• Parrish Pitts posted an update 2 months ago

    To review the evidence on the usefulness of the multifocal visual evoked potential (mfVEP) test in patients with optic neuritis (ON) and/or multiple sclerosis (MS).

    We critically review key published evidence on the use of mfVEP in ON/MS patients and its association with other functional and structural tests.

    Multifocal VEP tests are useful in detecting abnormality in patients with ON/MS and monitor the progression of lesions (remyelination, atrophy). In addition, mfVEP has good correlation with conventional visual evoked potential (VEP), standard automated perimetry, optical coherence tomography and magnetic resonance imaging. In patients with ON, mfVEP might be useful in predicting the risk of conversion to MS.

    Multifocal VEP tests are useful in detecting abnormality in patients with ON/MS and monitor the progression of lesions (remyelination, atrophy). In addition, mfVEP has good correlation with conventional visual evoked potential (VEP), standard automated perimetry, optical coherence tomography and magnetic resonance imaging. In patients with ON, mfVEP might be useful in predicting the risk of conversion to MS.Typically, bioprocesses on an industrial scale are dynamic systems with a certain degree of variability, system inhomogeneities, and even population heterogeneities. Therefore, the scaling of such processes from laboratory to industrial scale and vice versa is not a trivial task. Traditional scale-down methodologies consider several technical parameters, so that systems on the laboratory scale tend to qualitatively reflect large-scale effects, but not the dynamic situation in an industrial bioreactor over the entire process, from the perspective of a cell. Supported by the enormous increase in computing power, the latest scientific focus is on the application of dynamic models, in combination with computational fluid dynamics to quantitatively describe cell behavior. These models allow the description of possible cellular lifelines which in turn can be used to derive a regime analysis for scale-down experiments. However, the approaches described so far, which were for a very few process examples, are very labor- and time-intensive and cannot be validated easily. In parallel, alternatives have been developed based on the description of the industrial process with hybrid process models, which describe a process mechanistically as far as possible in order to determine the essential process parameters with their respective variances. On-line analytical methods allow the characterization of population heterogeneity directly in the process. selleck This detailed information from the industrial process can be used in laboratory screening systems to select relevant conditions in which the cell and process related parameters reflect the situation in the industrial scale. In our opinion, these technologies, which are available in research for modeling biological systems, in combination with process analytical techniques are so far developed that they can be implemented in industrial routines for faster development of new processes and optimization of existing ones.Intelligence quotient (IQ), has been found to relate to the presence of internalising symptoms in autism spectrum disorder (ASD). This meta-analysis sought to clarify the direction of the relationship between IQ and two prevalent internalising symptoms, anxiety and depression, in adolescents with ASD. Secondly, this study aimed to highlight methodological factors contributing to inconsistent findings in existing research. Self-reported anxiety was found to be significantly higher in youth with a lower IQ, while depression was positively associated with IQ. Consequently, parents, schools and clinicians should be cautious of underestimating anxiety in youth with a lower IQ. However, care should also be taken to ensure adolescents with ASD without intellectual disabilities are not overlooked with regards to social and emotional support.Human induced pluripotent stem cells (hiPSCs) have the potential to be used in a variety of biomedical applications, including drug discovery and Regenerative Medicine. The success of these approaches is, however, limited by the difficulty of generating the large quantities of cells required in a reproducible and controlled system. Bioreactors, widely used for industrial manufacture of biological products, constitute a viable strategy for large-scale production of stem cell derivatives. In this chapter, we describe the expansion of hiPSCs using the Vertical-Wheel™ bioreactor, a novel bioreactor configuration specifically designed for the culture of shear-sensitive cells. We provide protocols for the expansion of hiPSCs in suspension, both as floating aggregates and using microcarriers for cell adhesion. These methods may be important for the establishment of a scalable culture of hiPSCs, allowing the manufacturing of industrial- or clinical-scale cell numbers.Cardiac explant-derived cells (cEDC), also referred as cardiac progenitors cells (CPC) (Barile et al., Cardiovasc Res 103(4)530-541, 2014; Barile et al., Cardiovasc Res 114(7)992-1005, 2018), represent promising candidates for the development of cell-based therapies, a novel and interesting treatment for cardioprotective strategy in heart failure (Kreke et al., Expert Rev Cardiovasc Ther 10(9)1185-1194, 2012). CPC have been tested in a preclinical setting for direct cell transplantation and tissue engineering or as a source for production of extracellular vesicles (EV) (Oh et al., J Cardiol 68(5)361-367, 2016; Barile et al., Eur Heart J 38(18)1372-1379, 2017; Rosen et al., J Am Coll Cardiol 64(9)922-937, 2014). CPC cultured as cardiospheres derived cells went through favorable Phase 1 and 2 studies demonstrating safety and possible efficacy (Makkar et al., Lancet 379(9819)895-904, 2012; Ishigami et al., Circ Res 120(7)1162-1173, 2017; Ishigami et al., Circ Res 116 (4)653-664, 2015; Tarui et al., J Thorac Cardods have been implemented to assess the safety (sterility, endotoxin, mycoplasma, cell senescence, tumorigenicity) and identity/potency/purity (cell count and viability, RT-PCR, immunophenotype) of the cells (Andriolo et al., Front Physiol 91169, 2018).

