ohPITbDaCgEfAwTYaYjq5ARV+AlMZRpIJ/ykp+YOs6opQglVL
OTdnDj/BUJi7e4xqIIT2hhDrHFR81fjwgvxXogXVE6RfCfXzBa5xHETYoaBtzfYEOhnGS4hgW+Uob0InzoA
OrCLMgxbfgmfyMKdg2PylVzDgFUaD+EAV6+xEKW/k4wf6tq8wyaG7SdISvIsC5Oyc7ZC565IGrzgcgAIHiH
vHgMlAKD4eOcCGYuvBQCUce+FsBzXPDY62Am+EKYDoNFM/zVCEtDoBJAAISkuw8AZovmIiL3C8NUOjkOS6I
mkIdYKebfhAZB7VYzh8fH2Qu9zvvuGUGIMs8Y35oV79IpcgvMD/7waJlAGq48eIWqgAfVR7xDWQ8T1LYZ9m
lN+EVUoHiHGL/zg/4l/fnXH+xQxTwjQE8KJ42ek6MvvvkNIMOwEdD76SzeDRpsAYlAIzcs/h/i+IAs/ZRs/
i0gDVfACXLC5d6MEZfACW9AGALAFn6sFSsAFW0AG48OFD1w/hdAGW2i1oZuI+7st5jM2qzODqfO/DiAGA0s
BYjCD/aPBgyIGHHS+hJMfGjADZHu025C9BQSQ/KC9wFO1WaOENKCEWbOvhEiDe+OEJmQI/KI8olO+FjxAh4
AANTiuCVA66SNDAAjDMjy2CRBDNGSIBEAwIhQ/JAS/BlS0LlwtF3SQBIQ0Onw9O3wQFszDL6wPPjRCP6xDJ
VRBARHEqtJDATHE2DhCRJzEjP+gvVyoBfm7woyAP5EIhaETOodoxH1ivgEsA2I4LoTzt4yAH5NoxesbwoaI
RPtARAW0Q3ajBPMDAE6wwIX4xC2Ewl20wvlDvk9kiF9MiE/MxXv7xFAsPOTbPTx0xH2bgCxKgYMSw9IrNjg
sNqgDgGpECK9TvW8cx4TgxoRgw+MKKzjchVgMQ4WYRc+pRUkEvN1DxsVThVxQv4RAwVoYvJzzAmXwOVUYsX
cLPlzwRwBIt5/TRQ30goQ8hTH4OcOLyICEQokEwfiTRlIEu9BLiA4oNjMwgw5IsRyMwQ7oABIYwhTDPmIgy
WBTyTJQOoQQyZdEuAD0PDS8hAAcQpekwYT/iEfXIIKBIcqiNMqjRMqkVMqlZMqmdMqnhMqolMqkrESMSDRl
QMF8NL4r3EeECIVT+Ln1C0XDM0hVQzyEeD+F+MqwBDqyRAih44QOdLmN9CQ9pL6Z7LeFSIB2pAEA6Dw1iMX
tA8zTy8lge0UA2Esz6Mt9SzFicKXBvIRjA8oijI3zsMzLxMzM1MzN5MzO9MzPBM3QFM3RJM3OrMd4M76HvM
AxULkHPAV3E8sRc0tnPMv0o0JVeM3atE3gG7GIxE2NLDOwK71wlEmFSAAaSAE1cL6/DMycHMycbLTnREzkV
M7CJMzoHEI1IIHZmsx59E61SDS55ARb+MQ0QAbyTAgv/8iFxavNsfxHAKDN3VM89UzP9US/xFs8wys/WAtG
9gRORjPOcDQ9hJvJ63O65Ry45xTM5ixOjwQAgEOIHzyu42rMgWtHxIzQ7vzODQ0xleOE3pNLhNA9r+w9W2h
P2XzP+KS/4UvGEn054TO8XFCFTEyDDx2D+js8ulwi5pOASyiD/QOANtC+w6Q+EuhL5rzOB23OfrO6hSjSvo
QAH92+CbgEElBJAJDSVwxKDuXSh1hCRtTR9nnEANnSLjVThfjSABnFuiRE+ijTMz3TNP2PNd3RNo2PN4XTL
pXT/aBTMbXT9cDTPOXQPdWPPu2cMf2PQBXU7yTU/DBUzkHU/VDURYydxy4QvhvF1EzV1E3l1E711E8FVU7V
hjA91KrTvlNF1VRV1VVl1VZ1VVe9BMqk1DNFhaay1VvF1VzV1TBgn+dKADIA1mAV1mEl1mI11mNF1mRN1mK
b1WZ11meF1miV1mml1mq11mvF1mzV1m3l1m711m8F13AV13El13I113NF13RV13Vl13Z1V90ICAA7);\">"
,
" </div>",
" <div class=\"lgnd\">",
" A) Schematic representation of TR",
" _{",
" &beta;",
"}",
" and its functional domains for interaction with TREs (DNA-binding), with
hormone (T3-binding), with activating and repressing cofactors, and with nuclear
receptor partners (dimerization). Note their relationship to the three clusters of
natural mutations. B) The T3-binding domain and distal end of the hinge region,
which contain the three mutation clusters, are expanded and show the positions of
CpG dinucleotide, which are mutational \"hot spots\" in the RT",
" _{",
" &beta;",
"}",
" gene.",
" <br>",
" The location of 124 different mutations detected in 343 unrelated families
(published and our unpublished data) are each indicated by a symbol. Identical
mutations in members of unrelated families are indicated vertically by the same
color and symbol. \"Cold regions\" are areas devoid of mutations associated with
RTH. Amino acids are numbered consecutively starting at the amino terminus of the
TR",
" _{",
" &beta;",
"}",
" 1 molecule according to the consensus statement of the First International
Workshop on RTH [Beck-Peccoz 1993]. TR",
" _{",
" &beta;",
"}",
" 2 has 15 additional residues at the amino terminus.",
" <div class=\"footnotes\">",
" AF2: hormone-dependent activation function (12th amphipatic helix); RBE:
corepressor-binding enhancer; RBI: corepressor-binding inhibitor; SSD: silencing
subdomain; NucL: nuclear localization; SigM: signature motif.",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: WWW.THYROIDMANAGER.ORG, the comprehensive
free on-line web textbook, Chapter 16d, by Samuel Refetoff, MD, version 7 June
2008.",
" </div>",
" </br>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6180=[""].join("\n");
var outline_f6_2_6180=null;
var title_f6_2_6181="Cefdinir: Pediatric drug information";
var content_f6_2_6181=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"2\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"drugTitle\">",
" Cefdinir: Pediatric drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" (For additional information",
" <a class=\"drug drug_general\" href=\"UTD.htm?5/21/5461?source=see_link\">",
" see \"Cefdinir: Drug information\"",
" </a>",
" and",
" <a class=\"drug drug_patient\" href=\"UTD.htm?16/40/17028?source=see_link\">",
" see \"Cefdinir: Patient drug information\"",
" </a>",
" )",
" <br/>",
" For abbreviations and symbols that may be used in Lexicomp (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
" show table",
" </a>",
" )",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F147178\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Omnicef&reg; [DSC]",
" </li>",
" </ul>",
" </div>",
" <div class=\"list_set htclist drugH1Div drugBrandNames\" id=\"F1045906\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Therapeutic Category",
" </span>",
" <ul>",
" <li>",
" <span class=\"list-set-name\">",
" Antibiotic, Cephalosporin (Third Generation)",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"block dos drugH1Div\" id=\"F1045898\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Usual",
" </span>",
" <p>",
" (For additional information",
" <a class=\"drug drug_general\" href=\"UTD.htm?5/21/5461?source=see_link\">",
" see \"Cefdinir: Drug information\"",
" </a>",
" )",
" </p>",
" <p style=\"text-indent:0em;display:inline\">",
" Oral:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Infants and Children (&ge;6 months to 12 years):",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Otitis media or pharyngitis/tonsillitis: 14 mg/kg/day divided every 12 hours
for 5-10 days or 14 mg/kg/day once daily for 10 days; maximum: 600 mg/day",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Skin and skin structure infection: 14 mg/kg/day divided twice daily for 10
days; maximum: 600 mg/day",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Acute maxillary sinusitis: 14 mg/kg/day divided every 12 hours for 10 days or
14 mg/kg/day once daily for 10 days; maximum: 600 mg/day",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Children &gt;12 years and Adults:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Acute exacerbations of chronic bronchitis or pharyngitis/tonsillitis: 600 mg
once daily for 10 days or 300 mg every 12 hours for 5-10 days",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Skin and skin structure infection or community-acquired pneumonia: 300 mg
every 12 hours for 10 days",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Acute maxillary sinusitis: 600 mg once daily for 10 days or 300 mg every 12
hours for 10 days",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Dosing adjustment in renal impairment:",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Cl",
" _{",
" cr",
"}",
" &lt;30 mL/minute:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Children &ge;6 months to 12 years: 7 mg/kg/dose once daily; maximum: 300
mg/dose",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Adults: 300 mg once daily",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Patients receiving hemodialysis: 300 mg or 7 mg/kg/dose starting at the
conclusion of each hemodialysis session with subsequent doses every other day",
" </p>",
" </div>",
" <div class=\"block foc drugH1Div\" id=\"F147161\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosage Forms: U.S.",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Excipient information presented when available (limited, particularly for
generics); consult specific product labeling. [DSC] = Discontinued product",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Capsule, oral: 300 mg",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Omnicef&reg;: 300 mg [DSC]",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Powder for suspension, oral: 125 mg/5 mL (60 mL, 100 mL); 250 mg/5 mL (60 mL,
100 mL)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Omnicef&reg;: 125 mg/5 mL (60 mL [DSC], 100 mL [DSC]); 250 mg/5 mL (60 mL
[DSC], 100 mL [DSC]) [contains sodium benzoate, sucrose 2.86 g/5 mL; strawberry
flavor]",
" </p>",
" </div>",
" <div class=\"block geq drugH1Div\" id=\"F147146\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Generic Equivalent Available: U.S.",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Yes",
" </p>",
" </div>",
" <div class=\"block adm drugH1Div\" id=\"F1045909\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Administration",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Oral: May administer with or without food; administer with food if stomach
upset occurs; administer cefdinir at least 2 hours before or after antacids or iron
supplements; shake suspension well before use",
" </p>",
" </div>",
" <div class=\"block sta drugH1Div\" id=\"F1045902\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Stability",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Store at room temperature; reconstituted suspension stable for 10 days at
room temperature",
" </p>",
" </div>",
" <div class=\"block use drugH1Div\" id=\"F1045908\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Use",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Infections caused by susceptible organisms including",
" <i>",
" S. pneumoniae",
" </i>",
" (penicillin-susceptible strains only; inadequate activity against resistant
pneumococcus),",
" <i>",
" H. influenzae",
" </i>",
" (including beta-lactamase-producing strains),",
" <i>",
" H. parainfluenzae",
" </i>",
" (including beta-lactamase-producing strains),",
" <i>",
" M. catarrhalis",
" </i>",
" (including beta-lactamase-producing strains),",
" <i>",
" S. aureus",
" </i>",
" (inactive against methicillin-resistant staphylococci), and",
" <i>",
" S. pyogenes",
" </i>",
" .",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" FDA approved in Infants and Children &ge;6 months: Treatment of acute
bacterial otitis media, acute maxillary sinusitis, pharyngitis/tonsillitis, and
uncomplicated skin and skin structure infection",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" FDA approved in Adolescents and Adults: Treatment of community-acquired
pneumonia, acute exacerbations of chronic bronchitis, acute maxillary sinusitis,
pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections",
" </p>",
" </div>",
" <div class=\"block arm drugH1Div\" id=\"F147202\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Adverse Reactions",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Central nervous system: Headache",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Dermatologic: Rash",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Endocrine &amp; metabolic: Bicarbonate decreased, hyperglycemia,
hyperphosphatemia",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Genitourinary: Urine leukocytes increased, urine pH increased, urine specific
gravity increased, vaginal moniliasis, vaginitis",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Hematologic: Eosinophils increased, lymphocytes decreased/increased,
platelets increased, PMN changes, WBC decreased/increased",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Hepatic: Alkaline phosphatase increased, ALT increased",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Renal: Glycosuria, microhematuria, proteinuria",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Miscellaneous: GGT increased, lactate dehydrogenase increased",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Rare but important or life-threatening: Allergic vasculitis, amylase
increased, anaphylaxis, anorexia, asthma, AST increased, bilirubin increased,
bleeding tendency, bloody diarrhea, BUN increased, cardiac failure, chest pain,
cholestasis, coagulation disorder, conjunctivitis, constipation, cutaneous
moniliasis, disseminated intravascular coagulation (DIC), dizziness, dyspepsia,
enterocolitis (acute), eosinophilic pneumonia, erythema multiforme, erythema
nodosum, exfoliative dermatitis, facial edema, fever, flatulence, fulminant
hepatitis, granulocytopenia, hemoglobin decreased, hemolytic anemia, hemorrhagic
colitis, hepatic failure, hepatitis (acute), hyperkalemia, hyperkinesia,
hypertension, hypocalcemia, hypophosphatemia, idiopathic thrombocytopenia purpura,
ileus, insomnia, interstitial pneumonia (idiopathic), involuntary movement,
jaundice, laryngeal edema, leukopenia, leukorrhea, loss of consciousness,
maculopapular rash, melena, moniliasis, monocytes increased, myocardial infarction,
nephropathy, pancytopenia, peptic ulcer, pneumonia (drug-induced), pruritus,
pseudomembranous colitis, renal failure (acute), respiratory failure (acute),
rhabdomyolysis, serum sickness, shock, somnolence, Stevens-Johnson syndrome,
stomatitis, stools abnormal, thrombocytopenia, toxic epidermal necrolysis, upper GI
bleed, urine specific gravity decreased, weakness, xerostomia",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Additional reactions reported with other cephalosporins: Agranulocytosis,
angioedema, aplastic anemia, asterixis, encephalopathy, hemorrhage, interstitial
nephritis, neuromuscular excitability, PT prolonged, seizure, superinfection, and
toxic nephropathy",
" </p>",
" </div>",
" <div class=\"block coi drugH1Div\" id=\"F1045912\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Contraindications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Hypersensitivity to cefdinir, any component, or cephalosporins",
" </p>",
" </div>",
" <div class=\"block pre drugH1Div\" id=\"F1045897\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Precautions",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Use with caution in patients with impaired renal function, history of
colitis, or in penicillin-sensitive patients; modify dosage in patients with severe
renal impairment",
" </p>",
" </div>",
" <div class=\"block war drugH1Div\" id=\"F1045896\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warnings",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Pseudomembranous colitis has been reported with cefdinir; prolonged use may
result in superinfection; serum sickness-like reactions have been reported with
signs and symptoms occurring after a few days of therapy and resolving a few days
after drug discontinuation. Do not use in patients with immediate-type
hypersensitivity reactions to penicillin. If an allergic reaction occurs,
discontinue cefdinir. Powder for oral suspension contains sodium benzoate; benzoic
acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol
(&ge;99 mg/kg/day) have been associated with a potentially fatal toxicity
(&ldquo;gasping syndrome&rdquo;) in neonates; avoid use of cefdinir products
containing sodium benzoate in neonates;",
" <i>",
" in vitro",
" </i>",
" and animal studies have shown that benzoate displaces bilirubin from protein
binding sites",
" </p>",
" </div>",
" <div class=\"block cyt drugH1Div\" id=\"F13298986\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Metabolism/Transport Effects",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" None known.",
" </p>",
" </div>",
" <div class=\"block dri drugH1Div\" id=\"F147155\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Drug Interactions",
" </span>",
" <br/>",
" <br/>",
" <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
" (For additional information:",
" <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
" Launch Lexi-Interact&trade; Drug Interactions Program",
" </a>",
" )",
" </div>",
" <div class=\"lexi\" id=\"lexiInteractImgB\">",
" <img border=\"0\" height=\"17\"
src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Aminoglycosides: Cephalosporins (3rd Generation) may enhance the nephrotoxic
effect of Aminoglycosides.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" BCG: Antibiotics may diminish the therapeutic effect of BCG.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Iron Salts: May decrease the serum concentration of Cefdinir. Red-appearing,
non-bloody stools may also develop due to the formation of an insoluble iron-
cefdinir complex. Management: Avoid concurrent cefdinir and oral iron when
possible. Separating doses by several hours may minimize interaction. Iron-
containing infant formulas do not appear to interact with cefdinir.",
" <b>",
" Exceptions:",
" </b>",
" Ferumoxytol; Iron Dextran Complex; Iron Sucrose.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum
concentration of Cefdinir. Specifically, Iron Salts may decrease the serum
concentration of Cefdinir. Red-appearing, non-bloody stools may also develop due to
the formation of an insoluble iron-cefdinir complex. Management: Avoid concurrent
cefdinir and oral iron-containing multivitamins when possible. Separating doses by
several hours may minimize interaction. Iron-containing infant formulas do not
appear to interact with cefdinir.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Probenecid: May increase the serum concentration of Cephalosporins.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium
Picosulfate. Management: Consider using an alternative product for bowel cleansing
prior to a colonoscopy in patients who have recently used or are concurrently using
an antibiotic.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid
Vaccine. Only the live attenuated Ty21a strain is affected. Management:
Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in
patients being treated with systemic antibacterial agents. Use of this vaccine
should be postponed until at least 24 hours after cessation of antibacterial
agents.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the
anticoagulant effect of Vitamin K Antagonists.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" </div>",
" <div class=\"block foi drugH1Div\" id=\"F1045915\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Food Interactions",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Total absorption is not affected by food. Iron-fortified infant formula has
no significant effect on cefdinir absorption (cefdinir can be administered with
iron-fortified infant formula)",
" </p>",
" </div>",
" <div class=\"block prf drugH1Div\" id=\"F147157\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Risk Factor",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" B (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
" show table",
" </a>",
" )",
" </p>",
" </div>",
" <div class=\"block pri drugH1Div\" id=\"F854704\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Implications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Teratogenic events have not been observed in animal reproduction studies. An
increase in most types of birth defects was not found following first trimester
exposure to cephalosporins.",
" </p>",
" </div>",
" <div class=\"block mop drugH1Div\" id=\"F1045905\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Monitoring Parameters",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Evaluate renal function before and during therapy; with prolonged therapy,
monitor coagulation tests, CBC, liver function test periodically, and number and
type of stools/day for diarrhea",
" </p>",
" </div>",
" <div class=\"block pha drugH1Div\" id=\"F1045895\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Mechanism of Action",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Inhibits bacterial cell wall synthesis by binding to one or more of the
penicillin-binding proteins resulting in disruption of cell wall synthesis and cell
lysis",
" </p>",
" </div>",
" <div class=\"block phk drugH1Div\" id=\"F1045911\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacokinetics (Adult data unless noted)",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Absorption: High-fat meal decreases extent of absorption by 10%",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Distribution: Penetrates into blister fluid, middle ear fluid, tonsils,
sinus, and lung tissues",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" V",
" _{",
" d",
"}",
" :",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Children 6 months to 12 years: 0.67 L/kg",
" </p>",
" <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
" Adults: 0.35 L/kg",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Protein binding: 60% to 70%",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Bioavailability:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Capsules: 16% to 21%",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Suspension: 25%",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Half-life, elimination: 1.7 (&plusmn; 0.6) hours with normal renal function",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Time to peak serum concentration: 2-4 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Elimination: 11.6% to 18.4% of a dose is excreted unchanged in urine",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Dialysis: &sim;63% is removed by hemodialysis (4 hours duration)",
" </p>",
" </div>",
" <div class=\"block pai drugH1Div\" id=\"F1045904\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Patient Information",
" </span>",
" <p>",
" (For additional information",
" <a class=\"drug drug_patient\" href=\"UTD.htm?16/40/17028?
source=see_link\">",
" see \"Cefdinir: Patient drug information\"",
" </a>",
" )",
" </p>",
" <p style=\"text-indent:0em;display:inline\">",
" Report persistent diarrhea to physician; may discolor stools red if taken
with iron",
" </p>",
" </div>",
" <div class=\"block adi drugH1Div\" id=\"F1045913\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Additional Information",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Oral suspension contains 2.86 g of sucrose per 5 mL.",
" </p>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <div class=\"reference\">",
" Bradley JS, Byington CL, Shah SS, et al, &ldquo;The Management of Community-
Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical
Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious
Diseases Society of America&rdquo;,",
" <i>",
" Clin Infect Dis",
" </i>",
" , 2011, 53(7):e25-76.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6181/abstract-text/21880587/pubmed\" id=\"21880587\"
target=\"_blank\">",
" 21880587",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Klein JO and McCracken GH Jr, &ldquo;Summary: Role of a New Oral
Cephalosporin, Cefdinir, for Therapy of Infections of Infants and
Children,&rdquo;",
" <i>",
" Pediatr Infect Dis J",
" </i>",
" , 2000, 19(12 Suppl):S181-3.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6181/abstract-text/11144402/pubmed\" id=\"11144402\"
target=\"_blank\">",
" 11144402",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Perry CM and Scott LJ, \"Cefdinir: A Review of Its Use in the Management of
Mild-to-Moderate Bacterial Infections,\"",
" <i>",
" Drugs",
" </i>",
" , 2004, 64(13):1433-64.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6181/abstract-text/15212560/pubmed\" id=\"15212560\"
target=\"_blank\">",
" 15212560",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 13125 Version 37.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0604-60.18.131.125-92069A6D88-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6181=[""].join("\n");
var outline_f6_2_6181=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F147178\">",
" Brand Names: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045906\">",
" Therapeutic Category",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045898\">",
" Dosing: Usual",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F147161\">",
" Dosage Forms: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F147146\">",
" Generic Equivalent Available: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045909\">",
" Administration",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045902\">",
" Stability",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045908\">",
" Use",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F147202\">",
" Adverse Reactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045912\">",
" Contraindications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045897\">",
" Precautions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045896\">",
" Warnings",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F13298986\">",
" Metabolism/Transport Effects",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F147155\">",
" Drug Interactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045915\">",
" Food Interactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F147157\">",
" Pregnancy Risk Factor",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F854704\">",
" Pregnancy Implications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045905\">",
" Monitoring Parameters",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045895\">",
" Mechanism of Action",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045911\">",
" Pharmacokinetics (Adult data unless noted)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045904\">",
" Patient Information",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F1045913\">",
" Additional Information",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"DRUG_PED/13125\"
rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"DRUG_PED/13125|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
title=\"Lexicomp clinical abbreviations\">",
" Lexicomp clinical abbreviations",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_general\" href=\"UTD.htm?5/21/5461?
source=related_link\">",
" Cefdinir: Drug information",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_patient\" href=\"UTD.htm?16/40/17028?
source=related_link\">",
" Cefdinir: Patient drug information",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_2_6182="Atomoxetine: Patient drug information";
var content_f6_2_6182=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"2\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"disclaimer\">",
" The content on the UpToDate website is not intended nor recommended as a
substitute",
"for medical advice, diagnosis, or treatment. Always seek the advice of your own
physician or",
"other qualified health care professional regarding any medical questions or
conditions. The",
"use of this website is governed by the",
" <a href=\"/home/terms-use\" target=\"_blank\">",
" UpToDate Terms of Use",
" </a>",
" &copy;2013 UpToDate, Inc.",
" </div>",
" <div id=\"drugTitle\">",
" Atomoxetine: Patient drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" <p>",
" (For additional information",
" <a class=\"drug drug_general\" href=\"UTD.htm?0/62/999?source=see_link\">",
" see \"Atomoxetine: Drug information\"",
" </a>",
" and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/46/12007?
source=see_link\">",
" see \"Atomoxetine: Pediatric drug information\"",
" </a>",
" )",
" </p>",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F137799\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Strattera&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F855136\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: Canada",
" </span>",
" <ul>",
" <li>",
" Apo-Atomoxetine&reg;;",
" </li>",
" <li>",
" Mylan-Atomoxetine;",
" </li>",
" <li>",
" PMS-Atomoxetine;",
" </li>",
" <li>",
" Sandoz-Atomoxetine;",
" </li>",
" <li>",
" Strattera&reg;;",
" </li>",
" <li>",
" Teva-Atomoxetine",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt war-os drugH1Div\" id=\"F10026586\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warning",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2700203",
" </span>",
" </span>",
" <span class=\"content\">",
" Children and teenagers: Watch your child closely for a want to harm
him/herself. Ask your child to talk with you if he/she is planning to harm
him/herself. Take your child to the nearest ER (emergency room) if he/she wants to
harm him/herself. Talk with the doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2700602",
" </span>",
" </span>",
" <span class=\"content\">",
" Sometimes drugs are not safe when you take them with certain other drugs.
Taking them together can cause bad side effects. This is one of those drugs. Be
sure to talk to your doctor about all the drugs you take.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2700454",
" </span>",
" </span>",
" <span class=\"content\">",
" This drug comes with an extra patient fact sheet called a Medication Guide.
Read it with care. Read it again each time this drug is refilled.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yya-os drugH1Div\" id=\"F10026588\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What is this drug used for?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2691740",
" </span>",
" </span>",
" <span class=\"content\">",
" It is used to treat attention deficit problems with hyperactivity. It may
take 8 weeks to see the full effect.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt coi-os drugH1Div\" id=\"F10026587\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What do I need to tell my doctor before I take this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2701564",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have an allergy to atomoxetine or any other part of this drug.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2705171",
" </span>",
" </span>",
" <span class=\"content\">",
" If you are allergic to any drugs, foods, or other substances. Tell your
doctor about the allergy and what signs you had, like rash; hives; itching;
shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or
any other signs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s3854479",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have any of these health problems: Glaucoma, very bad heart disease,
high blood pressure, or pheochromocytoma.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2703859",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have taken certain drugs used for low mood (depression) like
isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease
like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days
of those drugs can cause very bad high blood pressure. Talk with your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2701047",
" </span>",
" </span>",
" <span class=\"content\">",
" If you are breast-feeding.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yye-os drugH1Div\" id=\"F10026592\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some things I need to know or do while I take this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699677",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep a list of all your drugs (prescription, natural products, vitamins,
OTC) with you. Give this list to your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697797",
" </span>",
" </span>",
" <span class=\"content\">",
" You may have some heart tests before starting this drug. Talk with your
doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697133",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have a fast heartbeat, talk with your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697258",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have heart disease, talk with your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697265",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have high blood pressure, talk with your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697290",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have liver disease, talk with your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697307",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have mental illness, talk with your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698416",
" </span>",
" </span>",
" <span class=\"content\">",
" Have your blood pressure and heart rate checked often. Talk with your
doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696717",
" </span>",
" </span>",
" <span class=\"content\">",
" Check all drugs you are taking with your doctor. This drug may not mix well
with some other drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696635",
" </span>",
" </span>",
" <span class=\"content\">",
" Avoid use of caffeine (for example, tea, coffee, cola) and chocolate. Use
with this drug may cause high blood pressure, nervousness, shakiness, a fast
heartbeat, and anxiety.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697111",
" </span>",
" </span>",
" <span class=\"content\">",
" If you are taking this drug and have high blood pressure, talk with your
doctor before using OTC products that may raise blood pressure. These include cough
or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural
products or aids.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697641",
" </span>",
" </span>",
" <span class=\"content\">",
" Tell your doctor if you are pregnant or plan on getting pregnant. You will
need to talk about the benefits and risks of using this drug while you are
pregnant.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyf-os drugH1Div\" id=\"F10026593\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some side effects of this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698051",
" </span>",
" </span>",
" <span class=\"content\">",
" Feeling dizzy. Rise slowly over a few minutes when sitting or lying down.
Be careful climbing.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698134",
" </span>",
" </span>",
" <span class=\"content\">",
" High blood pressure.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698119",
" </span>",
" </span>",
" <span class=\"content\">",
" Headache.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697891",
" </span>",
" </span>",
" <span class=\"content\">",
" Belly pain.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698162",
" </span>",
" </span>",
" <span class=\"content\">",
" Not able to sleep.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698272",
" </span>",
" </span>",
" <span class=\"content\">",
" Upset stomach or throwing up. Many small meals, good mouth care, sucking
hard, sugar-free candy, or chewing sugar-free gum may help.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698984",
" </span>",
" </span>",
" <span class=\"content\">",
" Not hungry.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698257",
" </span>",
" </span>",
" <span class=\"content\">",
" Nose stuffiness.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698027",
" </span>",
" </span>",
" <span class=\"content\">",
" Dry mouth. Good mouth care, sucking hard, sugar-free candy, or chewing
sugar-free gum may help. See a dentist often.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697978",
" </span>",
" </span>",
" <span class=\"content\">",
" Hard stools (constipation). Drinking more liquids, working out, or adding
fiber to your diet may help. Talk with your doctor about a stool softener or
laxative.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697963",
" </span>",
" </span>",
" <span class=\"content\">",
" Change in sex ability.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698201",
" </span>",
" </span>",
" <span class=\"content\">",
" Harm to the liver may rarely happen.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyh-os drugH1Div\" id=\"F10026595\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some side effects that I need to call my doctor about right away?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698721",
" </span>",
" </span>",
" <span class=\"content\">",
" If you think there has been an overdose, call 1-800-222-1222 (the American
Association of Poison Control Centers), your local poison control center
(file://www.aapcc.org), or emergency room (ER) right away.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699066",
" </span>",
" </span>",
" <span class=\"content\">",
" Signs of an allergic reaction, like rash; hives; itching; red, swollen,
blistered, or peeling skin with or without fever; wheezing; tightness in the chest
or throat; trouble breathing or talking; unusual hoarseness; or swelling of the
mouth, face, lips, tongue, or throat.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699075",
" </span>",
" </span>",
" <span class=\"content\">",
" Signs of low mood (depression), thoughts of killing yourself, nervousness,
emotional ups and downs, thinking that is not normal, anxiety, or lack of interest
in life.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698625",
" </span>",
" </span>",
" <span class=\"content\">",
" Chest pain or pressure, a fast heartbeat, or passing out.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699005",
" </span>",
" </span>",
" <span class=\"content\">",
" Very bad problems with how you act.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698663",
" </span>",
" </span>",
" <span class=\"content\">",
" Flu-like signs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699008",
" </span>",
" </span>",
" <span class=\"content\">",
" Very bad belly pain.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699031",
" </span>",
" </span>",
" <span class=\"content\">",
" Very bad headache.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699032",
" </span>",
" </span>",
" <span class=\"content\">",
" Very bad itching.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699064",
" </span>",
" </span>",
" <span class=\"content\">",
" A big weight loss.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698981",
" </span>",
" </span>",
" <span class=\"content\">",
" Not able to eat.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698634",
" </span>",
" </span>",
" <span class=\"content\">",
" Dark urine or yellow skin or eyes.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699104",
" </span>",
" </span>",
" <span class=\"content\">",
" Not able to pass urine.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699112",
" </span>",
" </span>",
" <span class=\"content\">",
" Very nervous and excitable.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698603",
" </span>",
" </span>",
" <span class=\"content\">",
" Any rash.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698977",
" </span>",
" </span>",
" <span class=\"content\">",
" Side effect or health problem is not better or you are feeling worse.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyc-os drugH1Div\" id=\"F10026590\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" How is this drug best taken?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696213",
" </span>",
" </span>",
" <span class=\"content\">",
" Use this drug early in the day to stop sleep problems.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2695852",
" </span>",
" </span>",
" <span class=\"content\">",
" Take this drug at the same time of day.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2695914",
" </span>",
" </span>",
" <span class=\"content\">",
" Take with or without food. Take with food if it causes an upset stomach.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2695714",
" </span>",
" </span>",
" <span class=\"content\">",
" Swallow whole. Do not chew, break, or crush.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyd-os drugH1Div\" id=\"F10026591\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What do I do if I miss a dose?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696563",
" </span>",
" </span>",
" <span class=\"content\">",
" Take a missed dose as soon as you think about it.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696496",
" </span>",
" </span>",
" <span class=\"content\">",
" If it is close to the time for your next dose, skip the missed dose and go
back to your normal time.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696475",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not take 2 doses at the same time or extra doses.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696457",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not change the dose or stop this drug. Talk with the doctor.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyi-os drugH1Div\" id=\"F10026596\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" How do I store and/or throw out this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699336",
" </span>",
" </span>",
" <span class=\"content\">",
" Store at room temperature.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699262",
" </span>",
" </span>",
" <span class=\"content\">",
" Protect from heat.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699264",
" </span>",
" </span>",
" <span class=\"content\">",
" Protect from light.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699266",
" </span>",
" </span>",
" <span class=\"content\">",
" Store in a dry place. Do not store in a bathroom.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyj-os drugH1Div\" id=\"F10026597\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" General drug facts",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699675",
" </span>",
" </span>",
" <span class=\"content\">",
" If your symptoms or health problems do not get better or if they become
worse, call your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699673",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not share your drugs with others and do not take anyone else's drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699678",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep all drugs out of the reach of children and pets.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699709",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have any questions about this drug, please talk with your doctor,
pharmacist, or other health care provider.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s3302581",
" </span>",
" </span>",
" <span class=\"content\">",
" In Canada, take any unused drugs to the pharmacy. Also, visit
file://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/disposal-defaire-eng.php#th to learn about
the right way to get rid of unused drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699677",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep a list of all your drugs (prescription, natural products, vitamins,
OTC) with you. Give this list to your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699671",
" </span>",
" </span>",
" <span class=\"content\">",
" These are not all of the side effects that may occur. If you have questions
about side effects, call your doctor. Call your doctor for medical advice about
side effects.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699683",
" </span>",
" </span>",
" <span class=\"content\">",
" Talk with the doctor before starting any new drug, including prescription
or OTC, natural products, or vitamins.",
" </span>",
" </li>",
" </ul>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 11042 Version 39.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [1105-183.1.191.153-E85F879F22-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6182=[""].join("\n");
var outline_f6_2_6182=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F137799\">",
" Brand Names: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F855136\">",
" Brand Names: Canada",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026586\">",
" Warning",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026588\">",
" What is this drug used for?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026587\">",
" What do I need to tell my doctor before I take this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026592\">",
" What are some things I need to know or do while I take this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026593\">",
" What are some side effects of this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026595\">",
" What are some side effects that I need to call my doctor about right away?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026590\">",
" How is this drug best taken?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026591\">",
" What do I do if I miss a dose?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026596\">",
" How do I store and/or throw out this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10026597\">",
" General drug facts",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_general\" href=\"UTD.htm?0/62/999?
source=related_link\">",
" Atomoxetine: Drug information",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/46/12007?
source=related_link\">",
" Atomoxetine: Pediatric drug information",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_2_6183="Dofetilide: Drug information";
var content_f6_2_6183=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"4\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"drugTitle\">",
" Dofetilide: Drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" (For additional information",
" <a class=\"drug drug_patient\" href=\"UTD.htm?28/18/28964?source=see_link\">",
" see \"Dofetilide: Patient drug information\"",
" </a>",
" )",
" <br/>",
" For abbreviations and symbols that may be used in Lexicomp (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
" show table",
" </a>",
" )",
" <div class=\"block black-box-warn drugH1Div\" id=\"F5708707\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" ALERT: U.S. Boxed Warning",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" The FDA-approved labeling includes a boxed warning. See Warnings/Precautions
section for a concise summary of this information. For verbatim wording of the
boxed warning, consult the product labeling or",
" <a href=\"file://www.fda.gov\" target=\"_blank\">",
" www.fda.gov",
" </a>",
" .",
" </p>",
" </div>",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F162348\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Tikosyn&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F162349\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: Canada",
" </span>",
" <ul>",
" <li>",
" Tikosyn&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F162368\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacologic Category",
" </span>",
" <ul>",
" <li>",
" Antiarrhythmic Agent, Class III",
" </li>",
" </ul>",
" </div>",
" <div class=\"block doa drugH1Div\" id=\"F162351\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Adult",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" <b>",
" Note:",
" </b>",
" QT or QT",
" _{",
" c",
"}",
" must be determined prior to first dose. If QT",
" _{",
" c",
"}",
" &gt;440 msec (&gt;500 msec in patients with ventricular conduction
abnormalities), dofetilide is contraindicated.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Antiarrhythmic:",
" </b>",
" Oral:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Initial: 500 mcg twice daily. Initial dosage must be adjusted in patients
with estimated Cl",
" _{",
" cr",
"}",
" &lt;60 mL/minute (see dosage adjustment in renal impairment). Dofetilide may
be initiated at lower doses than recommended based on physician discretion.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <i>",
" Modification of dosage in response to",
" <b>",
" initial",
" </b>",
" dose:",
" </i>",
" QT",
" _{",
" c",
"}",
" interval should be measured 2-3 hours after the initial dose. If the QT",
" _{",
" c",
"}",
" is &gt;15% of baseline, or if the QT",
" _{",
" c",
"}",
" is &gt;500 msec (550 msec in patients with ventricular conduction
abnormalities), dofetilide should be reduced. If the starting dose was 500 mcg
twice daily, then reduce to 250 mcg twice daily. If the starting dose was 250 mcg
twice daily, then reduce to 125 mcg twice daily. If the starting dose was 125 mcg
twice daily, then reduce to 125 mcg once daily. If at any time after the second
dose is given the QT",
" _{",
" c",
"}",
" is &gt;500 msec (550 msec in patients with ventricular conduction
abnormalities), dofetilide should be discontinued.",
" </p>",
" </div>",
" <div class=\"block doe drugH1Div\" id=\"F162352\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Geriatric",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Refer to adult dosing. No specific dosage adjustments are recommended based
on age; however, careful assessment of renal function is particularly important in
this population.",
" </p>",
" </div>",
" <div class=\"block dor drugH1Div\" id=\"F162353\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Renal Impairment",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" <b>",
" Note:",
" </b>",
" Using the Modification of Diet in Renal Disease (MDRD) equation and
subsequent eGFR to determine dose may lead to overestimation of creatinine
clearance and overdose of medication; use only the Cockcroft-Gault equation to
estimate creatinine clearance (Denetclaw, 2011). Use actual body weight when using
the Cockcroft-Gault equation to calculate creatinine clearance.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Cl",
" _{",
" cr",
"}",
" &gt;60 mL/minute: Administer 500 mcg twice daily.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Cl",
" _{",
" cr",
"}",
" 40-60 mL/minute: Administer 250 mcg twice daily.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Cl",
" _{",
" cr",
"}",
" 20-39 mL/minute: Administer 125 mcg twice daily.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Cl",
" _{",
" cr",
"}",
" &lt;20 mL/minute: Contraindicated.",
" </p>",
" </div>",
" <div class=\"block doh drugH1Div\" id=\"F162354\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Hepatic Impairment",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" No dosage adjustments required in Child-Pugh class A and B; patients with
severe hepatic impairment were not studied.",
" </p>",
" </div>",
" <div class=\"block foc drugH1Div\" id=\"F162327\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosage Forms: U.S.",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Excipient information presented when available (limited, particularly for
generics); consult specific product labeling.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Capsule, oral:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Tikosyn&reg;: 125 mcg, 250 mcg, 500 mcg",
" </p>",
" </div>",
" <div class=\"block geq drugH1Div\" id=\"F162313\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Generic Equivalent Available: U.S.",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" No",
" </p>",
" </div>",
" <div class=\"block accres drugH1Div\" id=\"F11233706\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Prescribing and Access Restrictions",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" As a requirement of the REMS program, access to this medication is
restricted. Tikosyn&reg; is only available to prescribers and hospitals that have
confirmed their participation in a designated Tikosyn&reg; Education Program. The
program provides comprehensive education about the importance of in-hospital
treatment initiation and individualized dosing.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" T.I.P.S. is the Tikosyn&reg; In Pharmacy System designated to allow retail
pharmacies to stock and dispense Tikosyn&reg; once they have been enrolled. A
participating pharmacy must confirm receipt of the T.I.P.S. program materials and
educate its pharmacy staff about the procedures required to fill an outpatient
prescription for Tikosyn&reg;. The T.I.P.S. enrollment form is available at
www.tikosyn.com. Tikosyn&reg; is only available from a special mail order pharmacy,
and enrolled retail pharmacies. Pharmacists must verify that the
hospital/prescriber is a confirmed participant before Tikosyn&reg; is provided. For
participant verification, the pharmacist may call 1-800-788-7353 or use the web
site located at www.tikosynlist.com. Further details and directions on the program
are provided at www.tikosyn.com.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" Dofetilide therapy must be initiated/adjusted in a hospital setting with
proper monitoring under the guidance of experienced personnel.",
" </p>",
" </div>",
" <div class=\"block meg drugH1Div\" id=\"F13160861\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Medication Guide",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" An FDA-approved patient medication guide, which is available with the product
information and at",
" <a href=\"file://www.fda.gov/downloads/Drugs/DrugSafety/UCM266314.pdf\"
target=\"_blank\">",
" file://www.fda.gov/downloads/Drugs/DrugSafety/UCM266314.pdf",
" </a>",
" , must be dispensed with this medication.",
" </p>",
" </div>",
" <div class=\"block use drugH1Div\" id=\"F162328\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Use",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Maintenance of normal sinus rhythm in patients with chronic atrial
fibrillation/atrial flutter of longer than 1-week duration who have been converted
to normal sinus rhythm; conversion of atrial fibrillation and atrial flutter to
normal sinus rhythm",
" </p>",
" </div>",
" <div class=\"block usu drugH1Div\" id=\"F13657230\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Use - Unlabeled",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Alternative antiarrhythmic for the treatment of atrial fibrillation in
patients with hypertrophic cardiomyopathy (HCM)",
" </p>",
" </div>",
" <div class=\"block mst drugH1Div\" id=\"F13934279\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Medication Safety Issues",
" </span>",
" <div class=\"collapsible\">",
" <span class=\"collapsible-title\">",
" Sound-alike/look-alike issues:",
" </span>",
" <div class=\"collapsible-wrap\">",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Dofetilide may be confused with defibrotide",
" </p>",
" </div>",
" </div>",
" </div>",
" <div class=\"block ars drugH1Div\" id=\"F162366\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Adverse Reactions Significant",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Supraventricular arrhythmia patients:",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" &gt;10%: Central nervous system: Headache (11%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" 2% to 10%:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Central nervous system: Dizziness (8%), insomnia (4%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Cardiovascular: Ventricular tachycardia (2.6% to 3.7%), chest pain (10%),
torsade de pointes (3.3% in HF patients and 0.9% in patients with a recent MI; up
to 10.5% in patients receiving doses in excess of those recommended). Torsade de
pointes occurs most frequently within the first 3 days of therapy.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Dermatologic: Rash (3%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Gastrointestinal: Nausea (5%), diarrhea (3%), abdominal pain (3%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Neuromuscular &amp; skeletal: Back pain (3%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Respiratory: Respiratory tract infection (7%), dyspnea (6%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Miscellaneous: Flu-like syndrome (4%)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" &lt;2%:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Central nervous system: CVA, facial paralysis, flaccid paralysis, migraine,
paralysis",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Cardiovascular: AV block (0.4% to 1.5%), bundle branch block (0.1% to 0.5%),
heart block (0.1% to 0.5%), ventricular fibrillation (0% to 0.4%), bradycardia,
cardiac arrest, edema, MI, sudden death, syncope",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Dermatologic: Angioedema",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Gastrointestinal: Liver damage",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Neuromuscular &amp; skeletal: Paresthesia",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Respiratory: Cough",
" </p>",
" </div>",
" <div class=\"block coi drugH1Div\" id=\"F162332\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Contraindications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Hypersensitivity to dofetilide or any component of the formulation; patients
with congenital or acquired long QT syndromes, do not use if baseline QT interval
or QT",
" _{",
" c",
"}",
" is &gt;440 msec (500 msec in patients with ventricular conduction
abnormalities); severe renal impairment (Cl",
" _{",
" cr",
"}",
" &lt;20 mL/minute [Cockcroft-Gault method]); concurrent use with verapamil,
cimetidine, hydrochlorothiazide (alone or in combinations), trimethoprim (alone or
in combination with sulfamethoxazole), itraconazole (according to itraconazole
prescribing information) ketoconazole, prochlorperazine, or megestrol",
" </p>",
" </div>",
" <div class=\"block war drugH1Div\" id=\"F162317\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warnings/Precautions",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Concerns related to adverse effects:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Proarrhythmic effects: Watch for proarrhythmic effects; monitor and
adjust dose to prevent QT",
" _{",
" c",
"}",
" prolongation. Risk of torsade de pointes (TdP) significantly increases with
doses greater than the maximum dose of 500 mcg twice daily. The risk of TdP may be
higher in certain patient subgroups (eg, patients with heart failure). Most
episodes of TdP occur within the first 3 days of therapy.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Disease-related concerns:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Arrhythmias: Appropriate use: Reserve for patients who are highly
symptomatic with atrial fibrillation/atrial flutter.",
" <b>",
" [U.S. Boxed Warning]: Must be initiated (or reinitiated) in a setting with
continuous monitoring and staff familiar with the recognition and treatment of
life-threatening arrhythmias. Patients must be monitored with continuous ECG for a
minimum of 3 days,",
" </b>",
" or for a minimum of 12 hours after electrical or pharmacological
cardioversion to normal sinus rhythm, whichever is greater. Patients should be
readmitted for continuous monitoring if dosage is later increased.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Conduction disturbances: Use with caution in patients with second or
third-degree heart block and/or sick sinus syndrome unless a functional pacemaker
is in place; these patients were not included in phase 3 clinical trials. However,
no effect on AV nodal conduction seen in patients with normal conduction and those
with pre-existing heart block and/or sick sinus syndrome. Defibrillation threshold
is reduced in patients with ventricular tachycardia or ventricular fibrillation
undergoing implantation of a cardioverter-defibrillator device.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Electrolyte imbalance: Correct electrolyte disturbances, especially
hypokalemia or hypomagnesemia, prior to use and throughout therapy.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Hepatic impairment: Use with caution in patients with severe hepatic
impairment; not studied.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Renal impairment: Use with caution in patients with renal
impairment;",
" <b>",
" dose adjustment required for patients with Cl",
" _{",
" cr",
"}",
" &le;60 mL/minute.",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Concurrent drug therapy issues:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Drugs with QT prolongation potential: Concurrent use with other drugs
known to prolong QT",
" _{",
" c",
"}",
" interval is not recommended. Hold class I or class III antiarrhythmics for at
least three half-lives prior to starting dofetilide; may use in patients previously
on amiodarone therapy only if serum amiodarone level is &lt;0.3 mg/L or if
amiodarone was discontinued &ge;3 months ago.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Potassium-depleting diuretics: Risk of hypokalemia and/or
hypomagnesemia may be increased by potassium-depleting diuretics, increasing the
risk of malignant arrhythmias such as TdP.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Special populations:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Elderly: In the treatment of atrial fibrillation, avoid
antiarrhythmics as first-line treatment. In older adults, data suggests rate
control may provide more benefits than risks compared to rhythm control for most
patients (Beers Criteria).",
" </p>",
" </div>",
" <div class=\"block cyt drugH1Div\" id=\"F162363\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Metabolism/Transport Effects",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" <b>",
" Substrate",
" </b>",
" of CYP3A4 (minor);",
" <b>",
" Note:",
" </b>",
" Assignment of Major/Minor substrate status based on clinically relevant drug
interaction potential",
" </p>",
" </div>",
" <div class=\"block dri drugH1Div\" id=\"F162322\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Drug Interactions",
" </span>",
" <br/>",
" <br/>",
" <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
" (For additional information:",
" <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
" Launch Lexi-Interact&trade; Drug Interactions Program",
" </a>",
" )",
" </div>",
" <div class=\"lexi\" id=\"lexiInteractImgB\">",
" <img border=\"0\" height=\"17\"
src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" AMILoride: May increase the serum concentration of Dofetilide.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism
of Dofetilide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Cimetidine: May increase the serum concentration of Dofetilide. This is
likely via inhibition of dofetilide renal tubular secretion (primarily) and
inhibition of dofetilide metabolism.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" EriBULin: May enhance the QTc-prolonging effect of Antiarrhythmic Agents
(Class III).",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Fingolimod: May enhance the arrhythmogenic effect of Antiarrhythmic Agents
(Class III).",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of
other Highest Risk QTc-Prolonging Agents.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-
Prolonging Agents.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Lidocaine (Topical): May enhance the arrhythmogenic effect of Antiarrhythmic
Agents (Class III). Antiarrhythmic Agents (Class III) may increase the serum
concentration of Lidocaine (Topical). This mechanism specifically applies to
amiodarone and dronedarone.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Loop Diuretics: May enhance the QTc-prolonging effect of Dofetilide.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Megestrol: May increase the serum concentration of Dofetilide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" MetFORMIN: May increase the serum concentration of Dofetilide.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Mifepristone: May enhance the QTc-prolonging effect of Highest Risk QTc-
Prolonging Agents.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of
Highest Risk QTc-Prolonging Agents.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Prochlorperazine: May increase the serum concentration of Dofetilide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Propafenone: May enhance the arrhythmogenic effect of Antiarrhythmic Agents
(Class III). Management: Concurrent use of propafenone with quinidine, amiodarone,
or other class IA or class III antiarrhythmics should be avoided. Treatment with
such agents should be withheld for at least 5 half-lives prior to initiation of
propafenone.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance
the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid
such combinations when possible. Use should be accompanied by close monitoring for
evidence of QT prolongation or other alterations of cardiac rhythm.",
" <i>",
" Risk D: Consider therapy modification",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Saquinavir: May enhance the arrhythmogenic effect of Dofetilide. Saquinavir
may increase the serum concentration of Dofetilide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Thiazide Diuretics: May enhance the QTc-prolonging effect of Dofetilide.
Thiazide Diuretics may increase the serum concentration of Dofetilide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Triamterene: May increase the serum concentration of Dofetilide.",
" <i>",
" Risk C: Monitor therapy",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Trimethoprim: May decrease the excretion of Dofetilide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Verapamil: May increase the serum concentration of Dofetilide.",
" <i>",
" Risk X: Avoid combination",
" </i>",
" </p>",
" </div>",
" <div class=\"block foi drugH1Div\" id=\"F162344\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Ethanol/Nutrition/Herb Interactions",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Herb/Nutraceutical: St John's wort may decrease dofetilide levels. Avoid
ephedra (may worsen arrhythmia).",
" </p>",
" </div>",
" <div class=\"block prf drugH1Div\" id=\"F162323\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Risk Factor",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" C (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
" show table",
" </a>",
" )",
" </p>",
" </div>",
" <div class=\"block pri drugH1Div\" id=\"F162335\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pregnancy Implications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Dofetilide has been shown to adversely affect",
" <i>",
" in utero",
" </i>",
" growth, organogenesis, and survival of rats and mice. There are no adequate
and well-controlled studies in pregnant women. Dofetilide should be used with
extreme caution in pregnant women and in women of childbearing age only when the
benefit to the patient unequivocally justifies the potential risk to the fetus.",
" </p>",
" </div>",
" <div class=\"block lac drugH1Div\" id=\"F162358\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Lactation",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Excretion in breast milk unknown/not recommended",
" </p>",
" </div>",
" <div class=\"block fee drugH1Div\" id=\"F162334\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pricing: U.S. (Medi-Span&reg;)",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" Capsules",
" </b>",
" (Tikosyn Oral)",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" 125 mcg (40): $199.06",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" 250 mcg (40): $199.06",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" 500 mcg (40): $199.06",
" </p>",
" </div>",
" <div class=\"block mop drugH1Div\" id=\"F162325\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Monitoring Parameters",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" ECG monitoring with attention to QT (if heart rate &lt;60 beats per minute)
or QT",
" _{",
" c",
"}",
" and occurrence of ventricular arrhythmias, baseline serum creatinine and
changes in serum creatinine. Upon initiation (or reinitiation) continuous ECG
monitoring recommended for a minimum of 3 days, or for at least 12 hours after
electrical or pharmacological conversion to normal sinus rhythm, whichever is
greater. Check serum potassium and magnesium levels at baseline and throughout
therapy especially if on medications where these electrolyte disturbances can
occur, or if patient has a history of hypokalemia or hypomagnesemia. QT or QT",
" _{",
" c",
"}",
" must be monitored at baseline prior to the first dose and 2-3 hours
afterwards. If at baseline, QT",
" _{",
" c",
"}",
" &gt;440 msec (&gt;500 msec in patients with ventricular conduction
abnormalities), dofetilide is contraindicated. If dofetilide initiated, QT",
" _{",
" c",
"}",
" interval must be determined 2-3 hours after each subsequent dose of
dofetilide for in-hospital doses 2-5. Thereafter, QT or QT",
" _{",
" c",
"}",
" and creatinine clearance should be evaluated every 3 months. If at any time
during therapy after the second dose the measured QT",
" _{",
" c",
"}",
" is &gt;500 msec (550 msec in patients with ventricular conduction
abnormalities), dofetilide should be discontinued.",
" </p>",
" </div>",
" <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F162336\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" International Brand Names",
" </span>",
" <ul>",
" <li>",
" Dicetel (AR, AT, BE, BR, CH, CL, CO, CZ, EC, FR, GR, HN, IT, KP, PT, TH, TW,
UY, VE);",
" </li>",
" <li>",
" Eldicet (CN, PH, PY);",
" </li>",
" <li>",
" Periplum (PE);",
" </li>",
" <li>",
" Tikosyn (NZ);",
" </li>",
" <li>",
" Tintel (KP)",
" </li>",
" </ul>",
" </div>",
" <div class=\"block pha drugH1Div\" id=\"F162316\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Mechanism of Action",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Vaughan Williams Class III antiarrhythmic activity. Blockade of the cardiac
ion channel carrying the rapid component of the delayed rectifier potassium
current. Dofetilide has no effect on sodium channels, adrenergic alpha-receptors,
or adrenergic beta-receptors. It increases the monophasic action potential duration
due to delayed repolarization. The increase in the QT interval is a function of
prolongation of both effective and functional refractory periods in the His-
Purkinje system and the ventricles. Changes in cardiac conduction velocity and
sinus node function have not been observed in patients with or without structural
heart disease. PR and QRS width remain the same in patients with pre-existing heart
block and or sick sinus syndrome.",
" </p>",
" </div>",
" <div class=\"block phk drugH1Div\" id=\"F162331\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacodynamics/Kinetics",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Absorption: Well absorbed",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Distribution: V",
" _{",
" d",
"}",
" : 3 L/kg",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Protein binding: 60% to 70%",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Metabolism: Hepatic via CYP3A4, but low affinity for it; metabolites formed
by N-dealkylation and N-oxidation",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Bioavailability: &gt;90%",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Half-life elimination: ~10 hours; prolonged with renal impairment",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Time to peak, serum: Fasting: 2-3 hours",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Excretion: Urine (80%; 80% as unchanged drug, 20% as inactive or minimally
active metabolites); renal elimination consists of glomerular filtration and active
tubular secretion via cationic transport system",
" </p>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <div class=\"reference\">",
" American Geriatrics Society 2012 Beers Criteria Update Expert
Panel, \"American Geriatrics Society Updated Beers Criteria for Potentially
Inappropriate Medication Use in Older Adults,\"",
" <i>",
" J Am Geriatr Soc",
" </i>",
" , 2012, 60(4):616-31.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/22376048/pubmed\" id=\"22376048\"
target=\"_blank\">",
" 22376048",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Choy AM, Darbar D, Dell'Orto S, et al, &ldquo;Exaggerated QT Prolongation
After Cardioversion of Arterial Fibrillation,&rdquo;",
" <i>",
" J Am Coll Cardiol",
" </i>",
" , 1999, 34(2):396-401.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/10440151/pubmed\" id=\"10440151\"
target=\"_blank\">",
" 10440151",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Denetclaw TH, Oshima N, and Dowling TC, &ldquo;Dofetilide Dose Calculation
Errors in Elderly Associated With Use of the Modification of Diet in Renal Disease
Equation,&rdquo;",
" <i>",
" Ann Pharmacother",
" </i>",
" , 2011, 45(7-8):e44.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/21712508/pubmed\" id=\"21712508\"
target=\"_blank\">",
" 21712508",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Falk RH, Pollak A, Singh SN, et al, &ldquo;Intravenous Dofetilide, A Class
III Antiarrhythmic Agent, for the Termination of Sustained Atrial Fibrillation or
Flutter. Intravenous Dofetilide Investigators,&rdquo;",
" <i>",
" J Am Coll Cardiol",
" </i>",
" , 1997, 29(2):385-90.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/9014993/pubmed\" id=\"9014993\"
target=\"_blank\">",
" 9014993",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Fuster V, Ryden LE, Cannom DS, et al, &ldquo;ACC/AHA/ESC 2006 Guidelines for
the Management of Patients With Atrial Fibrillation-Executive Summary. A Report of
the American College of Cardiology/American Heart Association Task Force on
Practice Guidelines and the European Society of Cardiology Committee for Practice
Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of
Patients With Atrial Fibrillation). Developed in Collaboration With the European
Heart Rhythm Association and the Heart Rhythm Society,&rdquo;",
" <i>",
" J Am Coll Cardiol",
" </i>",
" , 2006, 48(4):854-906.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/16904574 /pubmed\"
id=\"16904574 \" target=\"_blank\">",
" 16904574",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Gersh BJ, Maron BJ, Bonow RO, et al, &ldquo;2011 ACCF/AHA Guideline for the
Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American
College of Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines,&rdquo;",
" <i>",
" Circulation",
" </i>",
" , 2011, 124(24):e783-831.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/22068434/pubmed\" id=\"22068434\"
target=\"_blank\">",
" 22068434",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" K&oslash;ber L, Bloch Thomsen PE, M&oslash;ller M, et al, \"Effect of
Dofetilide in Patients With Recent Myocardial Infarction and Left-Ventricular
Dysfunction: A Randomised Trial,\"",
" <i>",
" Lancet",
" </i>",
" , 2000, 356(9247):2052-8.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/11145491/pubmed\" id=\"11145491\"
target=\"_blank\">",
" 11145491",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Mounsey JP and DiMarco JP, &ldquo;Dofetilide,&rdquo;",
" <i>",
" Circulation",
" </i>",
" , 2000, 102(21):2665-70.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/11085972/pubmed\" id=\"11085972\"
target=\"_blank\">",
" 11085972",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Naccarelli GV, Wolbrette DL, Khan M, et al, &ldquo;Old and New
Antiarrhythmic Drugs for Converting and Maintaining Sinus Rhythm in Atrial
Fibrillation: Comparative Efficacy and Results of Trials,&rdquo;",
" <i>",
" Am J Cardiol",
" </i>",
" , 2003, 91(6A):15D-26D.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/12670638/pubmed\" id=\"12670638\"
target=\"_blank\">",
" 12670638",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Norgaard BL, Wachtell K, Christensen PD, et al, &ldquo;Efficacy and Safety
of Intravenously Administered Dofetilide in Acute Termination of Atrial
Fibrillation and Flutter: A Multicenter, Randomized, Double-Blind, Placebo-
Controlled Trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study
Group,&rdquo;",
" <i>",
" Am Heart J",
" </i>",
" , 1999, 137(6):1062-9.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/10347332/pubmed\" id=\"10347332\"
target=\"_blank\">",
" 10347332",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Prystowsky EN, Benson DW Jr, Fuster V, et al, &ldquo;Management of Patients
With Atrial Fibrillation: A Statement for Healthcare Professionals. From the
Subcommittee on Electrocardiography and Electrophysiology, American Heart
Association,&rdquo;",
" <i>",
" Circulation",
" </i>",
" , 1996, 93(6):1262-77.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/8653857/pubmed\" id=\"8653857\"
target=\"_blank\">",
" 8653857",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Singh S, Zoble RG, Yellen L, et al, &ldquo;Efficacy and Safety of Oral
Dofetilide in Converting to and Maintaining Sinus Rhythm in Patients With Chronic
Atrial Fibrillation or Atrial Flutter,&rdquo;",
" <i>",
" Circulation",
" </i>",
" , 2000, 102(19):2385-90.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/11067793/pubmed\" id=\"11067793\"
target=\"_blank\">",
" 11067793",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Torp-Pederson C, Moller M, Bloch-Thomsen PE, et al, &ldquo;Dofetilide in
Patients with Congestive Heart Failure and Left Ventricular Dysfunction,&rdquo;",
" <i>",
" N Engl J Med",
" </i>",
" , 1999, 341(12):857-65.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/10486417/pubmed\" id=\"10486417\"
target=\"_blank\">",
" 10486417",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Wann SL, Curtis AB, January CT, et al, &ldquo;2011 ACCF/AHA/HRS Focused
Update on the Management of Patients With Atrial Fibrillation (Updating the 2006
Guideline): A Report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines,&rdquo;",
" <i>",
" Circulation",
" </i>",
" , 2011, 123 (1):104-23.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?6/2/6183/abstract-text/21173346/pubmed\" id=\"21173346\"
target=\"_blank\">",
" 21173346",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 8904 Version 40.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0503-61.234.146.186-D40D2B0C78-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6183=[""].join("\n");
var outline_f6_2_6183=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F5708707\">",
" ALERT: U.S. Boxed Warning",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162348\">",
" Brand Names: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162349\">",
" Brand Names: Canada",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162368\">",
" Pharmacologic Category",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162351\">",
" Dosing: Adult",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162352\">",
" Dosing: Geriatric",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162353\">",
" Dosing: Renal Impairment",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162354\">",
" Dosing: Hepatic Impairment",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162327\">",
" Dosage Forms: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162313\">",
" Generic Equivalent Available: U.S.",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F11233706\">",
" Prescribing and Access Restrictions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F13160861\">",
" Medication Guide",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162328\">",
" Use",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F13657230\">",
" Use - Unlabeled",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F13934279\">",
" Medication Safety Issues",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162366\">",
" Adverse Reactions Significant",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162332\">",
" Contraindications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162317\">",
" Warnings/Precautions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162363\">",
" Metabolism/Transport Effects",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162322\">",
" Drug Interactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162344\">",
" Ethanol/Nutrition/Herb Interactions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162323\">",
" Pregnancy Risk Factor",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162335\">",
" Pregnancy Implications",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162358\">",
" Lactation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162334\">",
" Pricing: U.S. (Medi-Span&reg;)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162325\">",
" Monitoring Parameters",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162336\">",
" International Brand Names",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162316\">",
" Mechanism of Action",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F162331\">",
" Pharmacodynamics/Kinetics",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/8904\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/8904|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
title=\"Lexicomp clinical abbreviations\">",
" Lexicomp clinical abbreviations",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_patient\" href=\"UTD.htm?28/18/28964?
source=related_link\">",
" Dofetilide: Patient drug information",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_2_6184="EPS tracing AVNRT dual AVN pathways II";
var content_f6_2_6184=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=CARD
%2F72161&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=CARD
%2F72161&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 575px\">",
" <div class=\"ttl\">",
" Electrophysiologic study (EPS) in a patient with atrioventricular nodal
reentrant tachycardia and dual AV nodal pathways",
" </div>",
" <div class=\"cntnt\" style=\"width: 555px; height: 410px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCAGaAi
sDASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwD6poopCQoJJAA5JNAC0VFBcwXG7yJopdvXYwbH5VLQAUUUUAFFFFABRX
m2tWviZfHlhpVt4z1C3tNSt729VVsbVjAIpIAsakx/dxOwy2T8q89c6Y8K+KMtu+IWrHjjGnWQwcf9cvWgD
tqK4YeFvFfly58f6r5mG8vFlZYzltuf3HTGzP8AwL2wq+GPE8hBHj7XEXeVIeysM4BYZGIO/wAp+meB0AB3
FFcYPCviPzOfH+uGP2tLDI+7/wBO/wDv/mvocwyeGfE0Vo7t471+SZQDtitNPO7gZxm3Hfd36YoA7miuNfw
t4i8wbPH2u+WTzm1sMgfN/wBO3P8AB6dG9RhG8LeIv3m3x7rvQ7M21h1+bGf9F/3P/HvbAB2dFcDdaLrket
WGnR+P9fEs4luCGs7A5gj2qwB+zYDb5Y+T2zxRpug+I7i4u4pvHeuj7NMYmZbaw+bKxupA+zcfK5B98H2oA
76iuOXwt4g8k7vHuvebt4xbaft3c/8ATr06frVZvDXiiSMGHxzriN5kikS29h90bwpGLXufLP03d8UAd1RX
JHwtre448e+ItvGP9G0/PXn/AJdfT/Paqd54f1+1j8yTx5r5QzRRri20/OHZF5/0brkt+nXuAdzRXGjwt4h
2Jnx9rwbb84+y2BGcdv8ARumf0pknhbxNvk8vx9rJXb8m60sc7vm64tun3Pr83TIwAdrRXGL4W8R/Nnx/rf
3uP9CsT8uTgf6jrjFMXwv4o3oG8faqUx85FlZZz8vAHkf7/wD4770AdtRXCv4W8XG3ynxA1IXGw/KbCy2bt
vHPk5xux+FEfhfxWzv/AMXA1YR8hd2n2W7ILDtD0xt+vPTIwAd1RXEnwv4rDKV+IGokA8g6dZ8jI7+X1xn8
cfSqzeGfGUaRs/j/AFBidqusemWhwxZRkfuxwPm57DHBwcgHf0VwUvhbxoI28n4h3Rkwdu/SrXGccZwnrj8
Ka/hjxwEGzx/Lv3Ny2lWxAX5tv8I5+4D/AMCx2wAd/RXnF3ofjS2ubaIePrmRp5RGv/EntgAMMxJPsqN+OK
Wz0XxrNe3tvL46lRreRQD/AGTbDzEZVIcDnjPmLk90PFAHo1FeX+ILDxro2lwXUvjlnaS7tLQqukQcGeeOH
OfYyZ+grUXw/wCNXwU8d/LyNx0iD/a5xnp92gDvKK800a28Zalquu2Y8Y+Wml3Mdp5p0qE+Y7QRzE4zwAsy
D6g1rPoXjCNMnxqHyQvGjxZ5IGfvUAdrRXFLofjTcgPjGHaRlidKj+U8cfe5/i59hSPoPjZY2MfjW2dwOFb
Ro8E4/wCunrQB21FcH/Y3jkTBB4wtyB95jo0eMfNgj95yflHH+1+U39g+N9xx43s8eh0Rf/jtAHbUV5T4mu
PG/h+XQ45/FVnK+ralFpybdFXbGzoz7j+
+yQAjD64/HdTRvHbpG6+MtPAbBIfQcEDHcefQB3NFcIdK8dxxu8/jHSoo0yS7aIMBRnkn7RwMAH8fyoKnxC
jt9IlufEuiIL4qs2NGY/Z3Zchf+Pj5gTlc8ckcc8AHpVFeY29x46k8X33h8+JNGEttZQXvn/2E211keRMY+
1cEGNv0rag07x8Y1aXxLoKtgEodBkPOOeRd+vH4UAdpRXFSWnjxG2R+IfD0zgZYHQpQQMNg/wDH53K4/Gpo
rPx2zN5mveHEAJx/xI5jnkj/AJ/PQA/jQB19FcebXx7tU/214cySMj+w5uMkZ/5fO2T+VR2cXjy5iikOteH
I0kQOC2hz5GQpwR9sz3I/4D70AdpRXHzWnj1EkMet+GpGCkqo0SYbjg8c3nHOB+NQMnj1JIUk1nwyhllaNN
2iznOA5B4uz1CA8/3vUcgHb0VxxtfH+8j+2vDJXd97+xZ+ny84+1+7f98+/EcMHxCfmTVPDCDHQ6TPnOFPa
6PQlh/wHPfgA7WiuNMHj4OVXV/C7EDJH9lXHA+bHP2n1AH4+3J9n8flmA1TwwAOjNpU/PLdvtPsp/4F7UAd
lRXGGD4gZUf2p4ZGcZP9lTHH3f8Ap6Hq3/fPvwRW/j+RA6614W2tgrnR7jkEA5/4+vUn8vfgA7OiuMNr8Qd
rn+2vC2RnaP7Gn569/tX0/P25imTx9DJCjaz4ZzLI0aD+xZ+SFdh/y98ZCD/vr25AO4orjxZ+P9xzrvhbb2
P9i3Gev/X16f571ELf4hAAtq/hgncoIGjz9Dtyf+Pvtl/rt9+ADtaK41LXx8wGNc8MBtvzA6JPw2Acf8ffP
U8+35I9r8QRKqrrPhYp3f8Asefjg9vtXqFH457UAdnRXFTRePooZpW1nwyEjVmH/EluCTjd2F0eoCnjJ+b2
5im/4T+PU7WzGr+GG85JJGf+x58IqMg6fauSd+ccdDyaAO6orgfCPiHxBceKoNK1640idZ9Me8IsrWSF4Jo
5likiYmWRWAYsMjHK131ABUN55X2Of7REZofLbfGE371xyNv8WR271NRQB47+zdpsemad4pQ+H7vR55tXmn
Q3OmvaGS2YnyQpZV3BRu+Ufd3dBnn2KiigAooooAKKKKAOJ8RTPD8VfChjt5ZydK1MbYyoI/eWZydxHHGPx
ro5tUnjhkcaRqEkqoWEKeVuc9lBL7cn3IA7kVhax/yVjwt/2CdT/wDRtlXYUAZT6pdquRoWpOckYD2+frzL
Un2rUpELQ6bHGR0W5uQpJ/4AriuFh8a65b/FPxFoWp21gNL0/RjqdsLZmaWQeZgb2YAAkA/KAQOOTXCaN8X
vE1pYQalrI0+
+i1Lw7d61bwQQGL7NJEx2xltx3IQBk9c0Ae5edrWwn7FpwYZwv2x8H058rj8jSxaheKWF1pNym04LxSRyIf
cchiP+A59q87+FfjPX9U8UtoniOezvGn0S11uKe2gMPlebw0RG47gCRg8HA59pNf8Ai22l+JrrSoPDN9exW
+pwaS1zHcxIGuJow0SqrEHknBJwB1yelAHoB1mNZnjez1FdoDbhauynk8AgHJGM/iMZOQE/t2xDhZPtcK95
JrOaKNeM8uyBR+J9q87T4wNNp+kG08M3c+rahc31n9hF1EvlS2qlpAZDhSMAnI/AHjOl8PPignjHWrewOiX
enLd6UNWtZZpo3EsXmCN8hSduHPGeo5wOlAHW6TuvtVvNTOTa7FtrTI4ZBlnlU9QHYhfQiJWBIIqHVpl0XW
ItUk2JYXSrbXkpOPKYE+VIecBcsyMcE/Mh4VSa4eH4kXlj4O1nxheWk9/pM+qG10qC3QKEt1byhNI+CQrOr
sSQcArgc12/gTxJH4u8M2+rRRQRpMzrthuUuE+ViOHXjt0IBHcCgC3/AG/p7EeQ1zcocgS21rLPGSDggOil
Tg5B56gjtSrrds7YS31E+pNhMuPzUfpWmAFACgADgAdqWgDMbVXIzBpmoTegEax59R87L+v4Z5qIatfHOPD
+pLgZ+aW259hiU8/p71sVyvxMuNQtvCyyaOEa/wD7S05Ylkcojbr2BSrMASFIJBIBwCeDQBqrfam5wmjshI
ODNcoAD77dx/IGntcasoDHT7NwOqpeMW6dsxgHn1IrnvtfxDz/AMgXwnj/ALDFx/8AItL9s+IOP+QJ4Uz/A
Nhm4/8AkWgDei1K8bIk0S/QjH/LSAg/T95/MCn3GoXMUEkiaRfzuuMRRvCGfkDgtIB3zyR0P0rn/tnxByP+
JH4Ux3/4nNx/8i0n2z4g7T/xI/Cm7sf7ZuMf+ktAHQHUboRs39jX5Izhd8GT/wCRMUkd5qMzHy9KMCj/AJ+
rhVJ+gTf+pFYH2z4g5/5AfhTGf+gzcf8AyLT/AIfXesXNz4pTX0iiuLfVFjSGCVpYo0NpbPhGZVJBZ3bkDl
iKANoz65kY0/TcZOf9Ofp2P+p/T9aemoXal1udKul2dZInjkRvdfmDH8VB9jXg97rukT/HdoPCOt3Ntqdn9
sjv1ubyR01C6ZSsdtFExKgIwOSAFGABk4Ncp4L1XXWtZG8LX2rXWtHwtey6ykk0srRXwdvLJVj8s2eFAwcY
4xQB9QtrlujhZLfUlY+lhM49eqqRTH8QWaBS8OpKCQCTp1xhfcnZgD37V43+z9etceK7mPRr69vdC/sGykv
GmnkmVNRP+sGXJ2uRu3Adx7Cn+J/HPjGLxrf2umarY21hB4jstDjgksBKStzECZGbcCdpOQBjPc4oA9Z064
XWdfN/assmnWcLQQzLys8jlWdlPQqoRV3DglnH8NP1qQ6VqUGriNmtSn2a9K4+RM5SU5/hQlwcdpCx4WvBt
a+KvizT/DNjJLq1iJoL/ULS6nWKKO4uRBIFQxpJ+7J5OUB3HjHevoXw7dS33h/TLu4EomntYpXE0PkuGZAT
uTJ2HJ5XJx0oA434keItPn8LWk1g82oRHVtMkSSygeaOTbqEGQsijYTkEY3deOtdfHqKqBHDYX55OB5W3PP
XLEAZ68/jisj4l/8AIuWf/Ya0n/0429dVQBwnhK+ul8S+OFi0q6fdq8R3l4lVT/Z9mMN8+ewPAPX1yK6oSa
s7bTbWMS/89PtDyEf8B2Ln86xvBv8AyMfjv/sNR/8Apus66qgDO8/VIywksreZR91opyC3T+FlwD7bj060r
3d/Efn03zVAH/HvOrHv/f2+n6jrzjQooAzW1byoy93Y38HPAEHnE+
+Ii9NGt2xYqkGosw/6cJwPzKAfrWpRQB5V8XNWt5LzwHtgv28rxLbuwNlMuQIJ+BlRuPsM16EdZhIylrqDA
DcT9jkHHrggH8OvtiuO+MADXnw+B6HxRbA/9+LivRKAOd1W8fWbf+zLC3u0+0OEuZLi0kjRIMjzOXUBiy5U
YyQWz0BrV1mwGp6ZPamQxOwDRygZMUikMjgdyrBWx7VdqvZ3treib7HcwXAhlaGXypA/lyL95Gx0YdweRQB
5zpOqunxg1J9TtbmG6Xw9ZxTRw20sy7xcXJJRlU5Q9QffBwwYDu/7csBjzJJYdxwBNbyRkn0wyj/69cxaZ/
4Xlqo7f8I5Z9/+nm5ruqAMr+27DBkjFzLlRlobSWTjsDtU+vT3p0WsJOD9ms9QkIAOGtmhzn/roFFadFAGf
/aE5GV0u+b8Yh/NxUB1W9HP9gakRnGBJb5+v+t6Vr0UAZP9tbEButO1K3P937P5xB9P3Rcfj0988UjeILNc
5h1Tj00y5P8A7TrXooAxx4isj/yw1Xpn/kF3X/xunf2/Z7gPJ1PJ/wCobc//AButaigDM/tu18vf5WoY9P7
Pnz+WzNA1y0P/ACy1AdOunzj/ANkrTooAzhrFswBEd9gjP/HjN/8AEUiazaugYRX+D62E4P5FM1pUUAZy6x
ascKl5yMg/YpsH/wAd9qgn1Kzmlt3aPUswyF1xYT8naV5+TphjWxRQBmnWbUf8sr//AMAJ/wD4ikbXLBE3T
STQj/ptbyRk/QMozWnRQBmSa3aIFJjv2DYwUsJ2/klImu2jttEOo5zjnTrgD8ylalFAGamt2TFt/wBqhVer
z2ksSj/gTqB+tM0bzbm6vNRmilhWfbDBHJuU+Um7DMh+6zM7n127M4IIGrSEgYyQCeB70AefxxPB8dQgkzb
v4fllSLaB5bm5j3nIHIbCnnodx/i49BrhZCf+F5QAjj/hHJMH/t6TP9K7qgAooooA5ST4i+DYpr2KTxNpKy
WWftKm5XMOHCHdzx8zBfqRW3oWt6Z4g08X2iX9tf2ZYoJreQOhI6jIrx+TR/FieJ/i1er4SvXg8R2kFvYEX
lqN5ihMBJBl4B37xn+FSDzgH0D4RWOpaX8OdC0zW9Pk0+/sbZLWSJ5Y5MlABuBRmGD9c0AdhRRRQAUUUUAc
frH/ACVjwt/2CdT/APRtlXYVw/iZbt/il4VFjNbxSf2VqeTPE0gI8yy4ADLznHOfXitydfEjQyRwyaSkjqV
WcrIRExHDbM/Pj+7uXPqO4BRh8AeHYfFsniaO0uv7akyHna/uGVlOcqYy+zbycLtwOwqPQ/hv4S0Oa7k03R
YYzc272kivI8qCFyWaJVdiEQkklVAB9K1Rb+IAcf2lphXA+Y2D5z34E3+ffrUptNVlAWbVIol7ta2gR+nq7
OMfhQBn+EvBHh7wi9w/h/T/ALNJOiRu7zSTNsQYVAzsxCjsowB6Ulz4G8O3N/NezaduuZdQg1R38+QZuYRi
OTAbHAH3eh7g1onTLzAxrmoZHcx2/P1/dfyxSBtciYqYtMuxkkSebJb4HYbdsn57vwoAzLbwF4atrq0uINN
2zWtxdXULefKdstypWZsFudwJ4PA7Yqt/wrvQ7TT2h0KKTS7tNKk0a2uo5Xka3t3bcQoZiCQ3IJyffHFdB9
p1MMQ+nRHAzlLnIJ7AZUfjnHtmmpf3zkJ/ZFwjn+J5otg+pDFsf8B/woA5PWfBmnanpeneEYkC6dpNgJIik
skUkM4Gy2kDIQeNs5PPXFdD4G03TtL8LafDpFgthbvGJmgDmQrI/wAz7nJJZtxOSSScVd0i1uYjcXOoGI3t
w+WERJSNBwsakgEgcnJAyzMcAHAzwJvDt052iXQp5mkZgMNYs5LMx/vRMxJJ6oWycpkxgHQ0Vlwa3BeAtp0
NxexjpLCgEbf7rsQrD3BIp6alK4JTS7849RGvPpy4/wAKANGis19RuVB26Nfvj0eAZ/OQVH/al6emhagCf7
0tuAPriQ0Aa1FZM8uuOVW2s9OhVsfvJrl3ZPqgQBvpvH1pDDry5YX+lyYB+T7FImT2+bzTgfgaANeisuO41
nrNp1iBj/lnesxz+MQqO9vNZFoy2GlQve5G37RdBIDzzl1DOOM4+Q8kZA5oA2KKzI59WCsJbC0Lg8FLo7WH
Y8pkfTnHqabK+uSMqQw6bbKeWlaWSYj2CbUz9dw+lAGrRWS0OvLESt7pkkg6A2ciA/j5px+RpseoapHhLvR
ZXkxy9ncRvH+chRv/AB38aANiiss6rKmfM0nUUx6LG+fT7rn/AOt3wOaDrCbtosdRJ5z/AKMwAx15P+T2zQ
BX8RW66ndWGkzK7Ws/mTXKhtoeNFxtJ6/fkjPH93njg2/D169/otpPO0Zudnl3Aj+6syErIv4OrD8Kj02C4
m1S61G7hMG5Ft4IXKsyopJZiVJALEjgE8IpOCSBTmlfw5ezTTsG0O5l3s+MGylc8k4HMTN8xY8ozEnKHMYB
W+Jf/IuWf/Ya0n/0429dVXB/FfWrS28O7E866uLXVtLeWC1iaV1IvrdwpCjhiMYU4JyMda6f+24wAr2OpLM
SB5f2R269PnAKd8/e474ORQBleDf+Rj8d/wDYaj/9N1nXVVwvhHUJl17xy8Wl3swbWImAUxKR/wAS+z4IZx
g9D+I75A6g3Opso8rToVY84mutuB6Harc/TI96ANKis1bvUo4wbjTFd+4tblXGPq4Tmn/ab9ULvp6leyRzg
v7cEBf/AB786AL9FZjas8SlrrTNQhQdWWNZvxAjZmP5Zpv9u2mD+51LgZ/5B1x6Z/uUAch8X/8Aj+
+Hv/Y023/oievRK8p+LmrW0138Pysd8oTxPbOd1lOmQIZuBlOTz0HJ5969BbXrQcCDU2bHAGnXHP4lMUAWt
WumsdLu7qNBI8MTyKhbaHIBIGe2TxWXpFq+k6tBY75ZIZNPQAnkCSEhXdieSziROT18unXSz649rEbSWDTk
kS4le4AVpSh3Iip1GHVSxbHAwAdxKz+I7S4mtoLrT0339jKLiGPgeaMFXjySACyMwBJADFSelAHNWpP/AAv
TVFxwfDdoc5/6ermu7rzOw1vT5fjJql5Fcb4P+Ectd22NyyYubncGUDKFehDYIPBFeiWV9aX8RlsbqC5iBx
vhkDjPpkUAWKKKz59Z06G5a2e8ha6H/LCNt8v/AHwuW/SgDQorJOtq7FbTT9TuXHVRbNDj/gUuxT+BNOW61
WXc0WmQRpkBRcXe1z6khFcD8z+FAGpRWUdRv4yFk0W7kbnLQTQsn5s6n9KX+1LoDLaJqQHf5oDgfhJz+GTQ
BqUVljVZ/LLNo+orjjGIic+nDn8+nvT/AO05NiudMvwh77UyP+A7t36UAaNFZY1u3x81vqK9iPsMxx+Smmf
29bhsPaamhxk/6BM2Pb5VP6UAa9FZX9vWewN5Op4P/UNuM/l5eaF160Zioh1LI9dNuAPz2UAatFZX9u2nmF
PJ1LOcf8g64x+ezFIPEFnuA8nU+f8AqGXP/wAboA1qKyxrloWVfJ1HJ4H/ABLrjH57OKmstWsL2Yw291E1w
oy0DHbKn+8hww/EUAXqKrX19a2EayXk8cKuwRNx5dj0VR1Zj2AyTVVdZhd9sVtqDt15s5UH5soFAGnXM+Ib
c399cMIndtMtlubcBAwacsWGM/xKIgOO0p9a021K6H3dF1Bh1BDQDPPvID7/AOcU/RrSa2inlvGRru6lM8w
jJKIdoUKueSAqqM4G4gnAzgAHIpNHP8b7d4iGVvDTOrDuGuVx/Ku+rzXRrSbT/jPHZyussUPhxkgkydxjF0
NqsPVRtXOTuxng16VQAUUUUAFFfOc1xr8XxBvfhf8Aa9SMN7rUerx33mtuTTCplkiV85ADoIx9SK6LwV4jt
v8AhofxXpLeJ5tQjltlW2tp7lWWOZWdpYY0UADYARjBbA5J60Ae1UUUUAFFFFAHI6sM/Fbwxx00jUz/AORb
GuquJkgiMkpIQYyQCepx0Fcb4knuLf4o+FmtrKS8zpWph1jkRSi+bZfN8xAPOBjOec84xVnXde1O20S7uLn
wvqMghXzGjt5YZXcA5ARd4LPgfdHUkBd1AHW0Vhy67dNC8lhoGq3SYPlsRFBvPptldXXn1UeoyMZludVv47
USQaBqEszdIvNt12n/AGj5mMfTNAGvRWRBrLKpXUtOvbOdULFViM6NjrsaPOfYEKx/u06PV5JollttJ1KWJ
hlWZEiJ/wCAyMrD8QKANWob25jsrO4upyRFBG0rkDJ2qMnj6Cs5dYndnVNF1QuqB8FYlBzngEuBnI6Z9D0O
aiv/ALVqs8Fm2nzw2IlWWeeV0AYRlWVVUMSdzAA5AG0P6rkAv6VfG+ilMkD208MnlywuQxQ4DDkZByrKeCe
uOoNXay7bdF4jvk+VYZbeGVR3ZwXVz+Ci
IflWpQAUVjHxRojFlt9St7uUdYrM/aZOuD8ke5uO/HFS/wBvacIDNJLLDECQWngkiGQcEfMo78UAalFYzeK
dASNZH1zTER1DKzXSAMp6EZPIPY96eniTQ3dUTWdNZ2AIUXSEkHp3oA1qKqWup2F3KY7S9tZ5AMlY5VY49c
A1HqesadpcKy395BCrZ2Bm+aQjqEUcsfYAmgC/UF5dQ2cSy3L7EaSOIHBPzO4RRx6swH481Sl12yjZVK3rM
wLAJZTPkDr0Q+ornfGXirT7fRUmnj1G3jjvrIs8um3AGPtUXfZ1PQDrkjigDtqKxh4jsn2fZotQuA5wjQ2M
zI4/vB9uwrxkNnBGME5GVOvxOYBa2GqztK2MfYpItgwTljIFAHGOuckcUAbFFUdL1ax1QSfYrhZJIsCWJgU
liJzgOjAMhODwQKhn8RaLb58/WNOjI677lBj9aANSis2LX9HmbbFq2nu2/ZhblCd3p16+1U9c1i3ey+yade
o9/eMLaH7O4d4y3BkwM8IpLnPHHuKANHStUs9Vhkm0+bzokcxltpUE4ByMgZUgghhkEEEEgg1cIDAhgCDwQ
e9Ytpbxad4iit7aKOO3msAiInGwQOAAB6YmA/4DW3QBxvjyztdP8I6faWFtDa2sWsaSscMKBEQf2jb8BRwK
7KuU+JnHhy0/7DOk/wDpxt66sn9aAOV8G/8AIx+O/wDsNR/
+m6zrqq5HwPNFP4h8eGGRJANbRSUYHBFhZgj8CCPqDXXUAFFFNkkSKN5JXVI0BZmY4CgdSTQA6isqPxBpsy
I9pcNexP0lsonuE6ZwWjDAH6nuPWpG1i1VipS83AZ2izmJx6420AcV8YyRefDzH/Q1Wv8A6Jnr0avKfjHrN
lHJ4DuZzNBbw+JreSSS4t5IlVRDPkkso6da9APiPRlOJtTtYT6TyCI/
+PYoA1qK5C91C4kuI9ehmmGlW80dvFECVS4jdwkk5/vKNylSR0jYqSJAa6+gDhbRj/wvLVVz8p8OWZI/7eb
n/Gur1DRdM1KRZL/T7S4lXBWSWFWZSOhDYyCOxHSuStQf+F66of4f+EbtM/8AgVc13lAGY+h2cn+sa8kXBU
o97MyMD1DKXwR7EVds7W3srWK2soIre2iG1IokCIg9ABwBU1FABRRRQAUUUwzRCQxmRPMABK7hkAkgHHuQf
yNAD6KCcDJ6U1JEcuEdWKHawBzg4zg/gRQA6iiigAooooAKKKKACq2oafZalB5Go2lvdw53eXPEsi59cEYq
zRQBRsdI03T5jLY2FrbylPLMkUSqxXrtyBnHtV6iigAorO124uIbWKKxKrd3MyQRsQPlB5dueCVQOwB6lQO
9N0FZoIbiymaWRbOXyopZWLNJHtVlJJJLEBthYklihJ5NAHKAj/hfTDI3Dw0Djvj7Ua76uBTJ+PU3TA8NJ9
ebp/8ACu+oAKKKKACiiigAooooAKKKKAOS1X/kq3hr/sD6n/6Osa1/FRYaFcFDhw0ZHOOd68Vk6n/yVTw5/
wBgbU//AEdY1f8AG96un+HZZ3DH9/bxqAM/M86IufbLDPtQBoaTqlnq0E0unzebHDcS2sh2ldskTlHXBHZl
PPQ9RkVdrJ0aKC3v9UihwDPKt4VB7OgXP4tG5rWoAKKKKACiiigDG1NUh8R6Jds0hkk8+xVR93DoJSx+n2c
Af7xqoYpPFDSpewLHoCSlRBIuWvijYy+eBFuGQvV8AkhSVbZ1SxXUbJ7Z5p4AxUiSB9jqQQeG7dMfQmprW3
itLWG2to1jghQRxoowFUDAA+gFAEtFFFABQRkYPSiigCne6Xp9/AIb6xtbmEciOaFXUcY6EelJY6RpunySS
WGn2drJJgu0MKoWwMDJA54q7RQAVgeNmK6NbEf9BLTx+d5CK365n4gz+Rotj8rMZNX02MYHTN7DyaANzTdQ
tNUs1u9OuYrm2ZmVZYm3KSrFWGfZgR+FWq5/wSlvb6VLZ2p+S3mJYejSqs5/WWugoAoalo+naoyNqFnBcFV
ZAZFzlG+8h9VOBlTwcDI4FXYo0hiSOJFSNAFVFGAoHQAdhTqKAIxDEDKREg81t0nyj5zgDJ9TgAfQCnhVXo
oHbgUtFAGPrTR2+q6LdOzKTO1qWycbZEJwfq6Rge9RapqF1emSw0DcLjf5Ut6yfurUfxMpIxI45AUZAb72O
h0NYs3v9PeCKUQzBklikZd6q6MHUsuRuXcoyAQSMjI60uk2KabYpbxncdzySPjG+R2Lu+O25mY4HAzgcUAc
P8V9Dt5PCcbzzX09wdU0wLKblg8bG+gUvHjCxvhmAZQCNxxxxXQWGjeGdYt5bhNPtNQXzZraSa8hM0jNHI0
cilpQWIDIy9cYHHGKq/FQsvhSApjcNX0ojIzz/aFvWl4WeYjUVlVlj+0LJCG7q8Mbsf8Av40lAHPeHfD+j6
lr/jdNQ0mwulj1eJIxNbo+xRp1ngLkcY9q6m2sb60j8mDUfNgX7n2qIyyKOy7wwLAerZY92J5rJ8G/8jH47
/7DUf8A6brOuqoAyhpl8QQ+uX3HClIoBx6nMZyfpgdOPVDokU8ofU7ifUQrBkjuNvlqQQQdigKxBAILAkEZ
GK1qKACiiigDzn4x/wDH58Pecf8AFVWv/omevRq85+MZxefD3/sarX/0TPXo1AFLW7aS90a/tYGCTT28kSM
RkBmUgH8zTotQtzpCajPLFBa+QLh5ZHCoibdxYseAAOc1brjtKhjv2s9Ckt2S20aQmaIkEYjbFqG9dy7ZeM
4KLnHQgHPWlxqGpfGbU3s4vsHneHrULJcA+akX2m5+fyivDHsrEbQQWBOYx3A0BZGdr7U9Wu3ZdgJu2g2r7
CHYM/7RBPvjiudtVH/C9tTbPI8N2gx/29XP+Fd5QBiyeGNLmCrdx3N5CMfuLy7luIiRyCyOxViCAQSDggEY
PNIPDGnRMBZi5sYcktBZ3MkETZH9xCAvrlcEnqeTnbooAyToURdX+3anvUbQftj4x6EZwenUjPbOMilfSJJ
ty3OralLCzBjGHSHGOwaNVcDOD97nGDxkHVooAxpfDGiTgi70y2u89ftSefk+vz559+tCeFvD6JsTQtKVPm
G0WcYHzABuMdwBn1xWzRQBhHwd4ZOc+HdGORg/6DFz/wCO1M/hnQXCB9E0xhHwgNpGdvXpxx1P51r0UAY0f
hfQ4tnkaVZwFMlDBEIypPGQVxg44yO3HSkh8MaTbmU2lvLatKxaVra4khMrE53OUYFj7nJraooAyD4fsyc+
dqn3t3/ITuev/fzpz06Uv9gWeMedqeP+wnc//HK1qKAMhdAtVjaMXOqbDnGdRnJXPXDF8/rx2xTU8O2aKgS
41Ubc4J1S5br65kOa2aKAMv8AsWEMrpd6kkqnIf7ZI3/jrEqfxBpF0do1/canqUcmNpkMokJH+64ZR9QM+9
atFAGQNFaVF+3apqNxIpJVlm8jHPHEW0H/AIFmlg0ZocbdU1NlXdsDzBtu45PJGW9txOO2K1qKAM620oJeR
3V1d3F7NEpWEzhAIt33iAiqMnAGTkgZAxk5YuyHxRIGkfzLuzUon8IETtuP1/fJ+QrUrI8QQai32afRxEbt
WMLGU8LG/BbHcqwRscZCkZGaAOVtZYpvj1dmKRHKeHI0bawO0i6kyD6GvQa830XTrXS/jS9pZQrFDB4YhRV
RQoP+lSkkgADJPJ9ya9IoAKKKKAPNNU+MWg6bZeIJ54LjzdG1MaXJbh4/Mmcsq70Utyvzfoabd/F/TrTxTP
pE+j6p5EOqxaM98piMYuJBlBt37yD6hT0rK1v4G6dqtv4laW7tP7T1fVhqcV+2nK81om5WMKtu3EHaRkEfe
PFOv/gpHL40uvFljrYtdebVV1G3nNlvWKPbteB13jerf3vlI7daAOom+JWjxfE+PwQ0Vz9vdM/ado8hZNhk
EROc79mDjHcVq/EDxhp3gfw1cazqwlkij+VIIRukmbBO1R7AMx9ApPauAuvgoZ7ptW/4Si9XxEdY/tgXQiJ
gDhuF8jf0CYTO7oPTiux+JPgDTvHem+Tez3VreQ29xBa3MEzoIjMmxiyKyiQYAypOCMjoTQB0HhvVote8O6
XrFtG8cGoWsV3GkmNyrIgYA44zg1yuhfEI6h48l8LX2gX+nXf2drqKSSWKUNGrAZcRsTGTkEBsE57cVN4b+
G+gaVo/hy21Czg1XUNDt4obfULuPfKrIdwKFixQBslVBwowBwBWfoPw81C1+IKeK9a8RpqF1FA9uiW+nJaG
VWwMzsrHzcAKBkADAIoA2tTYL8U/Du4gZ0bU+p/6b2NQ/FyRovBEsiEBlvrAjPT/AI/IetJr9na33xP8Nx3
1tDcxjR9TYLNGHAPnWPOCOuCefesT4x6RpWk+BZtQ0/StOhu4NQ050kS2RSCL2HuB7kfiaAOp0mby9T0+Zz
uTUdOiRZQDjfHlsZ6ZZZWIHojeldJWDpum22qeF9FS9jc+VDBNGY5WjdHCDkMpBHBKkZwVJByCQZ/
+EY0HYU/sTS9h52/ZI8fyoA16KyV8M6Cv3dE0wcY4tI+np0pB4Y0ADaND0sDGMfZI+n5UAa9Gf0rI/wCEZ0
HGBommY64+yR/4UreGtCYYbRdMI6YNrH/hQBquyopZ2CqOSScAUgkQruDqV6ZB4rMTw5oiSCRNG01ZBjDC1
QEY6c4px8P6MZGkOkadvYYZvsyZI9zigDSVgwypBHqKWshvDOgswZtE0wt6m0jz/Kk/4RjQMY/sPS8Yx/x6
R9PyoA2KKx/
+EX0Dn/iR6Vz1/wBEj/woHhfQF6aHpQ78Wkf+FAGxRWN/wi3h/Of7C0rPXP2OP/CnjwzoIz/xJNM5OT/okf