!function(e,t){"object"==typeof exports&&"undefined"!=typeof module?t(exports):"function"==typeof define&&define.amd?define(["exports"],t):t((e="undefined"!=typeof globalThis?globalThis:e||self).version={})}(this,(function(exports){"use strict";function __awaiter(e,t,n,i){return new(n||(n=Promise))((function(s,a){function o(e){try{d(i.next(e))}catch(e){a(e)}}function r(e){try{d(i.throw(e))}catch(e){a(e)}}function d(e){var t;e.done?s(e.value):(t=e.value,t instanceof n?t:new n((function(e){e(t)}))).then(o,r)}d((i=i.apply(e,t||[])).next())}))}var Blocking;"function"==typeof SuppressedError&&SuppressedError,function(e){e.PENDING="pending",e.NONE="none",e.BLOCKED="blocked",e.ALLOWED="allowed"}(Blocking||(Blocking={}));class Adblock{constructor(e){this.state=Blocking.PENDING,this._mocked=!1,e?(this.state=e,this._mocked=!0):this.state=Blocking.ALLOWED}inject(){return __awaiter(this,void 0,void 0,(function*(){}))}hasAdblocker(){if(void 0===window.google)return!0;const e=document.querySelectorAll("style");return Array.from(e).some((e=>!!e.innerHTML.includes("adblockkey")))}handleAdblocked(){this.removeAdblockKey(),this.state=Blocking.BLOCKED}removeAdblockKey(){var e;null===(e=document.documentElement.dataset)||void 0===e||delete e.adblockkey}get isBlocked(){return this.state===Blocking.BLOCKED}get isAllowed(){return this.state===Blocking.ALLOWED}toContext(){return{user_has_ad_blocker:null,is_ad_blocked:null}}}const OBFUSCATING_BASE_64_PREFIX="UxFdVMwNFNwN0wzODEybV",encode=e=>OBFUSCATING_BASE_64_PREFIX+btoa(unescape(encodeURIComponent(JSON.stringify(e))));function decode$1(e){return JSON.parse(decodeURIComponent(escape(atob(e.replace(OBFUSCATING_BASE_64_PREFIX,"")))))}var version="0.8.5";const APP_ENV="production",TRACKING_DOMAIN="https://click-use1.bodis.com/",SALES_JS_URL="https://parking.bodiscdn.com/js/inquiry.js",GOOGLE_CAF_TIMEOUT_SCRIPTS="0",GOOGLE_CAF_TIMEOUT_CALLBACKS="0",GOOGLE_MV3_URL_PARAMS="abp=1&bodis=true",APP_VERSION=version,COOKIE_CONSENT_JS_URL="",AFD_REFERRAL_CHEQ_LOAD_PERCENTAGE="25",AFD_ORGANIC_CHEQ_LOAD_PERCENTAGE="5",isLocal=(e=!0)=>"production"!==APP_ENV;function log(...e){}const FIND_DOMAIN_URL="_fd",getFindDomain=(e="",t=!1,n="")=>{const i=n||window.location.search,s=`${e}/${FIND_DOMAIN_URL}${i}`,a=e?"include":"same-origin",o=Object.assign({Accept:"application/json","Content-Type":"application/json"},t?{"X-HOST":window.location.host}:{});return fetch(s,{method:"POST",headers:o,credentials:a}).then((e=>e.text())).then(decode$1)};var ZeroClickReasons;!function(e){e.CAF_TIMEDOUT="caf_timedout",e.CAF_ADLOAD_FAIL_RS="caf_adloadfail_rs",e.CAF_ADLOAD_FAIL_ADS="caf_adloadfail_ads",e.DISABLED_GB="disabled_gb",e.DISABLED_AB="disabled_ab",e.DISABLED_DS="disabled_ds",e.AD_BLOCKED="ad_blocked",e.PREFERRED="preferred"}(ZeroClickReasons||(ZeroClickReasons={}));const getZeroClick=e=>__awaiter(void 0,void 0,void 0,(function*(){const t=Object.assign(Object.assign({},e),{type:"zc_fetch"});return fetch("/_zc",{method:"POST",body:JSON.stringify({signature:encode(t)}),headers:{Accept:"application/json","Content-Type":"application/json"}}).then((e=>__awaiter(void 0,void 0,void 0,(function*(){try{return decode$1(yield e.text())}catch(e){return{}}}))))})),waiter=(e,t)=>new Promise((n=>{t(e),e<=0&&n();let i=e;const s=()=>{i>0?(i-=1,t(i),setTimeout(s,1e3)):n()};s()})),decode=()=>JSON.parse(atob(window.park||""));var PAGE_STYLES='* {\n font-smoothing: antialiased;\n -webkit-font-smoothing: antialiased;\n -moz-osx-font-smoothing: grayscale;\n}\n\nhtml, body {\n width: 100%;\n margin: 0;\n}\n\nhtml {\n background-color: #2B2B2B;\n height: 100%;\n}\n\nbody {\n min-height: 90%;\n font-family: Arial, sans-serif;\n letter-spacing: 1.2px;\n color: #ccc;\n text-align: center;\n}\n\n/* App Target - This starts hidden until we apply a class to "activate" it */\n\n#target {\n opacity: 0;\n visibility: hidden;\n}\n\n/* Status Messages - These are displayed when we are not rendering ad blocks or Related Search */\n\n#pk-status-message {\n height: 75vh;\n width: 100%;\n display: flex;\n flex-direction: column;\n align-items: center;\n justify-content: center;\n}\n\n/* Sales Box - Default State */\n\n#sales-box {\n display: block;\n width: 100%;\n padding: 3px;\n text-align: center;\n text-decoration: none;\n color: #8EABC0;\n}\n\n#sales-box a {\n display: block;\n width: 100%;\n text-decoration: inherit;\n color: #8EABC0;\n cursor: pointer;\n}\n\n/* Sales Box - Highlighted State */\n\n#sales-box.is-highlighted {\n position: relative;\n z-index: 1;\n background: #032438 linear-gradient(to top, #044368 0%, #000 100%);\n box-shadow: 0 0 15px 0 #000;\n border-bottom: 3px solid #262626;\n}\n\n#sales-box.is-highlighted a {\n line-height: 1.3;\n display: inline-block;\n font-size: 18px;\n color: #fff;\n text-shadow: 1px 1px 0 rgba(0, 0, 0, 0.5);\n background: none;\n}\n\n/* Ellipsis Loader */\n\n.pk-loader {\n display: inline-block;\n position: relative;\n width: 80px;\n height: 80px;\n}\n\n.pk-loader div {\n position: absolute;\n top: 33px;\n width: 13px;\n height: 13px;\n border-radius: 50%;\n background: #ccc;\n animation-timing-function: cubic-bezier(0, 1, 1, 0);\n}\n\n.pk-loader div:nth-child(1) {\n left: 8px;\n animation: pk-anim-1 0.6s infinite;\n}\n\n.pk-loader div:nth-child(2) {\n left: 8px;\n animation: pk-anim-2 0.6s infinite;\n}\n\n.pk-loader div:nth-child(3) {\n left: 32px;\n animation: pk-anim-2 0.6s infinite;\n}\n\n.pk-loader div:nth-child(4) {\n left: 56px;\n animation: pk-anim-1 0.6s infinite;\n animation-direction: reverse;\n}\n\n.pk-loader-text {\n position: fixed;\n font-size: 12px;\n right: 20px;\n bottom: 20px;\n font-weight: lighter;\n}\n\n/* Utilities */\n\n.pk-message-title {\n font-size: 2em;\n font-weight: bold;\n}\n\n.pk-page-ready {\n opacity: 1 !important;\n visibility: visible !important;\n}\n\n.hide-sales-banner > #sales-banner {\n display: none;\n}\n\n@media only screen and (max-width: 600px) {\n .hidden-xs {\n opacity: 0;\n visibility: hidden;\n }\n}\n\n/* Animation */\n\n@keyframes pk-anim-1 {\n 0% {\n transform: scale(0);\n }\n 100% {\n transform: scale(1);\n }\n}\n\n@keyframes pk-anim-2 {\n 0% {\n transform: translate(0, 0);\n }\n 100% {\n transform: translate(24px, 0);\n }\n}\n';const APP_TARGET="#target",MESSAGE_TARGET="main",MESSAGE_SELECTOR="#pk-status-message",PAGE_READY_CLASS="pk-page-ready",MESSAGE_TEMPLATE='
';class Renderer{constructor(e){this._domIsReady=!1,this.revealPage=()=>{this.domNode&&this.domNode.classList.add(PAGE_READY_CLASS)},this.hideSalesBanner=()=>{this.domNode.classList.add("hide-sales-banner")},this.revealSalesBanner=()=>{this.domNode.classList.remove("hide-sales-banner")},this.injectMetaDescription=e=>{if(!e||0===e.length)return;window.document.title=e;const t=document.createElement("meta");t.setAttribute("name","description"),t.setAttribute("content",`See relevant content for ${e}`),document.getElementsByTagName("head")[0].appendChild(t)},this.domNode=document.querySelector(e)}get domIsReady(){return this._domIsReady}set domIsReady(e){this._domIsReady=e,e&&this.injectStyles(PAGE_STYLES)}message(e,t=""){if(this.injectMessage(MESSAGE_TEMPLATE),this.domNode){const t=this.domNode.querySelector(MESSAGE_SELECTOR);t&&(t.innerHTML=e)}t&&this.injectMetaDescription(t)}injectMessage(e){const t=document.querySelector(MESSAGE_TARGET);t?t.innerHTML=e:this.domNode&&(this.domNode.innerHTML=e)}salesBanner(e){if(!e)return;const{href:t,position:n,message:i,theme:s,status:a}=e,o=document.createElement("div"),r=n||"",d="HIGHLIGHT"===s?"is-highlighted":"";o.innerHTML=t?`\n
\n ${i}\n
\n `:`\n
\n ${i}\n
\n `,"BOTTOM"===n?(o.style.marginTop="30px",document.body.appendChild(o)):document.body.prepend(o)}loading(e){let t="a few";e>0&&(t=`${e}`),this.message(`\n
\n
\n
\n
\n
\n
\n \n `)}adBlockMessage(){this.message("\n

Ad block detected

\n Please disable your ad blocker and reload the page.\n ")}errorParkingUnavailable(){this.message("\n

An Error Occurred

\n

Parking is currently unavailable. We'll be right back.

\n ")}errorParkingServicesDisabled(){this.message("\n

An Error Occurred

\n

Services for this domain name have been disabled.

\n ")}errorParkingNoSponsors(e){this.message(`\n
\n No sponsors\n
\n \n ${window.location.hostname} currently does not have any sponsors for you.\n \n `,e)}imprint(e){if(!e)return;const t=document.querySelector("#imprint-text");t&&(t.innerHTML=e.replace(/(?:\r\n|\r|\n)/g,"
"))}injectStyles(e){if(!e)return;const t=document.createElement("style");t.innerHTML=e.toString(),document.head.appendChild(t)}injectScript(e){if(!e)return;const t=document.createElement("script");t.type="text/javascript",t.src=e,document.body.appendChild(t)}injectJS(js){js&&0!==js.length&&eval(js)}injectHTML(e){this.domNode?(e&&(this.domNode.innerHTML=e),this.domIsReady=!0):(this.domIsReady=!1,console.error("An error occurred when trying to render this page. DOM node not found."))}prerender(e){this.injectMetaDescription(e.domain),e.bannerAdblockerOnly&&this.hideSalesBanner(),this.injectHTML(e.html)}template(e){var t;this.domIsReady||this.prerender(e),this.injectStyles(e.stylesheet),this.imprint(e.imprint),this.salesBanner(e.salesBanner),e.bannerAdblockerOnly||this.injectJS(e.javascript),null===(t=e.scripts)||void 0===t||t.forEach((e=>{this.injectScript(e)}))}}const Render=new Renderer(APP_TARGET);var Type;!function(e){e[e.Failed=0]="Failed",e[e.Disabled=1]="Disabled",e[e.Redirect=2]="Redirect",e[e.Parking=3]="Parking",e[e.Sales=4]="Sales"}(Type||(Type={}));let State$2=class{get trackingType(){return this._trackingType}set trackingType(e){this._trackingType=e}get track(){return!!this.trackingType}};class Disabled extends State$2{constructor(){super(...arguments),this.type=Type.Disabled}static build(e,t){let n;switch(t===Blocking.BLOCKED&&(n="adblocker"),e.cannotPark){case"disabled_mr":case"disabled_rc":n=e.cannotPark}if(n){const t=new Disabled;return t.reason=n,t.domain=e.domainName,t}}get message(){switch(this.reason){case"adblocker":return"