J/KgDWri/ioWGlaGVBwNf03d7D7VH1roD4d0VsbtH044BAzbJwD17V5x8bdNsdNs/B1xp9na2sy+JrH5ool
QsDvGMjHrQB2fhqUW2px2rrsF5psF1G2c+a6Dy5T7bQbfr13cZwcdRWZHplrd6Zp0d7AJfs6o6b+CrbCpP4
qzKfUMQeCab/AMI9pLIyS2EE8ZbcEnXzVU/7IbIUewwOnpQBq0VnLoekqmxdLsQnHyi3THHTtUY8OaGCSNG
00E8E/ZU5/SgDVorIHhnQQxYaJpYYnJItI85/Knjw7ogORo+m565+yp/hQBqUVmtoOjsGDaVYEMMEG3Tn9K
iXwzoKfd0TS14xxaR9PyoAwfjA5i8EeYCQV1PTGBBweL+3rVsf9D1yzyzGG+sEhTcQFR4SWCj1Z1lY8dBCf
w4341aRpmm+BDPYabZWzLqenuzRQqn/AC9xdcD3/Wu51jTH1PQFhtjFBfRIstnLIm4QTqMo2OpAPBAIypI7
0AZvg0j/AISTx2MjI1mI4/7h1nXV1wXgzRrSbxF44k1GCC9u11lP38sK7gDYWjbVOMhRnAGcgY5J5PX/ANk
abjH9n2h+sK/4UAXqKoLo2lpnZptkufSBR/SmnQ9JLFjpdiWIwT9nTJ/SgDRoqgNG0vJI06yyep8hf8KDo2
mEYOm2RHTBgX/CgDifjCAb34e5z/yNVr0/64z16LXlvxd0vT4Lz4feTY2se7xRbIdkKjIMU/HTpkCvRf7J0
3Of7Ps89c+Sv+FAF2is6TRdPdsi3EeeoidowfqFIBpG0PTWABtVz3O45P1Ocn8aAOVtQf8AheuqHnA8N2g9
v+Pq5rvK82s9J05fjVqlstlAkX/COWjBVXb/AMvVxnp64GfoK7Ofw9pswYeVLEWG3dBcSQsPoUYEfUUAa1F
Yo8O284A1e4uNXQLtWO+CNGPcoqqrHgfMwJHOCMnKjwzpcbobWKezRBgRWV1LbRfUxxsqk+5GaANmislvD2
nsMbboc5yt5MCPoQ3FRjw1YBiRNqoyc4Gq3WPy8zFAG1RWKvhqxXGJ9X4GOdWuj/7Upv8Awi9h/wA/Gsf+D
i7/APjtAG5RWE3hbTyMG41n8NYux/7Vpx8MWBXBuNYx7avdj/2pQBt0Vijw3YgY8/Vv/Brdf/HKT/hGbDn9
/q/P/UXu/wD45QBt0VhnwxYH/l41j/wb3f8A8do/4RiwyT9o1jkY/wCQvd//AB2gDcorEXwzYqQRPq/HPOr
XZ/8AalL/AMI3Y5B8/Vsg5/5Ct1/8coA2qKyH8PWTHJm1TrnjU7kfykqO48OxGPNnfalb3KkPHI19PKoYHI
3Iz4ZT0KnqPQ4IANosoZVLAM3QE8mlrCTw3Z3by3GvWtjqV7MeWltwyRoPuogbcQo6nnlix4zgWIdAsYupv
JhzxcXs0wH0DuaANWisuXQrGQ5C3MZ45hupYjx7qwpkXh6yicsJNRfPVZdRuJFP/AWcj9KAOYhyPj1d8fKf
DUOD9LqX/Gu+rzuxtorX47XSQqwB8NRcs7McfapMAZJwBzwK9EoAKKKKACivNNU+MWg6bZeIJ54LjzdG1Ma
XJbh4/Mmcsq70Utyvzfoabd/F/TrTxTPpE+j6p5EOqxaM98piMYuJBlBt37yD6hT0oA9Norh5viVo8XxPj8
ENFc/b3TP2naPIWTYZBETnO/Zg4x3FbXjLXL7QNLF3p2h3esyAkvFbyxxeWgUsXZnYDHHQZJJoA3qKxfBfi
K08W+FtN13Tkljtb6LzUSZcOvJBB+hBHFZvhnxzY+IfFuvaBa2eoW9zo4jMz3UBiD792Cgb5iPl64wQQRkU
ALqI/wCLq+Hjn/mC6lx/23sKwP2jZWg+D2tSocPHNZOD7i7hNaviC+ttP+KPh2S9njhR9H1GNN5wXcz2OFU
fxMewGSa4n9pjX7G7+DPia0hF0XP2ZVka1kWNmFym5N5XbuG05Gcjp1yKAPXNAjEWhabGAQEto1wevCinRX
rPrN1YmMBIbeGYSbuWLtICMY4x5Y5zzntjm1BGIYY4lJKooUZ64Ark7PxBZP4t1SSFrm4tzYWZSS3tJZkbM
lzyrIpDDpyCRQB19FZaa/prgFJ3YZA+WFzgnkA8cHHOD25pn/CS6NjJ1G3AzjlqANeiss6/pgk2falLYzhV
Y44B5wOOCDSf8JBpmUBudrP91GjYMeM/dIzQBq0Vlya/pkRxPdCFufllRkbA6nBAOB3PQUw+JNIV1WS+jj3
EhDICiyY67CQA2OOmeo9RQBr0Vl/8JBpWwSNfRRwk7RNJlI92cbd5wu7P8Oc+1Rf8JPo20uNQiMQYK0oyY4
yem98bVz2yRntQBs0Vjr4m0WTd5GpW9wEG5zbt5ojX+8xXIVf9o4HXnihfE+iSHbbana3cuCwitH+0SEDqQ
iZY49hQBsUViHxb4fw3l6zYTOMYjhnWV2J6KqLlmY9lAJPYGnJ4p0IqhfVrOFmJHlzyiKRSOoZGwykdwQCK
ANmvKP2jGKeGvDL5A2+I7AnJxn5m79q71PFOishaXUIrZhjdFdg28q5GQWjkAYDHOSOgJ6CvJP2l9dsb3wR
pMFnKZJn1y0EavG0YmHzHchYDenT50yORzQB7oAFAA6ClorKj8QabLH5qTSfZ84E5gkELd8rIV2lfRgcH1o
A1aKyD4l0NThtZ05D2DXKLn6ZPNB8TaCM51vSxjGf9Lj4z0796ANeisgeJ9BJwNb0snr/x9x/40xPFfh9wS
muaYwBwcXSHH60AbVFYzeKdATcJNb0yNlOGWS6RSp7ggnIP1obxToKECTWdPQlQ6h7hV3KejDJ5U+o4oA4v
9o1/L+FN84GSt5ZHH0uoq9Jt/wDj3i4x8o49OK8a/aW1qxv/AIM6pFYTpcPPPaiNRkGX9+h+TI+b7vbPH1F
eyySR21s0k8iRxRJueRztVVA5JJ6CgDmfBv8AyMfjv/sNR/8Apus66quC8F63af2742lkS8iSTV43Bls5Uw
PsFmPmyvynjo2DyOOa6o6/pAOG1OyU5I+aZV6fU0AadFZX/CSaHx/xOdM56f6VHz+tLH4i0SQkR6xpzkddt
yhx+vuPzoA1KKym8R6KmRJq1ghH3g9wqlT6HJ4PsaRPEuhtj/icaeCega4RT9cE5x3B7jmgDj/jGA158PAR
n/iqrU9M/wDLGevRq8o+L2t6VLdeASuo2hWLxPbSOfNA2qIZst9ORz7j1r0I+I9EXG7VrBVP3WadQrfQk4P
UdPUetAGrRWR/wk2hbiBrGnkKAWYXClVz03HOBnnGeuDjoaV/Euhqm46xp23G4kXKHAzgnr0Hr0FAHM2oP/
C9tTO3j/hG7Tn0/wBKuf8AP4V3leZ2mt6a3xs1OaHULaaNvD9pEogkErO4ubkkKq5JIHJx0HJ4rt5fEeixC
HfqtiTMoeFVnVmmBGV2KDl89sA57UAatFYGu+JbTTtGj1GGaKWA3UFsxGSQXlWMrgchstjB6HrVm38Q6ZJp
cN9PdwWkUknkFbiZFMc+dphY5I8wMCpUE8g9aANaisxdf0hre6n/ALStFgtQGmleUKiKejFjxtJBAbpkEZy
DSwa7pU9zLBDqFs8kSsz4cYwpw+D0O043Y+7kZxkUAaVFZdt4h0e6uYoLXVLOaSXHl+XMrByQSACOCSATjr
gE9KJPEOjRzxwPq1gJpGKon2hckhtvTP8Ae+X68deKANSis2913SrIE3Wo2sWHMZBlGQw5II7YGSfQAk4Az
Ut7q2n2Kg3d7bw7lDKGkALAnAwOpyeBjqaALtFVG1OxW1juWvbZbeRDKkplUKyAZLA5xgDnNMttX065tIrm
G9t2glfy0feBl/7nPRuDleoweKAL1FZtrrulXcVxLb6javDb482QSDaoPQ56YPIB6ZBHUGltdc0u6uJobbU
LWWSJDI4SUEBQcMc9ODjPpkZxkUAaNFZttr2lXV4lra6hazTv91Y5A2TgnGRxnAJx1wCegNKdc0vzo4v7Qt
TJIQqgSg5JO1RnsSQQPUggUAaNFZ11rmlWjMtzqVnGysVYNMuVI65GeMd/TvT7zVtPsmZLq9t4pFxlGkG7n
p8vXnBoAvZ5x3orznXtT8n4i2lzbXBNudLjuU8hl/0v960aRAngqzTp3AzsOa7WXXNLgs7a6utQtbaC5j82
Jp5Vj3rt3EjJHQcn0oA0aKzotc0uSAzDULVYxL5DF5AhWTG7YwOCGwQdp5xTodZ02aOSRL638tArMxcAbWJ
Ctk9VJBAI4JBA6GgDkYufjxddePDUP63Un+Fd7XnmnXVtefHS+e0uIZwvhyFWMbhgD9qm4yO/XivQ6ACiii
gDx3W/gbp2q2/iVpbu0/tPV9WGpxX7acrzWiblYwq27cQdpGQR948U6/8AgpHL40uvFljrYtdebVV1G3nNl
vWKPbteB13jerf3vlI7da9gooA8duvgoZ7ptW/4Si9XxEdY/tgXQiJgDhuF8jf0CYTO7oPTiux+KHhTVPGW
gLpOl+IG0SCR/wDSytsZjcR45iJDoVU98HkcV2NFAHIaP4E0uO00V9fstK1TV9JVUtr1NPWARKjloxGmW2B
eMYPUZ71Q8O+CNX0r4j614puNftbmLVVSOazXTjGVSMERgSeaeRkZO3nHQV31FAHIagf+Lt6CuDxoeonP/b
xZVz37Tef+FG+J9pIOyDp/18R10F+f+LvaEM9NC1A4/wC3iyrH/aNi874KeKlyFxbo2T7Sof6UAdr4oleHw
5qbwytDP9ndYpF+8rlSFI99xFZ+lrHD431W2hjWOKLS7AIijCqvmXQAA7dKveJoxNpiRsAVa6tgwPcefHkf
lWNFfxW/xXu7B/8AW3mjQSIc/wDPKafIx7+bn8KAOuooooAKKKKACiiigAooooAKKKKACkCqHLhRuIAJxyQ
On8z+dLRQAhVS4cqNwBAOOQD1/kPyrzH9ohPN8CWcW0MZNYsUHHrOten1578eB/xbySVR88N/ZSpzxuW5jI
z6/SgDrfFUbXHh6+tY32PdR/ZVf+6ZCIwfw3ZrURVRFRFCoowABgAVk+J3ZdPtwmdzX1oPw+0R5/TNS6Vfy
Xl9rMDqgWyu1gQr1IMEUmT75kP4YoA0qKKKACiiigAooooA8t/aejaX4HeI44xudzaqo9SbqGu68VLHNpkd
tMu9Li6giKHoymV
dwPttDVynx+Fs3ws1FdQkeOzN3YCd0Teyp9tg3EKOpxnjvXZ6oAbrS1bobo/mIpCP5UAYvg3/AJGPx3/2Go
//AE3WddVXK+Df+Rj8d/8AYaj/APTdZ11VABRRRQAUUUUAec/GM4vPh7/2NVr/AOiZ69Grzv4wf8f3w9/7G
m2/9Ez16JQAUUUUAcHZ/L8c9TVchP8AhG7TgdP+Pq57V28FvDb+Z9nhji8xzI+xQu5j1Y46k+tcVaZ/4Xlq
vp/wjln/AOlVzXdUAZ97oumXtwtxdWFtJcqysJjGN4KsrD5uuMqvGcHFTLp1muoSXwtoheSIEabaNxA7Z/L
64HoKtUUAV7ixtLm4t57i1glntyTDJJGGaInqVJ5Gcdqbd6dZXkCQXdnbTwxsHSOWJWVWHQgEYB561aooAg
vrO2v7V7a+t4bm2fG6KZA6Ng5GQeDyAaBZ2wgeAW8PkuvlvHsG1lxjBHQjHGPSp6KAK1pp9nZBBZ2lvbhE8
tfKiVNq/wB0YHT2qKw0jTdOObDT7O1PBzDCqdBgdB6Eir1FAFKLSdNhuJZ4tPs0nlffJIsKhnbO7JOMk55z
68046bYtdTXLWVsbiZPLllMS75FwBtY4yRgAYPpVuigCtLYWc1xBcS2lvJPBxFI0YLR/7pxkfhRc2FndRQx
XNrbzRwsHiSSMMEYdCoI4I7EVZooAgvLO2vbZre9t4bi3YgtFKgdSQcjIPHBAP1FElnbS20ttJbwvbyqVki
ZAVcEYII6EY457VPRQBDbWlvaxLFbW8UMSLsVI0CgL6ADtz0qOx06y0+FYrCztrWJclUhiVFGeuAB3wKtUU
AcCmiRf8LRAkt5PsKac8sAC7Iw5uYZCARjJEiB8HON57ECuys9Ms7K4uJ7aBUmnYtI/JJySSBnoMktgYGWY
4ySS2azd9btL0Mvlw280JXuS7REH/wAhn86vUAVzZWpvTdm2gN20XkmcxjeY852buu3POOmaWeztp7iCee3
hkngyYpHQFo84ztJ5GcDp6VPRQBwkHy/HK6UABR4bhwB2/wBJlru64WI/8Xyuh/1LkP8A6VS13VABRRRQBy
F58RvDdnp2s3095IttpN8NNu28hzsnJUBQMcjLDkcVC/xN8NQ6vrWm3U19bTaNG0t889jMkcKDOGLlcENj5
cfe/hzXm3iP4GXmrReLboTWY1jUtbF/ZSm8uFijt96sVkQDaXwG/hbqOfTo5fA/iibxr441Se28NT6dr9rH
axwXE80nyxAqnmIIx94HnDfKemaAO38K+MLHxLK8dnaarbERLOhvbGSBZY26MhYYI6cdeRxWcfid4aHiv/h
H/tFybv7X/Z/nC2fyPtON3k+ZjG/Hb9aw/hF8PtU8G6tqdzcT29lpdxCkUGj2d7PdwRODkyB5gCCemAOnc8
Vgf8Kj13/ha3/CTi+0xE/tr+0vtqNILlrfYE+yGHb5WMZHmZ3ck96APWvEuvWnh3The38V7LCZBHttLWS4f
JBP3UBOOOuMVW8FeLdJ8Z6O2p6BNLNaLM0BaSFoiHXGRhgD3FY+seFNU0/wdrVj4M1O7bV76MRRXGs6ncXC
wZ4LKW3lSFJIwMEgZ6Vs+BfDVp4P8I6XoOn4MNlCEL4wZH6u592Yk/jQBg65dfZfi9obrb3Fwx0K+HlwgE/
8fFpzyRxwe9Zvxxvpb34ReLoItM1HetkzcxAAqCCzZzjCgFjnBwDita8P/F7tIHP/ACLt7/6U2tXvix/ySz
xl/wBgW9/9EPQBY1/VYxbwxm11AZu7YbltXYf61Ceg6cda5eLUrWb4tS6lHIslkdKsYVkI2mNnmvgQQcFTm
PaQcEHgjNdV4tdvM0GIYHm6nECP91Xf/wBlrm7Xw5bz/E/xRFqbLfWN9p1lKlo8QVIVWaZtvH3syh5Mnu5F
AHVR+Iree2huLKz1O6ilUOGS0dPlPQ/OFzwe2T7VKdZyf3em6k4zjPkbfx+YitWigDK/tnkj+zdT4/6Ydf1
/z2p/9sQbQWt79RjJ/wBDlOPbAU1pUUAYzapqEhMtno8slqpxmWUQzSD1SNh0/wB9kPXjpmQa3GkTSXVjqV
uAM4Nq0pI/7Z7v8a1aKAMeHxHp8/8Ax7G7uF7PDZzOh9gwTbn8an/teLr9lv8AbjIb7K/PtjGf0/pWjRQBl
f2zhudN1LaOS3kcD8M5P4Cl/tlNxAstRIHJP2Zh/wDr/CtSigDNbV0yPLs9QkBxgi2Zf/QsEY9/1obWIgV2
2uoNkZ4tJBj25FaVFAGedViygFvfHccH/RZPl+vH8s1598dNQW4+G12BZX+5buzds25AjUXUR3EnAxxjgkj
PTAJHqNcP8blV/hdrocZUJE2M46Sof6UAb2rX8BktI3iu8C6GdtrI2dqs2R8vTK9q4Dw1q8A+LXirU5dRiT
SXEFuuR8ocwry7HHllWt50Kt0bAOCcV6LrE3l6joaf89bxk6f9O8zf0rM8W28GnWU+pWjNZ3UlxZtcTRcNJ
FFOHZD7FDKD6hjQBpRa5bzD9xbak7Yztaxmj/V1UfrUi6qpOGs79Oec27HA9eM/l19q0aKAKH9q2/H7u95/
6c5v/iaa+s2qKzGK/wAA44sJyfyCc1o0UAYf9s3d2HfR9LluIIgN73Ja1LnPKxq6ZYgd22rkqN33tsza7bw
weZeW9/bEDMivaSP5frlkDLgdyCR71H4tlMWnWp9dQs09hm4jHP8AnritqgDxv9o7xFpd18HNfisb2O7cNa
sWtsyqoF1Ecllyo6dz14r0LVNWt21DSMRX/wAt05P+gzjpBKP7nPUf5FcZ+1H/AMkJ8Tf9uv8A6VRV6Jfrv
1bTBn7rSPjPX5CP/ZqAON8NeILWDxL43ggSa41CXV4nhsljKSuP7PtBuIbG1QQcs2AOO7KD2EOsxNlZrW/g
mU4ZDaSMAfZlUqR7gmsfwaP+Kj8dnv8A2zH/AOm6yrq6AMsarNn5tI1FU7MREcj1wHJH4jNWH1GFeqXXpxa
yn+S1cooAoHVbcEDy73n/AKc5v/iaBq1vk/u73jj/AI8pv/iKv0UAeYfFnUIpr74f+Wl0Nvie2c77WVePJn
6ZUZPt1r0H+04P+ed50z/x6S//ABNcR8YRm9+Ho/6mm2P/AJBnr0WgDIn12IMYrW0v7i6OAkX2SWMEnuXZQ
oHuT24ycCiPVLqJyt/p0ipjIms3+0x8dVIAD7gQf4COnOSQNeub+H91Be+Hpbi1dJIH1LUNrxsGVgLyYZBH
UHFAHKWuvaV/wuvUrlr+BIz4dtUw7bWDC6uNylT8wK9wRle+K7G38UWjyZvYLnTrZ4zNBdXuyOKdBgkg7iU
OCDtkCtjJAO1sYdoT/wALy1UZ4PhyzOP+3m5ruqAMyLXLOaNXiS+ZH+6wsZ8H3zs6e/Sk/ty0xnytR9P+Qf
cf/EVqUUAZba5aKSDDqPrxp1wf/ZKZ/wAJDZbseTqeTz/yDLn/AON1i2HxJ8NX+l+H9QtLuaS212aS3sCLd
8yuhYMMYyOVbr1qjb/FvwrPpuoX3m6jHDY3S2Mol0+dHa5JwIFUrlpc9UHIzk4FAHTHxHYgAmLUwD66Zcj/
ANp0HxLp4XcU1EL6nTrgD8/LpfDXiC38QW88lva6haSQSeXJDfWr28inAIOGHIII5GRWP4T+IWj+JYbua1i
vbWG1s476Z7uMIFicyAHgnn90/wCVAGsfE2nKW3JqK7cbi2m3IC/X93xQPEunEZAvyMZ/5B9xyPUfJzWJp3
xM8Oap4Q/4SXSZri90wXcdiTFCQ6yvIkagq2O8ifga6Dwtrtt4l0ODVbGOeO3maRFWdQrgpIyHIBPdTjnpi
gCKTxNpkYYyNdqFAJJspwOenOyhvFGkqSDcS5AyR9mlyOcY+71z2raooAwz4r0ZSQ11IpHUNbyjH5rTj4n0
kZHny7xzsFtLvx67duce+MVtUUAYp8T6UMfvp8nhQLWUlv8AdG3n8KUeJdM7vdAeps5gPz2Vs0UAYs3ifSo
EL3E80AAJAltpULH+6oKgsx7KMkngA0+PXbePz11RTpskKCZluXX/AFZOA24EqeflIByDjsyltemPFG8kbv
GjPGSUYgErkYOD244oAyv+EisAgcpqAjxu3/2dcbceudmMe9EfiTTJADDJcS5OP3VpK/Ppwp5rYooAyH8R6
ZEoa4mltozxvubeSFB9WdQB+NC62JIftMGn38tlkATpGMsD/GqE7yo9lyeoBHNa9FAHnun3KXPxxvGjEwUe
HIeJYmjP/H1L2YA16FXB2/8AyXW/9vDdv/6VTV3lABRRRQAUV8peL9d8XxaV8RXs71F0i38UrCZ2vJluof3
kYCRADaI+Rkbh1PFbtxqenv8AE34o2lj4sutPlhsh9jlF7POttOwb7SyxBj91uoA+T+HGKAPpCivCv2eNQe
bW9WsfKhuhb2kXmatpupXF1ZXLk9xMTtl6k47E57VgS69rKfHeSLU1OoXR16OyttNeS4SS2sTHuF1EqOIyg
xlyytn1FAH0pRXkHxXutcvfAMy+Irqw8Gn7bAI7uDUZ7hXX5iys0cSMmcY9Oeo4zsfALUJdT+HsVxLbTwr9
qmSOSW4mnFwgbAlRpvn2N2B9KALl2f8Ai+elDJx/wjl5x/29W1anxRjM3wz8XRg4L6RdqD9YXrndeW/f44a
UNKntYbgeHbosbmBpVZPtVvlRtZSCf73OPQ1o6/ovizVNC1HQ21PTJI9Stnilv5LVh9nDja6JCG+YYYlSz5
GPm3dwDe8QR+bqPh3ABA1AtnGRxbzV514h8VX0HxT8SaXpbQQzW+k2D/aSm8p/pXzIVJwQUmPPGO1dYyeMx
e2rXdtol1EnMX2V5IvKm8ooWk353Rks5wo3L8o+fJZeGm0a5h+O0MF7/pZ1LT4Zr64hj8uMv/pAI2FmKqVg
hXG48jPJJNAHtlFchpfiC+l0zS7bT7CO+1FbBZ72OS58nyWHybCdrfOXWRcHA/dvkjAzdWx8SvBuk1qzjmK
tJ5aWe5VkzlU3FgWiAwD8oduSGTOAAdFRXPC28TXgVp9R07TInILw21s08sYwMhZnYKSTk5MOADjBxuJHce
JLYQzX1pYXMSjy5obJm8x/
+myFyABxzEckA5DsV2sAR6vf3kWuq0M0q2lqbWN4YwhWdriUxnflSw2DY42kfeOc8Y6WsHSbNtR0/U5NTs5
LZNSlLm3dtsiJsSNclD8rEJu4OVyOQRUUN9qOiTNDrQkvdO3r5epoqKYlPGJ1BHQ4+dF24bLBApYgHR0VgX
uvvLK1nodtLdXhlMAmaFxbRFTh2aTGDswRtByW+XjDFS4l8R285kS3sbyKUeWkMbGMwt2dnY/Mh5JAXK8AB
uTQBv0VgvN4jt3SaS2sLuBF8t7e2YrLIe0qs5CqM8GM5wCSHJUKxN/wkxxIn9kr5Z8wwgyN5w/557jjZj+/
g5P8KgcgG9RXN+V4smieQXmjWru29IWtJJvKA6IXEi788ZYKuOQAeCJpH8S3C7reLS7HcNm2cvOUOOZPlKh
hnICZUkEMWBylAG9XGfGO2+2fDbWrcMF8xIwSTgAeama1N/iabAjTTLUxAxu0yvJ57E48xArDYoGG2sSWJK
ZTAkbN8R6Z4g1zQb3RZP7NDSDH291YRuNwKgQhtwIwd2WxwpGdxCAGvr4J1Xw3jPGoOTj/AK9bjrXJ+IdWm
1xtRsRG9vFH50CxyoMswjvk3g9wTEhH0rXKeLJtRiF5a6SAjvJb3UErskGVI2yRna0hAJAKlQ27kJjnmoLS
SD4nR6RPMLlbnTnaSf7rCSMSGQ7cHgm+BHPHTmgD1SiuQ0jW9WvtJsYtJtLS7uks4Tdz3N15aRTMvKYVWJd
SCWU7MBlwTni5BZ+IdLRWXVF1qFAGkhurdIriQ9G2SIVjXsVVk65BcAgoAdHRWCv/AAkl1G0iSabYCU7o4p
rdp3gXH3X2yBXY9SVIC8qN/wB+o7ubxLaederbafeQhM/2fE7pIuOSUlIxIx5wpVB0G4YJIBzPxgmY2tnjf
usb7TruNQ7AO/2tW+YDhsJDJwQeWB6gEekA5GR0rznW7y21uaz1TTLgzWjavp9vHNCcpIqMXJB6EZlZTjoV
I6gitBdQ1Dw1DFBcnTY9G02Xy5yXxJHZuzCGX7wCJGoVWLZ3bJG+ULlgDB/ahG74F+JVHUm1H/k1FXoVyc+
IrBSf+XadgPcNEP61wXx8MWtfDyTQ7OW3ln1TUrOwUF8qjfa4g2/aCQAcA8cbgOpAO/HN4i/t+K71LSLYYh
mt7VLO7Mqgu0RJmZkXaP3eQyhuCRt3ABwCbwb/AMjH47/7DUf/AKbrOtjQNTbVbJ5pIPs8iSshj37/AJc5R
sgfxIUfHbdjqK4Pwastv8SPGeoXcSwzyXDrcJFcPJHiOz08pjIUZxI+TtBOcEkKKvXGpv4S0LS9cW21DUIb
q2t4bnT7C1aeaSXyxtljC/xBRht3BVVwQVw4B6BRXl9x8R7MeA7fxrc6/ZWWjO+IoktXZnk3lfJcn5iRhs7
VBBG7lRgy+KfGsWhafYX2u6jqsFpdRC7lk0vTmmhtUYgRlpSh2qMjO4ZcjgKMoQD0uiuYFzrotBeTanoENt
LGFjcxSFNxHyS7i4yCSD5fuAJO5j03xNPffZ4IG0Sa7kVtmzUl2XRXIYxBQzbRjnIyDkc/eoAx/i9xffD3k
j/iqLbp/wBcLivQ68a+Imsy3+seCdOTUdJmu7fxNb77m0cPgmCcYMG8shHzA5YgfKeclV9KWTXreRoJIrW9
MnzR3SDyY4vVZELMx9VK5z0bZjcwBa8RuiaFfB5Xi8yIxK8ZIYM/yrjHfJGK5X4Uq8EfiaGeZmkk1y+uY4i
uPLha4kRcexaKQ1q6lfSXz2WlXFpJb6i9zDOUJ3oY4pFkeRWHVAVC8hWBdMqu5c5/h+wvItOlu9Je2lvoNQ
1RTFM7JHIsl1K4QsoO0hth3YbjeMfNkAEVoP8Ai+mqHJ/5Fu04/wC3q5ru68uh1/T7f4wXmo30r2cMvhm0c
rOjBoVFxcl2kAyEVMYZ2IVcjJ5GdSPVtZvNFfStT0mK61O5Z8xyhVgurRi7kAbtw/dhYjvAxIwJBU5IBtaN
4ntfFFhLceE57e8hSea2e7bJhjeM7SQBzJkkEbSAR/EOM9DGCsahmLsAAWOAT78VzukTadpumi28LaE0MBb
EcEFn9ji3nG7cCq7QONxxnggBmBWp4jrd9czynGlQx4jhilRJvNP8bttbpyAoBB4JYHIUAHjng74GX3h218
CXKy2Lazo17NcajIL24aKZCzlBEjDaDhlz8q9+T30NO+GviY+HPFWma5p3hPUItZ12XWvIku7koPN+8gdY1
ZGXauHGerDAr1EW/iNt8AvrGJYVPlXbQmRrg548yMFQoAyDtb5jhh5YGwqkuv2tw9r9ngv1P7xLx5BAijjM
bKAzbs52kLjb1OR84Bg/CHwhqng7Rr+11bUPtCz3Rmt7VLiS4jso8ACNJJAGYcZyQPp1zo/FDQtU8T+Cr/Q
9Fube1mv9tvNPMxGyAsPN2gA5YpkAHA56irk9/wCIIT5f9jW0sky4ikgu90cL9/NLKrbehBQEnkYGAWjkvf
EdnMLi6020urV8J9lsJC00bf398hRWUngjC7euWydoBy/wv8A6t4G8S68zanbX2halHDKg8vypY7hBtP7tV
2bSuOQc5UcdTXpdYElz4lj2TNpumtGg/eW0F20kkmcZ2O6IoIwcBhhs/eTHKRW3iWceZcalp9qdm9IYLRn2
Oc4SR2f50AwCVEZYjIKDigDoKKwvsWvsGlGr20MkpLNC1p5scP8AdWMgoxH94tktzt8vgAiv9eKZk0S3U/c
x9uH38ct93/V5zg/exglASQADdorDXXZ1ASfRtRE0ZxdeVHvSL0ZGOPNB6jYCwH3lVvlpw1m7fMaaJfrd5J
8uQoE2DoxkDFOem0EtnqAPmoA2qKwm1TWFk8o6GPNkw0LC6BjA7+a235GA7AODngnnCPqWuRSqJdDjkSRSq
G3vA2xwf+Wm5VwhGTldxGOhJAoA3qbHIkilo3V1BK5U55BwR+BBFczrmuavpunyyXGnW8LSAwQSR3JlH2hg
RECCi/Kz7UBJzuYDGDmmaKbfwv5+khdSuvn+1LIIDKZN/MsjFFChjJ5jsABy/wAq8gUAdXRWCmpa5MqzQaJ
CLdwXUT3nlzbRjAKeWQGPOBu4xyQeA77Rr13HLJaW1nZxyrthF5uaSI4PzuiHDZJHyBlIC5LZbagBuVhahd
Tpr9lm8ENgkohaJACZpWRztckEgD92RjGS3JwMFx1i7tmjfVdOWzsyfKkn+0BwknPzYA/1RxgOSGyRlFHIy
/La4ubWObdBc6m9xcqxiwyldnkuVOMMqLFkHuCD3oAp2rf8X01Nf+pctT/5NXFd3XnmiR3Ufxo1Nb+4juLg
eHLMmSKHylObi4yMFm4yDjngcHJG4+h0AFFFFABRWLP4r0GC2vribWLFILG4FpcyNMAIZiQBGx7Nkjj3qvD
448Lzapd6bH4g0xr6z8w3EH2lQ0IjzvLDPG3BznpigDoqKwfDfjDw94mmni0HV7S+lhUO6Qvlgp6Njup9Rx
V251vS7XWrPSLjULaLVLxWe3tGkAllVQSxVepAAP5GgDRorN8Qa7pfh3TH1HXb63sbJCFaadtq5PQe59qfo
Ws6br+lw6jot7BfWM2dk0DhlODgj6g8YoA424z/AML/ANPHb/hGLn/0rgr0GvOpz/xkPZD08LTn/wAm4a9F
oAK8y1nV20X4uajdeT58baTpNqU37dvn6jNFv6H7ocsfXbjI616bXkfiCey1bx5rNxbTLJHb6WYJtyFdstp
K8nXHIBlHtlT1oA9VtbO1tGna1toYGnkMspjjCmRz1ZsdTx1NT0UUAFFFFABTJoo5oXimRZIpFKujjIYHgg
juK5zVdW1ODXIWtntF0a3uYbS8WSFzM7yjavluG2gBpIM5U5BfkEAHpqAI7aCG1t4re2ijhgiQRxxxqFVFA
wFAHAAHGKkoooAKKKKACiiigAooooAK8f8AHy3v/Cb3MumzNBdnT7mCKVCdyky6X+Q+Y/n9a9gryZp11X4i
6nb7sLFfSwpv43bYtMLdR/eJHv2oA9TtraC1WRbaCKESO0riNAu52OWY46knknvU1UdBunvtC067kBV7i2j
lYHqCygn+dXqACiiigDC8UwoYNMAG0LqUD4XjJ39/xOaqWatJ8SPEEcqhrdtH08BWGQT517u4+m2qPxH1O9
s1sfsUVqbWzube9v5biUoUgEoz5QAIZ+G4YgY9+mtCMePLpwDiTTo0z7pI5/8Aan+eKAMP4gaVp2maDpn9n
6faWp/tfR4AYIVjxGt9BtTgfdGOB0Fd5XHfFMkaFpWMc69pWf8AwOhrsaAPK77VbDQbzx7qWq3KWtv/AGr9
k81s4DSabZbQcdBlRkngdTgAmuZ+Ivxm068Gn+EfhlrdnJr+o3UVgt4UfyLdXyuVkCkFs7QCAwGSeoFa+s/
Drw/4/wBd8axeILC8meHWI/Kntp/LZM6dacAE4PXPIPb3rzLT/wBnKG18e2E+g+IPtun6dfQy31tIxhuoUD
5wrxtyTtIDLtwQ2DlSAAd1rfwY1PV/h1Y6Ql3ZaVqGnW09ta2ttKZrSQyEFpJHki3h25yygEbiBwTWx448E
+NtX8NaB4csL3RrvRre3jXVEvZpIJL1kIIj3RRHEfyjONrHpx369/A+lKTiXxQ/08SX/wDW4pp8E6YM4bxU
fp4kvv8A5JoAr/EfwnfeL/AEGiomnQ3RltJZo2LfZ8RyIzovykkYUgAgZ4zivnvT9S8H6d8R7+wkvNI0a/0
7xfdXfnTwNEhtfL8ryVkReMPuO0lV6kHNfRo8EaWTgyeKR7nxJff/ACRXg837MdxqvjTWb/VNUmt9HnvJZo
IoD59w0bMWAeSRvvc43HeT1PU0AP0rwHqHhnxB4F1Bb/SJdDl123htYLCf7WAxjnYss7RoypgY2ZfOcluBX
1LXgur/AA+8N/Do+C
m0KwuoSPEMclxPcTmR5FS2uGJwGxnC54Ar2vRdWttYtWuLPzPLDlQXXG9f4XXsUZcMCOoPrkAAv1g+DWR9M
unjKsrX92wK9Dmdzmtm7uEtbaSeU/IgzjIBJ7AZ7k8CvOvDniK4svBFpMbN7W9Otw2FxbuNxUzXSBmGOMMs
gcH0YGgBfD2m/Zfjf4ga8kW4m/sW3a1cJgpDLd3LujHJBO8DBGPlCjGQSfQ2tYHvIrtoYzdRRvEkpUblRip
ZQeoBKISO+0elcbZg/wDC7tXPYeHbIf8AkzdV3FABRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUA
FFFFABXJ+IGI+IfhFQrEGK+JI6DCR9fzrrK4bXbu4k+KPhWOG0drKIXkE1yWACytCjquCcn5RnIyO30AGab
LDP8b9f8maKR7bQbGGZUYExuZ7lwreh2lTg9mB7iu8rzrwvaW9v8a/GVzbqQ1/pthPKSTy6PcQHg9OIgOPT
PevRaACiiigD5s8UfCjxXqNn43ntjqKy33iFby002O7gW2uoPMQ+a4PIYAHALKflHHr0t94Z17UPHPxGmv8
Awjc3Oja5ZQ2kBOoW8XneSCuchyybs5UleP4sV7dRQB5R8HPD/izRdWvxrT6inh+O2jhsbfV7iC5vI2B5xJ
DkeXgAYJ9OBWLqPw78Wp8dfD/iyO4sL+0W8u5J7loir2ls0QSOAgy/P8u4KUUYdmZgQcV7jRQBw+qaf4j0f
w9drFdap4tvJ2CIpe0sprVSrAyRMI1TcMj734ehg+B3h7VfDPgRNP120itLk3U8yQrIskio77h5rr8rScnJ
XjpXf0UAeZanDJcftBWccN1NasPC058yEKW/4+4uPnVhj8M11t54duLuFI5fEetqFmjm3QvDGx2MDtJWMfK
2MMO4rnJ8/wDDQtiO3/CLXH/pXDXodAGT/ZV5tkH9v6nlsYOy2+X6fuv55rzwaRaw/Fj+ywXFrcaNcwuXkG
6QsYzI/qzHdlm9W969ZrzPWMHx/wCIb+FQZ9J0aQk9081AVOCe/kMOP7pzQBseCLzUvFugWGqavHc6bE1uq
fY0lKO0wAEkjupzgMGVVBHALNksAm0unatEdkGtl4RyPtNqryZ9CylQV6cbd3X5vSXw5FFa2lxZxcfZ7mUM
OOC7GQfpIK1aAMOPw8MNLNqWom9kOZp47hkDc52qmSqKOgAGQO5JYmafSriMeZp2pXMVwO07GaJx6MpPA91
Kn3I4rWooAwjZ29tpFyviBorgX9wonBjJQvIyxogGM4HyKCfTJx2V4dT0hUazefVbRAQ1tKU+0Ac7fLkYqG
xwCJDkj5i5Iw2J49vryLW9Fs4wradI0Us/AyJRf2Sxc9ejTcd8e1dZDqVpNqt1psUwa9tYop5owD8iSFwhz
05Mb8ZyMc9RkAowprd9Cj3EtvpgdiWhiTzpUXPH7wnYGIxkbGAyQCeGqZtOuySV1m+GexjgOPp+76/XNadF
AGWNMuwwP9uakcDGNlvz7/6qmjSrrcpOu6mSv+zAPzAirWooAyDpF1/DruqDueIDk+vMXH0GB7U86Zdnd/x
PdSGf9i34/wDIValFAGV/Zd5x/wAT7U+Bj/V2/P8A5CqOXRbmQ2xOvaspgkEg2+QN/BGGHlcgg9PUAjBANb
NNd1jRnkYKiglmY4AHqaAMw6ZelSg1y+CkH5/Kg3g9sHy8Y+qn6+vC6TZrb/FNoVdjFDLcKGdtzsTaWBySf
vElGJJ5yc5zWN8Ifi3deMfHGpaVqB09bG6hkvdH8hv3nkpM8ZWbk4kICvjA+XnvXTX0f2D4r6a0rxj+0JpG
iweSfspBU/XyWP8AwGgDpLfw/LZJEbHU7tJITsiWU74VhGcRGIEAgA8P9/IGWI+U2Rpt5K7SXeqziX/ln9l
QRJGPXa27cSODuJHoAea1aKAMWTw+kkjzPqWqfa2cOs4uSuzB4URgeXjsQVOe+TzSy6bqcau9nrc7THkLdw
RyRZ9wio35NXiv/C6db8v7N/Z7/a/
+Er/sj7T9gk+yfZvM27fNzt832z+FfQdAHDamLm9uVTW9Ohj+1lY2tmcTo8SyQIQeMFS00vBAyu3IU5UV5L
caDrc2oxXOo3zWcjxPEd8zpZlI2aNVUEuVeRXBwXI+XJAAritT+KE97cWFvLpiweI01x9CayE2QGWeCTzd2
PuFEJzj/GvTdNuCfGGpIRwtzJEP/Aa1egDmvHdzf614S0W+a4jsrW51zSpbZIUZpWia8h2Fy4AV8EMV2kAj
GW613IstUaUebqwEWORDaqr57YLFhjHXg89MdKwPiucaLo3OM6/pX4/6bFXaUAeceHLZbLxb4ovnnUvHr8c
NzdzKiu8LaZbbULAAY8wx/l9a6TTdM+2aZp+oRSm21Ah7hJUTjExMjRsp5ZMsMjg5UHIPNUfDcNtcav8AEC
K/jhltW1ePzEmUMhX+zrPO4HjH1qH4ZfEjSfiEmqHSoLu2ewkRWjuVCs8brujlABPysAcfSgDoha6wTh9Tt
AvUFLMhvxJkIx+APvUosLrB3atebjz8qQgD6fIePrmtCigDOfT7pmY/2xfJnsqQ4H0zGT+dNi0kht1xqOoX
Dj7paUR7R6YjCg/VgT71p1xXxT8dReAdP0O+uoYntL7VoNPuJZJCgt43DlpeAc7QmcUAYHxg0uZ5/BcEeoz
+Xc+IY4dk6rIqK9tcBscBycEgZY4z0IGK71vD9krxC082xgSBLUwWbeSjRR58tPlAZAm5sBCvXByOK8eu/i
BbeO9e0IackTWGmeMbe3guYpNwuFNpcHfggY+leweMNcXw14Y1LWpLSe7isYTPJDBjeUXliMkDgZP4UAZ+s
C+tLOQarLHPpdqy38l8VCyJHCwkKMg4LZRcMoAI3ZClV38m2gTSeG/IS4W2t9S1CzlupoJSksLhIY90ZB4L
KkeCNpQ5b5ugd458bWGueF9W0TR47i5n1Pwpdaqk0YG2KF4mWPdzncxPA9jWyt1b33haO8sJhcWc00E1vOC
TvVYUYMM4PO00Ac9bwXes/Gm7tL25liiXwza/a1tH2f6Sl3NsYMPmXHzsBnByM5xXWpb6tqcg0bX7RJ7SGY
yT3QUCG9t8N5aMuch923euCp2HoHC1k+E9NOlfF3xapmE73unWd48hUKwzcXgVffaoVc+iivQ6AMi30Z7WH
ybTVtRht1GI48xyeWPQM6MxH1J/Lij7LrgARdVsSo43PYMXI9SRKF3Y77cZ7Y4rXooAyBZaxu2/2xF5Sn5T
9jHmEf7Tbtp/BVp7aXdMgX+3NSBBzuCQZ/8ARValFAGR/Y9xkltb1QhhhhmEZ9+I+Pwx71Xg8Nhld9R1PUb
28LZS483yTEoJKqqxhV4yckglujZAAG/RQBjpo9ypz/buqFgRgnyOB6Y8vB+p59CKWSHW7aCQ211Z3rrzHH
cxmIvx0aRMgc9xGeOMHrWvRQBkB9enyPJ0yyHUOZHuSfYriPH/AH0af9j1OVm8/VVjXGF+y2yoQe5Jcvn8v
z61qUUAZR0m4faJda1J0H3lHkpu+pWMEfgRSDSbiLcLXWNQjQncqOY5Qp9MupYj23d+CK1qKAMf7FrIJUax
EYyMktZguGx2IYDbnsVJx3PWj7JrYxjVrQ7h8+6xJx/uYkGP+Bbu347FFAGBqi63p9jPfWlx/aU0AL/YfJV
PPQDO1SORKexJ2nptGdwo2f2nxZH/AGkn9qaRbpGv2JJ0e3mEvV3lhYDIBwgVuCA5HDKTY8V+N9A8Kajo1j
rt99mudWm8i0XYzb2yo5IGFGXXk4HNdLQBlFNbZdguNNjYc+b5Dvn22bxj1zuPpjvTYdJulPmyazffaH5lM
YQRk8YCoysEUc4wckH5ixAI164//hY/hr+zvt32yX7P/a39i7vIfP2rONmMdM/xdKANqSLV7YJNHcw3u0/v
LcxCIuuf4GzwwHPzZDHjKA5GBf6X9svNGt9WjLO95PcMVkKPGWWVo8OpBDKqhcqexxxXXX91HY2NxdzBzFB
G0r7FLNhRk4A5J46V54vjnRtW8TeFZtPvDPbasYpLMKhJkHl3gclcZXaQM56UASeBojH8SPEZkup7uT+zrc
GaYru4vdQUDCgAABQOAM4yckk16NXB+EY9nxJ8S5zn+zrU9PW91E13lABRRRQBiz+K9Bgtr64m1ixSCxuBa
XMjTACGYkARsezZI496rw+OPC82qXemx+INMa+s/MNxB9pUNCI87ywzxtwc56Yrw7xR8KPFeo2fjee2OorL
feIVvLTTY7uBba6g8xD5rg8hgAcAsp+UcevS33hnXtQ8c/Eaa/8ACNzc6NrllDaQE6hbxed5IK5yHLJuzlS
V4/ixQB6h4b8YeHvE008Wg6vaX0sKh3SF8sFPRsd1PqOKb/wmnhv/AISj/hHP7asf7c6fYvNHmZ27sY9cc4
61xHwc8P8AizRdWvxrT6inh+O2jhsbfV7iC5vI2B5xJDkeXgAYJ9OBVfxLp3ijXPixo0t74Rkbwto94s9tc
QXluplmbCm4lBfftQZIQLk45zwKAPWL67trC0lur2eK3tolLPLKwVVA7knpSade22pWMF7YTx3FpOgkimjb
crqeQQe4rhfFvhnVX8Aa/p15Nd+M7m8hMdtb3cNnF5TkEK4wsa/KSGySSNvHNaPwgs9T0z4daJpeuaZLp19
p9ulq8Ukscm/YoG8GNmGDz1OeOlAGXNj/AIaIs+mf+EVn7f8AT3FXfzXMEEsMc88UckzbYldwC5xnCg9Tj0
rzfWNPttS+PlpBfxRz258LzHym55F3FyRXbQ+GdHjinjewiuVnZGk+1k3BbZ9wZkLHC9QOgJJGMmgDYrzS5
uo7/wAY/EVIAzCPQLS38xhhGYNfbtp/iAJ2kjoysOorrn8I6A/nH+yrVGl6tGuxkPJyhGChyScrg55681yu
tQw6f4u1eG2QQwzaJb26RRAqoEa3xVABwBgnA6cDjpQB1eiRi28Q+IoWcNJcTw3wX+6jQpCP/Hrd617q4ht
LaW4u5o4LeJS8ksjBVRR1JJ4A96rXmmW91ci4YzRTbPLZ4ZWjLpnIVipGcHkdxk44Zgadt4ctFvVvNQln1S
8QgxS3pVvJ6f6tFUIpyM7goY9yeMAEzeINIW6srf8AtG2Mt4cW+1wwkO1WABHGSrqQM8gjGa1K5/TvCOkWV
zrE5ha6fVpBJdLdN5iPhmZRtPy4BcgcZwFBJ2jDX8LQojx2GoajYwAFre3tptkVvIc/OqgcjPPlsWj/ANmg
DnviEVj1G2uFkO59T0ezAB6H7Z5jD8QV/KtLTTef8Jobx49llcPeQZA6sgt1TJ/7YzkfWvPvFcusTePvC1l
qNtKjX19a3VzbKd0URt5CPPypIXeUixk5wyKecgegPCE8B2Gp6Moa4tVGrwie4KrK7hnlDOxwN6ySrlshd4
OPlGADsqK87sPEWmeJdEXxJrl9BYeHBi3jhF+piklLbXMrxttcbvkVCcEZLAlgF3bXTvDkmo3Gk6fctFeWB
WZ7O1vpY/s28ZUiNWAUEZwMY5PHJyAdPRWPN4b0y6EYv4ZL5EJYR3kzzRlj1JRiVz6ccZOMZqG70PRrWwdt
Rec2MWJJBeX80kQC9NwdypA64PHA9BQBevdZ06xvUtLy8igndA4EhwACwUZboCWOACcsQcZwcaFcpL4h8Ge
HfDUesm90iw0S+cBLmMKsVwxBAxtHzHCn14X0FZ1/rfgTSdM0+
+m16Gx0+/DSWhg1KWKKQfxFFRwABnnAwCecGgDvKranY2+p6bdWF6jPa3UTwSqrshZGBDDcpBHBPIINZ1no
OkiCOTTBJBA4WRDZ3Ukcb9w+EYKxOcliDu4zmodW0OYWs0+kXFwdW2gRvc30wiY9PnUErjBbgL1PG04IAMP
xD4X8MeFdEj8R2eg2/wBr8LWE81gIZWgbCwkFC4+9uVQuXDdc18veIPjVpXizxtperXXw4sL6eN1RrWSVJ3
uh5cyBCTDk/NLGwGDzEPUY+nk+HK6kqz+L9bvtcvgyuqyKq2kRX+5bENH/AMCcO3cEGvLdO+DEHg7xjrV54
SkefWLVbS50zzk3Lai4nnibI53BEXdk9dvagD0XQ/CvhZ/DEOqeKfhz4Z0S5kwTZR2MV265OFX5YgS5/uqD
+NXT4Z+HqyWw07wf4evrmYeZElppluSFBxvLEAKAQRkkcggZPFb+ji61ua11fUbZ7OCMF7KymTEqFl2mSXP
3X2llCj7oZskkgJupFHG8jxxoryHc7KoBY4xk+vFAHGab4O8JahpZtI9LeONNU/teW1lmlWSK93E72G7PUE
gAlGHK5BBPV3epWVlNFDd3dvBLKcIkkgUtyBwD7kD6kDqRWFqUceheJ5tdWzvriO/tUtbpraNpjGYWdocRq
Cx3edKCRnGE4AyavaFpsps7i51qKN9Q1EZuo2w6xpg7bcHoyoGI9GYu2BvIoA8+8UeBtDt/itF4rRJG1eeK
J/KZ1Me5Z7ePzVTG4tsbaTkjkcZIz0+ng/8ACZ6i56DVzGOfXToD/wCy/wCeK4bxVqN14c1bw9NNFbR2emQ
z2kxctst7AX9uPOPcsIbdP+BNnGOD3S+fa6xq11Ckcirr9v5is5U7JLOCHI4PILg47gHvQA34sf8AIG0T/s
YNK/8ASyKu1rzX4wzT3Q0awt7qW0SDWNKmldIgTIZL1UjVS2V+XY7ng8qnBDGuzfRp5JWmfWdSE+0LGyNGq
xjjOE2bWJx1cNjnbtzQByLaPc+ILb4oaRY6h/Z099qS24uhF5hjVtOsgxC7l52kgcjGc9qzvCvgLSPAnjE6
tpPiG5NrFYJpt5YXGbgqF2mNy4P7pUXb1XaFPUA5rX8KaVNJ4g8bOup3ouodYjEcpYbcmwsyd8ahUfIwvIy
APlKsS1dtptlHp9otvEzsAzOzuRud2YszHGBksxOAAOeABxQBPHIksaSROrxuAyspyGB6EGlZgqlmICgZJP
AArMm8P6TLMkrWEAZeoRdqvzkB1GA4B5AYHB5HNRHwzpBBX7J+6LbvKEr+XjIO3ZnbtJGSuNpPOKALUGs6Z
PPFDDqNnJNL/q41mUs/GeBnJ4547c1neL/Ctj4q/sX+0JbmP+ydTg1WDyGUbpYt21WyDlfmOQMH3Fbdzbw3
UDw3MUc0LjDRyKGVh7g9az5PD+luVKWiwFVCg2zNBwOmdhGcdvTtigDzfxf4TstA8VeHdQsZLmWfWfF0N3c
LKylUYWlwPkwAQMDuTXquofZfsNwNQMQtGQrKZSAmwjByTxjFecfFLQtMN74JjezEn2rxAsM7szGSVGtbkE
NJncRjjGeAAOgxXdQ6Hb/bVvL531C8jCrFLchT5IH9xQAqknksBknAzhVCgHlXhvwDY/Dr4feJ7+HWpNYjv
LdRDcMmPKtEzsiX5myPnbJ4ByOBiul0Wyg0jwXY6Pbu4SwaSzAc5fCWsgGffjPan+NIlttE13RSrLBeulzb
8ZGJZ0EyjHORI+8kn/lsAOFwOZtNcS413xXZgh2sLya7Lhs/ehvo9nsR5P6igDuLAH/hb+unHH9haeM/9vF
7XXRyJLGkkTq8bgMrKchgehBrz/VIWuPiL4gt03n7TpGlWzqhwxje6vfMwe2Iw5z1445xWxFDquj3A0fR7G
L+zpDvtLnjyrGIbd0TJkHgk+WF4x8p2BAWAOnmljhiaSZ1jjUZZnOAB6k1WtdV0+7iMtpf2k8YcRl4plYBz
jC5B6nI496oW2k3VxqQu9cmt7oQDbawxxFY42ycykEn94RgA/wgHB+Zs6VzYWd0zNdWlvMzIYmMkYYlD1U5
HTk8UASPcQoJC8saiPG8lgNuemfShbiFrmS3WaNp0UM8YYblBzgkdQDg/lVIaFpA8rGlWH7oYj/0dPkHXjj
jqaSbQNHmt44JNLsWhjYuieQu1WPUgY4zjn170AWZdSsodQisZbu3S9lXdHA0gDuOeQvU9D+R9DVqqI0fTB
Zy2g0+zFrK2+SEQqEduDkrjBPA59hVK38M6faSyNp5uLGKTk29rM0UIbJJcIOATk5xwepBPNAGjqOoWmmxJ
JfTpCjuI03HlmwTgDqTgE8dgT0Bqa3miuYI57eVJYZFDpJGwZWU9CCOCKpaZounaZI8tnaRpcPnzJ2y8smT
k7pGyzc+pPb0qtPpMllevfaDHbRTyn/Sbd8xxXPU7yVB2yAn7+DkZDA/KUANqq97e2thCJb65gtoidoeaQI
M9cZP0P5VkA6zq+6KSKTRbYDbIwdJJ5G7+WQSqpwPmYbjk/KhAJt6doGladIZLOxgjlZPLaTbuYjOTknkkn
knqTycmgCK28Q288kTfZ7uOyncJBeugEMzHgYwdygngMwVWONpO5c7NVdVsIdT064sroMYZkKEqcMvoynsw
OCD2IBrMgXxJ5UazPpIcDY0gWR84/5aY+X73/PP+H+
+1AG7RWQLDVpHMk+s+Ww4CW1qixkdyQ+9i3XBDADjg4OQ6PcMB5mt6ozqAEceUu055YhYwrEjjDAj0APNAH
mHxO+E+teO9f1+
+m1m1srd9PjsdMhWPzD8rCVjKSuYyZVTlCTtH4V6toCajFoWnprjwPqiW6LdPAxMbShRuZSQDgnJ5AqjN4d
kuI5Eudd1pwRlCkyQmN+zgxouf91tyeqmo7fw8b6b7X4o+zX90FCJAqH7NCB1KoxOWY8knJHAHTJAN65nit
oHmuJEihjG5ndsKo9Sa+b7P4WQ3d2GjvrBfED+Kv7WhaS9nWOazGycqkRG0yBZB/Dng/NgV9AWHh/SbAhrW
wgV1IKuy73XHQBmyQB2AOB2xVbTvCej2EmrPHaCU6rP9ou1uGMqyPkkfK2QACeAB6egoA3AQwBUgg8gjvXh
fgb4W3nhX4pRancX1vLotrdXFvo1pHu3W8c0cszq2QAMZAGCc5PSvVdR0u30m1uNQ0smwaD/AEiWOPPkyqo
+ZTGDtBKjG4DIIB5xg0YNWhvPG91pSq2+xmt7vzSRtbzreZQq+48osfZhQBB4bUL8S/EgAx/xLLI9fW71E1
2tcboAx8TPEfvpVgfzutQrsqACiiigAorzIfF/Th4pbSJdH1RIBrI0EXw8pozdHou3fv2kc7tuBVm2+K2lz
6Kl4thfC9bWv7AOnkL5y3W7BB5xgD5ic9KAPRKK4fRfiXo+r/EXU/B9vFcreWSvi5cAQTOmzzI0Ocll3jIx
2NWPif8AEDSvh5oSajq0dxcNI+yK2tgGkkx95sEgBVHJJ45A7igDsKKhiuBJZpcIjkNGJAg+8cjOPrXGeCf
H58R+JtT0G80K+0nULGFLhlmlimXYxIAZo2YK/H3Tz19KAM+Q/wDGSFsOw8Jy/h/pkf8AhXpNeaXMkUH7RA
nnkSKNPCTszuwVQBdrknPYetd3PrelQGzE+p2MZvWVLUPcIPPY9AmT8xODgCgDQrhPHjpD4g0wkAGS0u8kH
BIWJsfX75+ldrPd29vLDHPPFFJM22JHcKZD6KD1P0rzP4p3ttD4x8GySXMEcTrfxO7yKoI8pQRkkAHmgD1K
iqlxqVjbw3E1xe20UVt/rneVVWL/AHiT8v41Wn8RaJBKI59Y02KQ8hXukBPGehPpQBqUVBBeWtxHHJb3MMq
S52MkgYPg4OCOuDTItRspop5Iry2eO3LLMyyqRGVGWDHPGO+aAOG+JzG3stUvUl8oxvpKeYDjbi+ywz7qwz
7GpPiToWt3PwvPhnwpEGurqOHTWmMiotvbnCySHJBICAjAyeeAadr2l2/ibwjef2nb+bYavqVlKIC5G6ATw
BMkEEblTfjgjfjqK7uSRIo3kldUjQFmZjgKB1JNAHzXffDLxraeCvF/hO00y1lsLvULXUdOexnSOJCZFM0a
rI+5QoUEZ44OOuK9E+HHgvV/DXxN8YX99c3+oabfW9oltqF/PFJLMyK28EIFxtJwMqOPWvQrTXNJvLpba01
SxnuGGRFFcIzkYznAOehqzc3ltatGLm4hhMjbEEjhdzegz1PtQB5n4t8Aa1q/iK9v7SaxW
CZgVEmpalE3CgcrFOqDp/Co/Oux+Idk2peCtWs00ddaknh2JYt5WJGJG0/vSE+U4fk/w8c4rcurqC1gae6n
ihhUgGSRwqgk4AyfcgVKrK4yjBh7HNAHi2i2/jzw/wDBHSdG0nwiW8S2o+x7bi6tmWFSpzcL+82t94qFLA5
zkY680fh14h0vS9HbRPC1w8Ufh6+0J9PuL63MsMkzswnZt2wqxYkhSSAcY7V9GTyxwQyTTyJHFGpd3dgFVQ
MkknoBVCPXtHknSGPVbB5nICotwhZs9MDPNAHDax4U1y1+AX/CL6Yxn16DSYrSMwzCPdKqqCFdiMDg4JI4r
hZfhhr9lr97daTZ36xW+saXd6eTqrMFj8tPtr4aU5JYHO4ZbtkV7/bXdtdNIttcQzNE21xG4bYfQ46Gq1zr
Ol2t9HZXOo2cV5KcJA86rIx2luFJyflUn6A0AeQ/Dnwf4p0r4o3eqahYSjS5TcvJdX9ykk+Wb5FjaOQ71x2
kjXaOnOK9YtrSdPFWo3jRgW0tlbQo+RksjzlhjrwJF/P61fN1biWGIzxCWYFokLjLgDJKjvx6Us1zBAUE00
UZkO1N7gbj6D1PBoAloqCe8tbeCSae5hihjba7vIFVT6Enoad9oh8tpPNj8tV3s24YC4zkn0xQBLRTBNESo
EiZZdyjcOR6j2qCz1GyvRmzvLa45I/dSq/I6jg9qAPKvi3ocjWHxCvJJVkhm8OPJGu05iZASwPYg+UhHoQ3
tXez2N1ND4hXT3t1vZLuOeAzgmMSJDCVD7SDjKDOOcVz/i521rwF471CMsLK50i5tLQkH96iRS5mH+yzOdp
GQyqrAkMK7fT0xJePjHmTk5x1wqr/AOy4/CgDzfxa73fhnSdTmhvbd9R8UaXcfZrsFWgAuYIwoUgFQRGGwe
cuc46V6nXnXxP1jSrzTNBittTsZpj4h0vYkdwrMx+1x5AAPPAJ/A16LnnHegDlfBv/ACMfjv8A7DUf/pus6
6quR8JTRQ+IvHHmyJHv1yJF3MBuY6dZ4A9T7V1xIHXigAopsjrGjPIwVFBLMxwAB3NU4dY0yeSNINRspHkB
ZFSdSWA6kAHkUAXqKrW1/Z3UCzW11bzQs2xXjkDKW6YBB6+1SJcwOzqk8TMjbGAcHa3ofQ+1AHEfFIMdU+H
+3r/wkkX5fZbnP6V3lcJ8TCW1jwCsZBceIoyRnoPst1z+QP5V3RYbguRuIyBnn/PIoA4r4nSyWqeH54fIxL
qtvZTLIVDPDK4yEyfvBkjbHJIQjBzXF+AYDqninxXbXzbml17U7YuVAcwLFHsjz1KqbmUj/ePrXpWoWdrq/
im0iu4obmPS4xdiOVAwjndsRSDIwHUJLgjkb/cViaHbxp4t08hUSST+2bh9i7fMYXcKBm45IUgZPYUAYXg+
+HiL4tz31r9p+x2mgWXnGaKS3b7R5t0F+R1BZSjyHcBjpgmvWK4qwv7Nfi/4ht2u7YTjRNPzEZF3/LNeMeO
vAZSfZl9RXa0AFFICGGQQR6igEHkEEdOKAFooqp/aVj9vWyF7bfbWXetv5q+YV9Quc496ALdFAIOMEc8iig
AoprusaFpGVVHUscAU6gAooooAKKM/pSZG7GRkc4oAWikLAEAkAnoM9aWgAooooAKKKAcjI6UAIQGBDAEHg
g968qn0Mab4r0DXdY81r631GOzAhkPlMZLZrcSEdyflOP4Q55Oc16lNPFBDLNPLHHDEpaR3YKqADJJJ6ADm
uO1iOa+0yC+lUiGXWrK5t0I+ZYvMiRSQehOC2Oo3AHBBoAXw02/4ja62MbtG0049P9Iv67SuE8Fv5vjTUJM
k+Z4d0l8kYPMt8f613dABRRRQB49/wpRIPGcvizTtbW3106zJqUczWW9RDIuHtnXeNw64fIIycDvWxH8K7e
L4rz+M4tScRPmdNMMOYluzH5Xnk7uflzxgHJzmvSaKAPH9E+Cg0fUfD2rW3ia/k1vTb6S8ubiZC0V0Jc+eo
i3fuy4wN2W6dD23/ir8L9O+INlP5t5dWGptbfZIrqORyix+YHIaIOquCVHB9Aewr0GigDlrfwLolu9neJZw
vrdpbC3g1WdBNcphCobe+SSAT1JrH8EfD+90LxjqPiXV9eTUb+8tRaMlrYJZRMA+/wAx1Vjvkzn5zzgkfT0
GigDzeaFJv2hlEqLIg8LhgrqCAwvMgjPQ/wCA9K7s6VpxE4NhaETnMo8lf3hznLcc8gda4df+Th5OT/yKy/
T/AI+2r0WgDMtdA0e1M5ttKsITOoWXZbou8DoDgcj2rgvHVhYWvxE8ErbWkELMl0AI7dNrfPbphuOmJDXqF
ebfEBd3xT8A8E/u7zIH/XW0Of0oA7xtP06Jkna0tEaDLJIYlHl+pBxx1NWYViEYMCx+W3zgoBg55zxXm/x2
g1bWNB03w1oul3N//a94i3mwmONLWP8AeSB5cERltqqCeuTjPSj9n+PWtN8FSeHvEen3dnd6LdSWkTzKds8
Gd0bI+AHABK5H90etAHoM2mWE7O09layM5BcvEpLEdCcjnqabc6Tp11Gkd1YWkyIAFWSFWCgHIABHGDV2ig
DO8QD/AIlUjkZELxznp/A6v3/3apaxGdX1iDSXUGwhRbu9BP8ArQSwiixjlSyszcj/AFYUhlc4t+KFD+GtW
U55tJRwM4+Q0zQx5lzql5sAWe5xG27JZERU/Abg+PrnvQBpXEENxGY7iKOWM8lXUMPyNQRaZYRK6xWVqiuu
1gsSgMPQ8dK8P8aeNvE3h7xd4l8HxX0kmq61LaP4amaIHyUmfZKDxjEZDEZz05r3e3jaK3ijeRpWRQpkbqx
A6n3NAFSDRdLt7sXcGm2UV0MkTJAiuM8H5gM81E/h3RJGRn0fTWZOVJtUJXvxxWpRQBlReHNEhlWSLR9NSR
XEistqgKsDkMDjg55zWnJGkqFJEV0PBVhkGnUUAVptPs5wgntLeQIuxQ8anavoMjpTYtMsIbSO0hsbWO1jO
5IViUIp9QuMA1booAojR9MEE0A06zEMzb5Y/IXa7erDHJ+tOi0rT4WdobG0jLqEYrCo3KOgPHIq5RQBUi02
xiljkisrZJIxhGWJQV+hxxSPpWnvIkj2FozoSysYVJUnkkHHBqw00S3CQNKgndWdYyw3MqkBiB1IBZcntuH
rUlAFGTR9NkVlk06zdWfzGDQKQW9Tx196W/0rTtRjMeoWFpdIQAVnhVwQOgwRV2igDF8Y24k8F65bxqqhtP
njUYwB+7YD8Kg1G3fUZrfTF4tJZZJ707QQ8SvgREHPEhODkYZUkHfI1NciE2i6hE2Nr28inPuprm/hpr9v4
u0qTxDbW01sl0sSKkjZ+XZ5vH0MzKfdaAK/xcijk0HRInjjeI6/palWUEY+2RDGP0rpI/DmiRhgmkacoIAI
FsmMDoOnSsD4rEjRNG4znX9KH0/02Gu0oA4jwbpWn/8ACQePE+wWmw6tHER5K42HT7M7enTJPHuaXxVBp+j
zW81tplgHeaztuLdCQk15FCwxjptkPParng3/AJGPx3/2Go//AE3WdU/FkqS+KLSylKj91b3QHUny72Ak49
BgfnQB0cfh/RonV49I09GUhlK2yAgjoRx7VoSxRyoUljR1JyQy5Bp9FAFWfTbG4leWeytpZXXYzvErFl9CS
OntQdNsSiIbO22ouxR5S4VfQccD2q1RQB5z8RNK0+31PwDHb6fZxofEaEosKKD/AKLcnOMeoB+oFdqdD0kq
ynS7HazBiPs6YJHQ9Otcv8TF3av4AGM/8VEh/K0ujXc0AQWdnbWUbR2dvDbozF2WJAgLHqSB3964a/vm0/x
haGKNXmi0zWZUEj7QW+0WbKpPPUuK9ArhtTtmuvHVp5SjdG00R+YYC5sZmyPfy8fjQA3w5pUFp4/1qylVbk
R6NpjO8qgmSQ3F+zSEf3mYlj7mulbw3obFS2jaaSpyCbWPg+3Fc1fXz6Z488VXcQRmi0XSyA/Tm4vhz+dVP
jN8VNL+G2giaQpd6zcqfsVkG+//ALb46IPXv0HcgA7BvDWhtOZjo+necQFMgtkDYHQZxmmy+HdBWPdJpGmI
kaEBvs6LsXrwccV8p/AL4reNfEHxDvNIuNVtp59c3SxvfRtJFbSRoW/dxqy8bFI2gqDgc+v03rXhzVtU8D6
rokviJxqF/E8J1A2igQq4wwSNSvG3OMsSCc5OMUAcLofxN8Eat4W8S6/Jpd2lvouxrmO5jDzXMb8xOAzfOG
J+XcffjrXUWPjXwFe2ulWYvdLjGqrHLaWU0aqZS8hiXCYwW3qy8eh7c1zSfA+0s5tSj0nXr+HT9R0VtGuLe
4HnnAGInViwxsAxtweMgEZrpvCfgW70fxRaa7qOsRX91BoiaKVjs/IDBJmkWT77Y+UhSPUZzzgAGVa+KvAU
Xh3TtY1mz0WxGpRvMPKthcIVRipYyLH0GepAHNX/AA7J4X1zxb4g0a18OaTs0mG0lF0sETJOtwjuCoC8ABe
uTnNcld/A24m8J6NoKeKSbew0+4sHWaxMkTmVywmWPzQFkXdjJLcDjB5ruPAXgX/hE9X1S+/tH7X9ustPs9
nkeXs+yxNHuzuOd27OOMdMmgDnPD/inwzqnjq98P6d4MiSSxvJbKW98q1REZASSF3byOOynr9ah8R+Ovhzp
+k3Oo6dZaNqht5oxII4FjUq8qxNIJCm11UsMkEjgc1PpHwjbT/HWsa82p6bcW+p3c9zJFJo6G6jWVGQpHc7
9yDDdhzzxzSf8Kq1R/CVt4Zn8VJJo9k0H2NP7MVZEWKZJB5jiT5zhNuQFHOSCaANJfEfwyutIk1VJNEe0S7
W2LrajeZx8wQIF3lu+ADkZ7Zro9G03wnrWmQajpOnaNd2Nwu6OaK2jKuMkenY5GOxyK5PUvhXJN4mv/EFhr
gtdUk1RNTtWaz8yOEiDyWR13jeGGTkFSDXXeAPC8Xg/wAL2ujxXMl20bySyzuoUySSOzu20cKMscAdBjr1o
As/8IvoG1V/sPStqjCj7JHgD24pV8MaCqbBoumbQd2PsqdfyrXooAyF8M6Eu/boumDf97FqnP6Ug8MaACSN
E0vkEf8AHpH+PatiigDIHhnQVYMNE0sEdCLSPj9KB4Y0EEY0TTBjpi0j/wAK02niSeOBpFE0isyITywXGSB
7ZH51JQBlN4c0NiS2jaaSepNqnP6UHw5ohkLnR9NLk5LfZUyT+VatFAGYvh/RlkjddJ08PGQUYWyAqQcgjj
jHak8RhTp8QYkD7Za9Bnn7RHitSuX+JzXkfgPWJ9MnS3vLaIXUUz8qhjYSZPB/u+hoAx/ALKfFt4gYFk8N6
MrAHlTvvTg/gR+degV5t8OPsVx478Qarp27ydW0XSL8bk2MFY3YjBXJwRGsYP0r0mgAooooA830Dxt4j8T+
IL8+HtD09/DenaodMuLi5vGS4kKMBLJGgQrtXOQGILY7Z4yfh58Wrjxf4pj057fSLDdLNFJptxdSJqNuEDY
Zo2jCPnaMqrHaGzk4NdJb/DTTrLxLcatper67p0VzerqFxp1rdhLSecEEsybSfmIG4BgD0PFGk/DXTrPxDp
us32ra1rF3piutj/aM6SCDeNrHKorOccZdmxQA/wAd+Nbrwx4j8L6bHoz3NrrN9HZNetOqpEzZ4C8sWwM9A
uO+a5jXfi3ead4n1KKLSLeTQNM1W10m7uGnInMkw5dE242qSBgnJ9q6zx14Ct/GOoaVd3WtazYNpkq3Fsli
8Kqsy5xId8bEtg4649qo6j8KdC1DxJJq9xc6lia6gvrmyWZRbXFxCMJI67c59QGAPcGgBPH/AMUNG8O+HNR
vdIvdM1e/s5o4JbaK9Qi3Z5BHumK5KKCeSR14q58LPGzeNNP1Zp4bWO70u/ksJntJvOgmKgESRtgEqQR1rf
13QoNV0m7sY5pbA3OA9xaJH5mAwYj50ZTnGDlTwT9areCvCem+DtHfT9JEzLLM9zPNO+
+WeVsbnc4AyQAOABgDigDitU1SHSf2gJJriC/mVvDEaKtnaS3JB+1SE7hGp28LwTgHGBzgV1//AAl0OOdH8
QZZWeEf2bL+9UdT0/dnrhZNjHspyM4Vup/4aCv2xwPC9uP/ACbn/wAK9CoA51fFlrwX03XUDkKhOlzncxGc
YCkr1HLbV568HHnPxG1+K48deBbpLDWIlt7qaCUtZSIyky22QFODKvy/ejDr3BNe0V5Z8Xo/M8a/Dw4JYaj
xt6/62Anj045oA0ppV1Px7b62rPLaaVcrpUKxndGftFukrXGRxyZIEHoA/XeNvQjxRA9qby307VLjTipdLq
C38xZVBwWRAfMYdwQnzDBTcCMw6P4StYPCVzoGsLHqVpcPOJRIvDxPIxjQ9/kj2ID2CLjGBXTAYGB0oAwIP
FNnd4+wWmqXW8lYylhKiORycO6qgHuWAPQEnikTxJLcOBYaDrVyqkLIzQLbbDnBGJmQtjrlQVwDgk4B6Cig
DnI/F+jPZXcl/JJYNbQmae2voWilEWB84QjLqdyjK5+Y7fvAqOej1+HQNCs/DuiaJqWk3oEVrawzW5uY7RJ
CUimmdHYFdwIIL7i3XjLV3tzZ2120LXVvDM0LiSMyIG2MOjLnofcVPQBw9rq+n3EtnqHirw+LbxJayGOKOK
xe9nt1kUspR0jLBSnyswwm8OuTjnSbxjbCaRP7J8QmMBPLlGlT7Zmb+EDbuXHGWcKoz14OOmooAwpfE0ECM
8+m60sacOy6fLKVbjjagZm69VBHvUKeL7F0hdbDXsSdc6NdKY/94GPP5Z/KujooAwl8SwSqTbadrM2MnB0+
WI4HU/vAvT06n+EGqn/Ca2bXDQwaV4jlbC7D/Y1zGrs38IZ0UDHcsQozgnPFdRRQBzf/AAl9qLm3tn0vX0u
ZvlKf2VOyxvwNjShTGOTjfvKcE7sYJm/4SizDpG1nrAmd9nljTZ2wSMgkhCoBx94nGep61vUUAc7aeLbS4j
V207XYN+Siy6VcAsB3OEO3PYNtPtS3HiqBLJbm30vWrlGztUWLwtkAnBEuzYMBjubavGM7ioPQ02RFkjZHA
ZGBBB6EUAcsrwTeLoNUESGVpX0iGbkkoqPLLjjj95GFPX/VVag8WWNzteztdUubYjebmKxlMWzOFdWx+8Dc
EGPdwcnA5qLQvD07eCdN0jxJL9ovIo0NxLbzOu+QHJw4wxB5B6bgWB4JFdMBgYHSgDnH8X2QmaKOw12RxIq
ZXSLkK2TywYoFwBkk57cZJAMq+JBcLG2naRrV2GwWzaG1KA9z9oMf5DJ9q3qKAMRvEGk3NpMj3sVtJ5MkjQ
3mYJERR8zMjgMFGRk4xgg9xXnXwh8Rf2Z8JtCt7DR9Su76Yy/ZYIrSVYMSTyGMtMEKRxgEEk5Kr/CT8p9T1
lYBps811FHItupnXegfayDIYA9xjiuY+C1rLafCjwrHcDErWEczfNuyXG/OffdmgDA+I/ie0l0fTbO//wBF
1m217TDPp8e6aTC3cLb49q5kjIIIfABJCkB8oO3Hiiw3SKbfVhsG7J0q5+b6fu+T7deDxgVj/FckaLowGcH
X9KB+n22L/wCtXaUAea+D/FNsureMbr+z9bMVxqqOANMn3ow0+yAR0271Y/N1GMDJIyu6t4w1Oe41f7S2mX
VpJbobdorgRs2MNIHyjsNpKKMZzkcgV1Pg3/kY/Hf/AGGo/wD03Wdcx4rVLjVfG0VxkxxWliy7D83z+apA9
DxxQB258RWzJcS2dvd31rbkCS4tIxKmf4goB3OV7hAfQZbimv4osFjLi31Z1wWGzSrptw56Yj9v85FU/hl5
z+CrC5urGPT7i8aa9ktkJPltNK8pBz/F8/I7HIrqKAMOTxRpsZIdNTUbQwJ0y5wc9AD5eC3+yOc8YzTj4ls
Qis1vqwy23aNKuiQfcCPp79PetqigDzPx5r1ld6r4EZUv4ymvRyMkthOjjdaXQHylMnnjj0PoSOvPinTxuz
b6z8pAP/Enu+/p+65rG+I4zrPgH/sYV/8ASO6rtqAOdtPF9hNMRdW+oabAzbIbnUbZraOZx1Vd+CCMjG4Lu
52bsNjk5NdgPjuO8hM8+nQXVyJLiG1llUk2duVjQqp3lsMQF3A7cdcA+mSxpNG0cqK8bjaysMgj0IrCtS8X
i64i6rKksxP935bZV/PD/lQB5t431m4fxJ4lhtrIxT3WlaSrR3cio6W/2u7Ek6qCc7d68HGCRux0NjwtqOg
+LNHsddv/AADFql1JbtLLexadDL5cIeRYlLSESO5jRWKIGOGHA3KDteJY7aXxN43S9dUgPh7T8s3TPnX+36
844HJ7Vf8Ag1pH9ieBILNkRZVurkMVGNwEzrHn3Eaxj2xigCzZ6n4R0yVDplpAjiLcrWGmu+BnGwGND8//A
Ez+9gE4wCa028UaakSSP9uQMcMDYT5i/wCug2fIPQtgEcjI5rbooA5+LxfpMsTPH/aJdXVGg/sy589cjIYx
eXvC8/fK7c5GcgikTxfpbsAsWrsC2Aw0i7Kt7hhFgg9iODXQ0UAYP/CV6WGnDDUF8oE5bTrgeaR1WL5P3je
yZJ5x0OE/4S3SxcQwsupo0uQrvpd0secZwXMe0HtgkHPHXit+igDBfxXpqvtEeptjliumXJCD1J8vgf8A6+
mTRN4s0mJGbdeyhWKkQafcSkgfxAKhJTtvHykgjOQa3qKAME+LNIaEzW0l1eQkApJZ2c1wkuf+ebIhV8d9p
OO+KSXxfoym3EU9zd+fnb9is5rnYR2k8tG8s9eHwSQR2Nb9FAGDH4s0t0RtupKG6h9MuUKcZAcGMFSewbGe
g5qM+M9GAuQzagr25VXibTblZCW/uoY9z4HJKg7QQWwCDXRUUAc9N4x0eB3S4e+hkA+RJdPuEac4J2wqUzK
2FJ2puOOcYpsfjPR3lEZOpRFkLq02l3USvjqFZowGb/ZBzweOK6OigDzfxD4tjOvDU9JubO403RLO6ku3V9
xlfYjG36fIQDG5fJI4XbycdZN4hEE0zTaZqAsI5TEb1ESSPjgnarGQANlSdmBtJOF5rm/icFkv9NtpDFsub
d7dllXcrCS7so2BHcFXYfjXZaHYHS9Jt7R52uZUBMs7LtMsjEs7kDgbmJOB0zQBnyeK9LAzAb68jPSWysJ7
mNuAeHjQqevY9eOtTT+JNNiUlXuZ8HGLa0mnP1wik7f9rpnjNbFFAGCvimxcs0EGoTW8f+unSzk2xNu27SC
NxbOchQdm079vGcrx5qmmaj8O9bkMoksGX7LcAqyttZ1Rlxjdkq2VwMkMpXOQT2dcl8RtKsbnQbq9mtbdr2
NY447hogzovmo2AevUAj0NAGd4QuYLj4o+LBbRzRRw6XpcQWaF4iMPdkcMASMEc/h1BA76uK0Fw3xc8YAY+
XTNLB5/27w/1rtaACiiigAoryvwj4i8W+Mte1e/07UNJ0/QtK1l9MNhNaNJNOkbKJHaTeNjkE7QFI6Z9Tke
BPiD4kvvHFlpXjBzol7dSzqNJn0l1jkRVYr9nu95EhGFJJUA5YDHGQD2uivC/jX8TfEvhTxXJY6CLb7Ha2E
d3K5tTcBXaYJi4IYGGPb0YAkn9PS28TRau13pOgXTw62sO+OebTrh7UHjkSFVSQc8bX5oA6mivM/gn4p8Re
LE8Q3etT6fd6VbXv2PT7u0t2hFzsyJJMFm+UkqFOexr0ygDgbYf8X71I9/+EZtf/Sq4rvq8x1DUZdM+OOoT
Rabe6gp8N2qlbTYXDG5uNo2sy8McLu6LkFiq5YdPdeLmhSPZ4e8QTTO6qYks+VDLlSWJ2YLYU/N8pOW2qCw
AOnrnr3H/CwdGG05Gl33zdv9bacVWg8XTyRBm8MeIUZWCzr9nT910BIy48wBty5TdnbuAKMjNkavrusReKd
Omt/Cepz3QsLwRW32i2Xevm2uSz+btUjHTnORj+LAB1Gs61DpOpW/264gt9P+yzTTSSnG0q8Kqc+n7wj8RW
zXm+o6pNqnjPRNOvoYoZo5ruyu4oZWeN1MMMwAYqpI2umcgcg+1bVt
qPii0021to/Da3NzCq28ssuoRxpIwXHmqQGYxlsZyA4BY7CQAwB11Fc0vizaJI59C1+K8jIDW4si/JOFxKp
MTZ4OQ525+fbzTR4k1OaaZbPwpqzJAXEpneCEsVIwIsvhy2SQcheOWFAHT0wzRLOkJkQTOrOsZYbmVSASB6
AsuT7j1rAHiyzis55NStb/AE67hALWVxDmVySqqIyhZJcmSMfu2YAuqnDcVz90dSh8c6X4m1KwvIbd1GiRW
fnRuLZZyJGuX25GTJHDDtB98nigD0KiuWuNZ157+eTSNJtr7TEka1G+4MMvnKQDJkggxBiytj5l2EqJMhaJ
vEWtWcpS+8K3kirKd8+n3CXEUcHaQhtkjNjd+7RHb5eM5XIB1NFcvJ4ruorRJ5vCniJMwtO0YigkdUUgNkJ
K2WwQQgyzZwoJDAPfxLexz+XN4U15AzFI2H2aQOQGP8Ex2g7RgvtHzDOOcAHS0Vyt54wa0FvPN4f1safMm7
7T5C7lZmAiQxbvMBcnGCoKkjeFycWIvEl1LceWvhjXtu5AZGWBVAb+LmUEgHIIAyMZxggkA6KiuT/4TQ/Zp
Z18MeJmWJn3L9iAbYrAeYFLAsCDuCrlyM/LkYqx/wAJTIZTt8O68YC6xRzfZ1AdycY2Fw6gdS7KF9/UA6Si
sA+KrQOoFhrZXLiRhpVxiPbnqNmWyRgbQ2eD0INUT4tv55VtbHwprLX6Dfcw3PlwpAueP3u4xyMwztEbOAR
hzGaALfxAS7k8K3Q024mt7sSQukkJIb5ZUYjj1AIPsTXRVhJqsV+mlO0EsBnvJLdoJtpeN0jlyDtJH8BOQT
2rH0PxLOLDTNKtrK41HVY4Ft7i4UEWkdzGh8xJZVDbCCp/hPJUdTQB2tFc4viDUluYBc+F9Uhs5FYvOJIZT
CeNoaNHLHOWB2hsYHYkqk3i+2Fu8lppus3c0SNLNax2TRzRRgH5ikm0sCVKqF3FznaGCsQAaniMZ8P6oMbs
2svHr8hqn4EXZ4I8PJgjbp1uMHt+6Wn2mrWusfarARXVvceWQYru2eEuuAGKbgA4BYAlSQCR2Kk87Za7f/2
DbS6AlldaZpkCrd3bsWiuQiDeLZ1PzbcMMlQueM5DYAJ/isAdE0bPbX9Kxz/0+w12leW/FPVtRmks4bKyhu
NMs9e0u3uSWKzif7TbSqUz8hQq6ryQdzdgvPW2fiyJt8N9p2pQ3tt8l5FBayXKQyYUhQ6KQ4IdWG0Z2n5gp
BAAIvBv/Ix+O/8AsNR/
+m6zrkPElysHinxwfNVJVi0eRQSM4WdskDqcZHtyKt+CvFkNzrPjJtO03VLm7udWSWK0e2NvIEFjaLvfzdo
QZHc7iCCAc1ynja2ml8VeKtbubYW18dLsrKOAkSsqm5ibJYcAlnwVUlflByc4AB7F4YZ/7MEMmN8LYJBznc
A4/RxWvXLw6zYaPqeo2E8im/kMVxBYw4eeSMxpGCsY5xujYE4CjBJIAJE8vifYpYaJrjrGkjXG205hZFDbM
ZzKTyAYt4JXGeVyAdDRWLN4jtLZWN7balbCNPMlZrKVljGwucugK9AeQSAeM5wKjufFFnDG7JZa1O6jOyPS
rjJ+6TglAOjevYgZIIoAyPiIM614BH/UwA/
+SV1Xa15t8QNcjfU/Bs8Gn6rMltrJlKrZujv/AKBdnaivtLHHoOPrxXUf8JZZ+SWFjrZlUqpiGlXG4M3QZ2
bTzwWB2juQOaAOhqhDpwj1271Pz5Wa4tobbySfkTy2lbcPdvNwf9xaxJ9V13TDJqOsW9hHouYy0cAke4tUI
CsXIyrgMQzMMBVVvvferqqAPLfHcoh1vxrIwBC6JpJ5OP8Al7vK73w8yeXdxR4/dTDcAc4Zo0kP6uT+NeUe
JTBq/j3xHqagmP8A4R+3t7SVZDskiZ71zIQRjJaH5WG4FDkH5+PQ4NSttCj1a5um3K629yqRgb5GkRYURQT
y7NEFUdyQKAOpormrPxRMbiGDVPD2t6fLIm8MYBcxqScBS8LOAccnOAMdemaknxD0QWpnhj1W5QqZIzb6dN
IJkGDvjYLtcbCrjByVIIB6UAdhRXO23i/T7nL29tq0tt5hiW4j06d0ZwxVgAFLAA8FiAvoThsRyeNNOj3Fr
PWwPM8pN2k3KtK+TkIpQM2AN2QMFckZwcAHTUVzT+MbCOIySWerII4mmuBJYyIbZFJBZ8gZHDY27t20lcjm
lTxlpkqIlul5NfkFn09ICLmIAjdvjONuMg8/eHK7sjIB0lFc1H410kY+3rf6YrOyxtqFnJAsmGwMFhjkAtt
OGCqzEAAkOtPF+n3c5SG11fyg7x+e2mzrHuVgpXJTOdxYdOqN7ZAOjornT4ts0Mhn0/XIUVS4dtLnYMoYjP
yqSOmcHBwQcU2LxdbyXEMa6Tr4VwWeRtLmVYsMV+bK5J3AfdByGDD5QzAA6SiucfxbasFW007WbieRN0UP9
nywGQ54UNKEUEjJwWGACTimXPjOwiiU29jrN5OxRfJt9OmJDs23YzlRGjA9QzDaOTgc0AdNRXNN4wtvNmjj
0rXpHt0L3AGmyqIgM5wWAEh4OBEXJxxnIytl4vs726uLW1sNYa5hRJTFJYSRFkcZjYFwBhsN1IwVYNtIxQB
ifEhYpNZ05J0SRE0+7uNjHGWimtJAR7gqGHuBXf15z4huI9W8e+GLee2uoI57fU7GVJQFYho4W7E8FRkdx3
AwRXSr4otLfRtJuL4sdQ1CBJIbGBd80zsgYqiDnA7scKo5YgAmgDoaKwRrt6hhe58PanbwMR5khMUpiByBl
Indid2PuggBsk8EBbfxPZGGJ7+G90veBn7fbtEqHHKtJygIOR97kjK5BBIBu1jeL0Enh+4Rvus8QP8A38Wq
cPi+x1HU20/w6Dq88eRPNbsPs1sRjiSXkBufurubg8AAkaVpeLqZnt73Tbm2MQjkKXSoVYHJBBVmU4Kkdcg
jPQgkA5Xwu+74x+PBz8tjpQ/S5P8AWu9rzP4d6lZ6x8UfH19psvnWzQ6bEH2svzKk2RhgD3FemUAFFFFAHI
3Hw48KT+Jv+EgfSFGqmdLlpY55UV5UOVdo1YIzA85Kk5p2g/DvwvoOpW9/pmmMlzbKyW5luZpltwwwwiV3K
x5HB2gcV1lFAHKeJvh54W8T6n/aGt6UtxdmIQO4mkjEsYbcEkVGAcA84YGuhvLC2vNMn0+aMizmhaB442Mf
yEbSAVIK8dwQR2q1RQBneHtF07w7otppOi2qWmnWqbIYVJIUZJPJJJJJJJJJJNaNFFAHCWg/4vpqh548N2g
/8mrmu7rhrMf8Xw1Y9/8AhHbP/wBKbqu5oAKwboN/wnWmHjYNNuwPr5tv/wDWrerBuSP+E804YO7+zbnn28
2CgDjfEMwt/jr4RtIlUC4gvLqUkkEsYVQEdjxCOv8AjXqFcpP4Xe5+JkHiWWXEFppwtYYxzudnkLk+mFK49
dx9OeroAKKKKAK1xp9lc3treXFpby3dru+zzyRKzw7hhtjEZXI4OOtVPE9nc3+gXsGn+QNQCeZaNPny1uEO
+JmxztDqpPsK1KKAM/w/py6Vo1rZjO9FLSMWLF5GJZ2JPUlix7de1aFFFABRRRQAUUUUAFFFFABRRRQBy8N
hZyeNFlMMTTWvnzITyY3kSBdwHYkbxn3Pqa6isWx0eS18W6vqxn3wXttbRLCesbxmXcR7MHj/ABU1tUAFFF
FAGR4n8O6Z4n0p9P1m3E9u3IIYqyNjG5WHIPNagijEPkiNPK27Nm0bduMYx6U+igDz/wCIWnW+l+FfD9nZr
IIIdf0vG+RpGJN7ESWdiWYkkkkkkk816BXEfFo/8SfQevPiHSun/X3HXb0Acj4Hbd4g8eH/AKjiD8rCzrj/
AIowmO41u5aQL5n2KNMsRjF1a9T25aut8AkNrvj0j/oOgf8AkjaVzfxju4rDQNeu3Cf6NGs7BjyypLaMRx2
OMUAeqBRuLYG4jBOOf88mloByMjpRQAUUUUAcj44Qv4g8BgYyNcc8+1heH+lddXIeO1kfXfAiwuqP/bbnLL
uGPsF5njI7Z5zx1rpViu0j2JcQ8YClomY+
+SXyf89aALEkaSxvHKivG4KsrDIYHqCKoSaLZS2rW0qzPbMNrRNcSFCuMFSN3K44weParEiXhP7ue3Ucfeh
Y/X+MUBLzvcQY9oCP/Z6APKfiJMbPxR4mkhwpj0C22gcBSItWI6ehA6V6LaaJYXNzpGr3lnDJq1na+VDcMC
TGHUbsZ79QCeQGYAgM2eB8QqR8VEhvDHMssekxEbMKyk6oCCGJzkZB9c103w1uLmXSrcPMJLBtOsZrRAiqI
lMW1lGBkjchPP8Aex0FAHZUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAeZ+Jty/GHwpI/EELzsznorSw
eWo+pK4H4131hpGn6fcTT2VnBDNNw8iIAxGS23P93LMcdAWJ7muI8UShfG18zMFW1i0WXLHAHmX06En/AIC
D+Vdzo2oJqul219FFLCsyBjFMAJIm7owBIDKcg4JGQeTQBcpssaTRPHKivG4KsjDIYHqCO4p1FABWZrGg6Z
rMsL6larOYkeMAswVo3xvjcA4dG2rlGypwMitOigDz7wWS3xb+I5OcKNNQZP8A0wY/1r0GuA8E5/4Wn8Rzj
/lrp4zn/p1H+Nd/QAUUUUAfPvhi/wBHn+Imrr491fWLbxjH4g8vS7Rbi4jT7NvXyBHGnyNGwzuJB4yTjOTk
/CbU50+JWk2st8niie5e5lfV7O/ulmiQq2BeWz/Ig5AVcDBVcZI5+mKKAPnL9oXWNVsvHaRTuH0qHSVmsdP
le4SPULlp9jopgdC0oUjaCSAOdvOa9I8a6h4gu/CPiCO/tLTw/p0mnv5eqLfySTQOygAtEkQK4JOSGOMfl6
LRQB4x+zffPcweI7YTS6jbWksEUesLd3E0F8dhLbBMSVKn723jLDHABr2eiigDz2SO/k+NGrf2bcWkDDw9Z
bmuLdpv+Xm6xgB0x79e3Suk+zeJ/LONW0Uvzj/iVy49v+XisqxA/wCFy60e40CwH/kxeV2dAGGlt4kw27Vd
HyRxjTJOD/4Ec/pVVtG11tYh1FtX0zzord7cKNNcLtdkYn/X5zlPXvXTUUAeX/EnxD4g8LJZyNfwTpOsplW
K08tFUFEGPnLhsyg7gx+70rrdP0zxDYw/ZYtZspbWFfLt3urSSacqOnmv5w3sBgbsZOMnk1lfFy3RfCl/qT
gOba0lhEZXOfNaMbvwxn/9VJrfxL0fSPiLpng+5iuWvL0IPtSAeRC7hzHG5zkM3lnAx3FAHRLb69uYtqemY
x8oGnuOff8Afc/pQtvr2wB9T0wv3K6fIB+A881r0UAY/wBn8QbGH9p6Vv42n+zpMD1yPP5qrdaHqd6Fhvdc
keykKtcxRQeS7Y52xyIwKITjIO8kZG4ZzXRVx2ofEDTNM8Ua1ompRT2sumaZ/a5mcDZNbjIZk5zlSMHNAFq
xTxHABpsXk+VbswGp3zecZoycoojQqxYD5WZivIBG/cdt0W3iPjOq6R05/wCJZJ1/8CKn8L6sNf8ADunast
rPaJewJcJDPjeisMjdjjOCK06AMR7bxJkbNV0fHfOmS/8AyRSfZvE2P+QtoxPP/MLlH0/5eK3KKAMM23iXb
xq2jhvU6XL/APJFOitvEQcmXVdJZccBdNkUg+uftBraooAx1t/EH8Wp6Ufpp0g/9r0j2/iEltmqaSB2zpsh
x/5HrZooAxTbeIscappPbrpsnr/139KFt/EWF3appJOfmI02Qf8AtetqigDjtd1HxPp8sdhbW0GoXGosIbW
6t7V44rIgMXkuMu3yhQCuCCzfLgZ3DRsrHWdOiFlZS2b2FvxbvdPJLM0fZGPqvQOSxYAZ5yx3LiaO3gknnd
Y4Y1Lu7HAVQMkn2rjvhf8AEXS/iJYX1zpdtd2jWcqo8F2oWQo6B0kABPysDwe+DQBuLF4hZ/nvNJjUDtaSO
SfX/WDH05pXh8QKBsvtKc89bORfw/1p/OtiigDFZvERUxrFpKs3AnMsjBPfy9o3euN69cZ4yVNhrJcSjWox
KQFaIWa+RjPJVd28OfUuVH901s1jXXibTLXxXZeHbiZo9VvYHubeModsip94BumR1x1xzQBxPxKGtWuj6Rb
3Btr5E8QaWYbqSTynkH2qLCuqpjfuzkqAu3nAPynuS+usMrDpkR/umaR/wztX88ce9cN418Qad4n8K6DqGj
StPZjxRp0IlKlQzJeorEZ6jIIyPSvT6APN/AL60Nb8cmKLTH/4nv7xTLIvzfY7XIB2ntjnHXPGMVzHx+TVZ
fDNzZTyW9s2pslrAlsDIX8yW1jZXZgAB8zEYAJKocjlT3vw/jeLXPHqydTr24c54NjaEfoRVD4saM2sXnhG
JNjbtWSNkYclArTEg56r5AbvnHrQBo+GJNXuNP8A7Ts4rd01ONLkrdzyK0cuNhIG0jaUWM7Rt5Df3uNoya6
x4ttMjB4z9okfb7/cG76cfU1qRosaKkahUUAKqjAAHYU6gDG8vxDhz9p0rIztT7PJz0xlt/HfsaXb4gKA+b
pQYjlfKkIU49d3OT7DHv32KKAOA8Wf22Nd8D+edNMp1l9uwOFH+gXm4HPXAzg8ZIHTPHURf28EHm/2W7EEE
L5ihT2PfP04+tZnjL/kY/An/Yak/wDTdeV1VAGMf+EghLEf2VeAjhf3ltg/X95kfgKeX1yd1CRafZp1Lu73
DH/Z2gIB9dx6dOcjWooA8U8WtqKfEq3kv5oLeaF9ELNaqXEqibUNx+YfuwV8zI+bHADd66f4em9g8KeHZdO
ge6gt4LjTXi3qmCkuyORy3O1REwOAW+fIU9KyPiCoTxb4kvH4Ww0Wyvd23IUxrqrAk9ucc13fgPTm0vwxb2
753PLPcHKlSPNmeToen36AJg3iKWTmPSbVOP8AlpJcE+v8Kf5Hvwf8VECOdJbnBGJF4/vd/wDvn36nHO1RQ
Bi7/EUYGIdJnOBk+dJFj1P3Wz9P50hPiRWUhNHlUcld8iE8dM4bHPOcH0x3rbooAw1HiVHbc+jypwVISWMn
1B5b8/070sn/AAkgwI/7IbPUt5g2/hzux+GfatuigDCjHiYEmVtGfsAqyr/wLOT/AN84/HvTy3iM4xFpA2j
BzLId59fu/L64+bpjPORtUUAYefEvPGjHIyBmUYPpnHPTrx16cfMvl+I2IH2nSE3dT9nkbZ7Y3jd6Zyvrjt
W3RQBhvH4k/gudH69DbScj/vv/ADj34R4vEqgmO90aQ9kazlT/AMe80/y/Kt2igDDC+JY25m0edf8ArlLEe
n+83em7fFDt/rdFiXnnypZD7fxL1/THfqN6igDx34s21/pum3+raneJPJcW8FoILODyoyFvICjtuZmLK0jg
cgAMe5zXo0H9qWVxdWlpptvJAZXninafykIc7mVsBm37y5+7t27TnOQMn4lafLq0Oi6dEiut1fBJgxxiNUe
Qkds7o1/DNdlQBirF4iZdzXmkxt/cFpI4P/AvMH8qer6+vDQaXJg43CeRN/vjYdv0yenXnA16KAMnztd3Z+
w6YF6bftkmfrnyv0x+NHna6x2/YtMT/b+2SNj/AID5Qz+da1FAHnnw/WZfiT8R/tMiSSi4sAzIhRf+PROgJ
P8AM16HXB+Bgf8AhY/xIbP/AC+2S4+llCf613lABRRRQBzl5448L2fiOLQLrXtPi1mV1jW0aYeZvbG1SOzH
IwDycj1osPHHhjUdd/sax12wuNT3Ogt45QWZkBLKOxIAOQORg+lcH4M0TxN4S8Ra5p7+FrfV9O1XXW1Max9
siTy43dT88bfOXjwSMDBPTHWsn4beDPFfh/xbpKWFlqWjeFoGmlu9O1C/t72CNmVtotCn7xfmYkltvBPXJB
APZNa1vS9Digl1jULayjnlEETTyBA8h6KM9T7VZ1C9ttOsZ72/nitrS3QySzSsFVFAySSegrxr47fDvxT4r
1Wy1TRJ7O9S1kt1trKaPDW2JA0koYyKpzhcjG4qoAIyc+h3Wn69Ym+1Eajca4TD+70Ro7eCBn44WQpvHQ43
uRzz60AaPhfxTofiq0luvDuqWuowRPskaB87G64I6itmvL/gx4e17SNU8Xahr2nvYx6rdRT26XVzHcXZ2pt
cyyR/IVzjaByMnPrXqFAHH2AH/C39dbuNC08f+TF7XXPIqMiscF22rx1OCf5A1xK2k158VNf+z6jd2JTRdO
UmBYjuzNfdd6N09sdec8UzxJp9zaax4YjfXNYmF9qbQSZmSP5fslw/AjRR1Re3agDuiAeCAR15paxk0W6SP
YviDVsDG0kQMVHpkxHP1OTTk0a4Rdqa3qgXO4gmJiTnJ5MZP4dB2xQBz/xouI4Phvqyu6h5RHHGmcF2Lqdq
jucAnHsa5DWPg9beKJdc1iLxbdHV73VVvLe8thugtWt22RxmIPh2j2yJu3Agk8DGKt/HTRhaeApb4XN5d3c
F1bGOS4k3+SGlVWZUGFztZgTjO1mA4OK7jSNFiFrDd6de3lkbqJJJUgdWjZio+YLIrBSepKgZPJyc0AdDGG
CKJCGfHzFRgE+w5xTqxP8AhG7dnMkt9q8k5JbzP7RmQZ/3FYJj224pU0AQxlLXVdWhPUMbnziDzz+9DevTp
7ZoA2q8p+L3gXSPHPiTw9az61NpuooHjljghaQ3Vq3zNC7AgRhhE+0t12vgHBx3Y0fUPMB/4STU/LAPHk22
SfUnyu30qO48OIul3sdlcyjUriVLo3sx3M8yFShfbj5PkUFF2jbkcZNAG6iLGipGoVFACqowAPQU6uftLDW
rwPc6jqtxp8kn3bKzEMkcI7fO8RZmPUngc4A4ybA0e5AK/wBuapsycL+54z2z5ef1/pQBsUVkppFwox/bep
kehMJ/Xy8006NOf+Y3qm0rtYbovmH12ZB91wffpQBsUVix6FLEcw63q6tjblpI5OOww6EfjjJ7k1J/ZV3hv
+J9qfPT5Lf5fp+6/nmgDWppdRIqE/OwLAewxn+YrMGlXfRtd1NhjBBW3GffIiBzXJ+INFkj8TaFaDXNeEWo
yXKzBL9k6RlwRtA24YDGMYHHTigD0GislNImQALrOp8AAZaI8DoOU/Xqc8npSLo84wDrWqMg5VSYuD9RHk/
iT70AZfxV0+41T4ceIrO1vvsDy2Um6fZvxGBl1xkfeUMuc8bs84xXM/DTwJYaF4rvtc8O6tqJ097f+yrqwv
0Z2aS3fZHIshIwoQAKMEFWBB5rZ8faZLB4V1Rhqt8xuYJLQrNIpRjMpiUY24B3umCBkYx0JBs+G9OudR0PT
NTW/vdPe/sbaW7toijDf5QzhmUlSRhSR2UYwckgHX0Vl/2VOuBBrGpRRjGEzFJjH+06Mx/E0q6XcKm0axqO
R0Y+USB+MeD+OaANOvMfjl4autetPD8+haxYaP4ntL0rp1xeSFFfzI2WSIEAnLKAcAHO3Heu1Ok6jk7fEOo
Y7bobcnP/AH7HH+c0w+GrWaC7F9Pc3lzcwmB7qZxvVT/zzAAWPkKflUZKqTkgGgDifFegQeF/h/4K0SzIMF
hrWkQbsYLkXUeW+pOSfrXqEjbE3bWbpwvX615D8VG163s/B66pqKI114l0y2eC0jRo8LMG8ws6btxZA2BgD
7vzDLN6V/ZV5uz/AG/qeN2dvl22Men+q6UAZXgwg+IvHZBBH9tRjj/sH2dXfEig6z4VJxxqTkf+AdzXLfD+
xup9X8e7NYv4iNfZcokGTi0tueYz7D6Ad8k9Ze6C99bT21/q2o3NlOjRzW58pBIjKVK7kRWAIPUMD70AReE
NbXVLMQzTGS/SPzpAYyv7tpZURs4CnPlN054ycZGegryv4Q6fqD+GLS7S8P26MhzJdoZA6XUEFzIu1SuNsj
kL6Bcd8j0FrC+l3NJrFzG7Y4t4olRcegdWPPfJPtigDTorL/sy7yxGuajycgGO3wPb/VUh0y9IC/25fAZJ3
CKDcc9v9XjA7cZ9SelAGV4y/wCRj8Cf9hq
T/wBN15XVVwvjCyuj4h8EmTVLnc+sSAbI4gExp95yoKk5PfJI5OAOMdMdOvWCA6zdrsGMxxQjf7vlDz67do
9hQBqUVmx2eoQgBNUabGebmBGJ+uzZx9MVEdM1CQ5k1y7TAwBBDCufdtyNk/TA9qAOK8axefqPxJhC7jJ4R
tk2+uTqIxXSeG9clvPEGs2U0U7Kt5MsUnGyNYo7cbTznLNIzDAxw2ccZxE0i51P4g+KLLUdSkEc2hWEMn2S
JYt8bTXwwd28ggZ5Ur16dKxvhxa6kZ9UeziizZ3EbW8Ms7RpKFM9u4ZgrEYC5HByUHTOQAeuUVjjTNSkQNP
rt3HMSGZbaGFYxx0UOjNj6sT70v8AZd+M7devzzkboYD+BxGOPyPvQBr0VkNpl+5Yvrt6hPQQwwAD/vqNj+
tNOlagxXPiC/ULx8sNv8w9TmM/N7jA9u9AGzRWSdLvWPOu6guBj5Ircficxnn9PamnSb09PEOqD/tnbf8Ax
mgDYorGGkXwPPiLVCPeO2/+M08aVehUB17UiR1Pl2/zf+QqANaisk6VeFCo17Uwf73l22f/AEVilbTLwowG
u6iCeh8u34/8hUAatFZK6VeK2Tr+psOeDHbf0ipq6TegknxDqh9vLtsdP+uNAGxRWRHpN6ud3iDU3z0zHbD
H/kKhtJvSxI8QaoATnAjtsD/yDQBevhaxot5eukUdmGm82R9ixjaQzE5xgKTyelU/D2py6ol+8kMSRw3bwQ
vHJvEsagYfpxnJ456ZzzWJ4w0+SHw/cyXesX88RxCY5fKRGEp8o7giKW4kPBOMgHGQDTPCVjrVvoejyRrBb
zT2MC3a3YYvA67mIEYxuY7ypyy7doPzdKAOzorKGmXmwg67qOT38u34/wDIVH9l3oHy67qBPq0duf5RCgDV
orMWwv42Jj1eaTnIFxDGw+h2Kpx+OfftTlt9UZcS39sD2MVqVP8A487cUAcz4IjA8d/EWTHLalar+Vhb/wC
NdvXE+AYWh8VePxLM88n9rQ5kcKCf9AtSBgADAzge3XJ5rtqACiiigAorjH+JGgHxNJolv/aF3cQ3SWU9xb
WMstvbzsQBHJKq7VOSAecDvjBp/h74iaJ4h1G3t9JTUp7a5kkit9QFjKLSZ4wxYLNjb/A/PQ7TgmgDsKK5P
xr4+0bwbLGNbj1FYGVXluoLKSWC3Vm2gySKCFye3Wuku722s7Ca+up4orOGJppJ3YBEjAyWJ9ABnNAFiisT
wh4p0nxfpB1Tw/cm6sfNeES7CoLKcHAIHHvW3QBxuiMW+LXi0cfLpWljj/rpeH+tL8QJ1tdX8FXErMkUWsS
yOVBJ2rp94TwOTwKg8PNu+L3jQcfLp2ljr/tXZ/rVjx8kkms+CY4ZTDI+sSqsigEoTp15yAeOPegDK8EfFC
HxcjXdhol7/ZJiklS5jnhncbM/K8MbtIjNg4GCScDqa3vh94ys/G+k3moafa3lrFbXstkyXceyTcmMkr1HX
oeR3rkvDPwmk0fxafEj6rp/9qx2stvC1jpC2aO7/wDLSdUciUjrgbBmtv4W+CtR8FQatBe63b6pDf3kl/iO
xNuY5ZDl+fMfK8DA4x6mgC/8S7BtT8LfYhkCe9tImYYyqtcRqW/AHNdJZW62lnBbocpDGsY+gGKo+I7eS60
+FIo/MZby1kx6BZ42J/AAn8K0YZY5oUlhdZIpFDI6HIYHkEHuKAH0UUUAFFFIGDZwQcHBx2NAC0UUUAFFFF
ABRRRQAVw/i5yvxL8AoGIDPf5X1xb13FcT4sUH4leBOBuU3x6Z48gD8OooA09U8ceGNK1ldJ1HXLC31ElFM
DygMpb7ob+6T2zjNakOs6bNrEukw39tJqcUXnSWqyAyImcbivUDPFeM+JvBnitfH1/qHg2y1LS2v72J7uaS
/t5tNuohgM8kDfvA+3IwAfYitnQ9B1fT/j3quvQeE3tNEvrH7G95HNbKHlEhczsivvO7AGSu7pkUAeqX1lb
X9v5F9bxXEO9JPLlUMu5GDqcHuGUEe4FTRosaKkahUUAKqjAAHYU6mQyxzxiSGRJEJIDIQRkHB5HuMUAPoo
ooAK4/TfiJomp6wbHT01K5iFy1n9uisZWtPOXqnmgY68Z6Z712FeL6R8LdZtPiJa6/bHSdDhS8e5vG0q7uf
+JgpzhHt3HlpnPJDH1AoAx/il4/0fxB4i8C6NaxalbahH4m0+5WO9spLfzYvNK+Ym8Dcme/0r6Ar5f8a+E/
GMPj/wAKeI/GzaLc3E/iLT4oZbCeVvs8QnG2FUaNQFyxYsSSSBX1BQBw/wANDu1fx+cEf8VE45/69LWu4rh
fhkhTVvH4YYP/AAkch/A2lsRXdUAc78PLZbfwPoOECyvp9s0vOcsIUXJxx0UDj0roqo6DZvp2hadZSFS9tb
RwsVOQSqgHBPbir1ABRRRQByvjL/kY/An/AGGpP/TdeV1Vcr4y/wCRj8Cf9hqT/wBN15XVUAFFFFAHK6b/A
MlT8Q/9gXTP/R9/VnwLaCz0OaMAf8hC/YELt4N5MwGP+BVW03/kqfiH/sC6Z/6Pv63dHtmtbSSN1CFrieTA
OeHldgfxDZoAu0UUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAY3jDSZNb8Pz2ELIHeSJxvJA+SVXIyPZa2
aKKACiiigAooooA5HwWB/wlPj1u51iEf+U+0rrq5Xwb/yMfjv/sNR/wDpus66qgAooooA8w8LeEvF/hHXtT
t9FudCuPDepas2pyPdeaLuJZGBljVVG1uBhWJGO+elY/gf4W6zofjmx1pf7J0Szi81ry20e7uXiv2ZSBmGQ
BIgCc4Bb8Otez0UAeZfF7wv4v8AFt1YWGkHQ5PDCbZr2zvriWJ7yRWJCMUjb90MIcAgk5zxiupt/D8tlcXW
r2s95Lq8tuwW0n1O4NiJSowBGSVRdwAyEyBnjtXSUUAee/Bjwvr/AIR0PUNO8QjSyJLyS7hksbiSTJkZmZW
DxpjHy4Iznnp39CoooA870Wytb74weNxfWsFwEsNL2CaMPt/4+emaXxpo+lw+K/AUUOmWKCXVpgwWBRuUWN
yTkAc9B1qTwq2fjJ4/H92y0of+O3FJ8T9OtNW1/wAE2GoIsttNqE4eIsVLj7JMDgjnv2NAFHxr43+GPg4yL
rEmjG8Xra21sk0xPoVUHaf97FbfgSXwv4z8K2HiDStEs0s7xX2LNaRhwFdkIbGe6nua8j8a/ssaHfeZP4S1
S40ubqLe5/fw/QN99fqS1d58MPhPB4b8DaZpes3uqtqMAkMzWGt3sEBLSMw2okiKOCOijPU8k0AdxqfhTQ9
Q067spdMtEjuY2jd4oEVxkfeU44YdQexANJZeEfDtlBHDbaJpqpGoVc2yEgDoMkZ9qo/8IHpH/P54k/8ACj
1H/wCP0f8ACB6R/wA/niT/AMKPUf8A4/QBq/8ACN6Hz/xJtM56/wCix8/pTh4f0ZV2jSdPC+gtk/wrlfE3h
zQPD3h3UtZvbvxO1tYW8lzIqeI9QLMEUnA/f9TjFeQ2XjKwk8J6lqky6m2pI1nHa6XH4o1dZI2uGIXzmkdQ
VxtO6MMDyM9CQD6IbQNIZdr6XZOv914FYfkRTD4a0XB2aXZxbsBjDEIywHYlcEj2PFeDvr8cUUulSWesf8J
Quvx6CqL4r1P7KWddwmLebu24ByuM12fw5tdK8VeGLzUL4+IrO7sLueyu4o/E2oyIJIThihMwJBGD074oA9
HHh7RRn/iUadycn/Rk5P5Uv/CP6NgD+yNOwOg+zJx+leJjxx8PzbPcIPiI0S2gv1YajqmHt921pR+/
+4p4LHA6YzW7DqHgu68Wjw9YXPjO9vMxCSSDXNRMcXmKHUtm4DY2kEkAgdyOaAPTX8OaG4w+jaaw9Daof6U
p8O6KwwdH04jOcG2Tr+VZP/CB6R/z+eJP/Cj1H/4/R/wgekf8/niT/wAKPUf/AI/QBqf8I1oXH/El0zjIH+
ix8Z69qcPDuiAYGj6b6f8AHqn+FZP/AAgekf8AP54k/wDCj1H/AOP0h8BaQQQL3xKM9x4j1Dj/AMj0AZXhP
xF8N/FMxg0CXQLi5Riv2fyEjlz0OEYAkcdQCKj8S6VpkXxL8EQpp1isckeoZUW684ij9vSvnDwh+zB4t1C6
367e2mi2yPwwbz5mAPBVVOB+LA+1e2r4ETQfEXg7RT4h8QXryQX6re3F5maEbI8+UcfL2GOeKAO78Rz+CvC
9r9q18aFp0WMqZ441Zv8AdGMsfYA1J4Zj8KeJtDtdX0Sw025066DNFKLRV3YJU8FQRypHPpXzr8Rf2Y9cub
ufUfD/AIjfV5n5MerORO3/AG15DH6ha9T+Dnw+8RaB8ONI07UfE2t6RdxCUyWNsllJHCWldsBngcnIIJ+Y8
k444oA9Ifw3opjdV0nTlLAjP2ZO/wCFZvhXwVpWiaBp9jPaW15dW8CRy3Mse9pXA+ZhuJIBbJ25wMmuIi14
3HxLPgq18beLZr5IXkkuUt9N8lGUBmj3fZclgGUkAcbgDzUGleJxfw+Lp38Y+NrO38MqHuzdWGnxOw2M/wA
qNahuinGQM5HrQB6kfD2ikDOkacQP+nZP8KU+H9H2kDS7ED2gUf0ry7wDrmoeLNTl06bxN4w0q/FlDqUUVx
Fpb+dbS/dcFbY4PTKnkZ+tXNW8Q6NpGryaXqfxb1e1v4n8uSKSLTwUbbuAY/ZMDI6ZPPQZNAHoY8O6RuJbT
4Hz2kG8fkciuP8AC2ufDbxXM8Ph250j7arkGO2H2W4znnGNrkcckcGsqTxDow0iy1D/AIWvrrWl8ZFtzHbW
LPJsOHwi2e8be5wMZHqK8A8Cfs0+J9dWC91PULLSdOkxJFKrefLIh5V1VSAARg8sDz0oA97+NOladby+Bo4
bG0RW8R2IbEQywM8YIPHOc85616YuhaUpyunWg5zxEBzXjPi/wkfCFp4E08a1rGr7fEFixk1G480ri5hGF4
4X5unNe8UAec/DjSrCXVvHe+zgPl+IXVfkxgfZbb/E12o0PTgcraqp5IIYjGfxrl/hoMav4/HH/IxOeP8Ar
0ta7mgDBtfCekW15eXQgeSa5ZWLSysxQKgUBCTlQME+uWbnmrf9h2ezZuvCuc4N7Mef+
+606KAMr+wbPnEmoLn+7qFwP5PSf2BZ4x52p/8Agzuf/jla1FAHBeLtFtY9f8DosuoEPrEindqE7HH2C8PB
L5Bz3HOOOnFdIfDliTkz6t/4Nbr/AOOVneMv+Rj8Cf8AYak/9N15XVUAZB8PWWQfO1Tj/qJ3P/xz3pR4fst
yky6k2Dna2o3DKfYgvgj2PFa1FAHAWGjWk3xT8RpvvI1TStNYLDezRgEy3oxhXGBgD5eg5IGSSdS28Ixtqt
3JqlzcX+mh1azs7i4eVIjtG4sGJ3Nu3MCScZ4xgYZpJz8VvE3tpGmf+jr6uuoAxl8N2KggT6t+Oq3R/nJQf
Dlkcfv9V4/6it1/8crZooAxv+Ecscg+fq3H/UVuv/jlH/COWP8Az31b/wAGt1/8crZooAyT4fsyuDNqZGc/
8hK5/wDjlMbw3p7fea/x6f2hcY/LfitmigDJ/wCEe0/cGIuyRyCbyY4/8f8Aeg+HtOJ5jn9f+PmX/wCKrWo
oAyT4e0xvvW7HjHMzn29f1p39g6bjH2bHO7iRhk+/PNalFAGYug6aq7Uttg/2XYfyPvTf+Ef00dIHXrwszj
r9GrVooAyW8Pacy7THPj2uZR/7NSf8I5puc7LnPr9rl/8Aiq16KAMv+wbHDAi5O4YJN3Ln893/AOqqlj4U0
62UvM13e3pUKb26uHecAY+6+R5Y45CbQTkkZJzv0UAZI8P2WADJqLADGH1G4Yfq9KdBssnEmoDPpqFwP5PW
rRQBkf8ACPWX/PbVO4/5Cdz3/wC2lKnh+zRgwm1MkcYbUrlh+IMmDWtRQByXgeJIde8dRxjCDWo8DOf+YfZ
11tcr4N/5GPx3/wBhqP8A9N1nXVUAFFFFAHjF98bDp10bO/0dUvIfEL6TdIs5IjtkKA3X3en71OD69atz/F
25/wCEJvddstDF1cS62+j6PaLOc3wV8eYTt+XhZDjkDb15zW3q3wl8N6r4j8Sa3d/bDd67YmwuFDrsjUqg3
xjb8r/u0OSSMjpTIvhB4ZGmeGtNuhe3enaDHMttbTyLskeQ5aSTaoJfOcEEAZPHNAGL4k+K+p2nw50bxpoe
i2N9pV7DEZ1lvWjkhmdwmwAIQwDZBOR06VJ4j8eeOdA1PQLC88L6G1xrNwbWDZqshVZACfmPk8DAHNay/CT
QY/BF74TiutTj0e4v/t6RrKm63O9XEcZKcRgr0OTyea6TxJ4UsfEGraDqF7LcpNot0bu3WJlCs5Xbh8g5GP
QigDztPi5qDeO5PDl1Z6Lpl1b3EVu9tqF5LFNdbgNzwN5ewrknaCctjtmvZK4XWPhrp2t6tFd6xq2tXtnFe
C+j06adGt0lByMfJ5gUH+Hft9q7qgDzTQtRsdO+MHj5766it91tpagyOBnCTnipPGOt6bceLfBE0Go2zRJf
TbiGz/yxK8cerj061a8I5/4Wz8QCenlaaB/36krQ8YBv+Ej8NOrMNkzE4PGC8S8/99UAao8TaMULLfxFQcE
gE/0p3/CRaX/z8k9BxG56/hWtRQBk/wDCRaZ/z3kP0gk/
+Jpq+JdMZdyyzke1rL/8TWxRQBz+r3mja3pF3pt+s81lewtBLH9mlG5HGCPu5HBrz6D4aeDF0nULK7vdevZ
LuK3gF3cBzPbxwY8lY2WMAbcDkgk9ya9hooA8nPgTwk2lPbPqOtvqD6kutf2qVP2oXKjAkB8rZgDjbs24PS
uj8J6d4f8ADHh2TRtOlv3imeWWaeeGRpZpJCS7s2wDcc+gHHSu1ooA8lg+HfhJNOSyS+1wxDQ5PD4PlEt9n
eQSFv8AVffyOvTHanyeA/Cs/ibS9burzXLiXTXiltopLY7EaFQqneIRJt4B279pPbtXq9FAGUdfsAQC1zz/
ANOkuP8A0GhtfsFbaWuc/wDXpL/8TWrRQBkDxFphH+ul/wDAeT/4ml/4SLTN20zyA+8Eg/8AZa1qKAMhfEe
lMQPtYBPQFGH8xXM69qumy/EDwpcfaotsMF8SSGyMrGPT2rvawNSyfGOibSflguNwz1BCdvqKALA8TaMSB/
aMHPqcUv8AwkmjYB/tK1AJxkyAc/5Na1FAHjmn+BPCWnfEWw8SaZ4llgW0E7SWL3kjiSSVtzNuMnyqSSSm3
DHk0zTPCNn9v8aPrfjjSL2z8UwmK8hgt1t2jYR+WrI5mYcKTxg5OOnSvZqKAPKvh54c0rwvrMmq6n4x07Vr
4adBpcDL5dusdtF90Eb23MSAS2R7CquqeENFuteu9Sbxfp0f2nxBY64I/kOPs6hfKz5nO7Gd2OPQ16/RQB4
Lq3wz0nULEWcPjTSo5vtt7epP9nBlj+0OG/dOk6sCvTqVbjK8V6zpWs6Np2lWlm2uxXZtYUhaeecPJIVUDe
57scZJ9c10NFAHj/xj1fTrq88FyQXtvIseuWjNhskAXVvk/TBr0pfEejv93Ubc/Rq4f4z5+3+DcEgf2zZ5x
3/022r06gDzT4ea9pVvrHjoTX8CeZr7yJluq/ZLYZ/MH8q7VfEejMARqdrz6yAVz/w4YvrPj4kkn/hIWHPt
Z2ortqAMv/hIdH76rYj/AHp1H9aVvEGjLjdq+nDPrcp/jWnRQBlDxHoZGRrOmkdMi6T/ABp66/o7EBdW08k
8AC5Tn9a0qKAOG8X6tp8viXwL5V/ZuF1eVmKzKdo/s+7569OR+YrqTrelD/mJ2P8A4EJ/jWD40b/iq/AK46
6vMf8Ayn3f+NddQBn/ANtaURkanY49ftCf40p1nSwcHUrLOM/69en51fooA4PS9TsIvip4nklvrRI20nTNr
GZQD+8vO+fcfmK6061pa9dSsh35nT/Gua0J93xb8XjOdul6WPp894f612lAGb/bukc/8TWw46/6QnH60p13
SP8AoKWHP/Twn+NaNFAGb/b+j/L/AMTbT+eR/pKc9vWmnxFoijJ1jTQPU3Sf41qUUAZJ8SaHnH9s6Zk9vtU
f+NDeJdCUZbWtMAPOTdR/41rUUAZS+I9Db7us6afpdJ/jSjxDopOBq+nE9cfaU/xrUooAy/8AhItF3Ef2tY
ZHb7Qn+NJ/wkei7c/2rY46589f8a1aKAMoeI9EJAGrWGT0/fr/AI04+INHGM6pYjJwMzr/AI1p0UAZI8SaI
SB/a+ngnpm4QZ/Wl/4SPRNwX+2dNz6fak/xrVooAyf+El0LGf7a0zH/AF9R/wCNH/CS6EBn+2tMx/19R/41
rUUAZf8AwkWi4J/tjTsDqftScfrS/wDCQaMQSNX0/A6n7Sn+NadFAGb/AG9o/wD0FbDpu/4+E6evX3px1zS
RnOqWIx1/0hOP1rQooA5DwLNHPr3juSGRJUOtoAyMGHGn2YIyPQjFdfXJeCXL+IPHhIx/xO0H5afZiutoAK
KKKACiuLX4k6FLqdxaWseqXcdvcmzmvLbT5ZbdJx1jMiqRnJA9MkDNUNP+L3hjULy5tLOPXJbm1UtPGukXJ
aLCl8MNnBIBwD17UAeh0Vwdp8WPCdzpuj6h9ruobPV7z7DZSz2ksSzSccgso+XLY3/dyCM8Gtvw54x0TxJr
OuaXo92bi80WVYL1QjARuSwwCRhuUYHHpQB0NFc1d+N9AtPHFn4RnvduvXcJnit9jEFcMeWxgHCMcE549xT
7HxnoN/4xuvC9lfpPrVpbm5ngjUkRKGVSGboGyy8ZzzQBi+ElI+K3j854Kadxnv5T1p+LCBrWkAnB4Iz0/w
CPq0H9f1rn9A1CCw+LHj3zkun3ppwH2e1lmxiF+pRSAfb6eta+u3ceoXkc8cd5FbWNs9zLLNZyxBSk0EigF
1GciJunpzjigDsqKKq3mo2Vlj7ZeW1vn/nrKqfzNAFqisdvE+gJnfrmlrjrm7jGP1pB4p0Jv9Vq9lMemIZh
If8Ax3NAGzRWUniDT3YKjXLkkABbSU9fotKNctCD+51Hj/qHXH/xHtQBqUVjv4iskIBg1Xn00u6P8o6YfE1
jgYt9XOf+oTdf/G6ANuisI+KLTa5FjrTFTjA0u4GR6jKf/Xpq+KLVgpFhrXzHHOmTjH1+X8c/14oA36Kw28
TWqdbLWPbGmTnP5J/OlPiaxAB+z6uR/wBgm6/+N0AbdFY3/CSWPH7jVuu3/kFXX/xv9aaviawbOINX49dJu
x/7ToA26xNUkWLXtPkcEBVK7jwMuyqFye5J+vFPHiKyK58jVcf9gu5/+N1kaxc/2lL5tpFdosc9gN9xbSQj
/j7XcBvUZ4B6dOPWgDr6KKq3Oo2VqwW5vLaFjwBJKqk/maALVFZZ8RaIGKnWNNDA4IN0mc4z6+lN/wCEk0P
bu/tjTiuM5Fyh4/OgDWorLXxBpL5MWoW8gHJaNt4X6kcDPbPWga/pjOFS5Dsf7qM2PrgcfjQBqUVmDXdPK7
llkdcZykEjD9F6+1O/tm17R3x69LGY/wDslAHD/F5N+oeFufualaSYx/1EbJf/AGavSa8v+Jt5HcX+hzpHc
pBDcWhkkmt5IlXOq6cQMso7K35V6hQBxPw4/wCQz4+/7GBv/SO1rtq4LwFd2tnrfj1bq7t4i3iAsN8qjrZ2
vrXUv4i0RHKPrGmq442m6QH8s0AalFZI8S6ETga1ph4zxdJ/jTh4g0hidmpWr+6SBh+lAGpRWZ/b2mYz9si
P0yaedYsskeY5I+8BE5I9M8cUAc941/5HD4f8j/kK3HH/AG4XVdjXBeM9Qtn8X/D+RZGKjU7lidjdBp9zk9
Pcf5zXXrq1o5ba0p29cQPxxn09xQBeorOOtWQIDNOCembeQf8AstKdYtASP9JyOCBay5zjOPu0Acv4dIPxf
8a4xxp2l/zu67ivOtA1G2i+LnjJ283Emn6WBtgckH/Sj82F4OCOtduuqQMCRHefjaSj+a0AXqKof2rb5x5d
71I/48pu3/AaZ/
bNt8v7q/55H+gT/wDxHFAGlRWX/btpz+51HgZ/5B1x/wDEU0a/Zn/ljqf/AILLn/43QBrUVkHxDZDH7nVOR
n/kF3P/AMbo/wCEhss48jVM/wDYMuf/AI3QBr0VjjxFZnpBquPfTLkf+06X/hIbPn9xqnBx/wAgy5/+N0Aa
9FYx8RWm0FbXVmJONv8AZtwD9eUo/wCEitO9rquOP+Ybcf8AxFAGzRWKPEdpj/j01YP/AHf7NuP57MfrSr4
htWzi11XIOOdOnGff7lAGzRWOniG1bJNtqqgeumz8/klA8RWX/PDVR/3C7n/43QBsUVknxBZgZMOp4/7Blz
/8bpD4gs/
+eOp+v/IMuf8A43QBr0Vkf8JBZ7tvk6nn/sGXOPz8upP7btdobytRwf8AqH3Gfy2UAadFZg1q1LYEWoZzj/
kHz+n+5Tk1i2dSRFfjBxzYzj+aUAYHgM517x4c5/4noH/kjaV2FcR8Np1udX8eyIxZf+EgZeVKniztQRgjP
GMV29ABRRRQB4xD8LdZX4jW/iCz/snQ0XUTeXdxpd3ch7+LJPlyW7DywWyNzBj3OOa6PSvCOtaTr3xD1S2b
Tpn194XsY5JnQLsiKHzSEO3k5G3dXolFAHg9h8HNZvfBPg7w34kk0r7Nos90J3tLiRmkhlicK6boxiRXcnB
4G0HJPFdd8LPhzL4F8U+LLqOeKbTNTjsFtiXLTs0MTLK83ygbndi2QTnJ6dK9KooA8K174SeKtR13UPFEGu
afHr51qLUbS3ZT5Aih+SJHl2bx+6LAgKVJP411g8MeKP8Ahdv/AAlxj0X+yf7L/sjy/tcvn+X53m+Zt8rbu
zxt3Y757V6TRQBwXg/n4q/ELnPGnDHp+4au2v7SDULC5s7yPzLa4jaGVMkbkYEEZHPIJ6VxPhL918TPiFNI
GCM9ioO0nOLbJ6detdmb+3ELS72Mas6lgjHlN24dO2xv8kZAM6Dw5bsEOrXV5rEiZ2m+ZSmP+uSKsZI5wxX
dyeau2Okabp//AB4afZ2vX/UwKnX6CrJnQZ+9wQPunqTgfrUcd7E8nl/OJRwy7CdpwpwTjH8a/r6HABZoql
DqlpNGXjlJQbeSjAchSOo9HX8/Y4SfU4IbiOLOWZiHzxsG2Q59/wDVsOPrQBeorOfWtOSSVJLpEMQLPuyAA
DID+sT/AJfSntq+nKMtf2gG7ZzMv3s4x160AXqKw4/FOkM6Br23VZdrRN5gO9T5eCfTmVRg/WrLa/pCqxOp
2Xy9R5656bvX0INAGnRWBe+LdHt7KaeK+tZmQSBEEyjeyCQlc9B/qn5PHFXP7f0jzCh1Oy3cf8t17lgO/qr
flQBp0VQTWdOknMMd7bvJnG1XB7qP5uv50JqcEphminiNm8JlLk4I+4V6+ofPTuKAL9FVpb62ilaKSUB1UM
Rgnghj/wCyN+VEV9bSkBJQSZGiAII+ZSwI590b8qALNVtSs4tRsLizuN3lTIUYodrDPcHsR1B7EZpkmp2sU
sccsgVpMeXgE7gSi546cyIOfXPSiPU7KRXZbmPahVWJOANwUj9HXn3oApQ+HbVlU6pLcatKF2l75gytz18p
QsQPbIQHFaFlp9nYJtsbS3tlxjEMSoMfgKgutYtIEbEqvJhtqZxuYBzjJ4H+qfk8fLUsepWUhYLdQ5UsCCw
BGGKnr7gigC3RVFNWsXWFluFImCtHgH5gxQD/ANGJ/wB9CoP7dsmvY4I54SpDb3aUJsIVGAweTkODx0oA1a
KpHVbERPJ9pj2Ju3HPTbvz/wCi3/75NTG7hEoj3/OSFAAJ5JYf+yt+VAE9FVo7tWmeN0eMg4QsPvjC8j05c
DnnINEN7BMoaN2IOP4COoUjt/tr+fsaAOG+MtlFqWjWdjcFxDc3dlA5RsEK2o2QOPfB611EPh+KTL6xcz6r
Keq3BAhAxjAiXCY64LBm5+8eK5H44TtF4XheF5I3+02bJIgOVYahaEHPY8d/Su9Go2pkdPN+ZMlgVPHLj0/
6Zv8Al7igDj/hnbQW+s+PBBBBEF14oPKjCAKLO1wOPr+eTXdgYGB0rhvh1cRPq/j51bCjxEY+Rj5haWq/zF
dQ2r24ntlG4xTpuEuCACWjCjHXnzR9Mc0AaNFRRXEUpYRvnaQDxjqAf5MPzqF9StEDFpcbSwPynjbvz2/6Z
v8Al7igC3RUccocsMEMDyPbJAP6VF9ut8Z3tjcq/cbq23Hb/bX8/Y0Acl43Yjx18O1ycHUro47cWFx/jXbV
wnjWTzPGnw5niRniOoXTAhcZzYXBA59RXZy3sESytIzARKXf5GOAN3tz91v8kUAWKKYsqOm5SSu4p0PUHH8
6h+2J9rEASRjglmCnCkbOD9d4P4HPSgDi/DDZ+MXjseljpQ/9Ka72uA8Jusnxc8bzRg+XLp+kurbSN4IucH
/PpXczXEUIzIxAGT90nsT/ACU/5IoAmoqtbXPmeaso2yIWJGD93cwU/iFp8l1DGQHYglgv3T1JUD9WX8/rQ
BNRVVL6GRUMLF9+0gAY4O3nn2dTTp7yCCNpJZNqKpcnBPABP8lP5UAWKKqnULXJBlwQSDlT23Z7f7Dfl9KH
vY1uhExXaRjfuH3twXbjr1IoAtUVSg1WynjV4rhWVtuDg87ghX8/MT/vqnSalZxxiR7mIKV3/eyduM5x16C
gC3RVBdVtcSebKsbIWyM54BcZyPaNzjtipzfWoODcRZ3bcbxnOcY/PigCxRVA6taM6RwyrJIzABQccEpk56
cCRDjvmpkvrV4w63ERUjP3u2M/yoAs0VTfUrREZmm4UsD8pJG3fnjH+w/5U0XKrqMivIfLZEVBzjcDIW/Rf
0oAvUUzzU3hc/MckDHoQD/MVF9sg2K+87WKgHaerbcdv9pf8g0AWKKit5fNt4pWRkLoH2MOVyOh96c8qI6o
xO5jxhSexP8AQ0APoqPzlONoZgWKkhemM5/lj8qV5FT72RkgdD1JA/qKAOF+Fj79U+IB/wCpllHX0trYf0r
va8/+EgIuvHjEY3eJ7o9MZxFCP6V6BQAUUUUAFFFFABRRRQAUUUUAcje/DTwVf39xe3vhfSLi7uJGlllltl
ZncnJJJ7kmmp8MfAqdPB/h8/XT4j/Na7CigDlF+G/gdQAPBvhvpjnTIT/7LS/8K48D/wDQm+G//BXB/wDE1
1VFAHK/8K48D/8AQm+G/wDwVwf/ABNH/CuPA/8A0Jvhv/wVwf8AxNdVRQByv/CuPA//AEJvhv8A8FcH/wAT
QPhz4IGceDvDYzx/yC4P/ia6qigDlx8PPBQ6eD/Dnr/yDIP/AIn3NH/CvPBec/8ACIeHc/8AYMg/
+JrqKKAOX/4V54Kzn/hD/Dmemf7Mg/8AiaQfDrwSBgeDvDgH/YMg/wDia6migDlf+FceB/8AoTfDf/grg/8
AiaP+FceB/wDoTfDf/grg/wDia6qigDlf+FceB/8AoTfDf/grg/8AiaP+FceB/wDoTfDf/grg/wDia6qigD
lf+FceB/8AoTfDf/grg/8AiaP+FceB/wDoTfDf/grg/wDia6qigDlf+FceB/8AoTfDf/grg/8AiaP+FceB/
wDoTfDf/grg/wDia6qigDlf+FceB/8AoTfDf/grg/8AiaP+FceB/wDoTfDf/grg/wDia6qigDlf+FceB/8A
oTfDf/grg/8AiaP+FceB/wDoTfDf/grg/wDia6qigDlf+FceB/8AoTfDf/grg/8AiaP+FceB/wDoTfDf/gr
g/wDia6qigDlf+FceB/8AoTfDf/grg/8AiaP+FceB/wDoTfDf/grg/wDia6qigDlf+FceB/8AoTfDf/grg/
8AiaP+FceB/wDoTfDf/grg/wDia6qigDlf+FceB/8AoTfDf/grg/8AiaP+FceB/wDoTfDf/grg/wDia6qig
Dlf+FceB/8AoTfDf/grg/8AiaP+FceB/wDoTfDf/grg/wDia6qigDk3+G3gdxg+DvDn4aZCP5LUbfDHwM3X
wjoX4WMf+FdhRQBxr/C7wK4AbwlonHTFmg9fb3NKvwv8DKSR4T0XJ6/6In+HtXY0UAcYfhb4EYc+ENDPbmz
T/CpE+GPgVOng7w+e/OnxH+a+1dfRQByY+G3gcYx4O8OceumQn/2Wnf8ACuPA/wD0Jvhv/wAFcH/xNdVRQB
yv/CuPA/8A0Jvhv/wVwf8AxNH/AArjwP8A9Cb4b/8ABXB/8TXVUUAcr/wrjwP/ANCb4b/8FcH/AMTR/wAK4
8D/APQm+G//AAVwf/E11VFAHK/8K48D/wDQm+G//BXB/wDE0H4c+CCcnwb4bz/2C4P/AImuqooA5YfDvwSB
geD/AA4B1x/ZkH/xNIPhz4IHTwd4bHf/AJBcH/xNdVRQByv/AArnwRjH/CG+G8f9guD/AOJo/wCFceB/
+hN8N/8Agrg/+JrqqKAOV/4Vx4H/AOhN8N/+CuD/AOJo/wCFceB/+hN8N/8Agrg/
+JrqqKAOV/4Vx4H/AOhN8N/+CuD/AOJpD8OPA5GP+EN8N/8Agrg/
+Jrq6KAOQPwx8Ckg/wDCH+HwRzxYRD/2Wmt8L/A5GP8AhFdIA6cWyj+X1NdjRQBxf/CrPA4GB4Z04D2jx/W
kPwr8EEYPhyyxnPRuvr1/zgeldrRQBl+HfD+leG7F7PQrGGytXkaZo4hwztjLHPUnA/KtSiigD//Z);\">"
,
" </div>",
" <div class=\"lgnd\">",
" The tracing shows three surface ECG leads (I, II, V1) and intracardiac
recordings from the high right atrium (HRA), bundle of His (HIS), right ventricular
apex (RVA), and coronary sinus (CS). During atrial pacing (S1) at a cycle length of
600 ms (100 beats per minute); the AH interval is 120 ms. An atrial premature beat
(S2) is added at a coupling cyle of 410 ms; this results in a prolongation of the
PR interval and increase in the AH interval to 242 ms, which represents a 60 ms
increase compared to the AH when a premature beat was added with a coupling
interval of 420 ms. This represents a \"jump\" due to a shift of AV nodal
conduction from the fast to slow AV nodal pathway. Since the fast pathway has time
to recover, there is retrograde VA conduction via the fast pathway, resulting in
the occurrence of a retrograde His depolarization (HIS \"A\") and an atrial echo
beat at the CS os area (CS 10-9).",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Courtesy of Martin Burke, DO.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6184=[""].join("\n");
var outline_f6_2_6184=null;