Content blocked

Please turn off your ad blocker.";case"disabled_mr":return`

Invalid URL

Referral traffic for ${this.domain} does not meet requirements.`;default:return`

No sponsors

${this.domain} currently does not have any sponsors for you.`}}get trackingType(){switch(this.reason){case"adblocker":return"ad_blocked_message";case"disabled_mr":return"invalid_referral";case"disabled_rc":return"revenue_cap_reached";default:return"no_sponsors_message"}}toContext(){return{cannotPark:this.reason}}}class Failed extends State$2{constructor(){super(...arguments),this.type=Type.Failed}static cannotPark({cannotPark:e}){switch(e){case"disabled_b":case"prohibited_ua":case"disabled_fr":case"revenue_cap_reached":case"disabled_mr":case"disabled_rc":case"disabled_cp":case"invalid_domain":case"disabled_tos":{const t=new Failed;return t.reason=e,t}}}static noSponsors({cannotLoadAds:e}){if(e){const e=new Failed;return e.reason="no_sponsors",e}}static fromError(e){const t=new Failed;return t.reason="js_error",t.error=e,t}get track(){return!!this.trackingType}get message(){switch(this.reason){case"disabled_fr":case"disabled_rc":case"disabled_tos":case"no_sponsors":return`\n

No Sponsors

\n

${this.domain} currently does not have any sponsors for you.

`;case"disabled_mr":return`\n

Invalid URL

\n

Referral traffic for ${this.domain} does not meet requirements.

`;case"js_error":return"\n

An Error Occurred

\n

Parking is currently unavailable. We'll be right back.

\n ";default:return"\n

An Error Occurred

\n

Services for this domain name have been disabled.