var title_f6_2_6185="Normal neutrophil development and kinetics";
var content_f6_2_6185=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"4\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Normal neutrophil development and kinetics",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/2/6185/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6185/contributors\">",
" Thomas D Coates, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/2/6185/contributors\">",
" Section Editors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6185/contributors\">",
" E Richard Stiehm, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6185/contributors\">",
" Laurence A Boxer, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/2/6185/contributors\">",
" Deputy Editors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6185/contributors\">",
" Jennifer S Tirnauer, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6185/contributors\">",
" Elizabeth TePas, MD, MS",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?6/2/6185/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Jan 7, 2013.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;The circulating blood cells are formed in bone marrow
through a process called hematopoiesis. The bone marrow has an enormous production
capacity; it is estimated that 10",
" ^{",
" 10",
"}",
" erythrocytes and 10",
" ^{",
" 8",
"}",
" to 10",
" ^{",
" 9",
"}",
" leukocytes are produced per hour in the steady state. Furthermore, while cell
numbers are maintained within fairly narrow limits, they can be greatly amplified
on demand.",
" </p>",
" <p>",
" These huge cell numbers are immediate descendants of maturing precursors that
arise from a smaller pool of progenitors. The progenitors in turn arise from an
even smaller pool of hematopoietic stem cells that are thought to be mostly in a
resting or non-dividing state and have the capacity to self-renew (and thus
maintain their numbers).",
" </p>",
" <p>",
" Hematopoietic stem cells are multipotent and have the capacity to
differentiate into the cells of all 10 blood lineages &mdash; erythrocytes,
platelets, neutrophils, eosinophils, basophils, monocytes, T and B lymphocytes,
natural killer cells, and dendritic cells (",
" <a class=\"graphic graphic_algorithm graphicRef52024 \" href=\"UTD.htm?
34/9/34968\">",
" algorithm 1",
" </a>",
" )&nbsp;[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/1\">",
" 1",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/34/25129?
source=see_link\">",
" \"Overview of hematopoiesis and stem cell function\"",
" </a>",
" .) The multipotent stem cell can give rise to the myeloid stem cell, also
referred to as CFU-GEMM because it is the precursor to lineage-specific stem cells
for Granulocytes, Erythrocytes, Monocytes, and Megakaryocytes. CFU stands for
colony forming units that grow as pure colonies of 50 to 100 cells after 7 to 14
days in semisolid medium at 37&ordm;C.",
" </p>",
" <p>",
" The CFU-GEMM can be identified using CD34 and HLA-DR as markers. Some human
myeloid stem cells express an additional marker, ie, CD64, which identifies a
specific stem cell dedicated to granulocyte and monocyte development. This CD34,
HLA-DR, and CD-64 positive stem cell is called CFU-GM because colonies of mature
Granulocytes and",
" <span class=\"nowrap\">",
" Monocytes/Macrophages",
" </span>",
" form when the stem cell is cultured in semisolid medium with appropriate
growth factors [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/2,3\">",
" 2,3",
" </a>",
" ]. The major growth factors required for maturing CFU-GEMM into CFU-GM are
Steel factor (also called stem cell factor or c-kit ligand), interleukin (IL)-3,
IL-6 (induced by IL-3), Flt3 ligand, and granulocyte-macrophage colony-stimulating
factor (GM-CSF) (",
" <a class=\"graphic graphic_algorithm graphicRef52024 \" href=\"UTD.htm?
34/9/34968\">",
" algorithm 1",
" </a>",
" ). GM-CSF receptor expression begins in immature precursor cells and is
progressively increased during differentiation into mature granulocytes and
macrophages [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p>",
" Neutrophil development and kinetics will be reviewed here. The factors
responsible for the regulation of myelopoiesis are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/44/6858?
source=see_link\">",
" \"Regulation of myelopoiesis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" MORPHOLOGY OF DEVELOPING NEUTROPHILS",
" </span>",
" &nbsp;&mdash;&nbsp;The six stages of polymorphonuclear neutrophil (PMN)
development are characterized by six morphological criteria of developing myeloid
cells, as seen by light microscopy. These criteria are: relative size, nuclear
volume, chromatin density, prominence of nucleoli, granule number, and cytoplasmic
staining. The ultrastructure of granulocytes is of biologic importance but
contributes little to identifying the stages of development based upon morphologic
criteria utilizing Wright-Giemsa polychrome stained bone marrow smear. In general,
cell maturation is accompanied by reduction in cell size, diminished cell volume,
increased chromatin condensation of the nucleus, loss of nuclear nucleoli,
appearance of cytoplasmic granules, and change in cytoplasmic basophilia (",
" <a class=\"graphic graphic_figure graphicRef75855 \" href=\"UTD.htm?
30/58/31651\">",
" figure 1",
" </a>",
" ).",
" </p>",
" <p>",
" The factors determining the regulation of myeloid differentiation through
these developmental stages continue to be a focus of research. This process is
regulated by a wide array of transcriptional regulatory proteins leading to a
biochemical and morphological progression in the same manner as that occurring in
erythropoiesis [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/5-9\">",
" 5-9",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/10/20650?
source=see_link\">",
" \"Regulation of erythropoiesis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h2\">",
" Myeloblast stage",
" </span>",
" &nbsp;&mdash;&nbsp;The myeloblast is the earliest myeloid precursor
recognizable with the light microscope in the bone marrow. The size is medium (15
to 20 microns in diameter), the nucleus is large and round with finely granular
chromatin, nucleoli are present, granules are usually absent by light microscopy,
and cytoplasm is scanty (",
" <a class=\"graphic graphic_picture graphicRef74014 \" href=\"UTD.htm?
37/11/38067\">",
" picture 1",
" </a>",
" ). Electron microscopy reveals numerous round or oval mitochondria (&lt;1
micron in diameter), Golgi apparatus with a centriole, vesicles and sacs, many free
cytoplasmic ribosomes and free polyribosomes.",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Promyelocyte stage",
" </span>",
" &nbsp;&mdash;&nbsp;Promyelocytes are larger than myeloblasts and myelocytes
(&gt;20 microns). The nucleus, nuclear chromatin, and nucleoli resemble myeloblasts
but the cardinal feature is the presence of many violet stained granules with
either a dense or coarse pattern often obscuring other cell landmarks (",
" <a class=\"graphic graphic_picture graphicRef73480 \" href=\"UTD.htm?
21/25/21908\">",
" picture 2",
" </a>",
" ). These so-called azurophilic or primary granules measure 0.8 microns in
diameter and are homogeneous, dense, and round to ovoid in shape and are bounded by
a unit membrane.",
" </p>",
" <p>",
" Azurophilic granules are made primarily by promyelocytes and contain a variety
of bactericidal cationic proteins, proteolytic enzymes, and myeloperoxidase (often
used as a marker for azurophilic granules) (",
" <a class=\"graphic graphic_table graphicRef57400 \" href=\"UTD.htm?
41/7/42109\">",
" table 1",
" </a>",
" )&nbsp;[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/10-12\">",
" 10-12",
" </a>",
" ]; myeloperoxidase synthesis can also be demonstrated in myeloblasts [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/13\">",
" 13",
" </a>",
" ]. Electron microscopy has shown that the prototypic protein myeloperoxidase
is synthesized and packaged into storage granules by the pathway defined for other
secretory proteins, ie, through endoplasmic reticulum to Golgi complex via vesicles
to granules.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Myelocyte stage",
" </span>",
" &nbsp;&mdash;&nbsp;The myelocyte is the last myeloid precursor capable of
mitosis. Three cell divisions take place in the myelocyte pool; with each division,
the cells change in size, shape, and color. Myelocyte progeny are progressively
smaller, being reduced in diameter from &gt;20 microns to 14 microns. During
myelocyte development, specific (or secondary) granules are synthesized, while the
primary azurophilic granules are distributed throughout the myelocyte pool [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/13\">",
" 13",
" </a>",
" ].",
" </p>",
" <p>",
" Specific granules are a marker of commitment to terminal myeloid
differentiation [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/5\">",
" 5",
" </a>",
" ]. These granules are smaller (0.5 microns), more numerous, and less dense
than primary azurophilic granules, and are difficult to see by light microscopy;
they fill the cytosol with proteins that stain pale pink or lilac. They contain a
variety of adhesive proteins including lactoferrin (often used as a marker for
these granules) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/10\">",
" 10",
" </a>",
" ], the beta 2 integrin",
" <span class=\"nowrap\">",
" CD11/CD18,",
" </span>",
" the cytochrome",
" <span class=\"nowrap\">",
" b/gp91",
" ^{",
" phox",
"}",
" </span>",
" component of the NADPH oxidase, binding protein for cobalamin, and unique PMN
marker antigens (",
" <a class=\"graphic graphic_table graphicRef57400 \" href=\"UTD.htm?
41/7/42109\">",
" table 1",
" </a>",
" )&nbsp;[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/11,12\">",
" 11,12",
" </a>",
" ].",
" </p>",
" <p>",
" As the myelocyte divides and matures, the nucleus becomes smaller and
irregularly round, nuclear chromatin becomes coarse and clumped, and nucleoli are
sparse to absent (",
" <a class=\"graphic graphic_picture graphicRef54089 \" href=\"UTD.htm?
1/7/1138\">",
" picture 3",
" </a>",
" ). A pink region where specific granules are beginning to form is evident on
the flattened side of the nucleus of smaller, more mature myelocytes. The nuclear
to cytoplasmic ratio is reduced.",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h2\">",
" Metamyelocyte stage",
" </span>",
" &nbsp;&mdash;&nbsp;Metamyelocytes are slightly smaller than myelocytes. During
metamyelocyte development, the cytoplasm resembles that of the mature PMN and band
forms and is uniformly pink; granules are finely dispersed throughout the cytoplasm
(",
" <a class=\"graphic graphic_picture graphicRef59197 \" href=\"UTD.htm?
25/60/26563\">",
" picture 4",
" </a>",
" ). The nucleus is indented like a kidney bean and the nuclear chromatin is
coarse, clumped, and condensed peripherally.",
" </p>",
" <p>",
" The metamyelocyte cannot divide, and further maturation consists predominantly
of nuclear elongation and segmentation. The cell lacks nucleoli, polyribosomes, and
endoplasmic reticulum necessary for ongoing protein synthesis.",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h2\">",
" Band form",
" </span>",
" &nbsp;&mdash;&nbsp;The band form is also called the stab form or juvenile form
because the nucleus is nonsegmented and elongated, taking the shape of a horseshoe
(",
" <a class=\"graphic graphic_picture graphicRef82140 \" href=\"UTD.htm?
16/42/17060\">",
" picture 5",
" </a>",
" ). No nuclear lobulations are evident, although constrictions may be visible.
The nuclear chromatin is aggregated into evenly arranged clumps. The cytoplasm is
like that of the mature PMN with pink staining and fine azure bluish granules; the
proportion of azurophilic primary to specific secondary granules based upon
cytohistochemistry is about 1:2 [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/14\">",
" 14",
" </a>",
" ]. These cells also contain gelatinase or tertiary granules, which are a
marker of terminal neutrophil differentiation (see below) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/13\">",
" 13",
" </a>",
" ].",
" </p>",
" <p>",
" Band forms are fully functional phagocytes and normally comprise 3 to 5
percent of the differential count. They should be included when calculating (",
" <a class=\"calc calc_professional\" href=\"UTD.htm?12/1/12305?
source=see_link\">",
" calculator 1",
" </a>",
" ) the absolute neutrophil count (ANC).",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h2\">",
" Polymorphonuclear neutrophil",
" </span>",
" &nbsp;&mdash;&nbsp;The PMN or segmented neutrophil is the end-stage of full
maturation of the granulocyte. The mature PMN is of uniform size (13 microns in
diameter). The nucleus is segmented into two to five (mean equals three) lobes
connected by thin chromatin strands (",
" <a class=\"graphic graphic_picture graphicRef60666 \" href=\"UTD.htm?
30/37/31316\">",
" picture 6",
" </a>",
" ). The nuclear chromatin is coarse, clumped and stains deep purple with
Wright-Giemsa. Five to 10 percent of PMN contain nuclear irregularities such as
nicks, appendices, fibrillar bodies and bridges. In addition, approximately 3
percent of PMN in normal females have a drumstick oval mass of dense chromatin 1.5
micron in size called a Barr body attached to one of the lobes by a slender
filament [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/15\">",
" 15",
" </a>",
" ].",
" </p>",
" <p>",
" The cytoplasm contains fine azure bluish granules and predominant specific
secondary granules, which are finely dispersed and stain the cytoplasm faintly
pink. The granules show considerable heterogeneity in size and density as seen by
electron microscopy (",
" <a class=\"graphic graphic_picture graphicRef74658 \" href=\"UTD.htm?
3/28/3524\">",
" picture 7",
" </a>",
" ). Peroxidase staining reveals both smaller peroxidase-negative granules
(secondary specific granules, tertiary gelatinase granules) and larger dense
peroxidase-positive granules (primary granules). The Golgi region of the PMN is
small compared with the promyelocyte and myelocyte and is no longer forming
granules; the rough endoplasmic reticulum and mitochondria are scant. PMN contain
an abundance of glycogen, as the cell depends on anaerobic glycolysis for the
generation of ATP.",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h1\">",
" REGULATION OF GRANULOCYTE DIFFERENTIATION",
" </span>",
" &nbsp;&mdash;&nbsp;Genomic studies using microarray technology have uncovered
transcriptional gene expression patterns from highly enriched populations of
myeloblasts, promyelocytes, myelocytes, metamyelocytes, band cells, and neutrophils
from human bone marrow and neutrophils from peripheral blood [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/8\">",
" 8",
" </a>",
" ]. Gene expression was profiled employing over 44,000 probe sets including
almost 11,000 probe sets for 6700 differentially regulated genes. These
differentially regulated genes were assigned to four functional categories of cell
cycle, apoptosis, receptors, and receptor ligands.",
" </p>",
" <p>",
" Flow cytometry analysis demonstrated an abrupt decrease in proliferation at
the promyelocyte to myelocyte transition coincident with a marked decrease in pro-
proliferative genes, including E2F target genes and E2F-activity promoting kinases
of the CDK family. The transcription factors of the",
" <span class=\"nowrap\">",
" C/EBP",
" </span>",
" family repress E2F-mediated transcription and remained expressed, suggesting a
mechanism for cell cycle exit.",
" </p>",
" <p>",
" Expression patterns for apoptosis-related genes indicated death control
through the p53-dependent pathway in proliferating promyelocytes and through H1.2
death receptor pathways in bone marrow neutrophils.",
" </p>",
" <p>",
" Effector proteins critical for host defense were expressed successively
throughout granulocyte differentiation, whereas receptors and receptor ligands
essential for the host defense program were terminally upregulated in bone marrow
neutrophils. The upregulation of ligand-receptor pairs, which are defined inducers
as well as target genes of nuclear factor-kB (NF-kB) suggests a constitutive
activation of NF-kB in bone marrow neutrophils by autocrine loops.",
" </p>",
" <p>",
" Overall, these results define a granulocyte differentiation model regulated by
a highly coordinated program, allowing granulocyte differentiation before bone
marrow neutrophils acquire responsiveness toward stimuli activated during
inflammation or infection [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/6,8,9\">",
" 6,8,9",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h1\">",
" CONTENT OF PMN GRANULES",
" </span>",
" &nbsp;&mdash;&nbsp;PMN contain three subsets of granules (azurophilic,
specific, and gelatinase) and one group of secretory vesicles identified by marker
enzymes or other proteins present in the granule matrix or membranes of granules
and vesicles (",
" <a class=\"graphic graphic_table graphicRef57400 \" href=\"UTD.htm?
41/7/42109\">",
" table 1",
" </a>",
" ). Hepatocyte growth factor has been identified in specific and getatinase
granules as well as in secretory vesicles of PMN.",
" </p>",
" <p>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/16\">",
" 16",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h2\">",
" Azurophilic granules",
" </span>",
" &nbsp;&mdash;&nbsp;There are myeloperoxidase-positive azurophil granules in
promyelocytes and in all further differentiated stages of PMN. The matrix of
azurophil granules contains microbicidal proteins and acid hydrolases involved in
oxidative and nonoxidative killing of bacteria and fungi. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/31/6650?
source=see_link\">",
" \"Neutrophil functions other than movement\"",
" </a>",
" .) Azurophil granule membranes contain receptors and proteins for signal
transduction.",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h2\">",
" Specific granules",
" </span>",
" &nbsp;&mdash;&nbsp;Lactoferrin is localized to specific granules and serves as
a convenient marker of these granules [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/10,13\">",
" 10,13",
" </a>",
" ]. Specific granule matrix contains hydrolases distinct from those in the
azurophil granules and vitamin B12 binding protein. Specific granule membranes
contain chemotactic, opsonic and adhesion protein receptors and the cytochrome",
" <span class=\"nowrap\">",
" b/gp91",
" ^{",
" phox",
"}",
" </span>",
" component of the phagocytic NADPH oxidase.",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h2\">",
" Secretory vesicles",
" </span>",
" &nbsp;&mdash;&nbsp;Alkaline phosphatase initially was thought to be a marker
for specific granules, as it is present in myelocytes and all further stages of
differentiated PMN [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/17,18\">",
" 17,18",
" </a>",
" ]. Later studies showed that alkaline phosphatase is contained in secretory
vesicles scattered throughout the cytoplasm and plasma membrane of myelocytes,
metamyelocytes, band forms and PMN [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/11\">",
" 11",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h2\">",
" Gelatinase granules",
" </span>",
" &nbsp;&mdash;&nbsp;Another subset of specific-type granules has been
identified by subcellular fractionation combined with double labeling
immunoelectron microscopy [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/19,20\">",
" 19,20",
" </a>",
" ]. These granules are rich in gelatinase but low in lactoferrin and do not
contain myeloperoxidase [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/19\">",
" 19",
" </a>",
" ]. Unless the granule is devoid of lactoferrin, it is considered part of the
specific granule subset.",
" </p>",
" <p>",
" Gelatinase granules are a marker of terminal neutrophil differentiation [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/13\">",
" 13",
" </a>",
" ]. They more readily secrete their contents in response to secretagogues than
azurophilic or specific granules [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/20\">",
" 20",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h1\">",
" GRANULOCYTE KINETICS",
" </span>",
" &nbsp;&mdash;&nbsp;PMN are distributed within the bone marrow, the circulating
blood, and in various tissues throughout the body depending upon specific need (",
" <a class=\"graphic graphic_figure graphicRef75855 \" href=\"UTD.htm?
30/58/31651\">",
" figure 1",
" </a>",
" ).",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" The bone marrow is the largest compartment; it contains approximately 2.3 x
10",
" ^{",
" 9",
"}",
" PMN per kg body weight [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/21\">",
" 21",
" </a>",
" ].",
" </li>",
" <li>",
" The peripheral blood compartment is one-third the size of the bone marrow
compartment (0.7 x 10",
" ^{",
" 9",
"}",
" cells per kg). One-half of these PMN is in the main stream of the
circulation, while the other half is tumbling or loosely adhering to the
endothelium of the microvasculature (",
" <a class=\"graphic graphic_figure graphicRef78149 \" href=\"UTD.htm?
18/63/19445\">",
" figure 2",
" </a>",
" )&nbsp;[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/22\">",
" 22",
" </a>",
" ]. These two compartments are referred to as the circulating granulocyte
pool (CGP) and marginating granulocyte pool (MGP), respectively; the two pools are
in a constant state of dynamic equilibrium [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/23,24\">",
" 23,24",
" </a>",
" ].",
" </li>",
" <li>",
" The size of the extravascular tissue compartment has not been quantified but
it varies depending on the body's need for PMN at sites of infection or
inflammation [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/25\">",
" 25",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H16\">",
" <span class=\"h2\">",
" Bone marrow compartments",
" </span>",
" &nbsp;&mdash;&nbsp;There are three bone marrow compartments of developing
myeloid precursors: the stem cell compartment, the mitotic compartment containing
replicating myeloblasts, promyelocytes, and myelocytes, and the maturation-storage
compartment containing nonreplicating maturing metamyelocytes, band forms and PMN.
The size of the stem cell compartment has not been quantified but is very small
compared with the mitotic compartment (2.1 x 10",
" ^{",
" 9",
"}",
" cells per kg) and to the almost three-fold larger maturation-storage
compartment (5.6 x 10",
" ^{",
" 9",
"}",
" cells per kg) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/26\">",
" 26",
" </a>",
" ]. Studies in dogs suggest that rate of PMN production is approximately 1.7 x
10",
" ^{",
" 9",
"}",
" per kg per day [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/26\">",
" 26",
" </a>",
" ]. The factors regulating bone marrow PMN production are not well understood.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/44/6858?
source=see_link\">",
" \"Regulation of myelopoiesis\"",
" </a>",
" .)",
" </p>",
" <p>",
" The transit times of developing myeloid cells have been derived from studies
using tritiated thymidine [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/26,27\">",
" 26,27",
" </a>",
" ]. The entire process requires approximately 10 days under normal conditions
(",
" <a class=\"graphic graphic_figure graphicRef75855 \" href=\"UTD.htm?
30/58/31651\">",
" figure 1",
" </a>",
" ). The myeloblast stage is 15 hours, promyelocyte stage 24 hours, and
myelocyte stage 104 hours, during which the myelocyte replicates up to three times.
Thus, the replicating phase of myeloid development is about six days. Maturation of
metamyelocyte to band form to PMN requires an additional four to five days. PMN may
spend another three or four days in the storage compartment before emerging into
the circulation [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/26,28,29\">",
" 26,28,29",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H17\">",
" <span class=\"h2\">",
" Blood compartment",
" </span>",
" &nbsp;&mdash;&nbsp;The mechanisms controlling the release of PMN from the bone
marrow are only partially understood. A variety of compounds induce PMN movement
into the circulation including endotoxin, glucocorticoids, a leukocyte-mobilizing
factor derived from the third component of complement (C3e), chemoattractants such
as C5a, cytokines such as tumor necrosis factor (TNF)-alpha, and certain androgens
[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/30-34\">",
" 30-34",
" </a>",
" ]. To successfully emerge into the circulation, PMN must deform and migrate to
the luminal side of the endothelial sinusoidal surface. Endotoxin affects the
relationship between marrow sinus endothelial cells and the stromal macrophages
covering nonluminal sinusoidal surfaces; it induces retraction of macrophages away
from the endothelium which facilitates contact between PMN and endothelial cells
and allows PMN egress from the bone marrow [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/35,36\">",
" 35,36",
" </a>",
" ].",
" </p>",
" <p>",
" In rabbits, infusion of C5a or TNF-alpha induces leukocytosis, which is not
prevented when the principal adhesion proteins of PMN, beta-2 integrin and L-
selectin, are blocked by specific antibodies [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/33\">",
" 33",
" </a>",
" ]. This observation suggests that PMN egress from the bone marrow is mediated
by interactions different from those governing chemotaxis and diapedesis as
described below (",
" <a class=\"graphic graphic_figure graphicRef78149 \" href=\"UTD.htm?
18/63/19445\">",
" figure 2",
" </a>",
" ).",
" </p>",
" <p>",
" In early studies, when blood PMN were removed from the body, labeled, and
reinjected, their measured half-life in the circulation was about seven hours [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/24,37\">",
" 24,37",
" </a>",
" ]. However, when labeled in vivo, the measured half-life in five normal
volunteers was found to be considerably longer, at about 3.75 days (90 hours), for
a mean lifespan of approximately 5.4 days (range: 5.1 to 8.4 days) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/38\">",
" 38",
" </a>",
" ].",
" </p>",
" <p>",
" It is now known that, in addition to its role in the regulation of
granulopoiesis and maturation, G-CSF plays a significant role in reducing
granulocyte transit time through the granulocyte compartment and releasing mature
cells into the circulation. The CXC chemokine receptor 4 (CXCR4) also plays a
significant role. It is expressed at high levels on early granulocytes and
decreases with maturation to very low levels on mature granulocytes. The main
ligand for CXCR4 is stromal-derived-factor-1 (SDF-1) and the interaction between
these two proteins retains neutrophils in the marrow. This process also involves
interaction with the",
" <span class=\"nowrap\">",
" &alpha;",
" _{",
" 4",
"}",
" /&beta;",
" _{",
" 1",
"}",
" </span>",
" integrin VLA-4",
" <span class=\"nowrap\">",
" (CD49d/CD29),",
" </span>",
" which binds to VCMA1 and osteopontin, and crosstalk between the CXCR4-SDF-1
axis and VLA-4-VCAM-1 axis [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/39\">",
" 39",
" </a>",
" ]. The loss of CXCR4 as neutrophils mature results in their release from the
marrow. G-CSF can reduce expression of CXCR4 and cause release of granulocytes. As
neutrophils become apoptotic in the circulation, CXCR4 is again expressed on the
PMN surface and they return to the bone marrow where they are phagocytosed by
stromal macrophages. This in turn stimulates G-CSF production, increasing
production of neutrophils [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/39\">",
" 39",
" </a>",
" ].",
" </p>",
" <p>",
" The disappearance of labeled PMN follows a single exponential curve, implying
that PMN are destroyed or leave the blood randomly rather than according to their
age (senescence) as is true for erythrocytes and platelets. PMN do not return to
the circulation once they leave it. The granulocyte turnover rate is calculated
from the total blood pool of PMN and is estimated at 0.3 to 1.3 x",
" <span class=\"nowrap\">",
" 10",
" ^{",
" 9",
"}",
" /kg",
" </span>",
" per day [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/28\">",
" 28",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H18\">",
" <span class=\"h2\">",
" Circulating PMN interactions with endothelial cells",
" </span>",
" &nbsp;&mdash;&nbsp;PMN are subjected to strong shear forces as blood flows
through the arterial circulatory system at velocities of 300 to 1000",
" <span class=\"nowrap\">",
" &micro;m/sec",
" </span>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/40\">",
" 40",
" </a>",
" ]. When viewing the microcirculation with the cine microscope, the vast
majority of cells, including red cells, appear as an indistinguishable blur. But
within this rapid flow, a subset of PMN is noted to tumble along the periphery of
the blood vessel at a velocity about 100 times slower than the main flow. The loose
selectin-mediated PMN interactions with the endothelium results in tumbling or
rolling; it reflects early inflammatory responses of PMN and endothelial cells
preceding firm adhesion of PMN to endothelium [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/40,41\">",
" 40,41",
" </a>",
" ].",
" </p>",
" <p>",
" PMN recruitment to sites of inflammation involves a dynamic series of events
between PMN and endothelial cells that are orchestrated by several different
families of adhesion molecules and their ligands. Three families of adhesive
molecules mediate the bulk of leukocyte-endothelial interactions (",
" <a class=\"graphic graphic_table graphicRef57400 \" href=\"UTD.htm?
41/7/42109\">",
" table 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/42,43\">",
" 42,43",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/54/36711?
source=see_link\">",
" \"Leukocyte-endothelial adhesion in the pathogenesis of inflammation\"",
" </a>",
" .)",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Integrins &mdash; located on leukocytes",
" </li>",
" <li>",
" Members of the immunoglobulin superfamily of proteins, primarily the
intercellular adhesion molecules (ICAM) &mdash; largely expressed on endothelial
cells",
" </li>",
" <li>",
" Selectins &mdash; located on leukocytes and endothelial cells",
" </li>",
" </ul>",
" </p>",
" <p>",
" PMN and endothelial cells are transformed from a basal state to an activated
state by a variety of inflammatory mediators. This process can be divided into the
following phases (",
" <a class=\"graphic graphic_figure graphicRef78149 \" href=\"UTD.htm?