\n "}}get trackingType(){switch(this.reason){case"disabled_rc":return"revenue_cap_reached";case"disabled_mr":return"invalid_referral";case"adblock":return"ad_blocked_message";case"no_sponsors":return"no_sponsors_message";case"disabled_tos":return"tos_not_accepted"}}get domain(){return window.location.hostname}toContext(){return{cannotPark:this.reason}}}function unpackPHPArrayObject(e,t){const n=e[t];if(n&&!Array.isArray(n))return n}class Parking extends State$2{constructor(){super(...arguments),this.type=Type.Parking}static build(e,t){const n=new Parking;n.domain=e.domainName,n.html=e.template,n.scripts=e.scripts||[],n.javascript=e.inlineJs,n.stylesheet=e.styles,n.imprint=e.imprintText;const i=unpackPHPArrayObject(e,"salesSettings");n.bannerAdblockerOnly=null==i?void 0:i.banner_adblocker_only;const s=(null==i?void 0:i.status)&&"NOT_FOR_SALE"!==(null==i?void 0:i.status);if(s){const{status:e,location:t,message:s,link:a,type:o}=i;n.salesBanner={message:s,href:a,position:t,theme:o,status:e}}return t.wantsToServeAds?n.trackingType="ctr":s&&window.location.pathname.startsWith("/listing")?n.trackingType="sales":n.trackingType="visit",n}toContext(){return{}}}class Sales extends State$2{constructor(){super(...arguments),this.type=Type.Sales}static build(e){const t=unpackPHPArrayObject(e,"salesSettings");if(!t)return;const{status:n}=t;return["NOT_FOR_SALE","EXTERNAL_MARKET","URL"].includes(n)?void 0:window.location.pathname.startsWith("/listing")?new Sales:void 0}toContext(){return{}}get trackingType(){return"sales"}init(e){window.context=e;const t=document.createElement("script");t.type="text/javascript",t.src=SALES_JS_URL,document.head.append(t)}}class Redirect extends State$2{constructor(){super(...arguments),this.type=Type.Redirect}static build(e,t,n){const i=unpackPHPArrayObject(e,"salesSettings"),{zeroClickDelay:s,skenzoRedirect:a,skenzoUrl:o,showInquiryForm:r,canZeroClick:d,cannotPark:c}=e;if(window.location.pathname.startsWith("/listing")&&["EXTERNAL_MARKET","URL"].includes(null==i?void 0:i.status)){if(null==i?void 0:i.external)return Redirect.toState(i.external,"sales");if(null==i?void 0:i.link)return Redirect.toState(i.link,"sales")}if(n.cannotLoadAds&&n.wantsToServeAds)return Redirect.toState(n.noAdsRedirectUrl,"no_ads_redirect");if(d&&(null==t?void 0:t.reason)){if(null==t?void 0:t.redirect)return Redirect.toState(t.redirect,"zc_redirect",s);if(a&&o)return Redirect.toState(o,"skenzo_redirect")}return(null==i?void 0:i.status)&&"NOT_FOR_SALE"!==(null==i?void 0:i.status)&&!(null==i?void 0:i.banner_adblocker_only)&&(n.cannotLoadAds||n.cannotLoadAds&&!d||r)?Redirect.toState(`${window.location.origin}/listing`):void 0}static toState(e,t,n=0){const i=new Redirect;return i.url=e,i.delay=n,i.trackingType=t,i}toContext(){return{}}}const browserState=()=>{var e,t,n,i,s;const{screen:{width:a,height:o},self:r,top:d,matchMedia:c,opener:l}=window,{documentElement:{clientWidth:h,clientHeight:u}}=document;let p;try{p=(new Date).getTimezoneOffset()/60*-1}catch(e){p=null}return{popup:!(!l||l===window),timezone_offset:p,user_preference:null===(e=null===Intl||void 0===Intl?void 0:Intl.DateTimeFormat())||void 0===e?void 0:e.resolvedOptions(),user_using_darkmode:Boolean(c&&c("(prefers-color-scheme: dark)").matches),user_supports_darkmode:Boolean(c),window_resolution:{width:null!=h?h:0,height:null!=u?u:0},screen_resolution:{width:null!=a?a:0,height:null!=o?o:0},frame:d===r?null:{innerWidth:null!==(t=null==r?void 0:r.innerWidth)&&void 0!==t?t:0,innerHeight:null!==(n=null==r?void 0:r.innerHeight)&&void 0!==n?n:0,outerWidth:null!==(i=null==r?void 0:r.outerWidth)&&void 0!==i?i:0,outerHeight:null!==(s=null==r?void 0:r.outerHeight)&&void 0!==s?s:0}}},CAFKey="caf",ClickKey="click",NoCacheKey="nc",SessionKey="session",TRACKING_URL="_tr",buildSignature=({callbacks:e,context:t},n)=>{var i,s,a,o;return Object.assign({ad_loaded_callback:null==e?void 0:e.adLoadedCallback,app_version:version,caf_client_id:null===(i=null==t?void 0:t.pageOptions)||void 0===i?void 0:i.pubId,caf_timed_out:null==e?void 0:e.cafTimedOut,caf_loaded_ms:null==e?void 0:e.cafLoadedMs,channel:null===(s=null==t?void 0:t.pageOptions)||void 0===s?void 0:s.channel,desktop:t.desktop,terms:null===(a=null==t?void 0:t.pageOptions)||void 0===a?void 0:a.terms,fd_server_datetime:t.fd_server_datetime,fd_server:t.fd_server,flex_rule:t.flex_rule,host:t.host,ip:t.ip,ivt:null===(o=null==t?void 0:t.pageOptions)||void 0===o?void 0:o.ivt,js_error:t.js_error,mobile:t.mobile,no_ads_redirect:t.noAdsRedirect,page_headers:t.page_headers,page_loaded_callback:null==e?void 0:e.pageLoadedCallback,page_method:t.page_method,page_request:t.page_request,page_time:t.page_time,page_url:t.page_url,reportable_channel:t.reportableChannel,reportable_style_id:t.reportableStyleId,tablet:t.tablet,template_id:t.templateId,type:n,user_has_ad_blocker:t.user_has_ad_blocker,user_id:t.userId,uuid:t.uuid,zeroclick:t.zeroClick},browserState())},trackVisit=({callbacks:e,context:t},n,i="")=>{const s=`${i}/${TRACKING_URL}`,a=i?"include":"same-origin",o=buildSignature({callbacks:e,context:t},n);let r={};"click"===n&&(r={[ClickKey]:"true",[SessionKey]:t.uuid,[NoCacheKey]:Date.now().toString()}),fetch(s,{method:"POST",headers:{Accept:"application/json","Content-Type":"application/json"},credentials:a,body:JSON.stringify(Object.assign({signature:encode(o)},r))})};var State$1;!function(){if(!window.CustomEvent){function e(e,t){t=t||{bubbles:!1,cancelable:!1,detail:void 0};const n=document.createEvent("CustomEvent");return n.initCustomEvent(e,t.bubbles,t.cancelable,t.detail),n}e.prototype=window.Event.prototype,window.CustomEvent=e}}(),function(e){e[e.Pending=0]="Pending",e[e.Loaded=1]="Loaded",e[e.Failed=2]="Failed"}(State$1||(State$1={}));class Provider{get providerCtor(){return this.constructor}constructor(e){this.state=new Map,this.injectedAt=new Map,this.timeoutAt=new Map,this.timeoutSeconds=5,this.handlePixelEvent=e=>{this.keys.forEach((t=>{switch(this.state.get(t)){case State$1.Failed:break;case State$1.Pending:setTimeout((()=>this.handlePixelEvent(e)),100);break;case State$1.Loaded:this.onPixelEvent(e,t)}}))},this.watch=e=>{switch(this.state.get(e)){case State$1.Loaded:case State$1.Failed:break;case State$1.Pending:this.isLoaded(e)?this.state.set(e,State$1.Loaded):this.isTimedOut(e)?this.state.set(e,State$1.Failed):setTimeout((()=>this.watch(e)),50)}},this.config=e,this.keys.length>0?this.keys.forEach((e=>{this.state.set(e,State$1.Pending);const t=new Date;t.setSeconds(t.getSeconds()+this.timeoutAfter()),this.timeoutAt.set(e,t),this.injectPixel(e)})):this.state.set("",State$1.Failed)}get keys(){return this.config?Object.keys(this.config):[]}getPixelEvents(e){var t,n;return null===(n=null===(t=this.config)||void 0===t?void 0:t[e])||void 0===n?void 0:n.pixel_events}injectPixel(e){this.injectedAt.has(e)||(this.injectedAt.set(e,new Date),this.inject(e),this.watch(e))}inject(e){if(!this.providerCtor.scriptInjected){const e=document.createElement("script");e.text=this.getScript(),document.head.appendChild(e),this.providerCtor.scriptInjected=!0}this.init(e)}isTimedOut(e){return+new Date>=+(this.timeoutAt.get(e)||0)}timeoutAfter(){return this.timeoutSeconds}selectPixelEvents(e,t){const n=this.getPixelEvents(t);if(Array.isArray(n))return n.filter((t=>"term-view"===t.trigger&&"visit"===e||(!(!["term-click","ad-view"].includes(t.trigger)||"ctr"!==e)||"ad-click"===t.trigger&&"click"===e)))}}class Facebook extends Provider{getScript(){return"!function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function(){n.callMethod?n.callMethod.apply(n,arguments):n.queue.push(arguments)};if(!f._fbq)f._fbq=n;n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0;t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js');"}init(e){window.fbq&&window.fbq("init",e)}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&(e.custom?window.fbq("trackSingleCustom",t,e.event):window.fbq("trackSingle",t,e.event))}))}isLoaded(e){return!!window.fbq&&window.fbq.getState&&window.fbq.getState(e)}}Facebook.scriptInjected=!1;class Outbrain extends Provider{getScript(){return`!function(_window, _document) { var OB_ADV_ID = ${JSON.stringify(this.keys)}; if (_window.obApi) { var toArray = function(object) { return Object.prototype.toString.call(object) === '[object Array]' ? object : [object]; }; _window.obApi.marketerId = toArray(_window.obApi.marketerId).concat(toArray(OB_ADV_ID)); return; } var api = _window.obApi = function() { api.dispatch ? api.dispatch.apply(api, arguments) : api.queue.push(arguments); }; api.version = '1.1'; api.loaded = true; api.marketerId = OB_ADV_ID; api.queue = []; var tag = _document.createElement('script'); tag.async = true; tag.src = '//amplify.outbrain.com/cp/obtp.js'; tag.type = 'text/javascript'; var script = _document.getElementsByTagName('script')[0]; script.parentNode.insertBefore(tag, script); }(window, document);`}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.obApi("track",e.event)}))}isLoaded(e){return!!window.obApi}}Outbrain.scriptInjected=!1;class Revcontent extends Provider{getScript(){return"var script=document.createElement('script');script.src='https://assets.revcontent.com/master/rev.js';document.head.appendChild(script);"}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.rev("event",e.event)}))}isLoaded(e){return!!window.rev}}Revcontent.scriptInjected=!1;class Taboola extends Provider{getScript(){return`window._tfa = window._tfa || [];!function (t, f, a, x) {if (!document.getElementById(x)) {t.async = 1;t.src = a;t.id=x;f.parentNode.insertBefore(t, f);}}(document.createElement('script'),document.getElementsByTagName('script')[0],'//cdn.taboola.com/libtrc/unip/${this.keys[0]}/tfa.js','tb_tfa_script');`}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{if(e){const n=parseInt(t,10);window._tfa.push({notify:"event",name:e.event,id:n})}}))}isLoaded(e){return Array.isArray(window._tfa)}}Taboola.scriptInjected=!1;class Tiktok extends Provider{getScript(){return'!function (w, d, t) {w.TiktokAnalyticsObject=t;var ttq=w[t]=w[t]||[];ttq.methods=["page","track","identify","instances","debug","on","off","once","ready","alias","group","enableCookie","disableCookie"],ttq.setAndDefer=function(t,e){t[e]=function(){t.push([e].concat(Array.prototype.slice.call(arguments,0)))}};for(var i=0;i{e&&window.ttq.instance(t).track(e.event)}))}isLoaded(){return!!window.ttq}}Tiktok.scriptInjected=!1;class GoogleAds extends Provider{getScript(){return`var s=document.createElement('script');s.async=1;s.src='https://www.googletagmanager.com/gtag/js?id=${this.keys[0]}';document.head.appendChild(s);window.dataLayer=window.dataLayer||[];function