18/63/19445\">",
" figure 2",
" </a>",
" ):",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" The inactivated or quiescent state of PMN and endothelium prior to the
release of inflammatory mediators",
" </li>",
" <li>",
" The activated state of endothelium (by factors such as IL-1, TNF-alpha, and
endotoxin), leading to increased expression of adhesion molecules, particularly
ICAM-1",
" </li>",
" <li>",
" The activated or priming state of PMN, which is associated with alterations
in the expression of adhesion molecules, making PMN sticky to the endothelium",
" </li>",
" <li>",
" The transmigration phase when PMN tread between adjacent endothelial cells,
supported by adhesion molecules expressed on the lateral surfaces of endothelium",
" </li>",
" </ul>",
" </p>",
" <p>",
" Rolling, which slows down PMN within the bloodstream, is primarily mediated by
L-selectin on PMN and endothelial cells [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/40,44,45\">",
" 40,44,45",
" </a>",
" ]. Adhesion to endothelial cells and migration between endothelial cells to
extravascular sites requires activated neutrophils to shift expression from L-
selectin to beta-2 integrin, primarily Mac-1",
" <span class=\"nowrap\">",
" (CD11b/CD18)",
" </span>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/45-47\">",
" 45-47",
" </a>",
" ]; the beta-2 integrins mediate adhesion to ICAM-1 on the surface of inflamed
endothelium (",
" <a class=\"graphic graphic_figure graphicRef78149 \" href=\"UTD.htm?
18/63/19445\">",
" figure 2",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/48,49\">",
" 48,49",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/54/36711?
source=see_link\">",
" \"Leukocyte-endothelial adhesion in the pathogenesis of inflammation\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H19\">",
" <span class=\"h2\">",
" Extravascular tissue compartment",
" </span>",
" &nbsp;&mdash;&nbsp;Under normal conditions, PMN losses occur on mucosal
surfaces throughout the body. As an example, isotopically labeled blood PMN appear
in saliva and urine and increase markedly with inflammatory conditions such as
gingivitis and pyelonephritis, respectively [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/50,51\">",
" 50,51",
" </a>",
" ]. The exact size of the extravascular tissue compartment can only be
estimated. Although PMN exit the circulation randomly, they age and die at
inflammatory sites over the next 72 hours, in part by undergoing selective
intracellular programmed cell death (apoptosis) and in part by recognition and
engulfment by macrophages.",
" </p>",
" <p class=\"headingAnchor\" id=\"H20\">",
" <span class=\"h2\">",
" Apoptosis",
" </span>",
" &nbsp;&mdash;&nbsp;Apoptosis results in characteristic morphologic changes in
PMN volume and nuclear chromatin condensation called pyknocytosis. The apoptotic
PMN remains intact morphologically but loses the cytoskeletal functions of
attachment, spreading, shape change, and random migration. The expression of L-
selectin decreases, Fc gamma RIIIb (CD16) is shed [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/52\">",
" 52",
" </a>",
" ], but expression of the major adhesion protein Mac-1",
" <span class=\"nowrap\">",
" (CD11b/CD18)",
" </span>",
" increases [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/53,54\">",
" 53,54",
" </a>",
" ], and CXCR4 is again expressed on the cell surface [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/39\">",
" 39",
" </a>",
" ].",
" </p>",
" <p>",
" Apoptotic PMN cannot perform phagocytosis, degranulation, or respiratory burst
activities [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/55\">",
" 55",
" </a>",
" ]. Thus, PMN apoptosis represents a modulating event in control of
inflammation, marking PMN for disposal and minimizing their ability to generate and
release noxious products that could induce further damage to inflamed tissues [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/55,56\">",
" 55,56",
" </a>",
" ].",
" </p>",
" <p>",
" The apoptotic PMN becomes the phagocytic target of tissue macrophages; it is
recognized via adhesive proteins such as thrombospondin and ingested intact by the
macrophage [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/57\">",
" 57",
" </a>",
" ]. However, it is not clear if apoptosis is required for macrophage
phagocytosis. The proto-oncogene B cell",
" <span class=\"nowrap\">",
" leukemia/lymphoma",
" </span>",
" 2 (Bcl-2) is expressed in early myeloid differentiation but not in PMN. PMN
from transgenic mice expressing Bcl-2 show delayed apoptosis in vitro but are still
recognized and phagocytosed by macrophages [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/58\">",
" 58",
" </a>",
" ].",
" </p>",
" <p>",
" The precise molecular genetic site(s) for initiation of apoptosis in PMN is
not known. Sodium butyrate, which directly affects chromatin structure, delays PMN
apoptosis, suggesting that active gene expression is involved [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/59\">",
" 59",
" </a>",
" ]. One candidate for a molecular trigger of apoptosis in PMN is the Fas (CD95)
gene. Fas protein is expressed on the PMN plasma membrane and PMN constitutively
release Fas ligand [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/60\">",
" 60",
" </a>",
" ]. Since Fas ligand induces apoptosis in PMN, its release may provide a
paracrine pathway for PMN to mediate programmed cell death [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/60\">",
" 60",
" </a>",
" ]. As an example, high levels of circulating Fas ligand have been detected in
patients with large granular lymphocyte leukemia, a disorder in which chronic
neutropenia is a prominent feature [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/61\">",
" 61",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/33/21018?
source=see_link&amp;anchor=H458740684#H458740684\">",
" \"Clinical manifestations, pathologic features, and diagnosis of T cell large
granular lymphocyte leukemia\", section on 'Clinical features'",
" </a>",
" .)",
" </p>",
" <p>",
" Fas-mediated PMN apoptosis is suppressed in vitro by biologic molecules and
drugs (eg, glucocorticoids) known to delay apoptosis in PMN. Molecules known to
delay the onset of PMN apoptosis include G-CSF, GM-CSF, IL-3, IL-6, IL-15 [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/62-64\">",
" 62-64",
" </a>",
" ]. Glucocorticoids and G-CSF exert a protective effect on PMN survival in
vitro at concentrations that correlate with pharmacologic doses of",
" <a class=\"drug drug_general\" href=\"UTD.htm?33/4/33856?source=see_link\">",
" dexamethasone",
" </a>",
" and G-CSF achievable in vivo [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/65,66\">",
" 65,66",
" </a>",
" ]. Mediators of inflammation such as endotoxin, human recombinant C5a, TNF-
alpha and interferon gamma also inhibit PMN apoptosis in a concentration dependent
fashion in vitro [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/62\">",
" 62",
" </a>",
" ]. Lyn kinase, a src family tyrosine kinase, couples to the GM-CSF receptor
and is required for the delayed apoptosis induced by GM-CSF [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6185/abstract/67\">",
" 67",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H14873650\">",
" <span class=\"h1\">",
" SUMMARY",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H14873754\">",
" <span class=\"h2\">",
" Maturational stages",
" </span>",
" &nbsp;&mdash;&nbsp;The six stages of polymorphonuclear neutrophil (PMN)
development are characterized by morphological criteria of developing myeloid
cells, as seen by light microscopy. These criteria are: relative size, nuclear
volume, chromatin density, prominence of nucleoli, granule number, and cytoplasmic
staining. The stages are, as follows (see",
" <a class=\"local\" href=\"#H2\">",
" 'Morphology of developing neutrophils'",
" </a>",
" above):",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Myeloblast",
" </li>",
" <li>",
" Promyelocyte",
" </li>",
" <li>",
" Myelocyte",
" </li>",
" <li>",
" Band form",
" </li>",
" <li>",
" PMN (mature neutrophil)",
" </li>",
" </ul>",
" </p>",
" <p>",
" The entire maturation process within the bone marrow requires approximately 10
days under normal conditions (myeloblast stage 15 hours, promyelocyte stage 24
hours, myelocyte stage 104 hours). Maturation of metamyelocyte to band form to PMN
requires an additional four to five days. PMN may spend another three or four days
in the bone marrow storage compartment before emerging into the circulation (",
" <a class=\"graphic graphic_figure graphicRef75855 \" href=\"UTD.htm?
30/58/31651\">",
" figure 1",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H16\">",
" 'Bone marrow compartments'",
" </a>",
" above.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H14873761\">",
" <span class=\"h2\">",
" PMN granules",
" </span>",
" &nbsp;&mdash;&nbsp;PMN contain three subsets of granules (azurophilic,
specific, and gelatinase) and one group of secretory vesicles identified by marker
enzymes or other proteins present in the granule matrix or membranes of granules
and vesicles (",
" <a class=\"graphic graphic_table graphicRef57400 \" href=\"UTD.htm?
41/7/42109\">",
" table 1",
" </a>",
" ). The function of the various enzymes and proteins contained in these
granules is discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/31/6650?
source=see_link\">",
" \"Neutrophil functions other than movement\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H14873827\">",
" <span class=\"h2\">",
" PMN kinetics",
" </span>",
" &nbsp;&mdash;&nbsp;PMN are distributed within the bone marrow, the circulating
blood, and in various tissues throughout the body depending upon specific need, as
follows (see",
" <a class=\"local\" href=\"#H15\">",
" 'Granulocyte kinetics'",
" </a>",
" above):",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" When blood PMN were labeled in vivo, the measured half-life in five normal
volunteers was about 3.75 days, for a mean lifespan of approximately 5.4 days.",
" </li>",
" <li>",
" <a class=\"drug drug_general\" href=\"UTD.htm?23/13/23767?
source=see_link\">",
" Granulocyte colony-stimulating factor",
" </a>",
" (G-CSF) and the chemokine receptor 4 (CXCR4) play a significant role in
reducing granulocyte transit time through the granulocyte compartment and releasing
mature cells into the circulation. (See",
" <a class=\"local\" href=\"#H17\">",
" 'Blood compartment'",
" </a>",
" above.)",
" </li>",
" <li>",
" The disappearance of labeled PMN from the circulation follows a single
exponential curve, implying that PMN are destroyed or leave the blood randomly
rather than according to their age. PMN do not return to the circulation once they
leave it.",
" </li>",
" <li>",
" Although PMN exit the circulation randomly, they age and die at inflammatory
sites over the next 72 hours, in part by undergoing selective intracellular
programmed cell death (apoptosis) and in part by recognition and engulfment by
macrophages. (See",
" <a class=\"local\" href=\"#H19\">",
" 'Extravascular tissue compartment'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H20\">",
" 'Apoptosis'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" Golde DW, Baldwin GC. Myeloid growth factors. In: Inflammation: Basic
Principles and Clinical Correlates, 2nd ed, Gallin JI, Goldstein IM, Snyderman R
(Eds), Raven Press, New York 1992.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/2\">",
" Olweus J, Lund-Johansen F, Terstappen LW. CD64/Fc gamma RI is a granulo-
monocytic lineage marker on CD34+ hematopoietic progenitor cells. Blood 1995;
85:2402.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/3\">",
" Leary AG, Ogawa M, Strauss LC, Civin CI. Single cell origin of multilineage
colonies in culture. Evidence that differentiation of multipotent progenitors and
restriction of proliferative potential of monopotent progenitors are stochastic
processes. J Clin Invest 1984; 74:2193.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/4\">",
" Wognum AW, Westerman Y, Visser TP, Wagemaker G. Distribution of receptors
for granulocyte-macrophage colony-stimulating factor on immature CD34+ bone marrow
cells, differentiating monomyeloid progenitors, and mature blood cell subsets.
Blood 1994; 84:764.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/5\">",
" Sigurdsson F, Khanna-Gupta A, Lawson N, Berliner N. Control of late
neutrophil-specific gene expression: insights into regulation of myeloid
differentiation. Semin Hematol 1997; 34:303.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/6\">",
" Kawamoto H, Ikawa T, Masuda K, et al. A map for lineage restriction of
progenitors during hematopoiesis: the essence of the myeloid-based model. Immunol
Rev 2010; 238:23.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/7\">",
" Lian Z, Wang L, Yamaga S, et al. Genomic and proteomic analysis of the
myeloid differentiation program. Blood 2001; 98:513.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/8\">",
" Theilgaard-M&ouml;nch K, Jacobsen LC, Borup R, et al. The transcriptional
program of terminal granulocytic differentiation. Blood 2005; 105:1785.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/9\">",
" Rosenbauer F, Tenen DG. Transcription factors in myeloid development:
balancing differentiation with transformation. Nat Rev Immunol 2007; 7:105.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/10\">",
" Cramer E, Pryzwansky KB, Villeval JL, et al. Ultrastructural localization of
lactoferrin and myeloperoxidase in human neutrophils by immunogold. Blood 1985;
65:423.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/11\">",
" Borregaard N, Kjeldsen L, Lollike K, Sengel&oslash;v H. Granules and
secretory vesicles of the human neutrophil. Clin Exp Immunol 1995; 101 Suppl 1:6.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/12\">",
" Gullberg U, Andersson E, Garwicz D, et al. Biosynthesis, processing and
sorting of neutrophil proteins: insight into neutrophil granule development. Eur J
Haematol 1997; 58:137.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/13\">",
" Borregaard N, Sehested M, Nielsen BS, et al. Biosynthesis of granule
proteins in normal human bone marrow cells. Gelatinase is a marker of terminal
neutrophil differentiation. Blood 1995; 85:812.",
" </a>",
" </li>",
" <li>",
" Bainton DF. Developmental biology of neutrophils and eosinophils. In:
Inflammation Basic Principles and Clinical Correlates, 2nd ed, Raven Press, New
York 1992. p.303.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/15\">",
" DAVIDSON WM, SMITH DR. A morphological sex difference in the
polymorphonuclear neutrophil leucocytes. Br Med J 1954; 2:6.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/16\">",
" Grenier A, Chollet-Martin S, Crestani B, et al. Presence of a mobilizable
intracellular pool of hepatocyte growth factor in human polymorphonuclear
neutrophils. Blood 2002; 99:2997.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/17\">",
" Kaplow LS. Cytochemistry of leukocyte alkaline phosphatase. Use of complex
naphthol as phosphates in azo dyecoupling technics. Am J Clin Pathol 1963;
39:439.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/18\">",
" KAPLOW LS. SIMPLIFIED MYELOPEROXIDASE STAIN USING BENZIDINE DIHYDROCHLORIDE.
Blood 1965; 26:215.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/19\">",
" Kjeldsen L, Bainton DF, Sengel&oslash;v H, Borregaard N. Structural and
functional heterogeneity among peroxidase-negative granules in human neutrophils:
identification of a distinct gelatinase-containing granule subset by combined
immunocytochemistry and subcellular fractionation. Blood 1993; 82:3183.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/20\">",
" Dewald B, Bretz U, Baggiolini M. Release of gelatinase from a novel
secretory compartment of human neutrophils. J Clin Invest 1982; 70:518.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/21\">",
" ATHENS JW, RAAB SO, HAAB OP, et al. Leukokinetic studies. III. The
distribution of granulocytes in the blood of normal subjects. J Clin Invest 1961;
40:159.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/22\">",
" ATHENS JW, HAAB OP, RAAB SO, et al. Leukokinetic studies. IV. The total
blood, circulating and marginal granulocyte pools and the granulocyte turnover rate
in normal subjects. J Clin Invest 1961; 40:989.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/23\">",
" Boggs DR. The kinetics of neutrophilic leukocytes in health and in disease.
Semin Hematol 1967; 4:359.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/24\">",
" Mauer AM, Athens JW, Ashenbrucker H, et al. LEUKOKINETIC STUDIES. II. A
METHOD FOR LABELING GRANULOCYTES IN VITRO WITH RADIOACTIVE
DIISOPROPYLFLUOROPHOSPHATE (DFP). J Clin Invest 1960; 39:1481.",
" </a>",
" </li>",
" <li>",
" Bishop CR, Athens JW. Studies of granulocytopoiesis in abnormal conditions.
In: Hemopoietic Cellular Proliferation, Stohlman F Jr (Ed), Grune &amp; Stratton,
New York 1970.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/26\">",
" Deubelbeiss KA, Dancey JT, Harker LA, Finch CA. Neutrophil kinetics in the
dog. J Clin Invest 1975; 55:833.",
" </a>",
" </li>",
" <li>",
" Cronkite EP, Vincent PC. Granulocytopoiesis. In: Hemopoietic Cellular
Proliferation, Stohlman F Jr (Ed), Grune &amp; Stratton, New York 1970.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/28\">",
" Bishop CR, Rothstein G, Ashenbrucker HE, Athens JW. Leukokinetic studies.
XIV. Blood neutrophil kinetics in chronic, steady-state neutropenia. J Clin Invest
1971; 50:1678.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/29\">",
" CARTWRIGHT GE, ATHENS JW, WINTROBE MM. THE KINETICS OF GRANULOPOIESIS IN
NORMAL MAN. Blood 1964; 24:780.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/30\">",
" Deinard AS, Page AR. A study of steroid-induced granulocytosis in a patient
with chronic benign neutropenia of childhood. Br J Haematol 1974; 28:333.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/31\">",
" Ghebrehiwet B, M&uuml;ller-Eberhard HJ. C3e: an acidic fragment of human C3
with leukocytosis-inducing activity. J Immunol 1979; 123:616.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/32\">",
" Mitchell RH, McClelland RM, Kampschmidt RF. Comparison of neutrophilia
induced by leukocytic endogenous mediator and by cobra venom factor. Proc Soc Exp
Biol Med 1982; 169:309.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/33\">",
" Jagels MA, Chambers JD, Arfors KE, Hugli TE. C5a- and tumor necrosis factor-
alpha-induced leukocytosis occurs independently of beta 2 integrins and L-selectin:
differential effects on neutrophil adhesion molecule expression in vivo. Blood
1995; 85:2900.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/34\">",
" Vogel JM, Yankee RA, Kimball HR, et al. The effect of etiocholanolone on
granulocyte kinetics. Blood 1967; 30:474.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/35\">",
" Lichtman MA, Weed RI. Alteration of the cell periphery during granulocyte
maturation: relationship to cell function. Blood 1972; 39:301.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/36\">",
" Hirahata T, Bjorkman D, Chamberlain JK. Endotoxin: a twofold effect on bone
marrow ultrastructure. Scanning Microsc 1987; 1:1349.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/37\">",
" ATHENS JW, HAAB OP, RAAB SO, et al. LEUKOKINETIC STUDIES. XI. BLOOD
GRANULOCYTE KINETICS IN POLYCYTHEMIA VERA, INFECTION, AND MYELOFIBROSIS. J Clin
Invest 1965; 44:778.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/38\">",
" Pillay J, den Braber I, Vrisekoop N, et al. In vivo labeling with 2H2O
reveals a human neutrophil lifespan of 5.4 days. Blood 2010; 116:625.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/39\">",
" Summers C, Rankin SM, Condliffe AM, et al. Neutrophil kinetics in health and
disease. Trends Immunol 2010; 31:318.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/40\">",
" Kishimoto TK, Rothlein R. Integrins, ICAMs, and selectins: role and
regulation of adhesion molecules in neutrophil recruitment to inflammatory sites.
Adv Pharmacol 1994; 25:117.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/41\">",
" Varki A. Selectin ligands. Proc Natl Acad Sci U S A 1994; 91:7390.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/42\">",
" Cronstein BN, Weissmann G. The adhesion molecules of inflammation. Arthritis
Rheum 1993; 36:147.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/43\">",
" McEver RP. Adhesive interactions of leukocytes, platelets, and the vessel
wall during hemostasis and inflammation. Thromb Haemost 2001; 86:746.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/44\">",
" Smith CW, Rothlein R, Hughes BJ, et al. Recognition of an endothelial
determinant for CD 18-dependent human neutrophil adherence and transendothelial
migration. J Clin Invest 1988; 82:1746.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/45\">",
" Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow
rates: distinction from and prerequisite for adhesion through integrins. Cell 1991;
65:859.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/46\">",
" Springer TA, Thompson WS, Miller LJ, et al. Inherited deficiency of the Mac-
1, LFA-1, p150,95 glycoprotein family and its molecular basis. J Exp Med 1984;
160:1901.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/47\">",
" Gotsch U, J&auml;ger U, Dominis M, Vestweber D. Expression of P-selectin on
endothelial cells is upregulated by LPS and TNF-alpha in vivo. Cell Adhes Commun
1994; 2:7.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/48\">",
" Dustin ML, Rothlein R, Bhan AK, et al. Induction by IL 1 and interferon-
gamma: tissue distribution, biochemistry, and function of a natural adherence
molecule (ICAM-1). J Immunol 1986; 137:245.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/49\">",
" Hibbs ML, Xu H, Stacker SA, Springer TA. Regulation of adhesion of ICAM-1 by
the cytoplasmic domain of LFA-1 integrin beta subunit. Science 1991; 251:1611.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/50\">",
" GARNETT ES. OBSERVATIONS ON THE KINETICS OF URINARY GRANULOCYTE EXCRETION.
Clin Sci 1965; 28:157.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/51\">",
" FLIEDNER TM, CRONKITE EP, ROBERTSON JS. GRANULOCYTOPOIESIS. I. SENESCENCE
AND RANDOM LOSS OF NEUTROPHILIC GRANULOCYTES IN HUMAN BEINGS. Blood 1964; 24:402.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/52\">",
" Dransfield I, Buckle AM, Savill JS, et al. Neutrophil apoptosis is
associated with a reduction in CD16 (Fc gamma RIII) expression. J Immunol 1994;
153:1254.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/53\">",
" Coxon A, Rieu P, Barkalow FJ, et al. A novel role for the beta 2 integrin
CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation.
Immunity 1996; 5:653.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/54\">",
" Walzog B, Jeblonski F, Zakrzewicz A, Gaehtgens P. Beta2 integrins
(CD11/CD18) promote apoptosis of human neutrophils. FASEB J 1997; 11:1177.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/55\">",
" Whyte MK, Meagher LC, MacDermot J, Haslett C. Impairment of function in
aging neutrophils is associated with apoptosis. J Immunol 1993; 150:5124.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/56\">",
" Savill JS, Wyllie AH, Henson JE, et al. Macrophage phagocytosis of aging
neutrophils in inflammation. Programmed cell death in the neutrophil leads to its
recognition by macrophages. J Clin Invest 1989; 83:865.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/57\">",
" Savill J, Hogg N, Ren Y, Haslett C. Thrombospondin cooperates with CD36 and
the vitronectin receptor in macrophage recognition of neutrophils undergoing
apoptosis. J Clin Invest 1992; 90:1513.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/58\">",
" Lagasse E, Weissman IL. bcl-2 inhibits apoptosis of neutrophils but not
their engulfment by macrophages. J Exp Med 1994; 179:1047.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/59\">",
" Stringer RE, Hart CA, Edwards SW. Sodium butyrate delays neutrophil
apoptosis: role of protein biosynthesis in neutrophil survival. Br J Haematol 1996;
92:169.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/60\">",
" Liles WC, Kiener PA, Ledbetter JA, et al. Differential expression of Fas
(CD95) and Fas ligand on normal human phagocytes: implications for the regulation
of apoptosis in neutrophils. J Exp Med 1996; 184:429.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/61\">",
" Liu JH, Wei S, Lamy T, et al. Chronic neutropenia mediated by fas ligand.
Blood 2000; 95:3219.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/62\">",
" Lee A, Whyte MK, Haslett C. Inhibition of apoptosis and prolongation of
neutrophil functional longevity by inflammatory mediators. J Leukoc Biol 1993;
54:283.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/63\">",
" Maianski NA, Mul FP, van Buul JD, et al. Granulocyte colony-stimulating
factor inhibits the mitochondria-dependent activation of caspase-3 in neutrophils.
Blood 2002; 99:672.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/64\">",
" Basu S, Hodgson G, Katz M, Dunn AR. Evaluation of role of G-CSF in the
production, survival, and release of neutrophils from bone marrow into circulation.
Blood 2002; 100:854.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/65\">",
" Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils.
Separation of survival and activation outcomes. J Immunol 1995; 154:4719.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/66\">",
" Liles WC, Dale DC, Klebanoff SJ. Glucocorticoids inhibit apoptosis of human
neutrophils. Blood 1995; 86:3181.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6185/abstract/67\">",
" Wei S, Liu JH, Epling-Burnette PK, et al. Critical role of Lyn kinase in
inhibition of neutrophil apoptosis by granulocyte-macrophage colony-stimulating
factor. J Immunol 1996; 157:5155.",
" </a>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 8378 Version 10.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [0505-83.177.194.223-8B216F4EAC-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6185=[""].join("\n");
var outline_f6_2_6185=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H14873650\" id=\"summRecButton\">",
" <span>",
" SUMMARY",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" MORPHOLOGY OF DEVELOPING NEUTROPHILS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" Myeloblast stage",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" Promyelocyte stage",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" Myelocyte stage",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" Metamyelocyte stage",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H7\">",
" Band form",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H8\">",
" Polymorphonuclear neutrophil",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H9\">",
" REGULATION OF GRANULOCYTE DIFFERENTIATION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H10\">",
" CONTENT OF PMN GRANULES",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H11\">",
" Azurophilic granules",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H12\">",
" Specific granules",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H13\">",
" Secretory vesicles",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H14\">",
" Gelatinase granules",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H15\">",
" GRANULOCYTE KINETICS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H16\">",
" Bone marrow compartments",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H17\">",
" Blood compartment",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H18\">",
" Circulating PMN interactions with endothelial cells",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H19\">",
" Extravascular tissue compartment",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H20\">",
" Apoptosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H14873650\">",
" SUMMARY",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H14873754\">",
" Maturational stages",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H14873761\">",
" PMN granules",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H14873827\">",
" PMN kinetics",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"HEME/8378\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"HEME/8378|ALG\">",
" <a href=\"#\" title=\"ALGORITHMS\">",
" ALGORITHMS",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_algorithm\" href=\"UTD.htm?34/9/34968\"
title=\"algorithm 1\">",
" Hematopoiesis regulation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"HEME/8378|FIG\">",
" <a href=\"#\" title=\"FIGURES\">",
" FIGURES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?30/58/31651\"
title=\"figure 1\">",
" PMN development and kinetics",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_figure\" href=\"UTD.htm?18/63/19445\"
title=\"figure 2\">",
" Neutrophil migration",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"HEME/8378|PIC\">",
" <a href=\"#\" title=\"PICTURES\">",
" PICTURES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?37/11/38067\"
title=\"picture 1\">",
" Normal human myeloblast",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?21/25/21908\"
title=\"picture 2\">",
" Normal human promyelocyte",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?1/7/1138\"
title=\"picture 3\">",
" Normal human myelocyte",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?25/60/26563\"
title=\"picture 4\">",
" Normal human metamyelocyte",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?16/42/17060\"
title=\"picture 5\">",
" Normal human band form",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?30/37/31316\"
title=\"picture 6\">",
" Normal human PMN",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?3/28/3524\"
title=\"picture 7\">",
" Normal resting PMN EM",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"HEME/8378|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?41/7/42109\" title=\"table
1\">",
" PMN granule contents",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" CALCULATORS",
" </h1>",
" <div id=\"relatedCalculators\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"calc calc_professional\" href=\"UTD.htm?12/1/12305?
source=related_link\" title=\"calculator 1\">",
" Calculator: Absolute neutrophil count",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/33/21018?
source=related_link\">",
" Clinical manifestations, pathologic features, and diagnosis of T cell large
granular lymphocyte leukemia",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/54/36711?
source=related_link\">",
" Leukocyte-endothelial adhesion in the pathogenesis of inflammation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/31/6650?
source=related_link\">",
" Neutrophil functions other than movement",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/34/25129?
source=related_link\">",
" Overview of hematopoiesis and stem cell function",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?20/10/20650?
source=related_link\">",
" Regulation of erythropoiesis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?6/44/6858?
source=related_link\">",
" Regulation of myelopoiesis",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_2_6186="Hepatitis C virus infection in children";
var content_f6_2_6186=[" <noscript>",
" <div id=\"javascriptDisabled\">",
" It seems to us that you have your JavaScript turned off on your browser.
JavaScript is required in order for our site to behave correctly. Please enable
your JavaScript to continue use our site.",
" </div>",
" </noscript>",
" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" ^{",
" &reg;",
"}",
" <br>",
" <a href=\"file://www.uptodate.com\">",
" www.uptodate.com",
" </a>",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </br>",
" </div>",
" </br>",
" </img>",
" </img>",
" </div>",
" <div id=\"printHeaderLinks\">",
" <a class=\"TOPIC\" href=\"#\" id=\"printHeaderPrint\" rel=\"4\" title=\"Click
here to print\">",
" Print",
" </a>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a href=\"#\" id=\"printHeaderBack\" title=\"Back to normal view\">",
" Back",
" </a>",
" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"topicTitle\">",
" Hepatitis C virus infection in children",
" </div>",
" <div id=\"topicContributors\">",
" <div>",
" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/2/6186/contributors\">",
" Author",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6186/contributors\">",
" Maureen M Jonas, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/2/6186/contributors\">",
" Section Editors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6186/contributors\">",
" Morven S Edwards, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6186/contributors\">",
" Elizabeth B Rand, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?6/2/6186/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
6/2/6186/contributors\">",
" Alison G Hoppin, MD",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?6/2/6186/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Jan 30, 2013.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Children represent only a small proportion of the hepatitis
C virus (HCV)-infected population. Nevertheless, a substantial number of children
have chronic HCV infection and are at risk for complications.",
" </p>",
" <p>",
" The major issues related to HCV in children will be reviewed here. Perinatal
transmission of HCV is discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/19/26936?
source=see_link\">",
" \"Vertical transmission of hepatitis C virus\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" EPIDEMIOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;In the United States, antibodies to HCV are present in
approximately 0.2 percent of children ages 6 to 12 and in 0.4 percent of those ages
12 to 19, rates that are similar to the prevalence observed in volunteer adult
blood donors but that are lower than adult prevalence based upon National Health
and Nutrition Examination survey data [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/1-3\">",
" 1-3",
" </a>",
" ]. The prevalence rate in children is based upon screening tests performed on
a nationally representative sample [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/1\">",
" 1",
" </a>",
" ]. In comparison, the frequency of cases that are clinically identified is far
lower (5 percent of the expected number), suggesting that screening for and case
identification of pediatric HCV are grossly inadequate [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/4\">",
" 4",
" </a>",
" ]. The proportion of children who are HCV antibody-positive who are also HCV
RNA positive is not known precisely; based upon studies in adults, it is estimated
to be approximately 75 to 80 percent. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?2/7/2169?
source=see_link\">",
" \"Epidemiology and transmission of hepatitis C virus infection\"",
" </a>",
" .)",
" </p>",
" <p>",
" The prevalence is much higher (50 to 95 percent) in individuals who received
blood products for conditions such as thalassemia or hemophilia before 1990 (when a
first-generation ELISA test became available and routine screening of the blood
supply began) to as late as 1992 (when the second-generation ELISA test was
introduced) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/5-7\">",
" 5-7",
" </a>",
" ]. Seroprevalence rates of 10 to 20 percent have been reported among children
with a variety of other potential exposures such as malignancy, hemodialysis,
extracorporeal membrane oxygenation, or surgery for congenital heart disease [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/8-13\">",
" 8-13",
" </a>",
" ]. A 2 percent seroprevalence rate was found in an incarcerated juvenile
population in Washington, DC [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/14\">",
" 14",
" </a>",
" ]. As a general rule, the risk of HCV infection in children who were exposed
to blood products before routine screening is related to the number of units of
blood or blood products received [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/10,12,15\">",
" 10,12,15",
" </a>",
" ]. Most of these at-risk children are now young adults, as routine testing of
the blood supply has virtually eliminated transmission via this route.",
" </p>",
" <p>",
" There appears to be worldwide geographic variation in the prevalence of HCV
infection in children, the reasons for which are incompletely understood. Studies
in the early 1990s (which reflected populations of children who could have been
exposed to contaminated blood products) reported prevalence rates ranging from 0
percent in Japan and Taiwan [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/16,17\">",
" 16,17",
" </a>",
" ]; 0.4 percent in Italy [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/18\">",
" 18",
" </a>",
" ]; 0.6 percent in Malaysia [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/19\">",
" 19",
" </a>",
" ]; 0.9 percent in Saudi Arabia [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/20\">",
" 20",
" </a>",
" ]; 1.4 percent in Moldova [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/21\">",
" 21",
" </a>",
" ]; and up to 14.5 percent in Cameroon [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/22\">",
" 22",
" </a>",
" ]. Prevalence rates in Egypt were low in the 1990s among children without a
history of exposure to blood products [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/15\">",
" 15",
" </a>",
" ], but a more recent series reported HCV rates of 2 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/23\">",
" 23",
" </a>",
" ]. &nbsp;",
" </p>",
" <p>",
" Overall, approximately 28,000 new HCV infections occur in the United States
each year, although the specific incidence in children is unknown [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/24\">",
" 24",
" </a>",
" ]. Perinatal transmission is by far the most common source of infection in
children, accounting for about 750 new",
" <span class=\"nowrap\">",
" cases/year",
" </span>",
" in the United States [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/2\">",
" 2",
" </a>",
" ]. Adolescents may be exposed through high-risk behaviors such as intravenous
or intranasal drug use and use of shared tattoo equipment. The incidence of HCV
vertical transmission is approximately 2 to 5 percent in HCV RNA positive mothers,
with the highest risk in mothers with high HCV viral load. The risk also is
increased at least fourfold for mothers with HIV coinfection. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/19/26936?
source=see_link\">",
" \"Vertical transmission of hepatitis C virus\"",
" </a>",
" .)",
" </p>",
" <p>",
" The epidemiology of HCV infection in developed countries is changing. As an
example, the prevalence of HCV infection among Italian children dropped by more
than 40 percent in the late 1990s, and all new cases appeared to reflect perinatal
transmission [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/25\">",
" 25",
" </a>",
" ]. Some of this change is attributable to elimination of transfusion-
associated hepatitis because of donor screening programs. In addition, several
factors may have contributed to reductions in vertical transmission observed in
some populations. One such factor is that fewer women of childbearing age are
infected with HCV due to prevention campaigns; other factors include aging of women
infected by transfusions and changing patterns of drug abuse. In addition,
antiretroviral therapy in",
" <span class=\"nowrap\">",
" HIV/HCV",
" </span>",
" co-infected women and effective treatment of HCV reduces the rate of vertical
transmission by HCV infected women.",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" NATURAL HISTORY",
" </span>",
" &nbsp;&mdash;&nbsp;The natural history of HCV in children is incompletely
understood. Because the disease generally progresses slowly, serious consequences
such as cirrhosis or hepatocellular carcinoma are rare during childhood. The
following general observations have emerged from natural history studies in
children.",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h2\">",
" Spontaneous clearance",
" </span>",
" &nbsp;&mdash;&nbsp;Infections acquired during infancy (either by transfusion
or through perinatal transmission) are more likely to resolve spontaneously than
infections acquired later in life. Spontaneous clearance rates ranging from 20 to
45 percent have been described in such cases [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/2,26-32\">",
" 2,26-32",
" </a>",
" ]. Infants with vertically transmitted HCV have rates of clearance on the
lower end of this range. (See",
" <a class=\"local\" href=\"#H6\">",
" 'Factors associated with disease progression'",
" </a>",
" below.)",
" </p>",
" <p>",
" One of the largest series with long-term follow-up in perinatally acquired HCV
included 266 children who were followed for a median of 4.2 years [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/33\">",
" 33",
" </a>",
" ]. Approximately 20 percent cleared the infection while 80 percent had chronic
infection. Clearance was less likely in children who remained polymerase chain
reaction (PCR)-positive after the first year of life and those who were
persistently PCR positive during the first year of life. Most children with chronic
infection were asymptomatic. Hepatomegaly was observed in 10 percent.",
" </p>",
" <p>",
" There is also some evidence that the risk of developing chronic infection may
be lower in patients presenting with symptomatic acute HCV infection [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/34\">",
" 34",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/7/18554?
source=see_link&amp;anchor=H164590471#H164590471\">",
" \"Clinical manifestations, diagnosis, and treatment of acute hepatitis C in
adults\", section on 'Spontaneous viral clearance'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Advanced disease",
" </span>",
" &nbsp;&mdash;&nbsp;In many patients, fibrosis scores tend to increase with
age, suggesting there is slowly progressive histologic injury [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/35-38\">",
" 35-38",
" </a>",
" ]. The development of advanced liver disease is uncommon until more than 30
years after infection in children [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/26,27\">",
" 26,27",
" </a>",
" ]. However, progression to advanced fibrosis and cirrhosis during childhood
has been reported, as described in the following case series:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" In a series of 121 treatment-naive children with hepatitis C, 80 percent had
some fibrosis [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/38\">",
" 38",
" </a>",
" ]. This was usually mild, but five patients had bridging fibrosis, and two
had cirrhosis. The patients with advanced fibrosis tended to be older, suggesting
that fibrosis increases with time. Obesity and perhaps other cofactors probably
contribute to the severity of the liver disease.",
" </li>",
" <li>",
" In a series of 332 children with hepatitis C and persistent viremia, six
children progressed to decompensated cirrhosis; the duration of infection before
cirrhosis noted was 2 to 15 years [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/39\">",
" 39",
" </a>",
" ]. Five of the six children were infected with genotype 1a HCV, and only one
was co-infected with HIV.",
" </li>",
" <li>",
" In our practice, we have seen three children who developed decompensated
cirrhosis at ages 11, 13, and 16, respectively. Three children with decompensated
HCV-associated cirrhosis at ages 4, 6, and 11 years also have been reported by
other centers [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/40\">",
" 40",
" </a>",
" ]. In all of these children the HCV infection was acquired perinatally.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h2\">",
" Factors associated with disease progression",
" </span>",
" &nbsp;&mdash;&nbsp;Several factors associated with disease progression have
been described, although the strength of these associations is unclear. Clinical
predictors for disease progression in adults are discussed in detail separately.
(See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/50/31530?
source=see_link&amp;anchor=H6#H6\">",
" \"Clinical manifestations and natural history of chronic hepatitis C virus
infection\", section on 'Natural history'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h3\">",
" Reason for transfusion",
" </span>",
" &nbsp;&mdash;&nbsp;Some studies have suggested that the natural history of HCV
among children infected via transfusion depends upon the underlying disease for
which transfusion was required [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/13,28,29,32\">",
" 13,28,29,32",
" </a>",
" ].",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Congenital heart disease &mdash; Spontaneous clearance appears to occur
relatively commonly (45 to 55 percent) in children who received a blood transfusion
during surgery for congenital heart disease. Furthermore, severe histologic injury
in such patients appears to be uncommon [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/13,29,32\">",
" 13,29,32",
" </a>",
" ]. Despite this somewhat improved prognosis compared to other groups
infected with HCV, these individuals are at risk for significant disease and should
be treated accordingly. The risk for HCV infection after cardiac surgery has
dropped to less than 0.5 percent in some areas, underscoring the effectiveness of
blood donor screening programs [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/41\">",
" 41",
" </a>",
" ].",
" </li>",
" <li>",
" Thalassemia &mdash; End-stage liver disease during childhood is uncommon in
children who received transfusions for thalassemia [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/6\">",
" 6",
" </a>",
" ]. However, such patients are at risk for liver injury from secondary
hemochromatosis [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/42\">",
" 42",
" </a>",
" ]. Iron overload also may diminish the response to therapy for HCV [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/43\">",
" 43",
" </a>",
" ].",
" </li>",
" <li>",
" Hemophilia &mdash; HCV infection may contribute to morbidity and mortality
in children with hemophilia, although end-stage liver disease is uncommon before
adulthood [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/44,45\">",
" 44,45",
" </a>",
" ].",
" </li>",
" <li>",
" Leukemia &mdash; Children treated for leukemia before 1990 have a high rate
of HCV infection [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/46\">",
" 46",
" </a>",
" ]. In one report, serious liver disease did not develop after 13 to 27 years
of follow-up [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/47\">",
" 47",
" </a>",
" ]. On the other hand, another study of 77 HCV-infected children who had been
treated for cancer found one death from liver disease and two deaths from
hepatocellular carcinoma in the decades following HCV acquisition [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/48\">",
" 48",
" </a>",
" ]. In addition, 9 percent of patients developed cirrhosis 9 to 27 years
after diagnosis of the primary malignancy.",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h3\">",
" Perinatal transmission",
" </span>",
" &nbsp;&mdash;&nbsp;Perinatally acquired HCV infection has become the major
route of new infections in children in developed countries. Such children commonly
have elevated serum aminotransferases for a few years that often become normal [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/49\">",
" 49",
" </a>",
" ]. Ten to 20 percent of children with vertically transmitted HCV infection
clear the virus during the first two years of life [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/30,33\">",
" 30,33",
" </a>",
" ]. Estimated rates of spontaneous clearance vary, probably because different
standards are used to define the infected status at birth; one small series
suggested spontaneous clearance rates of up to 75 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/50\">",
" 50",
" </a>",
" ]. Almost all children who remain viremic thereafter have chronic hepatitis
[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/30,33,51,52\">",
" 30,33,51,52",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/19/26936?
source=see_link\">",
" \"Vertical transmission of hepatitis C virus\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h3\">",
" Other",
" </span>",
" &nbsp;&mdash;&nbsp;Several other factors associated with disease progression
have been identified including immunosuppression (from HIV infection or other
causes), chronic alcohol ingestion, and obesity [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/53\">",
" 53",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/50/31530?
source=see_link\">",
" \"Clinical manifestations and natural history of chronic hepatitis C virus
infection\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h1\">",
" SCREENING",
" </span>",
" &nbsp;&mdash;&nbsp;How to identify children at risk for having HCV is
uncertain. A review of 1034 children seen in an urban pediatric hospital found only
one who was HCV positive [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/54\">",
" 54",
" </a>",
" ]. A history of blood transfusion was reported by 7 percent of mothers and
intravenous drug use by 1.8 percent. Mothers tended to underreport prior use of
intravenous drugs compared with a review of their medical records. Based upon such
observations, most experts think that universal screening of children for HCV in
high-risk urban communities is not warranted.",
" </p>",
" <p>",
" We suggest that the following groups be screened for HCV [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/2\">",
" 2",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Children with clinical evidence of hepatitis, including unexplained
elevation of serum alanine aminotransferase (ALT)",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" aspartate aminotransferase (AST), even if asymptomatic",
" </li>",
" <li>",
" Children whose mothers are known to be infected with HCV or have a history
of intravenous drug use. For these infants, testing for HCV antibodies should be
performed after 18 months of age, because the results of this test in younger
infants may reflect passive transfer of maternal antibodies [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/55\">",
" 55",
" </a>",
" ]. If earlier diagnosis is desired, testing for HCV RNA may be performed at
four months of age [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/56\">",
" 56",
" </a>",
" ].",
" </li>",
" <li>",
" Children who are international adoptees or refugees, because most children
adopted into the United States in recent years have come from countries with
relatively high prevalence rates, including Africa, China, Russia, Eastern Europe
and Southeast Asia, and because risk factors for infection rarely are known [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/57\">",
" 57",
" </a>",
" ].",
" </li>",
" <li>",
" Children and adolescents with HIV infection",
" </li>",
" <li>",
" Adolescents or children who are victims of a sexual assault, or adolescents
with a history of multiple sexual partners",
" </li>",
" <li>",
" Adolescents with a history of drug use",
" </li>",
" <li>",
" Individuals who received blood products before 1992",
" </li>",
" <li>",
" Individuals with a history of care in a neonatal intensive care unit (NICU)
prior to 1992, whether or not they are aware of a history of blood transfusion.",
" </li>",
" </ul>",
" </p>",
" <p>",
" Individuals who received blood transfusions during infancy in neonatal
intensive care units (NICU) prior to 1992 are at risk for HCV infection and
represent a large risk group (approximately 500,000 in the United States) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/58\">",
" 58",
" </a>",
" ]. These individuals are now young adults. A study of children who had
received blood transfusions as in a NICU revealed that 3 percent had previously
unrecognized HCV infection [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/59\">",
" 59",
" </a>",
" ]. Only half of the patients or families were aware that they had received the
blood transfusion during the neonatal period. It is unclear whether systematic
screening programs for NICU graduates are a practicable or cost-effective approach
to identifying new cases of HCV [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/58\">",
" 58",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h1\">",
" DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;The principles of diagnosis of HCV infection in children
are similar to those employed in adults. Issues related to diagnosis in the
perinatal period are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/55/41849?
source=see_link\">",
" \"Screening for and diagnosis of chronic hepatitis C virus infection\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/19/26936?
source=see_link\">",
" \"Vertical transmission of hepatitis C virus\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h1\">",
" EVALUATION AND MONITORING",
" </span>",
" &nbsp;&mdash;&nbsp;When HCV infection is diagnosed in a child, further
evaluation is warranted to inform treatment decisions and to monitor for
progression of liver disease.",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h2\">",
" HCV genotyping",
" </span>",
" &nbsp;&mdash;&nbsp;HCV genotyping is useful for guiding the duration of
therapy and predicting the likelihood of response. As a result, we recommend HCV
genotyping for children with confirmed HCV infection. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/55/41849?
source=see_link\">",
" \"Screening for and diagnosis of chronic hepatitis C virus infection\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h2\">",
" Liver biopsy",
" </span>",
" &nbsp;&mdash;&nbsp;A liver biopsy is not required to establish the diagnosis
of HCV infection. However, liver histology (particularly the degree of fibrosis) is
useful for predicting the prognosis of the disease, and may therefore inform
treatment decisions (",
" <a class=\"graphic graphic_algorithm graphicRef72599 \" href=\"UTD.htm?
31/50/32558\">",
" algorithm 1",
" </a>",
" ). In our practice, most decisions about liver biopsies fall into one of the
following categories:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" For children with HCV genotype 1 who are older than five years of age, we
offer a liver biopsy if the family is unsure about whether to proceed to treatment.
This is because patients with this genotype 1 are less likely to respond to
treatment, and the biopsy may provide prognostic information that will help with
the treatment decision. We typically recommend a liver biopsy for prognostic
purposes in children older than 10 years of age, or if there is comorbid disease or
other features that raise concern for rapid progression.",
" </li>",
" <li>",
" For children with genotype 2 or 3, we do not generally perform liver
biopsies. These children are very likely to respond to combination treatment, and
we would recommend treatment regardless of the stage of liver disease. We do offer
a liver biopsy if the parents want to know the stage of disease in considering
treatment, or if the child has comorbid disease for which the results of a biopsy
might influence the decision to treat.",
" </li>",
" <li>",
" For a child with genotype 1 and HCV recently acquired through horizontal
transmission (eg, infection from intravenous drug use), liver biopsy may not be
necessary. Such individuals are unlikely to have advanced liver disease within a
few years of acquisition; thus, biopsy results are unlikely to influence the
treatment decision. (See",
" <a class=\"local\" href=\"#H24\">",
" 'Decision to treat'",
" </a>",
" below.)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h3\">",
" Histology",
" </span>",
" &nbsp;&mdash;&nbsp;Histologic features of HCV infection in children are
similar to those in adults. Characteristic findings include portal lymphoid
aggregates or follicles, steatosis, sinusoidal lymphocytes, and steatosis (",
" <a class=\"graphic graphic_picture graphicRef69510 \" href=\"UTD.htm?
11/63/12279\">",
" picture 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/36,37,60\">",
" 36,37,60",
" </a>",
" ]. Although the histologic features are similar, liver disease appears to be
less severe in children than in adults with similar duration of infection, HCV-RNA
level, and genotype (",
" <a class=\"graphic graphic_picture graphicRef53561 \" href=\"UTD.htm?
33/0/33799\">",
" picture 2",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/61\">",
" 61",
" </a>",
" ]. Cirrhosis is less common than in adults, but may occur during childhood or
adolescence (",
" <a class=\"graphic graphic_picture graphicRef73535 \" href=\"UTD.htm?
21/25/21910\">",
" picture 3",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H3\">",
" 'Natural history'",
" </a>",
" above.)",
" </p>",
" <p>",
" The best clinical predictors of disease progression in adults with chronic HCV
infection are the amount of inflammation and fibrosis on liver biopsy. Other
clinical factors that predict disease progression are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/50/31530?
source=see_link&amp;anchor=H15#H15\">",
" \"Clinical manifestations and natural history of chronic hepatitis C virus
infection\", section on 'Liver biopsy'",
" </a>",
" and",
" <a class=\"local\" href=\"#H6\">",
" 'Factors associated with disease progression'",
" </a>",
" above.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H16\">",
" <span class=\"h2\">",
" Serum aminotransferases",
" </span>",
" &nbsp;&mdash;&nbsp;Serum aminotransferase levels are not consistently related
to disease severity in HCV-infected patients. In one series of children with HCV
infection, one-third had normal aminotransferase levels, despite substantial
histopathological evidence of inflammation [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/38\">",
" 38",
" </a>",
" ]. However, serial measurements may be used to monitor disease activity.",
" </p>",
" <p>",
" In our practice, we monitor otherwise healthy HCV-infected children by
physical examination and measurement of alanine aminotransferase every 6 to 12
months. More frequent monitoring is performed in children with comorbidities, such
as coinfection with HIV, or those taking potentially hepatotoxic medications.",
" </p>",
" <p class=\"headingAnchor\" id=\"H17\">",
" <span class=\"h2\">",
" Malignancy",
" </span>",
" &nbsp;&mdash;&nbsp;Chronic infection with HCV has been associated with
hepatocellular carcinoma (HCC), which occurs almost exclusively in individuals with
cirrhosis [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/62\">",
" 62",
" </a>",
" ]. As a result, HCC is rare among children infected with HCV, but appears to
be more common in children who developed HCV after treatment for childhood leukemia
[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/48,62\">",
" 48,62",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/50/31530?
source=see_link\">",
" \"Clinical manifestations and natural history of chronic hepatitis C virus
infection\"",
" </a>",
" .)",
" </p>",
" <p>",
" In our practice, we monitor children for the possibility of HCC only in
patients with advanced cirrhosis or other risk factors for HCC, including
coinfection with hepatitis B virus (which can cause HCC in the absence of
cirrhosis) or a coexisting malignancy. In such patients, we perform liver
ultrasonography and measure serum alpha fetoprotein levels annually. Successful
treatment of HCV in cirrhotic patients probably does not eliminate the risk of HCC,
so we continue to monitor these patients. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/38/25194?
source=see_link&amp;anchor=H11#H11\">",
" \"Epidemiology and etiologic associations of hepatocellular carcinoma\",
section on 'Hepatitis C'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H18\">",
" <span class=\"h1\">",
" TREATMENT",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H19\">",
" <span class=\"h2\">",
" Acute infection",
" </span>",
" &nbsp;&mdash;&nbsp;Acute HCV infection is uncommonly recognized in children
except in rare outbreaks [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/34\">",
" 34",
" </a>",
" ]. Fulminant hepatitis is rare. There are no data regarding treatment of acute
HCV infection in children. We generally observe such patients for six to eight
weeks to determine whether there is spontaneous clearance, treating those who
continue to have HCV viremia. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/7/18554?
source=see_link\">",
" \"Clinical manifestations, diagnosis, and treatment of acute hepatitis C in
adults\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H20\">",
" <span class=\"h2\">",
" Chronic infection",
" </span>",
" &nbsp;&mdash;&nbsp;Treatment of HCV in children was initially guided by
experience in adults, but now includes multicenter trials in pediatric
populations.",
" </p>",
" <p class=\"headingAnchor\" id=\"H21\">",
" <span class=\"h3\">",
" Pegylated interferon plus ribavirin",
" </span>",
" &nbsp;&mdash;&nbsp;Pegylated interferon, in combination with",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" , is the treatment of choice for most adults and children with chronic HCV
infection who are considered to be appropriate candidates for therapy.",
" </p>",
" <p>",
" In adults, response rates are higher among patients treated with combination
therapy using pegylated interferon as compared to those treated combination therapy
using standard interferon. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/23/41337?
source=see_link\">",
" \"Mechanism of action and efficacy of peginterferon for the treatment of
chronic hepatitis C virus infection\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/45/43735?
source=see_link\">",
" \"Overview of the management of chronic hepatitis C virus infection\"",
" </a>",
" .)",
" </p>",
" <p>",
" Published data on this treatment in children are limited to small studies, as
illustrated by the following reports:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" In an open-labeled, uncontrolled pilot study, 62 children and adolescents, 2
to 17 years of age (mean 10.6 years), with chronic HCV were treated with
subcutaneous",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?37/12/38088?
source=see_link\">",
" pegylated interferon alfa-2b",
" </a>",
" and oral",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" for 48 weeks [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/63\">",
" 63",
" </a>",
" ]. The SVR rate in this cohort was 59 percent at 18 months.",
" </li>",
" <li>",
" A multicenter trial in 114 children with chronic HCV studied the combination
of",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/61/8152?
source=see_link\">",
" pegylated interferon alfa-2a",
" </a>",
" (180",
" <span class=\"nowrap\">",
" micrograms/1.73",
" </span>",
" <span class=\"nowrap\">",
" m",
" ^{",
" 2",
"}",
" /week)",
" </span>",
" and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" (15",
" <span class=\"nowrap\">",
" mg/kg/day",
" </span>",
" orally) as compared to pegylated interferon and placebo (PEDS-C trial) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/64\">",
" 64",
" </a>",
" ]. The SVR rate was substantially higher in children receiving combination
therapy (53 percent) than in those receiving pegylated interferon without ribavirin
(21 percent). Combination therapy was also more effective than peginterferon plus
placebo in both the subgroup with genotype 1 (SVR 47 percent versus 18 percent) and
in the subgroup with non-1 genotypes (SVR 80 percent versus 36 percent).",
" </li>",
" <li>",
" A multicenter trial in 107 children with chronic HCV evaluated the efficacy
and safety of",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?37/12/38088?
source=see_link\">",
" pegylated interferon alfa-2b",
" </a>",
" (60",
" <span class=\"nowrap\">",
" micrograms/m",
" ^{",
" 2",
"}",
" /week)",
" </span>",
" and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" (15",
" <span class=\"nowrap\">",
" mg/kg/day",
" </span>",
" orally) [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/65\">",
" 65",
" </a>",
" ]. Children with genotype 2 or 3 with a low viral load (&lt;600,000",
" <span class=\"nowrap\">",
" IU/mL)",
" </span>",
" were treated for 24 weeks, and those with genotype 1 or 4, or genotype 3
with a high viral load, were treated for 48 weeks. The SVR was 93 percent in
patients with genotype 2 or 3, and 53 percent in those with genotype 1. Adverse
effects included anxiety, depression, or irritability in 28 percent (most did not
require antidepressant treatment), and anemia, neutropenia, or weight loss
requiring dose reduction in 25 percent.",
" </li>",
" <li>",
" An international multicenter trial of",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/61/8152?
source=see_link\">",
" pegylated interferon alfa-2a",
" </a>",
" (100",
" <span class=\"nowrap\">",
" micrograms/m",
" ^{",
" 2",
"}",
" /week)",
" </span>",
" and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" achieved very similar results [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/66\">",
" 66",
" </a>",
" ]. Among 18 children with genotypes 2 and 3 (group A), who were treated for
24 weeks, the SVR was 89 percent. Among 47 children with genotypes 1, 4, 5 or 6
(group B), who were treated with combination therapy for 48 weeks, the SVR was 57
percent. Ten patients in group B stopped treatment prematurely: eight patients
because of lack of response, and two because of serious adverse events (acute
hepatitis or thyrotoxicosis). &nbsp; &nbsp;",
" </li>",
" </ul>",
" </p>",
" <p>",
" In 2008, the US Food and Drug administration (FDA) approved combination
therapy with",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?37/12/38088?
source=see_link\">",
" pegylated interferon alfa-2b",
" </a>",
" and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" for use in children with HCV three years and older with compensated liver
disease. This decision was supported by the results of the large trial described
above [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/65\">",
" 65",
" </a>",
" ]. In 2011,",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/61/8152?source=see_link\">",
" pegylated interferon alfa-2a",
" </a>",
" was approved for use with ribavirin in children in the United States.",
" </p>",
" <p>",
" The adverse effects of pegylated interferon are similar to those of standard
interferon, and include pyrexia, headache, gastrointestinal symptoms and
depression. Pegylated interferon is associated with weight loss or reduced weight
gain, slowed linear growth, and decreased body mass index during the course of
treatment [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/67\">",
" 67",
" </a>",
" ]. These effects generally reverse after cessation of therapy, but residual
effects on height may be seen almost two years after the end of treatment. Overall
quality of life and psychosocial functioning are not significantly affected [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/68\">",
" 68",
" </a>",
" ]. Retinopathy or uveitis develops in 2 to 3 percent of patients treated
with",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/61/8152?source=see_link\">",
" pegylated interferon alfa-2a",
" </a>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/69\">",
" 69",
" </a>",
" ]. Therefore, we perform a baseline ophthalmologic examination prior to
treatment, and repeat the examination during treatment if symptoms develop.
Neutropenia may be significant, but infections associated with the neutropenia are
rare. Important adverse effects of",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" include hemolytic anemia and teratogenicity. These adverse effects are similar
to those seen in adults [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/55\">",
" 55",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/9/16538?
source=see_link\">",
" \"Management of the side effects of peginterferon and ribavirin being used
for treatment of chronic hepatitis C virus infection\"",
" </a>",
" .)",
" </p>",
" <p>",
" In 2009, it was discovered that single nucleotide polymorphisms located near
the gene for interleukin-28B (IL28B) were strongly associated with likelihood of
achieving SVR with peginterferon and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" treatment. A particular polymorphism on chromosome 19, rs12979860, was found
to be strongly associated with SVR in a number of different adult patient groups
[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/70\">",
" 70",
" </a>",
" ]. It has become clear from numerous subsequent studies that host",
" <em>",
" IL28B",
" </em>",
" genotype has a profound effect on outcome of treatment, and this factor will
be incorporated into future therapeutic trials and perhaps even into the routine
management of HCV-infected patients. Testing for",
" <em>",
" IL28B",
" </em>",
" genotype has become more widely available, and could be considered when making
treatment decisions regarding likelihood of response and duration of therapy.
However,",
" <em>",
" IL28B",
" </em>",
" genotype has not yet been evaluated as a predictor of response in the
pediatric population.",
" </p>",
" <p class=\"headingAnchor\" id=\"H22\">",
" <span class=\"h3\">",
" Standard interferon plus ribavirin",
" </span>",
" &nbsp;&mdash;&nbsp;Combination therapy with interferon-alfa and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" was the first established treatment for HCV infection in children [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/71\">",
" 71",
" </a>",
" ]. For most children and adults, pegylated interferon is now preferred. (See",
" <a class=\"local\" href=\"#H21\">",
" 'Pegylated interferon plus ribavirin'",
" </a>",
" above.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H23\">",
" <span class=\"h3\">",
" Interferon monotherapy",
" </span>",
" &nbsp;&mdash;&nbsp;In early studies, interferon monotherapy (interferon
without",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" ) in children with HCV produced rates of sustained virologic response (SVR)
ranging from 33 to 45 percent [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/72\">",
" 72",
" </a>",
" ]. The SVR rate appeared to be higher in children than in adults. Nonetheless,
interferon monotherapy is not recommended because it has substantially lower SVR
rates than combination therapy, as discussed above.",
" </p>",
" <p class=\"headingAnchor\" id=\"H22932936\">",
" <span class=\"h3\">",
" Triple therapy",
" </span>",
" &nbsp;&mdash;&nbsp;As of May 2011, two protease inhibitors,",
" <a class=\"drug drug_general\" href=\"UTD.htm?26/40/27273?source=see_link\">",
" boceprevir",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/6/20585?source=see_link\">",
" telaprevir",
" </a>",
" , are licensed in the United States for use in combination with pegylated
interferon and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" in adults with chronic HCV genotype 1. This therapy is associated with a
significantly higher rate of sustained virologic response as compared with the
combination of pegylated interferon and ribavirin. A pediatric trial of combination
therapy with boceprevir is underway (",
" <a class=\"external\"
href=\"file://clinicaltrials.gov/ct2/show/NCT01590225\">",
" NCT01590225",
" </a>",
" ), and a trial of telaprevir is being planned. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?23/47/24314?
source=see_link\">",
" \"Treatment regimens for chronic hepatitis C virus genotype 1\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H24\">",
" <span class=\"h3\">",
" Decision to treat",
" </span>",
" &nbsp;&mdash;&nbsp;Practice recommendations for children with chronic HCV are
similar to those for adults [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/55\">",
" 55",
" </a>",
" ]. However, because of limited data in the pediatric age group, treatment
decisions may vary with the child's age and individual disease characteristics. The
following recommendations reflect our practice and are based on the pediatric
studies cited above, as well some extrapolations from adult treatment trials.",
" </p>",
" <p>",
" Combination treatment with peginterferon plus",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" should be considered for children with chronic HCV infection who are older
than three years and who appear to have progressive disease or advanced histologic
features. For these children, our course of action depends on the HCV genotype (",
" <a class=\"graphic graphic_algorithm graphicRef72599 \" href=\"UTD.htm?
31/50/32558\">",
" algorithm 1",
" </a>",
" ):",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" For those with genotype 2 or 3 (in whom response rates are highest), we
proceed to treatment. We do not generally recommend a liver biopsy before treatment
in such patients since the response rates are high. Exceptions are children whose
parents want to know the stage of disease in considering treatment, and those with
comorbid diseases in whom the results of a biopsy might influence the decision to
treat.",
" </li>",
" <li>",
" For those with genotype 1, we also encourage proceeding to treatment, but
the child's age, presence of comorbid diseases, and family's preference are
important components of the decision (",
" <a class=\"graphic graphic_algorithm graphicRef72599 \" href=\"UTD.htm?
31/50/32558\">",
" algorithm 1",
" </a>",
" ). We encourage treatment more strongly in children with perinatally
acquired HCV who are older than 10 years, and in those with a comorbid disease or
other features that raise concern for rapid progression; for these groups we
recommend a liver biopsy primarily for prognostic purposes rather than as part of a
treatment decision (see",
" <a class=\"local\" href=\"#H14\">",
" 'Liver biopsy'",
" </a>",
" above).",
" </li>",
" </ul>",
" </p>",
" <p>",
" For younger patients with genotype 1 (between 3 and 10 years old), some
families would like to have additional prognostic information prior to making a
treatment decision, because these patients are less likely to respond to treatment
than those with genotypes 2 or 3. In this case, we recommend a liver biopsy to
assist in the treatment decision (unless there are contraindications such as
hemophilia, or unless the HCV was clearly recently acquired). When a liver biopsy
is performed, our treatment recommendation depends on the results. For patients
with moderate or severe histopathology we recommend treatment, on the presumption
that this finding indicates more rapid disease progression. For those with mild
histopathologic features, we encourage treatment, but recognize that it is
reasonable to observe without treatment; we make this decision with the family
after consideration of the efficacy of treatment for this group and the potential
risks for the individual patient. If observation is chosen, we suggest reevaluation
with a liver biopsy in five to seven years.",
" </p>",
" <p>",
" For patients with genotype 1 who are close to 18 years of age, we may
recommend waiting until after the 18",
" ^{",
" th",
"}",
" birthday, then treating with the regimen recommended for adults, which now
includes the protease inhibitors",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/6/20585?source=see_link\">",
" telaprevir",
" </a>",
" or",
" <a class=\"drug drug_general\" href=\"UTD.htm?26/40/27273?source=see_link\">",
" boceprevir",
" </a>",
" . (See",
" <a class=\"local\" href=\"#H22932936\">",
" 'Triple therapy'",
" </a>",
" above and",
" <a class=\"medical medical_review\" href=\"UTD.htm?23/47/24314?
source=see_link\">",
" \"Treatment regimens for chronic hepatitis C virus genotype 1\"",
" </a>",
" .) &nbsp;",
" </p>",
" <p>",
" Patients with obesity are also somewhat less likely to respond to HCV therapy.
In one study using several different IFN-based treatments, each standard deviation
(1 Z-score unit) increase in Body Mass Index was associated with a 12 percent
decrease in the probability of a sustained virologic response [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/53\">",
" 53",
" </a>",
" ]. However, because of limited evidence we do not exclude overweight or obese
children from consideration of treatment. On the other hand, since progression of
liver injury from HCV is slow, for obese children we often encourage a period of
weight loss for several months or a year before initiating antiviral therapy. The
association between obesity and reduced treatment response has also been observed
in adults. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?14/8/14474?
source=see_link&amp;anchor=H16092975#H16092975\">",
" \"Predictors of a sustained virologic response following treatment with
peginterferon and ribavirin for chronic hepatitis C virus infection\", section on
'Other predictors'",
" </a>",
" .) &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H25\">",
" <span class=\"h3\">",
" How to treat",
" </span>",
" &nbsp;&mdash;&nbsp;When treatment is chosen for any of the above groups, we
recommend the combination of pegylated interferon with",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/55\">",
" 55",
" </a>",
" ].",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?37/12/38088?
source=see_link\">",
" Pegylated interferon alfa-2b",
" </a>",
" has been approved by the FDA for use in children three years and older (60",
" <span class=\"nowrap\">",
" mcg/m",
" ^{",
" 2",
"}",
" </span>",
" once weekly, maximum dose 1.5",
" <span class=\"nowrap\">",
" micrograms/kg)",
" </span>",
" in combination with ribavirin (15",
" <span class=\"nowrap\">",
" mg/kg/day",
" </span>",
" in two divided doses) (",
" <a class=\"graphic graphic_table graphicRef61219 \" href=\"UTD.htm?
14/14/14572\">",
" table 1",
" </a>",
" ).",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/61/8152?source=see_link\">",
" Pegylated interferon alfa-2a",
" </a>",
" (180",
" <span class=\"nowrap\">",
" micrograms/1.73",
" </span>",
" m",
" ^{",
" 2",
"}",
" weekly, maximum dose 180 micrograms) can also be used in combination with
ribavirin in children five years and older.",
" </p>",
" <p>",
" The treatment duration varies by genotype, as it does for adults [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/55\">",
" 55",
" </a>",
" ].",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" For genotype 2 or 3, we typically treat for 24 weeks (see",
" <a class=\"medical medical_review\" href=\"UTD.htm?0/37/600?
source=see_link\">",
" \"Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and
4\"",
" </a>",
" ).",
" </li>",
" <li>",
" For genotype 1, we use the same algorithm that is used for adults to
determine the length of treatment. Treatment is planned for 48 weeks, but may be
discontinued earlier in those who do not achieve an early virologic response (ie,
at least a 2-log decline from baseline of the HCV RNA level at week 12), or
extended to 72 weeks for those with a slow virologic response. These parameters for
deciding on treatment length are discussed in detail separately (see",
" <a class=\"medical medical_review\" href=\"UTD.htm?23/47/24314?
source=see_link&amp;anchor=H148834087#H148834087\">",
" \"Treatment regimens for chronic hepatitis C virus genotype 1\", section on
'Patients not receiving a protease inhibitor'",
" </a>",
" ). If possible, treatment of children with HCV genotype 1 might be deferred
until triple therapy is available for children, or done sooner if under the
auspices of a clinical trial (see",
" <a class=\"local\" href=\"#H22932936\">",
" 'Triple therapy'",
" </a>",
" above). &nbsp;",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H26\">",
" <span class=\"h1\">",
" COUNSELING",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H27\">",
" <span class=\"h2\">",
" Prevention of transmission",
" </span>",
" &nbsp;&mdash;&nbsp;The primary strategies to prevent HCV infection should
focus on perinatal transmission, which, as noted above, is the most common cause of
HCV acquisition in children. Universal testing of pregnant women for HCV is not
recommended. Optimal methods to reduce the risk of transmission in women known to
be HCV infected are incompletely understood, although several factors associated
with an increased risk of transmission have been described. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/19/26936?
source=see_link\">",
" \"Vertical transmission of hepatitis C virus\"",
" </a>",
" .)",
" </p>",
" <p>",
" HCV is not spread within households, school, or daycare settings [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/73,74\">",
" 73,74",
" </a>",
" ]. Because it is transmitted by blood, it may be prudent to avoid sharing
razors, toothbrushes, nail clippers, and other implements that may be contaminated
with blood of an infected individual. Although HCV can be detected in low levels in
saliva [",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/75\">",
" 75",
" </a>",
" ], the risk of transmission through saliva appears to be minimal. It is not
necessary to avoid sharing eating utensils, drinking glasses, or towels.",
" </p>",
" <p>",
" Prevention of new HCV infections in older children and adolescents focuses
mostly on counseling for high-risk behaviors. While commercial body piercing and
tattooing are not clearly associated with increased risk, self-tattooing and self-
piercing with shared needles are common practices and should be discouraged.
Similarly, the risk of transmission is increased with the use of intravenous
drugs",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" intranasal cocaine because of sharing of potentially contaminated equipment.
The risk of sexual transmission, albeit low, may not be appreciated by teenagers
[",
" <a class=\"abstract\" href=\"UTD.htm?6/2/6186/abstract/14\">",
" 14",
" </a>",
" ]. Sex with multiple partners is a risk factor for HCV infection, but may not
be directly responsible for transmission. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?2/7/2169?
source=see_link&amp;anchor=H9#H9\">",
" \"Epidemiology and transmission of hepatitis C virus infection\", section on
'Sexual or household contact'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H28\">",
" <span class=\"h2\">",
" Minimizing risk for disease progression",
" </span>",
" &nbsp;&mdash;&nbsp;The following general measures are recommended for patients
with chronic HCV:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Patients should avoid alcohol consumption. Alcohol promotes the progression
of chronic HCV. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?9/17/9496?
source=see_link\">",
" \"Hepatitis C and alcohol\"",
" </a>",
" .)",
" </li>",
" <li>",
" Patients should be immunized against hepatitis A and hepatitis B, if not
already immune. They should also receive standard immunizations that are applicable
to an otherwise healthy population. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/23/8569?
source=see_link\">",
" \"Immunizations for patients with chronic liver disease\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/56/39818?
source=see_link&amp;anchor=H2#H2\">",
" \"Standard immunizations for children and adolescents\", section on
'Overview'",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p>",
" There is no evidence that",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?19/15/19705?
source=see_link\">",
" acetaminophen",
" </a>",
" use promotes disease progression in patients with HCV and normal liver
function, but it is appropriate to remind patients to use no more than recommended
doses. Patients with advanced liver disease (HCV or other) should avoid non-
steroidal anti-inflammatory drugs such as",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/48/7946?source=see_link\">",
" ibuprofen",
" </a>",
" .",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" <span class=\"h1\">",
" INFORMATION FOR PATIENTS",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
&ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
education pieces are written in plain language, at the 5",
" ^{",
" th",
"}",
" to 6",
" ^{",
" th",
"}",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" ^{",
" th",
"}",
" to 12",
" ^{",
" th",
"}",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
&ldquo;patient info&rdquo; and the keyword(s) of interest.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Beyond the Basics topics (See",
" <a class=\"medical medical_patient\" href=\"UTD.htm?17/4/17478?
source=see_link\">",
" \"Patient information: Hepatitis C (Beyond the Basics)\"",
" </a>",
" .)",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H30\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" The prevalence of HCV infection is lower in children than in adults.
Perinatal transmission is by far the most common source of infection in children.
(See",
" <a class=\"local\" href=\"#H2\">",
" 'Epidemiology'",
" </a>",
" above and",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/19/26936?
source=see_link\">",
" \"Vertical transmission of hepatitis C virus\"",
" </a>",
" .)",
" </li>",
" <li>",
" Testing for HCV is generally recommended in children of mothers known to be
infected with HCV or with a history of intravenous drug use. Testing also should be
performed in children who received blood products prior to 1992. Testing also is
recommended for children who are international adoptees or refugees. (See",
" <a class=\"local\" href=\"#H10\">",
" 'Screening'",
" </a>",
" above.)",
" </li>",
" <li>",
" HCV generally progresses slowly in children, although there are exceptions.
(See",
" <a class=\"local\" href=\"#H3\">",
" 'Natural history'",
" </a>",
" above.)",
" </li>",
" <li>",
" As in adults, treatment response rates to combination therapy with pegylated
interferon (or standard interferon) and",
" <a class=\"drug drug_pediatric\" href=\"UTD.htm?11/59/12216?
source=see_link\">",
" ribavirin",
" </a>",
" are higher in individuals with HCV genotype 2 or 3 as compared to genotype
1. (See",
" <a class=\"local\" href=\"#H21\">",
" 'Pegylated interferon plus ribavirin'",
" </a>",
" above.)",
" </li>",
" <li>",
" For children with chronic HCV infection, the decision about whether to
evaluate with a liver biopsy depends on the HCV genotype and the child's age (or
duration of HCV infection if horizontally acquired) (",
" <a class=\"graphic graphic_algorithm graphicRef72599 \" href=\"UTD.htm?
31/50/32558\">",
" algorithm 1",
" </a>",
" ). For those with genotype 2 or 3 who are older than three years, we
generally proceed to treatment without liver biopsy. For children with genotype 1,
we encourage treatment, but offer a liver biopsy if families would like to have
additional prognostic information before making a treatment decision. (See",
" <a class=\"local\" href=\"#H14\">",
" 'Liver biopsy'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" For patients with HCV genotype 2 or 3, or for those with genotype 1 and
moderate or severe histopathology, we recommend treatment rather than observation
(",
" <a class=\"grade\" href=\"._grade_2?title=Grade 1B\">",
" Grade 1B",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H24\">",
" 'Decision to treat'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H25\">",
" 'How to treat'",
" </a>",
" above.)",
" </li>",
" <li>",
" For patients with HCV genotype 1 and mild histopathologic features, we
encourage treatment if the child is older than age three, but it is also reasonable
to observe without treatment. (See",
" <a class=\"local\" href=\"#H24\">",
" 'Decision to treat'",
" </a>",
" above.)",
" </li>",
" <li>",
" For children with HCV genotype 1, treatment might also be deferred until
triple therapy is available for children, or done sooner in the context of a
clinical trial. (See",
" <a class=\"local\" href=\"#H22932936\">",
" 'Triple therapy'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" For patients embarking on treatment for HCV we recommend treatment with
combination therapy rather than interferon monotherapy (",
" <a class=\"grade\" href=\"._grade_1?title=Grade 1A\">",
" Grade 1A",
" </a>",
" ) (",
" <a class=\"graphic graphic_table graphicRef61219 \" href=\"UTD.htm?
14/14/14572\">",
" table 1",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H21\">",
" 'Pegylated interferon plus ribavirin'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H25\">",
" 'How to treat'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/1\">",
" Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C
virus infection in the United States, 1988 through 1994. N Engl J Med 1999;
341:556.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/2\">",
" Jhaveri R. Diagnosis and management of hepatitis C virus-infected children.
Pediatr Infect Dis J 2011; 30:983.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/3\">",
" Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C
virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;
144:705.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/4\">",
" Delgado-Borrego A, Smith L, Jonas MM, et al. Expected and actual case
ascertainment and treatment rates for children infected with hepatitis C in Florida
and the United States: epidemiologic evidence from statewide and nationwide
surveys. J Pediatr 2012; 161:915.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/5\">",
" Resti M, Azzari C, Rossi ME, et al. Hepatitis C virus antibodies in a long-
term follow-up of beta-thalassaemic children with acute and chronic non-A non-B
hepatitis. Eur J Pediatr 1992; 151:573.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/6\">",
" Lai ME, De Virgilis S, Argiolu F, et al. Evaluation of antibodies to
hepatitis C virus in a long-term prospective study of posttransfusion hepatitis
among thalassemic children: comparison between first- and second-generation assay.
J Pediatr Gastroenterol Nutr 1993; 16:458.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/7\">",
" Blanchette VS, Vorstman E, Shore A, et al. Hepatitis C infection in children
with hemophilia A and B. Blood 1991; 78:285.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/8\">",
" Locasciulli A, Gornati G, Tagger A, et al. Hepatitis C virus infection and
chronic liver disease in children with leukemia in long-term remission. Blood 1991;
78:1619.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/9\">",
" Rossetti F, Cesaro S, Pizzocchero P, et al. Chronic hepatitis B surface
antigen-negative hepatitis after treatment of malignancy. J Pediatr 1992; 121:39.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/10\">",
" Jonas MM, Zilleruelo GE, LaRue SI, et al. Hepatitis C infection in a
pediatric dialysis population. Pediatrics 1992; 89:707.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/11\">",
" Greco M, Cristiano K, Leozappa G, et al. Hepatitis C infection in children
and adolescents on haemodialysis and after renal transplant. Pediatr Nephrol 1993;
7:424.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/12\">",
" Nelson SP, Jonas MM. Hepatitis C infection in children who received
extracorporeal membrane oxygenation. J Pediatr Surg 1996; 31:644.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/13\">",
" Ni YH, Chang MH, Lue HC, et al. Posttransfusion hepatitis C virus infection
in children. J Pediatr 1994; 124:709.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/14\">",
" Murray KF, Richardson LP, Morishima C, et al. Prevalence of hepatitis C
virus infection and risk factors in an incarcerated juvenile population: a pilot
study. Pediatrics 2003; 111:153.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/15\">",
" Khalifa AS, Mitchell BS, Watts DM, et al. Prevalence of hepatitis C viral
antibody in transfused and nontransfused Egyptian children. Am J Trop Med Hyg 1993;
49:316.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/16\">",
" Tanaka E, Kiyosawa K, Sodeyama T, et al. Prevalence of antibody to hepatitis
C virus in Japanese schoolchildren: comparison with adult blood donors. Am J Trop
Med Hyg 1992; 46:460.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/17\">",
" Lee SD, Chan CY, Wang YJ, et al. Seroepidemiology of hepatitis C virus
infection in Taiwan. Hepatology 1991; 13:830.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/18\">",
" Gessoni G, Manoni F. Prevalence of anti-hepatitis C virus antibodies among
teenagers in the Venetian area: a seroepidemiological study. Eur J Med 1993;
2:79.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/19\">",
" Lee WS, Ng KP. Seroprevalence of anti-HCV in an urban child population: a
preliminary study from Kuala Lumpur. Singapore Med J 2001; 42:100.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/20\">",
" al-Faleh FZ, Ayoola EA, al-Jeffry M, et al. Prevalence of antibody to
hepatitis C virus among Saudi Arabian children: a community-based study. Hepatology
1991; 14:215.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/21\">",
" Drobeniuc J, Hutin YJ, Harpaz R, et al. Prevalence of hepatitis B, D and C
virus infections among children and pregnant women in Moldova: additional evidence
supporting the need for routine hepatitis B vaccination of infants. Epidemiol
Infect 1999; 123:463.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/22\">",
" Ngatchu T, Stroffolini T, Rapicetta M, et al. Seroprevalence of anti-HCV in
an urban child population: a pilot survey in a developing area, Cameroon. J Trop
Med Hyg 1992; 95:57.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/23\">",
" El-Raziky MS, El-Hawary M, Esmat G, et al. Prevalence and risk factors of
asymptomatic hepatitis C virus infection in Egyptian children. World J
Gastroenterol 2007; 13:1828.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/24\">",
" Alter MJ. Epidemiology of hepatitis C. Hepatology 1997; 26:62S.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/25\">",
" Bortolotti F, Iorio R, Jorio R, et al. Epidemiological profile of 806
Italian children with hepatitis C virus infection over a 15-year period. J Hepatol
2007; 46:783.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/26\">",
" Minola E, Prati D, Suter F, et al. Age at infection affects the long-term
outcome of transfusion-associated chronic hepatitis C. Blood 2002; 99:4588.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/27\">",
" Casiraghi MA, De Paschale M, Roman&ograve; L, et al. Long-term outcome (35
years) of hepatitis C after acquisition of infection through mini transfusions of
blood given at birth. Hepatology 2004; 39:90.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/28\">",
" Matsuoka S, Tatara K, Hayabuchi Y, et al. Serologic, virologic, and
histologic characteristics of chronic phase hepatitis C virus disease in children
infected by transfusion. Pediatrics 1994; 94:919.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/29\">",
" Vogt M, Lang T, Fr&ouml;sner G, et al. Prevalence and clinical outcome of
hepatitis C infection in children who underwent cardiac surgery before the
implementation of blood-donor screening. N Engl J Med 1999; 341:866.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/30\">",
" Tovo PA, Pembrey LJ, Newell ML. Persistence rate and progression of
vertically acquired hepatitis C infection. European Paediatric Hepatitis C Virus
Infection. J Infect Dis 2000; 181:419.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/31\">",
" Mohan P, Colvin C, Glymph C, et al. Clinical spectrum and histopathologic
features of chronic hepatitis C infection in children. J Pediatr 2007; 150:168.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/32\">",
" Matsuoka S, Tatara K, Hayabuchi Y, et al. Post-transfusion chronic hepatitis
C in children. J Paediatr Child Health 1994; 30:544.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/33\">",
" European Paediatric Hepatitis C Virus Network. Three broad modalities in the
natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis
2005; 41:45.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/34\">",
" Jonas MM, Baron MJ, Bresee JS, Schneider LC. Clinical and virologic features
of hepatitis C virus infection associated with intravenous immunoglobulin.
Pediatrics 1996; 98:211.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/35\">",
" Jara P, Resti M, Hierro L, et al. Chronic hepatitis C virus infection in
childhood: clinical patterns and evolution in 224 white children. Clin Infect Dis
2003; 36:275.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/36\">",
" Badizadegan K, Jonas MM, Ott MJ, et al. Histopathology of the liver in
children with chronic hepatitis C viral infection. Hepatology 1998; 28:1416.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/37\">",
" Guido M, Rugge M, Jara P, et al. Chronic hepatitis C in children: the
pathological and clinical spectrum. Gastroenterology 1998; 115:1525.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/38\">",
" Goodman ZD, Makhlouf HR, Liu L, et al. Pathology of chronic hepatitis C in
children: liver biopsy findings in the Peds-C Trial. Hepatology 2008; 47:836.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/39\">",
" Bortolotti F, Verucchi G, Camm&agrave; C, et al. Long-term course of chronic
hepatitis C in children: from viral clearance to end-stage liver disease.
Gastroenterology 2008; 134:1900.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/40\">",
" Birnbaum AH, Shneider BL, Moy L. Hepatitis C in children. N Engl J Med 2000;
342:290.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/41\">",
" Vogt M, M&uuml;hlbauer F, Braun SL, et al. Prevalence and risk factors of
hepatitis C infection after cardiac surgery in childhood before and after blood
donor screening. Infection 2004; 32:134.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/42\">",
" Angelucci E, Muretto P, Nicolucci A, et al. Effects of iron overload and
hepatitis C virus positivity in determining progression of liver fibrosis in
thalassemia following bone marrow transplantation. Blood 2002; 100:17.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/43\">",
" Clemente MG, Congia M, Lai ME, et al. Effect of iron overload on the
response to recombinant interferon-alfa treatment in transfusion-dependent patients
with thalassemia major and chronic hepatitis C. J Pediatr 1994; 125:123.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/44\">",
" Makris M, Preston FE, Rosendaal FR, et al. The natural history of chronic
hepatitis C in haemophiliacs. Br J Haematol 1996; 94:746.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/45\">",
" Goedert JJ, Eyster ME, Lederman MM, et al. End-stage liver disease in
persons with hemophilia and transfusion-associated infections. Blood 2002;
100:1584.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/46\">",
" Aric&ograve; M, Maggiore G, Silini E, et al. Hepatitis C virus infection in
children treated for acute lymphoblastic leukemia. Blood 1994; 84:2919.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/47\">",
" Locasciulli A, Testa M, Pontisso P, et al. Prevalence and natural history of
hepatitis C infection in patients cured of childhood leukemia. Blood 1997;
90:4628.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/48\">",
" Strickland DK, Riely CA, Patrick CC, et al. Hepatitis C infection among
survivors of childhood cancer. Blood 2000; 95:3065.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/49\">",
" Giacchino R, Tasso L, Timitilli A, et al. Vertical transmission of hepatitis
C virus infection: usefulness of viremia detection in HIV-seronegative hepatitis C
virus-seropositive mothers. J Pediatr 1998; 132:167.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/50\">",
" Ceci O, Margiotta M, Marello F, et al. Vertical transmission of hepatitis C
virus in a cohort of 2,447 HIV-seronegative pregnant women: a 24-month prospective
study. J Pediatr Gastroenterol Nutr 2001; 33:570.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/51\">",
" Palomba E, Manzini P, Fiammengo P, et al. Natural history of perinatal
hepatitis C virus infection. Clin Infect Dis 1996; 23:47.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/52\">",
" Bortolotti F, Resti M, Giacchino R, et al. Hepatitis C virus infection and
related liver disease in children of mothers with antibodies to the virus. J
Pediatr 1997; 130:990.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/53\">",
" Delgado-Borrego A, Healey D, Negre B, et al. Influence of body mass index on
outcome of pediatric chronic hepatitis C virus infection. J Pediatr Gastroenterol
Nutr 2010; 51:191.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/54\">",
" El-Kamary SS, Serwint JR, Joffe A, et al. Prevalence of hepatitis C virus
infection in urban children. J Pediatr 2003; 143:54.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/55\">",
" Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment
of hepatitis C: an update. Hepatology 2009; 49:1335.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/56\">",
" Conte D, Fraquelli M, Prati D, et al. Prevalence and clinical course of
chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in
a cohort of 15,250 pregnant women. Hepatology 2000; 31:751.",
" </a>",
" </li>",
" <li>",
" American Academy of Pediatrics. Medical evaluation of internationally adopted
children for infectious diseases. In: Red Book: 2012 Report of the Committee on
Infectious Diseases, 29th ed, Pickering LK, Baker CJ, Kimberlin DW, Long SS, Eds
(Eds), American Academy of Pediatrics, Elk Grove Village, IL 2012. p.193.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/58\">",
" Jonas MM. Finding adolescents and young adults with transfusion-associated
hepatitis C: looking forward to looking back. Arch Pediatr Adolesc Med 2007;
161:202.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/59\">",
" Cagle HH, Jacob J, Homan CE, et al. Results of a general hepatitis C
lookback program for persons who received blood transfusions in a neonatal
intensive care unit between January 1975 and July 1992. Arch Pediatr Adolesc Med
2007; 161:125.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/60\">",
" Kage M, Fujisawa T, Shiraki K, et al. Pathology of chronic hepatitis C in
children. Child Liver Study Group of Japan. Hepatology 1997; 26:771.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/61\">",
" Murray KF, Finn LS, Taylor SL, et al. Liver histology and alanine
aminotransferase levels in children and adults with chronic hepatitis C infection.
J Pediatr Gastroenterol Nutr 2005; 41:634.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/62\">",
" Gonz&aacute;lez-Peralta RP, Langham MR Jr, Andres JM, et al. Hepatocellular
carcinoma in 2 young adolescents with chronic hepatitis C. J Pediatr Gastroenterol
Nutr 2009; 48:630.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/63\">",
" Wirth S, Pieper-Boustani H, Lang T, et al. Peginterferon alfa-2b plus
ribavirin treatment in children and adolescents with chronic hepatitis C.
Hepatology 2005; 41:1013.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/64\">",
" Schwarz KB, Gonzalez-Peralta RP, Murray KF, et al. The combination of
ribavirin and peginterferon is superior to peginterferon and placebo for children
and adolescents with chronic hepatitis C. Gastroenterology 2011; 140:450.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/65\">",
" Wirth S, Ribes-Koninckx C, Calzado MA, et al. High sustained virologic
response rates in children with chronic hepatitis C receiving peginterferon alfa-2b
plus ribavirin. J Hepatol 2010; 52:501.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/66\">",
" Sokal EM, Bourgois A, St&eacute;phenne X, et al. Peginterferon alfa-2a plus
ribavirin for chronic hepatitis C virus infection in children and adolescents. J
Hepatol 2010; 52:827.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/67\">",
" Jonas MM, Balistreri W, Gonzalez-Peralta RP, et al. Pegylated interferon for
chronic hepatitis C in children affects growth and body composition: results from
the pediatric study of hepatitis C (PEDS-C) trial. Hepatology 2012; 56:523.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/68\">",
" Rodrigue JR, Balistreri W, Haber B, et al. Peginterferon with or without
ribavirin has minimal effect on quality of life, behavioral/emotional, and
cognitive outcomes in children. Hepatology 2011; 53:1468.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/69\">",
" Narkewicz MR, Rosenthal P, Schwarz KB, et al. Ophthalmologic complications
in children with chronic hepatitis C treated with pegylated interferon. J Pediatr
Gastroenterol Nutr 2010; 51:183.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/70\">",
" Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts
hepatitis C treatment-induced viral clearance. Nature 2009; 461:399.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/71\">",
" Gonz&aacute;lez-Peralta RP, Kelly DA, Haber B, et al. Interferon alfa-2b in
combination with ribavirin for the treatment of chronic hepatitis C in children:
efficacy, safety, and pharmacokinetics. Hepatology 2005; 42:1010.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/72\">",
" Jacobson KR, Murray K, Zellos A, Schwarz KB. An analysis of published trials
of interferon monotherapy in children with chronic hepatitis C. J Pediatr
Gastroenterol Nutr 2002; 34:52.",
" </a>",
" </li>",
" <li>",
" American Academy of Pediatrics. Hepatitis C. In: Red Book: 2009 Report of the
Committee on Infectious Diseases, 28th, Pickering LK (Ed), American Academy of
Pediatrics, Elk Grove Village 2009.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/74\">",
" Vegnente A, Iorio R, Saviano A, et al. Lack of intrafamilial transmission of
hepatitis C virus in family members of children with chronic hepatitis c infection.
Pediatr Infect Dis J 1994; 13:886.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?6/2/6186/abstract/75\">",
" Suzuki T, Omata K, Satoh T, et al. Quantitative detection of hepatitis C
virus (HCV) RNA in saliva and gingival crevicular fluid of HCV-infected patients. J
Clin Microbiol 2005; 43:4413.",
" </a>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 5944 Version 18.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
" </span>",
" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [1104-180.241.123.62-8D972B75FE-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6186=[""].join("\n");
var outline_f6_2_6186=[" <div id=\"toggleOutline\">",
" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H30\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" EPIDEMIOLOGY",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" NATURAL HISTORY",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" Spontaneous clearance",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" Advanced disease",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" Factors associated with disease progression",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H7\">",
" - Reason for transfusion",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H8\">",
" - Perinatal transmission",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H9\">",
" - Other",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H10\">",
" SCREENING",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H11\">",
" DIAGNOSIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H12\">",
" EVALUATION AND MONITORING",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H13\">",
" HCV genotyping",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H14\">",
" Liver biopsy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H15\">",
" - Histology",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H16\">",
" Serum aminotransferases",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H17\">",
" Malignancy",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H18\">",
" TREATMENT",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H19\">",
" Acute infection",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H20\">",
" Chronic infection",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H21\">",
" - Pegylated interferon plus ribavirin",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H22\">",
" - Standard interferon plus ribavirin",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H23\">",
" - Interferon monotherapy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H22932936\">",
" - Triple therapy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H24\">",
" - Decision to treat",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H25\">",
" - How to treat",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H26\">",
" COUNSELING",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H27\">",
" Prevention of transmission",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H28\">",
" Minimizing risk for disease progression",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" INFORMATION FOR PATIENTS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H30\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"PEDS/5944\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"PEDS/5944|ALG\">",
" <a href=\"#\" title=\"ALGORITHMS\">",
" ALGORITHMS",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_algorithm\" href=\"UTD.htm?31/50/32558\"
title=\"algorithm 1\">",
" Approach HCV child",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"PEDS/5944|PIC\">",
" <a href=\"#\" title=\"PICTURES\">",
" PICTURES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?11/63/12279\"
title=\"picture 1\">",
" HCV hepatitis",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?33/0/33799\"
title=\"picture 2\">",
" HCV hepatitis Light",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_picture\" href=\"UTD.htm?21/25/21910\"
title=\"picture 3\">",
" HCV cirrhosis Light",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <div class=\"openRelatedGraphics\" id=\"PEDS/5944|TAB\">",
" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
" </div>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?14/14/14572\" title=\"table
1\">",
" PegIFN Rx child HCV",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?30/50/31530?
source=related_link\">",
" Clinical manifestations and natural history of chronic hepatitis C virus
infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?18/7/18554?
source=related_link\">",
" Clinical manifestations, diagnosis, and treatment of acute hepatitis C in
adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?24/38/25194?
source=related_link\">",
" Epidemiology and etiologic associations of hepatocellular carcinoma",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?2/7/2169?
source=related_link\">",
" Epidemiology and transmission of hepatitis C virus infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?9/17/9496?
source=related_link\">",
" Hepatitis C and alcohol",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/23/8569?
source=related_link\">",
" Immunizations for patients with chronic liver disease",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/9/16538?
source=related_link\">",
" Management of the side effects of peginterferon and ribavirin being used for
treatment of chronic hepatitis C virus infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/23/41337?
source=related_link\">",
" Mechanism of action and efficacy of peginterferon for the treatment of
chronic hepatitis C virus infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/45/43735?
source=related_link\">",
" Overview of the management of chronic hepatitis C virus infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_patient\" href=\"UTD.htm?17/4/17478?
source=related_link\">",
" Patient information: Hepatitis C (Beyond the Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?14/8/14474?
source=related_link\">",
" Predictors of a sustained virologic response following treatment with
peginterferon and ribavirin for chronic hepatitis C virus infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?40/55/41849?
source=related_link\">",
" Screening for and diagnosis of chronic hepatitis C virus infection",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/56/39818?
source=related_link\">",
" Standard immunizations for children and adolescents",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?23/47/24314?
source=related_link\">",
" Treatment regimens for chronic hepatitis C virus genotype 1",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?0/37/600?
source=related_link\">",
" Treatment regimens for chronic hepatitis C virus genotypes 2, 3, and 4",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?26/19/26936?