gtag(){dataLayer.push(arguments)}gtag('set','allow_ad_personalization_signals',false);gtag('js',new Date);`}init(e){window.gtag&&window.gtag("config",e)}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.gtag("event","conversion",{send_to:`${t}/${e.event}`})}))}isLoaded(e){return!!window.gtag}}GoogleAds.scriptInjected=!1;const ADS_PARAM$1=CAFKey,MESSAGE_PREFIX="FSXDC,.aCS:",ALLOWED_ORIGINS=["https://www.google.com","https://www.adsensecustomsearchads.com","https://syndicatedsearch.goog","https://googleadservices.com"];class Pixels{static build(e){const t=unpackPHPArrayObject(e,"pixel_tracking_data");if(t)return t.useAltTikTokEventsForAdsPlatformUser=e.is_ads,new Pixels(t)}constructor(e){this.onPixelEvent=e=>{const{detail:{type:t}}=e;switch(t){case"visit":case"ctr":case"click":this.providers.forEach((e=>e.handlePixelEvent(t)))}},this.providers=[],e.facebook&&Object.keys(e.facebook).forEach((t=>{this.providers.push(new Facebook({[t]:e.facebook[t]}))})),e.tiktok&&Object.keys(e.tiktok).forEach((t=>{this.providers.push(new Tiktok({[t]:e.tiktok[t]}))})),e.taboola&&Object.keys(e.taboola).forEach((t=>{this.providers.push(new Taboola({[t]:e.taboola[t]}))})),e.revcontent&&Object.keys(e.revcontent).forEach((t=>{this.providers.push(new Revcontent({[t]:e.revcontent[t]}))})),e.outbrain&&this.providers.push(new Outbrain(e.outbrain)),e.googleads&&Object.keys(e.googleads).forEach((t=>{this.providers.push(new GoogleAds({[t]:e.googleads[t]}))}))}listenForEvents(){document.addEventListener("pixel",(e=>{this.onPixelEvent(e)}));window.onmessage=e=>{const{origin:t,data:n}=e;ALLOWED_ORIGINS.includes(t)&&"string"==typeof n&&(null==n?void 0:n.startsWith(MESSAGE_PREFIX))&&new URLSearchParams(window.location.search).has(ADS_PARAM$1)&&document.dispatchEvent(new CustomEvent("pixel",{detail:{type:"click"}}))}}listenForPixelEvents(){document.addEventListener("pixel",(e=>{this.onPixelEvent(e)}))}dispatchEvent(e){document.dispatchEvent(new CustomEvent("pixel",{detail:e}))}}var State;!function(e){e[e.Pending=0]="Pending",e[e.Loaded=1]="Loaded",e[e.Failure=2]="Failure",e[e.TimedOut=3]="TimedOut",e[e.Errored=4]="Errored"}(State||(State={}));const CAF_SCRIPT_SRC=`https://www.google.com/adsense/domains/caf.js?${GOOGLE_MV3_URL_PARAMS}`,TIMEOUT_SCRIPTS=Number(GOOGLE_CAF_TIMEOUT_SCRIPTS),TIMEOUT_CALLBACKS=Number(GOOGLE_CAF_TIMEOUT_CALLBACKS);class StateMachine{constructor(){this.state=State.Pending}transitionTo(e){this.state=e}transitionFromPendingTo(e){this.done||(this.state=e)}get loaded(){return this.state===State.Loaded}get timedOut(){return this.state===State.TimedOut}get done(){return this.state!==State.Pending}}class Ads{constructor(e,t){this.state={script:new StateMachine,blocks:new StateMachine},this.blocksLoaded=[],this.injectScriptTags=()=>__awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=document.createElement("script");t.type="text/javascript",t.src=CAF_SCRIPT_SRC,t.addEventListener("load",(()=>e(!0))),t.addEventListener("error",(()=>e(!1))),document.body.appendChild(t),TIMEOUT_SCRIPTS>0&&setTimeout((()=>e(!1)),TIMEOUT_SCRIPTS)}))})),this.onPageLoaded=(e,t)=>{if(this.pageLoaded={requestAccepted:e,status:t},this.state.script.done)return;const n=null==t?void 0:t.error_code;n?(this.state.script.transitionTo(State.Failure),this.failureReason=`caf_pageloaderror_${n}`):this.state.script.transitionTo(State.Loaded)},this.onBlockLoaded=(e,t,n,i)=>{this.blocksLoaded.push({containerName:e,adsLoaded:t,isExperimentVariant:n,callbackOptions:i}),this.state.blocks.done||(t?this.state.blocks.transitionTo(State.Loaded):this.blocksLoaded.length>=this.blocks.length&&(this.state.blocks.transitionTo(State.Failure),this.failureReason=`caf_adloadfail_${e}`))},this.onTimeout=()=>{this.state.script.transitionFromPendingTo(State.TimedOut),this.state.blocks.transitionFromPendingTo(State.TimedOut)},this.blocks=e,this.options=t}get loaded(){return this.state.script.loaded&&!this.blocksLoaded.map((e=>e.adsLoaded)).includes(!1)}waitForBlocks(){return __awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=()=>{const n=performance.now();if(this.state.blocks.done)return this.cafLoadTime=Math.round(n-this.cafStartTime),void e();const i=this.blocksLoaded.map((e=>e.adsLoaded));i.includes(!1)||i.length>=this.blocks.length?e():setTimeout(t,50)};t()}))}))}inject(){return __awaiter(this,void 0,void 0,(function*(){try{const e=yield this.injectScriptTags();return this.cafStartTime=performance.now(),e&&void 0!==window.google?