source=related_link\">",
" Vertical transmission of hepatitis C virus",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f6_2_6187="Cutan react EGFR inhib";
var content_f6_2_6187=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=ONC
%2F57215&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=10\"
onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=ONC
%2F57215&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=10\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Cutaneous reactions associated with epidermal growth factor receptor
inhibitors",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1\">",
" Drugs",
" </td>",
" <td class=\"subtitle1\">",
" Reported cutaneous effects",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Cetuximab",
" </td>",
" <td rowspan=\"5\">",
" <p>",
" Abnormal scalp, facial hair, and/or eyelash growth;",
" </p>",
" <p>",
" papulopustular (acneiform) rash;",
" </p>",
" <p>",
" paronychia with or without pyogenic granuloma;",
" </p>",
" <p>",
" telangiectasias; xerosis; pruritus; purpuric xerotic dermatitis",
" </p>",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Erlotinib",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Gefitinib",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Lapatinib",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Panitumumab",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6187=[""].join("\n");
var outline_f6_2_6187=null;
var title_f6_2_6188="Crying framework";
var content_f6_2_6188=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=PEDS
%2F77427&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=6\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
%2F77427&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=6\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Lester's framework for colic and excessive crying",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Colic",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1_start\">",
" Meets the \"rule of three\" criterion:",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Greater than 3 hours per day",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Greater than 3 days per week",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Lasts at least 3 weeks",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1_start\">",
" Includes the additional four characteristics:",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Paroxysmal",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Qualitatively different from normal crying",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Associated with hypertonia",
" </td>",
" </tr>",
" <tr>",
" <td class=\"sublist1\">",
" Inconsolability",
" </td>",
" </tr>",
" <tr>",
" <td>",
" The infant is normal when not colicky",
" </td>",
" </tr>",
" <tr>",
" <td>",
" First few weeks of life are unremarkable",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Excessive crying",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Meets the definition of colic except does not have the additional four
characteristics",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Early onset",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Colic and/or excessive crying starts at or shortly after birth",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_single\">",
" Persistent crying",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Infant fusses or cries virtually all the time that he or she is awake
(except perhaps during feeding)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Infant is described as never being happy",
" </td>",
" </tr>",
" <tr>",
" <td>",
" May accompany colic or excessive crying",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Adapted from Lester, BM. In: Colic and Excessive Crying. Report of the 105th
Ross Conference on Pediatric Research, Lester, BM, Barr, RG (Eds), Ross Products
Division,Columbus, OH, 1997, p.18.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6188=[""].join("\n");
var outline_f6_2_6188=null;
var title_f6_2_6189="Comparison of bronchiolitis I";
var content_f6_2_6189=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=PULM%2F50736%7EPULM
%2F60031&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=12\"
onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PULM%2F50736%7EPULM
%2F60031&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=12\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Proliferative versus constrictive bronchiolitis",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1\">",
" &nbsp;",
" </td>",
" <td class=\"subtitle1\">",
" Proliferative bronchiolitis",
" </td>",
" <td class=\"subtitle1\">",
" Constrictive bronchiolitis",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Histopathologic manifestations",
" </td>",
" <td>",
" <p>",
" Common finding",
" </p>",
" <p>",
" Nonspecific reparative reaction to bronchiolar injury",
" </p>",
" <p>",
" Organizing intraluminal exudate",
" </p>",
" <p>",
" Most prominent in alveolar ducts",
" </p>",
" <p>",
" Inflammatory changes in surrounding alveolar walls",
" </p>",
" <p>",
" Foamy macrophages in alveoli",
" </p>",
" </td>",
" <td>",
" <p>",
" Very uncommon finding",
" </p>",
" <p>",
" Obliterans not a constant feature",
" </p>",
" <p>",
" Variety",
"of histologic changes: bronchiolar inflammation to progressive",
"concentric fibrosis; smooth muscle hyperplasia, bronchioloectasia with",
"mucus stasis; distortion and fibrosis of small airway walls with",
"bronchial metaplasia extending onto peribronchiolar alveolar septa",
" </p>",
" <p>",
" Follicular bronchitis (lymphoid hyperplasia)",
" </p>",
" <p>",
" Cellular bronchiolitis",
" </p>",
" <p>",
" Diffuse panbronchiolitis",
" </p>",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Radiographic abnormalities",
" </td>",
" <td>",
" <p>",
" Bilateral patchy airspace opacities",
" </p>",
" <p>",
" Interstitial opacities",
" </p>",
" <p>",
" Small rounded opacities",
" </p>",
" <p>",
" Opacities may be recurrent and migratory",
" </p>",
" </td>",
" <td>",
" <p>",
" May be normal",
" </p>",
" <p>",
" Progressive increase in lung volume on serial radiographs",
" </p>",
" <p>",
" HRCT scan may show marked heterogeneity of lung density",
" </p>",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Pulmonary function",
" </td>",
" <td>",
" Restrictive defect (a mixed pattern may be seen)",
" </td>",
" <td>",
" Obstructive defect with hyperinflation",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Adapted from King, TE Jr, Clin Chest Med 1993; 14:607.",
" </div>",
" </div>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Proliferative versus constrictive bronchiolitis",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tr>",
" <td class=\"subtitle1\">",
" &nbsp;",
" </td>",
" <td class=\"subtitle1\">",
" Proliferative bronchiolitis",
" </td>",
" <td class=\"subtitle1\">",
" Constrictive bronchiolitis",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Selected clinical syndromes",
" </td>",
" <td>",
" <p>",
" Cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans with
organizing pneumonia)",
" </p>",
" <p>",
" Collagen vascular disease (eg, dermatomyositis, SLE)",
" </p>",
" <p>",
" Chronic \"organizing\" pneumonia (especially influenza, Mycoplasma,
Pneumocystis carinii)",
" </p>",
" </td>",
" <td>",
" <p>",
" Allograft recipients (bone marrow, heart-lung, lung)",
" </p>",
" <p>",
" Collagen vascular disease (rheumatoid arthritis)",
" </p>",
" <p>",
" Post-infectious (especially respiratory syncytial virus, adenovirus,
influenza, parainfluenza, Mycoplasma)",
" </p>",
" <p>",
" Inhaled toxins (eg, nitrogen dioxide, sulfur dioxide, ammonia, chlorine,
phosgene)",
" </p>",
" <p>",
" Drugs (eg, penicillamine, lomustine)",
" </p>",
" <p>",
" Cigarette smoke",
" </p>",
" <p>",
" Mineral dust airway disease",
" </p>",
" <p>",
" Idiopathic",
" </p>",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Natural history",
" </td>",
" <td>",
" Glucocorticoid responsive and usually reversible",
" </td>",
" <td>",
" Relatively glucocorticoid unresponsive and usually progressive, with the
development of irreversible airflow obstruction and air trapping",
" </td>",
" </tr>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Adapted from King, TE Jr, Clin Chest Med 1993; 14:607.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6189=[""].join("\n");
var outline_f6_2_6189=null;
var title_f6_2_6190="Prostate ca incidence over time";
var content_f6_2_6190=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=PC
%2F75684&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PC
%2F75684&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 575px\">",
" <div class=\"ttl\">",
" Prostate cancer: Changes over time average annual age-adjusted incidence and
mortality rates in the United States, 1975-2007",
" </div>",
" <div class=\"cntnt\" style=\"width: 555px; height: 370px; background-image:
url(data:image/gif;base64,R0lGODlhKwJyAeYAAP///wAAAAAzmf8AAO7u7oiIiP+AgP9AQP/AwBERE
TMzM3d3d6qqqkRERMzMzLu7uxBAn/Dz+VVVVd3d3UBms5mZmWZmZtDZ7MDN5oCZzGCAvzBZrKCz2SIiIuDm
8yBNppCm01BzubDA33CNxv9VVTNcrczW6/93d4igz//MzP9gYP+IiP/Q0FV3u/
+QkP/w8P8REf+goP9wcP8wMP8gIKq73f+wsP8QEP/g4P+qqv/u7v8zM3eSyf9QUBFBoP8iIiJOp0RptEBAQ
O7x+P9ERJmt1v+7u93k8WaFwv9mZrvJ5P/d3f+ZmQAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACH5BA
AAAAAALAAAAAArAnIBAAf/gACCg4SFhoeIiYqLjI2Oj5CRkpOUlZaXmJmam5ydnp+goaKjpKWmp6ipqqusr
a6vsLGys7S1tre4ubq7vL2+v8DBwsPExcbHyMnKy8zNzs/Q0dLT1NXW19jZ2tvc3d7f4OHi4+Tl5ufo6err
7O3u7/Dx8vOdBA0BAQoEABX4+A8A7gWwQK+gwYPDJjQgQKBDAX4dCBXoQGBCAgYIM2rcaEvBw374HkpYIKj
BQ44oU6okVUBBoX4OTJYkuLKmzZuTLOgzFODByJInBQnx5w+n0aMpJyigKUhCBX4JCEyseFFRAKRYsxYEiS
9iAXwJngbExxTRVa1o02I9q7at25Rs/9/KnUsvLt27eNXZzcu3L7i9fgMLtgZ4sOHDzAojXsxYmOLGkCPje
iy5smVXlC9r3kwqM+fPoDV5Dt0LxAXSNUejzpVBwIfVKlXDrhUBggABImZzlK1bVuvbFHpr5C3clQfbIG6f
Lm6QOPNVGgQEj67heUHn1k95uI0BAIbbEbLLwy6eVAjpgygIyFAeHvn2oL4L8DCIg2v47t7j76S+OqEPAnC
w3zr6DZiJfPQR0lpwBqJTYIOWAMheIRFwB6E5D14oiX0QhGcIdRqSk2GIj0iIyHbzkRjOiCou0toHHh6i3o
QtdsNijYfUFqAiIggAAY42AhnKi4wAKKCQ2dyIJP8AxwnQ3SLJvbbkNUoiGR2Di+j45JTUVAkkilsuEl0IX
FbjJY7nkekIigmWGc2ZLSIIyXkjuCkNnCr2F8l3HdoJDZ4h8tlmiTv66QygGpq44X2GNoMohBzGCImOuTW6
zKMNKjrJgpZe2qkjUVrC5qfIYDrgeSBcAiKpxpi6322DTsKnpKwG4yp8PUp5yQbr1UrMre2NIECdmNinq6/
AAFser5ViYtuRyP6ibHYo0loJp9FKmy0h9mGJSYUCLLftLtNaF12qm6w6ri7lPmebuAf6aO26tLRb3AU+es
IruvTeYq9wrfnHibH9TrauetBuomXBtvyrG7ixaiKswAxXYg//PjsphY9YApV1iMOz9bgBKKNWXIlCDDkEg
AQSAMBAAFJRZBFGiYAMW3TEfjKjyZl4BEBVAPT0U0BBfTwugGF2QjDPlrQkSE9PVyBTQB4XYjNqKI5iJNOU
6LTPzzQLTRLRhAxF1NWkJafmkOhxDYlSZbHsMsxTzWzVtqiOUvJcJghQAjpcBRCRxgFwTNYiaIf2LinqIuT
DbQKg0EgNArRASN9/P/MAAwxMEEvin313bCizblSCACZUgrkzBSRA1EKvgM7ZxKZsrdHpqVNewuklDAEACp
Dz0LflJgAhwON/mxDEbUEcoTvvvhdhvN+/Qy65LA9grIACrjcQe7bMmpLc/8i3ow4A5UEAsDwKwFsuyPAAG
G/C6kD4MEQRAiCBvvqRY+579TyInwCOIIsFQG0QEoAZZqIFrnl9YmEZwd35KgcAHkSuBQKowSCGN4TjAQBz
fYOc3yhnOQuyTwABFAQGRajBWBjQc4OwgAJbITvN2Id8pmicQSRIwgpGrn0bpKAP7KcE6tWPgILooQn9Jwj
gIcEW/eiABRawgHu4ZIHIig6NSoEvATgQHo+7DQqUGLnq3UZ4FKSc36inPMi1gIySk95t/gY8yKVOFjIkSg
Ic8D1kAQhepdhZtB5QACpW4GtYrBW+fpSKpQ2SczDsY63UtgrbNItVrXsdIllRQ8sgbP8V2GJV9vKxve5Jk
lWwWsXePmVAgCBwhpz0Va5aQadavZAQMtykKjopGWHlTBU9YiSpojjFKubjlJ8C0CVVYTtS5dEfe0SmpbLm
ivH5ipCG1OUqeAmZbr0CXIDchgcwIIIMmEYjm+vc52qVt1foMBgXoEAIMkBPEGDgnuEEwAUwAIIMhIACABL
hbSAQgnPOI5P+gF0iP7W4V3Txi7u4gG0ESlEfqaeikKMABfw50YEWNJ/oGOX2uBcA7y3UUouUxb6GIVHpcI
CeGdCARgFa0Q9QQAPmxEA+LwCCEHTURx9dRysJkUBtooKbjAmYLBz5i5ZuAKKCGGfEGsFTn4oQAiD/DcctY
wjLbbKKVwlzhY4oxgunQpUTPNUAgLAKOMEV04rS9FMDZ2EfAZA1F2ZdRQR41adzPBMsfDypoURWi7pq4Kzf
5NVTW7FXASz2HNhcwCFhgVTE4MwWHLDNY2/R2M2yQkeePccEAitYPyHtFnm1RWPZCovUouNlEiCtVzu1HWH
awqlTFStfs6qKlnrLHA/oAD7GNltLURKvtmFtLFbL21W09K7gSKfnHFBIGn6qnblgLslyiwj1KJcW8oEuNx
CKD4Vat1Op3IV2N+EBEPAKqAZNRHS+W9jbiDcbIi1lSeNaJtH5orGFEpV7r3rVgiYNANFx0i7qukVuDPWVR
j1F/2UHQ7v/Jjisj4gABy56mxBwIDxV/al0MtCdC/eirhjOxlYFkcvSlkmZwTBxhjlwnox+GBFpDahAU4yL
3/DYGsSkIlxdPCWm/iLBI9jnPZfM5HvSWIQbAAF3DeEBDqj1Nj/GhYy58dcARJPIS9JUMH6DUYxGecqM8EB
ztWyhbkR2svxdUqSKkVmbzvTOeB4Bmqkx3wzsORrSXaehBCkcDns4G+QtaYQlbKjSMefJA9XAmkXF5HLC9N
L0RGwl8ktSk57XTur5JXM8kAEdR1nTkGhpmXcsigc3pau79JOc2oMBDXQ0BMu0REvtrFFMYxrVk1gxAFr86
TK9Uzwafq9r9P98Cde6IsjGvGKxp7TK/XhgBBOlb6o1C+xRdPnL017SsQckgvdmORHOjsWbF83oMoFJRRGo
sagZAdpub2PCeLkSjn5DAU131t6qsEDVUoFvukCwRpl17JobC6NbMOThBNhenFsUShy1FAIHJsR6a/Gysx0
TzCSi1JIAzC8K7RYXD3Dd2aQdyykRaUoRSPBdN36Lr0Bc4iAP0bPclBzHxojmt3gAywU+8RAZeUoisM0HTg
P0/EypmW66wFpF4N1Jn6PgbpmzoSLAYW3XnGaZeNkgAgeQjiEuzL3q1HytDgsF5KNolBDI2CMyiLoBzSxIc
nSnLsB2WMTMywuQrSSyN3b/f4hkbFPDu5AI7bZXMEAgEgB7JAj/kgDE5CQNGPggsJ4W+QC88aBwgAVcpwDJ
O4LyVvMJ4otmNqIs3q6gr0XMiPsI1DsFKjGjiumtBqQu/jn2qmD3IQRSOAB8xcuGG8jZcTRu4KPCARJQwAM
aQPviqqjazk+FRfDBgIkUfUD6zn4rFhCWAHAO1gRvUbzbLP5VLEAf5rd5ztuT8GG1vxX9SGADEuDpll/IAx
e1AX13f57wTODmfw2SAcnVYAS4ChWwAAUQSeEGHxfwXhTwew0ICkI3dv1nffARAcLiIyWXgcH3Mg/XD8I3C
pyXEhgQUCHweSSYCQTgcV72fQ+TYB+Q/2sxiAozeDYJAHexRn8TNQIwuIOaQABC93CCZh0iYGu3sQEZZ4Sr
wABUREVAmH7FoWE1dhsfwIBSyAoOsHI2eBlaKEIfkGRfOAtfcQ9VpHnthjWQ9oTxlYYFJH2W93hj2BgVCGV
SRoe38H4zyDLod1SkoSOO1Yd+iAsvA33llYeI8W+JyAv7IBUFkIIqGBprF4m7QAAMYImmsILo0HNRqImzkD
27N4GS0SMBRoq5oACHxBCUxRnPxYq70HH+wHIeKBkRACC/RYu2YIsY44iBwSsN54u6AHGeKAqgOA6ZaIzvs
Izh0HM66IzpAI3fIB8jSI0EUhmzqI24gIywKIx30f9Z3ogLbudxuBiEkOFdRViOoXCOYjh/fNGM7mgLBICC
DDE0qCgYKFaPuWBAgTV64ugWGnYbXuiPsvAVHbAAo5cAA4kW7cVh94WQsUB8AXCFhBgYIjACOuZYREiRuvC
AC+BK8pgVVbaFHcYBGAiSK3IXFzACyrZs08iStgB90kd9D4kSTfhTFICINNkL2xd/dLePOKGFHQUBGiAC7f
iTqkB+/XB+yfgJ1hgMJ2mGaMiUwwCI8TeIb4gT7RWTG5ABA4iVtZB/JcV/ORkOGDACeNaWM9WRPbmSZJkLB
ih46vgOJyliqwY5HraUc0kLDxiBsegOG9mRH5CUTZaYS/aXzbD/gYIgNWlJDBhwafa0mFTWUwLVk2PJmMrA
iTDDEChYksYQARvJYXvpWDQFOWc4k5xZDT3og5GpCx6wkTHpGjhFTzKlUbXJlz7Zmt3wmtCEkV2ZDFV2ZVA
2AkrpCJbpm+KAhBTBiXZ5l8RAmhlAASK2UcnJnAhhigZUfKIJXj3VkRZFYtqJEgtAER2QAB2QjljYCxdgZb
tJASPAAZtZnu3wfhNQUiY4CWInCISTfG74NGXFkQJ1mPZknzjxFQm0APsZCXLXFC1jgnZ3ipuHVwTqUSTml
wjqDgSgcqLHno2AekAjNkBxN7XwkjqGlKy5oTYxAQwKAJJFCah3QIUzNZln/6KeMJuXJgL39EUoCjkqyqJt
gYybxhYjqnolOgitVxSaQJ3WeZozRU8X6iNJKaRuAYwfN3hsITcSKjN3ZzSVEAGTGQLiOWIwpZurFqRW+hZ
YCqKLQHxP8Z8lcTg4CglNGJ/z2VxiSk4wtaJrmhUQp48ImCVW9lMboAEH+qebEagOmXNlqJojMIqKKhlY2q
j7+KhPeJWTGhrA+IPS9JV8KJeb2hgQt4SC0EVyKKqjuhgCJ3QjtT0NEJ2fWAgS5WGquqqMsT1Y2oiDiqvM8
QCbY36cwzluF5WcMJW+Sg8uWgjEJp3JWhzguA/ASpTPihrwSBRuOqvVyhzXeouxua2Mcf+Pn0kAgpqL4Dob
AMliltqr5wobCsmQCbCu5tquq2GRwqmt9CocIkmS1JqvnEGFVXivpYCs/poOYYit31qwgbGGAdCGCauwffF
+2eMAePidELsYWimIxtoJBHux5LCICbRfFuuxhzGJBVCJD0uyJNKxKisOVCgLLNuy4GBAGyuVMgsaNGuqN3
sZOTuYO6sZL6uzPxsZNjl91eesQ8sYQdl9Q8muSYsYTimsXImvT9sYWtl9UzuwVRsZZrl/HYi0W2sYdZmyY
YsVgSmBTlu2gQGOZKu2N7Gr5gW2bssXuyqy8zq3eWGCKVMA91CzmRCzeOsMW7U9PSu3gUsX76p/hdv/nofr
F/B4EUSXto2LuBA4AWhruJM7F9SFc/2auWkxAXzrrSPruS0asobns6QrFx3nii9DoRmZuqp7iwnkusMJu20
hesKFMQLbGbaLFz5Bem3buxlRAbvbCGQ3FspXp8ILGhXQtBOqvMvLGVxxeEmqeNGLGjBhowEKuNcrDiRKNk
rqcd0LGrdXAVHxvDUzvp9xfGExp8mbvur7CykwACQAF/H7CSQwAD8gCCswAAOgA4zQvyeACPNbvzswACkwv
ztwENz7rPk7ACsAAD/gvwC8CAJMwPRLCArMwPfrCfkLAz+wAjAAA/8LACfgvxBswvQLA0SAwv9Lwv5bvwUM
APmb/wIwPAA5oL8AYAQZ7HQdzAn5278DcAIkrAMX3MI5cML+ewIXTAgTbAQzXMMbDAAHnANJMABG8Iw/DMQ
4nL9LUMT5mwMqfAInHMEA0MRK7L85EMUIPMX9SwIwsMBavMWaEMaDUMRHjMNlzL8DkARnPABEQMM4zMYJrM
OCMMEDwATuQcd1jMN3XMJKDAMRvMcAoAMH/L8HHMeDnME1LMiOfML7u8iMXAyUPMejPAwjXMGmTCo4gACub
AMGEMsycAC0XMu2fMsqcMu6fMsyEMsG4MoIwAIs2cA44couYAA9cAA04MLM3MzO/MzQHM3NTAO03Msu4Mov
YIzErBEv4MqxTP/L0uy/tuzLvwzM5nzOxmwD6LzO3izLtbzM4UzNBxDLMRDMdLjN8GDMBjDLB3AD0UzNKmA
A9YwAt8AC7ZzLMxDOtBzQ14wA2Xx/
+BwO3ezKMeDLuazM4TwDB9DL6owDyWDQsGwAtAzP0EzNvYwAHg16EX0MEx3SFr3LtpzQ4ezCGt0DsazOwqw
NE33MCA3NM2DT9cwzK70JEw3Mx0zOSJ3USq3U/CzTMz3T4xzLDZ3T7WDQBpDL/tzMN3AAAV3PKZ0tlVXU7A
zMFb3UZh3LF73LWf3UbN3WA1DLSN3QY03QN9HNFX0ATj3NXG0A6vzQnYIoRV3WIk3Lee3Whn3Yz4z/y2e92
GetznTNGFY92NGs0Rsdy65M1UiiGK2sz9/8zoj92W8N07rM2Est1+j81W7SzuAczlu91+Xs1xBiFyyw1qDd
zLVs0/QMzFj5yu6M0dLc2r080PBhFwiAwq3t2nwNzJidrwaNADy92tEM3JZtz7Mx1LTYyiGdzIX9zJTdy8m
N0pdh3fXY3L1N2/+80MkN24Eh3mQJzL5cywo9z9e83HPB3gjq3iK93Sgsz1J92Wph34pq11fdz/Fczf3tyq
i9G6csCgZd1hdt3tJM2bjd0AnuwwuuCuQdy8kM3TNd07k91+Zc4WZy4bgQ2GhNyxBu2DagDQA+uRNd1hsu2
rcs/
+LT0OIkTiU3rhs2nuNdwuOwseM+/iZBjhpAPuSHYuShUeRI7ilLzhlK3uSlAuWb8eRSXgxUXuXDcOVYbitb
Xhla3uW+8OVgzgtiPubsYuaNUeZo7i9rLhdmB71tnhXoa71xjhZDk3hgWudoob1wrudGceesR4OCPuiEXui
GfuiInuiKvuiM3uiO/uiQHumSPumUXumWfumYnulCQAxz7giguIyf3iqibuXHygxvDgmhPuq/oupZzuqYUO
SpTuqyvuqz3uqbAOuu7hi5niy7ri237r297uu0Puy2TuyvDuy1XuzKruvJzuW/7ufQHu3SPu3UXu3Wfu2HW
0V1hzF8lP+7G5Ofp/sK2i4Ix6cAfBRcw+W+AYoK42583A4A6N6wAADuIeEK/enu+cBHhDM25e63ntDu5X7u
wtW+9H6RruAA50gTKSc4+n6OAPoKCE+nC98BDb8x804URRPxyTvxFV98f7XuySKyYchHTjMIYWi5AXC5nCT
ylmd8LqEAJPEyoOultPuJLE/yLx/zKZ+fKp8KDzryLr8yLTMBHcAAQA/zn3PzQe+p2VMRKR8LDwgAQO+p7y
f0c5N7doN/JDH1D1H1XAozPH8IUc/1MOoSX49IDSEWysC3grCIUg9LN0rvLQMLbD83fBSGBKATDhBc5Lp6s
VD3bo/3es/3cv8KlBf/
+DCjAHM/EiVf93RvUog/gydxEYUfCzPoAHgP71dxpIBu+ZaX+YR3pJVvCJcP+psfNiTpfczg+CHrOl/DAAk
ggQ7gqa/A+mABM0InQw/B54//Sl6G+0th8CZP+6xge7fvnGABgSal+r3/ar8vFbcPdrNfvKSAk5SXPfnpSj
WKeSBfCtZ/FthPo2o//cNHEtef8uLvn1+aDI5fd5aqMoWA56zQ/uTukFXRoQzQ+c0vEfYPCAwABAmCAIcNB
YeLjI2Oj5CRhw8BjgUJjQkFBQqHBQ2SoaKjjJ+WmIsOAQ6MiaSvsIcEChaHqgQAlACFhwEPEguIirHEobO1
ALe5lbwA/76tw4vHtgG4us3PABagxd3esaaMD5qeCbgABcEOCQ/f7ovhi+OKCeqFBR0EE83v7vGT5Oolu2e
vXb9uusSRW9TAnCpWCoId9MdN3kIAExSASjfQ4MRY4yowIregkwQJABhUw6eP38dXIUcqKgngZMqVBRWKXE
TSJEqVuFR5fEn0VYCjASZoOzqMULQHHY5KLGoUqVILTAFKRXQUGdWqR69mzZVgK9StX0U1QCoSa4BhE44qY
IVO7rm0o5AmXfr2UIWjEqxFDTAVbyS3XckG6MAq49GdawN4NQwJsWTFjDEqeJxrcGG+icctbrw5AGSUlFOr
Xs26tevXsGPLnk27tv/t27hz697Nu7fv38CDCx9OvLjx48iTK1/OvLnz59CjS59Ovbr169iza9/Ovbv37+D
Dix9Pvrz58+jTq1/Pvr379/Djy59Pv779+/jz69/Pv7///wAGKOCABBZo4IEIJqigfQWg1QgBR9G14IQUZt
egOXUloBRRcaHyCISrNIiaYRL0VeGJKOK1WTBRRfOSSp1AAqKEKdZo43EqSRZAjA5E1oEgCyCVgEgqJYCVI
bZENheIETLiwGZlhRgASkEeNaQnVgaAyWYSbKYALgSUqOVODVpZU18VDLbKjWy2KYqYAQhCQAf5qOLhMknl
eBSShKyyjzlFOhLVAzOKKE5YKuX/E+iKAGymiKONxtlgjIeUWICdd7mp6abSlIXaX3qt4gCcqwTayF8dHLJ
ZBaYukuggERo6ql4OBFnLon2VuEBce9kKakSsWMprPTtxamybkAKAaiZvzdjqIstGyqqWjbxa6JS7NBuhrT
dtmSthvCrFbQGITWBpSgtEWeyx7KKYbJ+KTNAAiA9QUiq1D5blwJ8EPDuIvrw6ICK99jrwVycXRqqIrgpHi
mS45y4S1brtVrxgsslEhm2ZpTngb5JysfLxr7FuLFeTVW6WKqQMh2mlSFUuJpKleppo8c04v4bViDn37LNw
UU6Z6c9EF2300UgnrfTSTDft9NNQRy311FRXHm311VhnrfXWXHft9ddghy322GSXbfbZaKetdoqBAAA7);\
">",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Source: SEER Program.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6190=[""].join("\n");
var outline_f6_2_6190=null;
var title_f6_2_6191="Proximal phalanx condylar fracture lateral xray";
var content_f6_2_6191=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" ^{",
" &reg;",
"}",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=EM
%2F70897&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=EM
%2F70897&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Condylar fracture of the proximal phalanx: Lateral x-ray",
" </div>",
" <div class=\"cntnt\" style=\"width: 400px; height: 517px; background-image:
url(data:image/jpeg;base64,/9j/4AAQSkZJRgABAQAAAQABAAD/2wBDAAYEBQYFBAYGBQYHBwYIChAK
CgkJChQODwwQFxQYGBcUFhYaHSUfGhsjHBYWICwgIyYnKSopGR8tMC0oMCUoKSj/2wBDAQcHBwoIChMKChM
oGhYaKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCgoKCj/wAARCAIFAZ
ADASIAAhEBAxEB/8QAHwAAAQUBAQEBAQEAAAAAAAAAAAECAwQFBgcICQoL/8QAtRAAAgEDAwIEAwUFBAQAA
AF9AQIDAAQRBRIhMUEGE1FhByJxFDKBkaEII0KxwRVS0fAkM2JyggkKFhcYGRolJicoKSo0NTY3ODk6Q0RF
RkdISUpTVFVWV1hZWmNkZWZnaGlqc3R1dnd4eXqDhIWGh4iJipKTlJWWl5iZmqKjpKWmp6ipqrKztLW2t7i
5usLDxMXGx8jJytLT1NXW19jZ2uHi4+Tl5ufo6erx8vP09fb3+Pn6/8QAHwEAAwEBAQEBAQEBAQAAAAAAAA
ECAwQFBgcICQoL/8QAtREAAgECBAQDBAcFBAQAAQJ3AAECAxEEBSExBhJBUQdhcRMiMoEIFEKRobHBCSMzU
vAVYnLRChYkNOEl8RcYGRomJygpKjU2Nzg5OkNERUZHSElKU1RVVldYWVpjZGVmZ2hpanN0dXZ3eHl6goOE
hYaHiImKkpOUlZaXmJmaoqOkpaanqKmqsrO0tba3uLm6wsPExcbHyMnK0tPU1dbX2Nna4uPk5ebn6Onq8vP
09fb3+Pn6/9oADAMBAAIRAxEAPwD5sppp5pppMBhpDTqSkIbSUtFAxKKWk60hBSUtFAxKKWkoATvS0UUxCd
6WigmgYlApRQaAE60tJS0CEpaKPwoGJRS0UCEoo70pFABSUvrxRQMSiiloEJR2opaACiilA5oAAOafjFAHt
TgKAExRinhc0EYHSgBlGBT8UnuKAIyKQipCKQimBGKWjHNKKQC0opBThTEOFX9NOJ1+tUBVyxOJV+tMD7S/
Z3l3+H2GeiivXq8P/ZtlB02RP9n/AAr3CgIn5iHmkNONNNJlDTTTTzTSKQDe9FLSUAJ3opTSUgEo70tFMQl
BoxR2pAJRS0lAwNFLiimISilopDEooooEH0o7UCimAUfSlpO9AAe1FL3opDE70UUCmIKKKKAAUUfhRQACpF
FMQZqUCgBQKljTOSegpijJq75W1ABzQBB0OaCAR0xT3TApo6cUAQsuDSEcVNIOKixTAbikIp1IRzSAjI60g
p5FN70xCilHWkpRQA4e9WrQ4kFVRVi2+
+KYH1f+zPcZDJk52kV9C18zfszz/wCnBM8kV9M0BE/MYjmmmntTaQxh6UlOpDSGMNFLSUAIRRinGkxxQA3v
RS96KQCHpRS0n1oASilo70CEopccUUDEo70fhRQAd6KKPagQUUUUAFAooFABRS0UAJSUtHfFMBKWij60AJR
S0DrQA9RxUg4pEGMU8CgET2abpgAKuS5iPI5qPTFG8n2p9y5Mh3fSgCIjfwajKFeDUqY3D0p0pBOBTArsAB
jFQHrVknNVz15pANpCKeRTSKYDDTWp5prYpAIKcKbThTEKOlT2/wB8VCKmh+8MUwPon9myXZrSZPtX1ZXx9
+zzPs1+AE9WHSvsGgI7n5kMKYalfrTDSGMNNNPIpp5qWMbSd6fikxQA3FFLS4oAYaKXvSYoASkp1BoATFJS
96KAEoNL+FFACUdKBSmgBKKWkxQAUUCigBKO9LQKBBRQetFAwpKWigQgo7UtJQAU5R0pBUiCmA9R709Rnim
ipYBlxQBftB5YLfhSSLvbJ5oBxgdBT0UtKApoAgAwetEq7efWppk2E+uaikycE9KAIAtRGpn4FQ0ANpDTqQ
0AMPemGpDTDQA2nCkHWlpoQ4VLF1qIVLH1phY9h+BUxj8R24Bxlh/OvtSM5RT6ivhn4PS7PENtg4+YV9xWj
brWJvVB/KgFufmg45phFSuOaYRSKGEc00ipMU3FSMZikp+KbikFhMUlOo70wGEUhpxppoEJRS0hoATvRS9a
MUAJRR2ooAKO9LSUAJS0YooASilNFAgxSd6WkoAKKWjvQMSilFJTAKKKUDmgQqLUqj1pFHpUi0AIBVi0XMn
sKhAzVyyXlj7UAPYEnNOEgzwOaQkZ56U0KN2KAJh8x571FP8AKOfyqxBgE/pVS7PzYoAgdgenFRinDnpSUw
ExTTTqQ9KQDO9NYU80xqYDRSiigUIQ4VJH1qMVIlMD0H4XTGLX7Zh/eAr7r0ht+l2rHvGv8q+Bvh9II9ati
Qcbx0r7y8NSeboVk3/TMUgW5+cUgG6o2FTyjDVERSLGY5phFSGmmkwGUlONNpDEIpppxpKYhppDSmkoEJSU
vag0AJRS8UlAB2opaSgA60UYooAMUUUYoAKSnUUANopaKAE9KMUppKACkpaKBCU5RzSCpEFMB6ipB0pop4F
ABir1qMRkjqapqOa0IkxCtICJsDrTlxTXBNKlMCxEo3jAqjdD94fWtC35YiqF0MS80AQfWm9qU0UCG96Q9a
caaaAGmmNTz0pjUDGilpKcOtNCFFSL1pgp60wOm8HyFNTt2z0cfzr7z8DSeb4Ysm/2K+BPDDYv4eeNw/nX3
f8ADSXzfCdp7DFIS3PgGcfMartVq5HzmqxqTUYaYelPIpp+lADKaacaaaSEIabTjSUwENN7U4ikoEJR2pcU
lACdKSlooAKSlooAKMc0o70lABzRRigUAFFFFACUtAFAFABSd6U0lABig9qKPwpiDFSoOlRr1qZR0oAcKeO
lNFSAZNADo1ywHvWjNhI1UdRVeyj3S5xwvNTyDcDSAh3ZHI5pQB6HNKFHrTkU8etMB8DYbOKq3qkSE1ZUEE
YHOaZeLkAigRnmjFOYYNN7UDG9KQ07tTT1oAaajantTHoAbTh1pBSjrQhDhxT1pg608VQGxoTbbuPHqK+5P
g3N5vg+EZ4XH8q+FdJbFwn1r7Y+Asgfwnj0xSDqfFF4MSGqjVevwfNYe9UmqTQjNNNPNMPTrQIYaaeaeabS
QDaKU0lMBtFKaKQWExSYpTSUwEFGKXFFAhKKU96QigA70UtJQAUYoooAKKKKAEopaKACkpaSgApKWkpgPQc
1MtRIKnWkIUDipV5pqj1q3ZW5lkyeFHJNAFqzTZFk8ZpxiYs2DwfarzIiwjaMnIFPiIEjDaOnemBlGMqpOK
UJ3PStMgOrNgewxUJzszsFAFWNG4I6Uy7XMeauK4AGMc9qguyPKagRjsMUztUj8nk0zFAxtNNPIpp60ARmm
NUjVE3WgBKcKQUtCEPFOH1pnpThVAaGmnE6fWvsv9niYt4ekQnOADXxjYnEq19c/s13G/T5Y/8AZpCPlTVB
idvrWc1ausj/AEl/rWU1T0NBhqM1IajNADTSUp60hNIBO9JmlNJTAQ0UUlABRRRQAGkpaSgA7UUUUCCkpaK
AEFApaKAEpaKMUAJRS0UAJ7UUtFACc5pKWigCRB0qdR0qKMZqde1Ah6DOK6DS4N6qmcA96wF/KtjTdTa2UL
gfjQB0UejSlB8y4U5NO/sxYLgtI4YEdqrReKCibZEVgaV/EaSHEcKoMd+adwFubdQvyKcH1GKozRhlCjAx3
p0t1NKAwLMO5qkxkbJx9aAI5Y8N8vbrVK5k+UrUsshXIzg1TdtxyetAELZptPNNx6UAMNNp5FMNADGqI9ak
ao+9ABS0gpwoQCjinCm04VQi3aHEgr6o/ZmuAS8Zxkr/AEr5Vtjhx9a+kv2apsaoqk9f8KTEzwrxCu27kGM
c1ht3rpfFaFNRmB6hjXNP1NStjQjNNanGmHgUANNIe9KaaaAEo70GkoAPaikFFAgpKWigBKKWkoAB0ooooA
KO1FFABRR2ooAD1opaPpSGFIKXvRQISilpKACgcmilUc0wJkHFTqKjjGcVOgzQAoHp0qVVLcDk0KuRWlZ2r
ZXjr3oEQ2unz3BAjA59a04tEaFd03JHbtV+1UQOCQOK10PmxfMvbjHamBzYLRErGBj07VDJJg5K1u3Vg0b7
gvB6CseeA7juGMdqAMu4jD5YDqaoMuDiteVTj7uFrPuVG7IoEVGGKZ071KfpTDigZGfemNTzTWoAiY9aiqR
6joAXpThim04UIBw6U4UwVIKoRNAfnFfQX7OU+zXIRnqRxXz5CfmFe2/AKcR+I7c8E5HFJiZwnjmPZqs49G
Ncg/BNd/8AEqEx65crjoxrgJO9THY0IzTCKeaYaYhtNNOptIBD0oopKBh2pKU0lAgooooATHNFLSUAFFLSd
qACijFLQAlL7UlFAC0tJR2pABoxRRQAUUtIKBiYqRF9KYBzU6CmIlQeoqZBTEqVRxQImtx+8Fb1iNxIA49K
xbRczKK6vSYAIWYjnpQBIFzsRQT7VqQBIyAS27GMVXmZIwCnykDBNJHIhj3bzxx70CLFxG5bBOSRjNYeobV
nKA7z61v7lMMTKxOBg5PeuZ1HJmbB5JNMDMuGbeST07VnTH16mrty2CSetZ8hJJJNAyInPtUbdakJ6Uw0AR
n0php5qN6AIn60ynP1pKACnCm04CgBwpwpopwqhE0WNwr1n4LSFPENt15YZ9q8lj6816R8KJvL162w2PmFJ
iZb+LkXl+ILkY/iNeYy8Ma9i+N8Hl+Ibjj+I14/MPmNTHY06kDUw1IaYelMQzFJTj7U00gGmig0GgYlHejv
R0oEFIaWj6UAIfekpaKADtSUoooAKKKBQAUUUUAFAoooAKWkopALSUvSigY5Bk1PGOKjjFTIKYiVccVKBUa
+1TKKALmnIXuUXHevQIYUtrNS2N56D3rm/Btj9ovQzdBXV64SlwVxgIoAoEYd1uJKE5zziorZWiZfMHGehp
8efNLsQTT5l8whu/fFAD23jGThOuKxtSYR5bNb0UZkiDEk4JrlddnDTbFPA60wMuRy7EnrUTc04nrTW6dKA
I2qM+9SP7Uw0ARmo5KkbpUT9KAIm5NJQetFACjpS0gp1AC08UynCmIlTrXb/DyXy9Ztiem8Vw6da6zwTII9
Vtyf7woYmep/tA2xTxBcMRgFjivCZ+HNfRn7R8BXWZWPQ8j8q+drkYc1MTRlU0w1IaYaYhlNpxpppANNFKa
SmAlFFFIApKU9KSgAoo7UUAFFFHagApRSUUALSUoooASl/nRRQAUg60d6UUAFKOtJTkFAEqDpUwFRqOKlQd
qQEsdTJ14NRIOlWrWPfKq9yaAPSPh/Y4tRIy8tzT9YcSzyjplug6iuh8NWwttEU4wQlczqIUyyvkde1MRmN
ERuBI+tMtQWn2Y/Opo2BDA4J7ZqzYxgzDOMt1PegC06iHTJjtB44NebXbl53btmvTteUxaOwXgkZ+teXzg7
jkc0wIe9I3T3pxWmsMj3pARt7VEafnnmmHpTAY1RSVI361FJQBF3paSloAKcOtNpaAHinCmCnimIevWuj8K
vs1CE+jCucWtvw82L2LPrTEz6T/aSt8Tq47qD+lfMF6P3jV9aftHW4azik55Wvk7UFxK2fWs1uzQoNTGp7U
w1Qhh4ppp5phpANopaTtQMSiik70CCiiigAooooAO1HtRRQAUtJRQAtFHeigA7UYopfrQMbRmnEUhFAgAqV
BUYHPFTKKBkiAGpUHFRoPyqZRxQIlTnpWvoEHn6lAo6lhWUgFdJ4MhMmrR+1ID16UC00RRjgjp0NcDeSh5G
GB1yT611niu8KWMNtEDnHNcOzYchjimIYQNwA4H1q7ppd5VVRk5qu8JIDJyKu6cvlTAgHIOc0AW/FgK6fGB
kEjn0rzW7TbKR+tekeKZxLaJjOa88vx+
+zxmmBSYdiaibpzUrdajakBEVzzTDUre1RnmmBExFQvUzVC/SgCLvSgUUUAApwpBU0DJ0kHGKAGCnCkJBbI
GB6UopiHr61qaO225T61lrWhpjYnTPTNMGfZH7QcAk0KJ+4Br481NcTMPevtb45xeZ4VB9Cf5V8X6yuLh/r
ULdlmQ3FRk1I1RmmIaaYe9PPWmmkA00hpTSUwEJooopAFJSmkoAKKKKACiiigAoopaAEpaKO9AAKWk70ooA
KSnUnegYqjNTpUSDNTqKBD0HrUydaYgqVR0IpASxjmux+H8YOoFmAwv61yEYzXd+BItkE0pJ9AaANrX7kNc
fNwB2rlZ5AZMMCOa0tauN7kYyelYhc7hnJ9aYi+JWUBA2AKtwzuCOe/rWIGJcYGO9W45CCB19qANTVnD2cT
Dntgdq4zUV/fHFdbMc2BAAyD3Ga5XUv9ZzQBmuMHpUTCpnHUioj0xTAibvUZqRxzUZ6UARNxUL1M31qCSgB
lFFKOtABSikpRQDHCnCmjpTxTQhy81dsDiVfrVJatWZxIv1piPvH4ww+b4QmwMkZ/lXxHry4upAfWvu34kJ
5nhG9HtXw14mTbeyjphjUfaNOhzrdajNSMMZqM0xDDTTTqaeQaTAaaSnGm0AJRRR9KACkNLSdqBhRS0UCE7
UUdqKACjvRQKAAdBRS0UAApaSlFAB3o70vegdcUDJEFTKKjTtUycUCJUHap4xz7VElTxgECkBKgzjtXoHhf
bBpLZGN3qa4KFN8igDqa7uy/dWCxN/dFAFHUSC7EHJ/nVD+AnAzWjNHlyWIOBxVPy2fIAAGaBFRjknnGOtP
iJ4LHAHenvGAcbsmhFIIHXFMDUtiJrKVVyW61zerrtkwBiuj0teWIGCRisbXYtr7hQBgsPTrUTGpmBA96ie
mBA/vULVM9RE0ARNUD81O1QPQAyiilpgFLSUooBjqcKaKeKEIctWLU4kWq4qeDhhTA/RDxtF5vhi/X0TNfD
PjFNuoz8Y+Y1956/GJdFvUPIMTfyr4Z+IERTVrgYwNx4FQ/iL6HDv3qI1NJ1NQmmIaaaacaaaAGGilNJSAT
iiiigYUhpaSgAoo6migBKKWkoEFKKQUtABRQKO9ABS0UUDFpVGTSDrUsS80ASItWEQUxBVhB0A4pAPjUAVY
UAAYpka+1WIwDSEXdKgEl2mQeOTXXsoMXXHFYvh+EANIy8t8ordVQxYZA4oQGfdwbTuz1FVMsoHftyK1JY2
cbRyMZqrJEwbbt/
+tVCKIXGSAd1KoA5P36s/Z2jnwQcY7VL5KMy8fMKAFtwqADPPXNUtaQSw9R0yK0DCMYLA89Kp3samM7fmoA
5KTg1A4q1criVh3BqtJTArPUTVM+fWoWoAhaoXqd/pUD9aAG0UUCmMKUUlOFIQopwpop4piFFTw/eFQj3qa
L71MD9Jr9PMsbhP7yMP0r4g+KMPl65dLjB3GvuSQZjYeoIr4s+McJj8Q3W7n5j/ADqJbl9DymXqahNTy8Ma
hNMQw9aYe9PPWmmkAw0lKaShAHtSUtFAxKKWkoATtRS0UAJxRRRQAUUUUCDvRS0lAwpRQKB1oEOUHNWIxUU
Y5qwmB2oGSovIqwg9ahXn61YjHHvSETJnuatQruYAD2quvY1at22yKffNIZ1mlwlnjRDtAGDXQx6emQzYI6
1iaJIC4IXO4flXX2VssqKro/zelNCMVrYx3MYKja38qkm0pCQwPfk11f2S0G0SqyuvGTzVC80tpwUhmUkcj
HFOwjGW3tYo95IZSccdaiKWjtkKAT396sXGkXKKu7A56etV722MTMqDIAoAzbsR7n2Ljg/jWRPkRFQcDuTV
263wRkkcnpWLezcnnIFMRh3H+tb3NVpOmMVYmOWJIqvIePegZXeoTUz9PaoXoAhk6GoG61M/WoWoAZS0UUw
FoHWilHWgBwpwpopwoAcKlj6iohUsfWmI/S6vjz45wFPEVxxj5j/M19h18p/tBwbdfuDjHJqJbotHgc4wxq
uas3AAc1WbvTEMNNNPOKYaAGGkpx6U2kMKP50UUwCkpaSkAneiloNACUUUUAFFFFABR+FKKKAClFJTl6igR
LGKnSokqdKQyZBzU8YqFOtWI/WgRNHx1FTqDwaiWpk7c0AaNlfXEBHlSFcdq3LfxNexKq7zkd6wLe2eUEqv
Suj0TwxcXpDNlEHJY+lCAu2eu3c0ilppMe/Sut0vVVZQHwSRznqKS28KW0NuCjkn1qvNpYghLo3Hr6UxGzO
qywbo/nPJGK52/haFSZB8x9asIbi3kDRSlc+lUdRnmuOHYMVPJxTEYGp7pn4G1QMe1crqClWbHSuqvCXUkk
jHUetYd5EDn0xSA56UfpVaQ/rVqddrkHmqzjHWmMrycmoWqdh7YqFhxQBA/SoD1qd+magbrQA3vRSmimAUo
pKUUAOFOFNHSnjpQIcKkQc81GKljBzTA/S2vmr9o6HGqM3qM19K18/ftIW/71ZOOUFRM0R8t3Q+c/WqrCrt
8MSN9apNTEMIpppx9KaaQhp602nGm0DEoIo60GgBKKWkNAAaKKKADtR1o7UUAJS0lLQAelFA60UAHanKOab
T0oEToKmQc96iQce1TpSAmX6VYj9a3vAXhe98Ra/p8KaXqN5pzXCLcvaxMdkZYBjuwQMD1r6bX9nnwYP+Wu
r/APgQv/xFO1wPk5OTV2zg804/hr1/x/4b+FvhEyWkNxquqasuR9mt7tNsZ9JH2YX6DJ9q8t05fNuGMKbUJ
JUZztHpnvStYDY0632KAoxjqTXf+Gyq2+wgl8dTwKwNI0tpETKEg85zXVWNstvhQSS3ahICy8zeXgN+NN80
FH8wDbjoKguT5gK/dUdF7/WmxDy4GEpy2OADzVCMy/ZomO37rdPas6Z1SIBuGfpzyK1tZf8A0SJ41G8vtJI
rn7kGWbdkgDjHrQIo3qKOd3Gc5rDuijM3UVt6vsTr1x0Fc/dupHoaAMK85mPaqb57irc+WYnNVn6UDKzZFQ
tU7jmoWxxQBA/NQN1qw/Sq70AN7UGijFMBe1KBSqmalSKkAxVJxUqxmpUi4BqwsfoKYECRcVagh+YelPjjJ
q1DH8w45pkn6J14j+0bDus4X77Mfzr26vJv2goN+hRSYHAIzUT2NFufHOoDErfWqDd61NUGJm+tZhpgRmmm
nmmGgQw/jTae1MpDCkpfpSUwCk+tLSGkAd6O9FHegApDS0UAJ3paO1FABQKK63wR4n0rw3Hdvf8AhXTtcvH
KmCW/djHCBnIMY4fPHXGMe9AGBpOk6jrFz9n0mwu76f8A5520LSN+Sg16Bp/wX8Vm2S71waf4esT/AMt9Xu
0gH/fPLD8QKg1X4zeM7y2NpY38GiWP8NtpMC2yp9CPmH/fVcLdXt1qFy1zf3M91cP96WaQux+pPNMD09fDn
w10E51vxbf67cLybfRbXYmfTzZOCPcYqVPiD4Z0bjwl4C0uOQdLrV5GvXJ9QpwFP0NeVpU8f6UgO81r4peM
9bj8u4125gt8YENni3QD0wgGR9c1t+KvjH4o8QaTbaZFP/Z1pHAkUxt2PmXDBQGZn64Jydox1wc9a8vXjmp
ozmlcCzBwQK6vw3bb5AcZJFcrDyR7V3vgCLz7tRjIH6UCO80KzaKxG9T04rSVEKE8ZA4PpWm8P2eyX5fUcV
hXsrLGAqlBnsKoRFkGXe3JHHHY01ERfNIfe/XPrRaATzkqTxirCqFuC5YBc4wOc0AULyN5reFY1G5jkk9qz
JraO3YGRw20bue5rT165dJ0EJwqjjArldUunETu/r60AYOt3a+c5xlzWDcTfIBn8alvrjfIW61myuWbB9KQ
EchBOOlVnqR+tRP9aYEDZ96hYVO3AzUJPPNAEDCoXq2I2fsaHg2jkUAU1Qk1KsQ9KmWPjpUqpigCNY6lWP2
qVEqZU5FAEax+1TpGKeiCp1TgcUxDFT2q1BFkilhhLMABmur8NeEr/VZVEULBD/ERTEfbdecfHGAy+FSwAO
Cf5V6PXF/FuDzvCE+c8H+hqZ7Gi3Ph3WU23D/Wshq3vECh
buQe9YTUIdiM00inGkIpCI2ptPNMNACdqKKKAEo5oo7daACkpaTvQAuKSlpKACgUUooAKMcUUc0AFSoKjHJ
FTJQBMlTxjFQL1z3qZM0ATr2qZAO1QpxirCYH0pATxEjp3r0z4YRFpQR0LV5onUYNev8Awmtw1tubpupiPS
dRcpAm9c4HSuVuZhIWAGOeldnriAWSA8DH41xYtW+0dSR9KoRYsIhFG7IuT0p88YtotzABjzz2qdCqsoHKj
0qHUz58qc/Ke1AGPexyTBTgADvmuI8Uv5SFcnOea9LuoUS298c15P4tmzdOqscA0gOXlfJ/lUD4x15qR+Wy
ajI5PPNICF1zyKgfOSassOvrSxwNJ0BxTAplS2AOalitCeWFa0NiB1X8qtR2gVenvSAyUtto6VXuYhit8xf
LnnFZ97EeeKYjGC4GMVMkfNSCHCZPXOKeqHvQA1UxzUqr3pQmelWIosnpQA2JMj3rW0nS7i/mEdvGWJ/Stv
wl4Pu9ZuFwpWH1Ir6G8D+AbawgUmMBh1yKN9hNnAeCfhhv8ua8TeSM49K9r0HwtbackeEUbR0ArfsrKK2jC
xqBikvJ/JjYjk46DtVpEvzLdcz8Ro/N8JXij0rpqxPGkXm+GL9f+mZNRLY2W58J+KY9t9KP9o1zb11vjJNm
ozjB+8a5KTqaS2BkfemmnHrTaYDDTaex5ph71ICGkpaSmAlKaO1JQAUGiigA7UUuKSgAooo68UAFJS96KAF
TrViPtUCdanT3oAlTrUydRUK1PH+tICdOT0qdeMVDHgipkFAE8WM17t8JbcLpkLMMEnPSvCrcEyKOpJxX0l
8N7XytGth32jjvQhG34ilKsIm5UDIrnZCMkevqa1/EThrogNj8etc1dSjfkMNo7VYideGPUkehp8YzIc43d
hVZHBIYE5q3poDXQyAfrQA3V3aHTCQOcV4jrkzS30pY969y8X4i0yRSM/LXgV+d11Ie2TQwKT5ye9NAZiMC
rEcLO2OcVp2tiBgYqQM+Cy3nLAk1qW1nt9vTNXYbfYmCo+tW0jO0/pQIpGAKq/LxSNEFHTA71plAUGc5HSo
3XCgHnJ9KYGcYyB0HNZWoLwRjit6ReuOMVi6ip2tTAyMfwjoKcqelCqScdK0NOsZbydYo03MaQFeGBpHVVU
kngYr0vwP4CuL2VJbhBs4YA1v+A/AQLJJcR7m4PI6fSvdvD+gQ2cSYXAx6U0ribKPhTwvBYW6FYlBAGOOK7
GKNY14AH0pyqEUAAACo5JMDiqXZBZLViSzBRgcmqM6+cRtYhj1zVz3I4oSPg8fjVLQh3ZYqhr6l9FvVAyTE
38qv1BfjdY3A9Y2/lWb2NkfCnxBj8vV7gYA+Y1w8vU16N8UItut3PGPmNedSjk1MdimRGmGnmmmgQw00040
00gG0d6O9H1pgJQaWkoAKKKO9AB2pDS0lABRRRQAd6SlpBQBJHUy1DH15qdKQEqip46hXrU8dAE0Yqdc9ai
i5AB7VMMnigDQ0eIzX8CY+84B/OvqDwhbiKxiAxgLivnHwTbmXXLcYyAc8V9MaETBYHAz8ufpTQjn9dZmuG
PGQcVzUzqx5OATyDWzrc/7xiehPIrnSVaUkgkdcdKYGnCQBjGPatLQh+/UDPJ5FYqS7kXHHrXReGI2kmJUZ
BGc0CM/4iytDp8nUblxXh62xklJYHGa988eWnmaYwf5scCvJFt1RzkcZoYFKG0wAdpA6Zq/FCMZ24qwseVB
xgVZitxnPIBH4CgCEQbupwKtrbhUCgfXirCQqU6Yb0qdFOAxA470CMzyyMgj2BNV5wo4C1ouoYkkH2NVLmM
88ZJ6UxFCRPl4x9KytQizEe31rZaJumCc9KWHSrjUJBFAmSe9AzlbCwlurlIoULMxwMV7n8OfAv2by5Z0Bl
YZzirfgDwJHamOSaPdKepxmvadL0qO0ROOQOBQkJ67EOi6RHawqCo4HetoAAcUvAqKWQAMB1Aqtw0iOdgBV
R5+cKOajlnYAFfpyajgbfKMkj61aViG7lu3YsxytWwKagwBTqhs0irBTZRuidfUEU6g9KRR8XfGOAxeIbkY
43GvKZvvGvavjxB5fiO4/3jXi84+Y1nHYtlc0w08000ySM96aaeaaaQxppKWkPNMQlFKaKAEzzRRzQetABS
fWl7Un5UDCigUUCEopTRQBJHU69KgSp04pASp71PGfaoVqZKALEeM1MDUSj0HNSqOnNAHd/C+383Vt+OB3r
38MkOmuwJBxjHrXjfwhtd7PJgEZ/OvXdYlSLT41H3jVIRyGsOXLdx71ixxn5iSCRzj0rXu1eYsqqT7ZqOws
2WT5174oAZZwNOPlG1e/vXoPhPTFSMEDnFY2mWO1sBOD0FdvooWMbOQTTQjlPiDbrDYlecV4+YCZSCPlzXt
3j2LdbZzu9a8lmi3Tkgc5NDBFSG23ZB4/CrMaYIG3gVcii4BKgUeSAflGPrSERIgI5P4Urtscjgg9jxVjy8
YLZ44qOdA45PSmIpSKSxUDA61VKHPPXOOe1apj5AyeP1rQ0bQ5dTuAsK4XuSKAMjTtGudQu1hhTPP3h0Fex
eD/AAQtrbgvGpJHJPrWz4Q8JQ2FuGkUcj05NdoiLGoVRgCgErlPT9PitIwoGSP0q9SE4GaTOaY9EDHiq8oV
fmbgH1qYg84phjyctz7GqRL1MuVmdgEUnNaNpb7Fy2M+mKmWJQOgqQDFDYKPcKKKKk0CiiigD5Y/aFg26/O
3qTXgdwPnNfSH7RkH/E0Z8da+croYc1lE0ZUNMNPI5phFUSMbrTDT26000gGdTQaU0lMBKKDQaBCUUUUAFF
BooAKSiigANFFFAySOrCdKhj7VOvakIlWpoxyKiSpkH40AWF9qkXOaYgwOas20e6RQBjJxQB7V8KbUpYREd
Sc13+swNKyLt4ArI+GOl7LCEsP4RxXXauFUsqjGOCapCOQW0CnJByPSrMNrucYGM9SanJX5iM5qW3mOSGXi
mIvafC+8MgPSuj0xGSVCQc+lZFhMp27htboAK6LT3DjdhRxxTAwvGqh7RzjGPQV5VNDmc7l49q9k8Sp5li4
A7dK8svrf96ShI59aGIoRJxj5to9qUxqMsM1fEQVT2PrTXiOC2ePT1pAUWViQSeD2prW/yYIx/Wrqxl35GM
V0/hnwtcarKGdCtuDkk0CMPw54em1aZQFfYDya9n8OeHbbS7ZBsBkA5yKv6RpVtplusVugHqa0KCrB0FFFF
MYh5zSClNIetMhi5FIopccUtIqwUUUUDCiiigAooooA8B/aOgHmo4HJUV8wXq4kavrP9oqDdZQSDrtr5Q1B
cSt65rJaNmu6M9hUbVI1MNUIjYUw9akNMPSkSxh60nFLRigBKT1oopgJ3o60CigBKKWigQlFLQKBiUAUUoo
Amjqwnaq8fFWFpCJV5NTxnHQVEoq1bRl2HHHrQwJoVLniug8O2Xn6jboR1YYqnZW3AzXa+CLES65bjbnDA9
KQM+gfB1kLawjYAKQvP5VX1hlLPySSa3gBaaKMDBYAVxWoTlpyAenWtBFWQjJxnPfNLBJ02jjPNRSMWBHTP
Gc1JBhU56envQI39PCyMBnB7V0tiAqfKuQOtchprgyHJODxXYaYoMICdcfnTAXUo1e3l6HjpXm17bjz2O3r
XqDQeYTkjBHSuM1awP20iMZPpQI53yRgDrj0oTTzczYRS3piuu0rw1PdDdIuwZ5967TStAs7BQRGryf3iKA
scp4Z8GKQs18pCg52Hqa7+CGOCMRwoEQDAAqSigdgooooGFFFFADW/KlXmlNAoFbUKKKKBhRRRQAUUUUAFF
FFAHk/7QEHmaHC56AEV8g6qMTMMd6+0PjhFv8AC27GcE18ZayNtw496y+0aLYyWphp7dajP1qrCGmmU80w0
g6jOtIacaaaYCUlONIaRIlFKaT6UDCkpfSimAlLRRQAlKoyaKco5oAnQVOgqKMcVYiQsQBSAmgTeeK3LG1G
F4zmq9ja+o5rorK2CgcA+1IRLaW4UYA+tei/DOyD6sH25Cgdq4yCDn0Neu/CqyJzIFz3poDuNen2WkUOcYG
a4ptssrYb64711HiXDTZJwB1rmREpdmDDJ9KsRC6jzFGfpViFW6OCADxTYYi8oGBgdCa2IbUsoEeD9KBEdj
AyyhsZFdzpMJMS4BIYelZuj6M7lSwKjrk9K7C2gWCNVHamBVjsACC5zjpQ+lwNL5hUZq/RQFhkcaxjCin0U
UDCiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooA4v4tReZ4RnOM7T0/CviTxAu26kz1zX3T8R4vO8
JXijqADXw74oTbfSjHQ1m/iLWxzrc0w96e3WmmmIYabinmmkVLGMIptPIppFMBppKcaQ0BYbRS0UxBSUtFI
BPwpaKOlMBKkjFMqeJc0gJolJOAK2LG36fWq1jb7jk10VlBtwcUh2LFpBgqQBke1bdrDjHTFQ20OMccVpWs
Z4wARQIntoxuwenSvafhtavDY+Z0GM4ryfTbZnnQHuRmvcdFi+xaKhwS23HpVoRmayxkumDYAJzmslYMuSo
yR0rUu4fOl4BOegrR0XRGYl5PXgUxFXS9MaZ13Lx3rr9K0ZI1Uugx1q9Y2Cw4wu3A7VpCmIaiKihVGBTqKK
BhRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQBjeMU3+G70f7Ga+G/GabNTnGOjGvu
7X4/N0a8Q8gxmvhv4gR7NXuAM/eNZv4ilscSw5phFSP14plMBp96QinUh6ZqWUMIppHNONNPWgY00hFONIe
lAhpopcUGmIbS0UEUAAo60UAUCFFXLSPcR61VQc9K2dLh3MDSY0athBwARXQ2cIUZbr6VQs4xwCOK3rKLcM
YyaQyzaRBh6EcVqQW/AB60WlmTgnj1rYt7UkAADHTNNCZY8N2THUIQeRur2B4ylvFEM4I6VwfgyzLavGAMk
DpXrMVgGZTJ9/HANaIkztK0ncN0mC2fyrftbJYceg7VZghWJQBUlMQUUUUAFFFFABRRRQAUUUUAFFFFABRR
RQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQBBfrvsp19UP8q+IfiemzXLkYx8xr7jkG6Nh6givi/4xW4i1+5
GB941Et0VHY8qf7xqOpZfvVHQNCd6aaUmkqWUNNNPWnHpSHrSAaaSndaDQA3FIRTvwpMc0xDfpRTqSmISgU
GnL1oAkhGWFdLpcPygY+tYVkm6QV12lxA44xUsEa2nW4fHGccV0un2fGWyFFVNItASpBI55OK6y2iACrgHP
tQkNi2kO04AyMd607a3K7V7sadbQZAwOAemO1b+j2HnzIzL8uatCZ0Pw800/ammcD5RgcV6KEUYwOlZHhqz
FtaMQMFjWzVogKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKAC
vkL46wFPENyMDhia+va+Wv2hLYR65Mw7mon0KifP8AMMPUNWLkfOarmgBKQ0Gg1LKQhFJSmkqShKDS0UwG0
Yp1JQA3FJT6aaLiEpV60UqjmmSaelJul6V3GjWpcgAEYrk9Bi3NkDnNel6HaFEB60MZt6XAI4gNvNblrGSw
CgD61Ttv4QRgelbenJj5iAQOgNNIRo6dbF2A4weprvNB0zCqu3v6VjeG7AS7WC5r0Cwt1ijGBg4xVpCZbjU
JGqjoBTqKKZIUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAFf
Nn7RqAam5H+eKKKifQqJ843Y/eGqrdKKKEUxppKKKTBbiUGiioGA60tFFMpgaTHWiikDDtSUUUxBihfvAUU
UCOw8KRguteoaVEqpuXg4oopgbtgn7w5OcV0emwq0ir2JooqkSz0/w5bRxwblGDnHFb6dKKKvoSx1FFFAgo
oooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigD/2Q==);\">",
" </div>",
" <div class=\"lgnd\">",
" This lateral radiograph shows a condylar fracture of the proximal phalanx.
Although less apparent here than on the AP view, the fracture is reflected in the
irregularity of the cortex before the white arrow.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f6_2_6191=[""].join("\n");
var outline_f6_2_6191=null;