(new window.google.ads.domains.Caf(Object.assign(Object.assign({},this.options),{pageLoadedCallback:this.onPageLoaded,adLoadedCallback:this.onBlockLoaded}),...this.blocks),TIMEOUT_CALLBACKS>0&&setTimeout(this.onTimeout,TIMEOUT_CALLBACKS),yield new Promise((e=>{const t=()=>{this.state.script.done?e():setTimeout(t,10)};t()}))):void this.state.script.transitionTo(State.Failure)}catch(e){return void(this.error=e.toString())}}))}toCallbacks(){return{adLoadedCallback:this.blocksLoaded.slice(-1)[0],pageLoadedCallback:this.pageLoaded,cafTimedOut:this.state.script.timedOut||this.state.blocks.timedOut,cafLoadedMs:this.cafLoadTime,googleAdsFailure:!!this.failureReason}}toContext(){const e={cafScriptWasLoaded:this.state.script.loaded,cafScriptLoadTime:this.cafLoadTime,callbacks:this.toCallbacks};return this.error&&(e.js_error={message:this.error}),this.state.script.loaded||(e.zeroclick={reason:"googleAdsFailure"}),e}mockFailedState(){this.state.blocks.transitionTo(State.Failure),this.state.script.transitionTo(State.Failure)}}class TagManager{constructor(e){this.injected=!1,this.identifier=e}inject(){if(this.injected)return;if(!this.identifier)return;if("TEST"===this.identifier)return;const e=document.createElement("script");e.setAttribute("src",`https://www.googletagmanager.com/gtag/js?id=${this.identifier}`),document.head.appendChild(e),this.track(),this.injected=!0}track(){this.push("js",new Date),this.push("config",this.identifier)}push(e,t){window.dataLayer||(window.dataLayer=[]),window.dataLayer.push(arguments)}}const ADS_PARAM=CAFKey,ADS_TRACKING_URL="_tr",BLOCKS_TYPE="ads",BLOCKS_CONTAINER="rs",KNOWN_CAF_PARAMS=["caf","query","afdToken","pcsa","nb","nm","nx","ny","is","clkt"];class Google{static build({pageOptions:e,preferredLanguage:t,blocks:n,googleAnalytics:i},s,a,o){let r={};e&&(r=Object.assign({},e),r.hl||(r.hl=t));let d=null==e?void 0:e.resultsPageBaseUrl;d||(d=window.location.origin);return new Google(s.uuid,n,r,i,d,o)}constructor(e,t,n,i,s,a){this._blocks=t,this._pageOptions=n,this.uuid=e,this._baseURL=new URL(s),this._signature=a,this.ads=new Ads(this.blocks,this.pageOptions),this.tagManager=new TagManager(i)}injectTagManager(){this.tagManager.inject()}injectAds(){return __awaiter(this,void 0,void 0,(function*(){yield this.ads.inject()}))}waitForBlocks(){return __awaiter(this,void 0,void 0,(function*(){return this.ads.waitForBlocks()}))}get blocks(){return(this._blocks||[]).filter((e=>this.wantsToServeAds?e.type===BLOCKS_TYPE:e.container===BLOCKS_CONTAINER)).map((e=>{const t=this.baseURL;new URLSearchParams(window.location.search).forEach(((e,n)=>{t.searchParams.has(n)||t.searchParams.append(n,e)}));const n=Object.assign({},e);if(n.resultsPageBaseUrl=t.toString(),this.wantsToServeAds){const e=new URLSearchParams;e.append("click","true"),e.append("session",this.uuid);const t=Object.assign({},this._signature);delete t.ad_loaded_callback,delete t.caf_loaded_ms,delete t.caf_timed_out,delete t.flex_rule,delete t.frame,delete t.js_error,delete t.no_ads_redirect,delete t.page_headers,delete t.page_request,delete t.page_loaded_callback,delete t.popup,delete t.screen_resolution,delete t.user_has_ad_blocker,delete t.user_preference,delete t.user_supports_darkmode,delete t.user_using_darkmode,delete t.zeroclick,e.append("signature",encode(t)),n.clicktrackUrl=`${TRACKING_DOMAIN}${ADS_TRACKING_URL}?${e.toString()}`}return n}))}get baseURL(){const e=new URL(this._baseURL.origin);return e.searchParams.append(ADS_PARAM,"1"),this._baseURL.searchParams.forEach(((t,n)=>{e.searchParams.append(n,t)})),e}get pageOptions(){const e=Object.assign({},this._pageOptions);return Object.keys(this._pageOptions).forEach((t=>{t.startsWith("bodis")&&delete e[t]})),e}get cannotLoadAds(){return!this.ads.loaded}get wantsToServeAds(){return new URLSearchParams(window.location.search).has(ADS_PARAM)}get adsMode(){return this.ads.loaded&&this.wantsToServeAds}get adsReady(){return this.wantsToServeAds&&!this.cannotLoadAds}get noAdsRedirectUrl(){const e=new URLSearchParams(window.location.search);return KNOWN_CAF_PARAMS.forEach((t=>e.delete(t))),`${window.location.origin}?${e.toString()}`}get callbacks(){return this.ads.toCallbacks()}toContext(){return Object.assign({blocks:this.blocks,pageOptions:this.pageOptions},this.ads.toContext())}}class CookieConsentManager{constructor(){this.injectScriptTag=()=>__awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=document.createElement("script");t.setAttribute("src",COOKIE_CONSENT_JS_URL),t.addEventListener("load",(()=>this.awaitConsent(e))),t.addEventListener("error",(()=>e(!1))),document.head.appendChild(t)}))}))}inject(){return __awaiter(this,void 0,void 0,(function*(){this.injected||!COOKIE_CONSENT_JS_URL||isLocal()||(this.injected=yield this.injectScriptTag())}))}awaitConsent(e){let t=0;const n=setInterval((()=>{t+=1,20===t&&(clearInterval(n),e(!0)),void 0!==window.__tcfapi&&(window.addEventListener("ConsentActivity",(t=>{const{detail:{status:n}}=t;n&&e(!0)})),clearInterval(n))}),50)}}class Cheq{constructor(e){let t;if(t="string"==typeof e?parseInt(e,10):e,t<0||t>100)throw new Error("Load percentage must be between 0 and 100");this.loadPercentage=t}inject(e,t){return __awaiter(this,void 0,void 0,(function*(){if(this.injected)return;100*Math.random()<=this.loadPercentage&&(this.injected=this.injectScriptTag(e,t))}))}injectScriptTag(e,t){const n=document.createElement("script");return n.type="text/javascript",n.async=!0,n.setAttribute("src","https://ob.forseasky.com/i/148870ae21863d775c347e8893c985af.js"),n.setAttribute("data-ch","cheq4ppc"),n.setAttribute("data-uvid",e),n.setAttribute("data-utm-campaign",t.toString()),n.className="ct_clicktrue_73521",document.head.appendChild(n),!0}}class App{main(){var e,t,n;return __awaiter(this,void 0,void 0,(function*(){if(this.parkResponse=decode(),this.findDomainResponse=yield getFindDomain(),!this.findDomainResponse)throw new Error("Domain failed to load.");this.pixels=Pixels.build(this.findDomainResponse),null===(e=this.pixels)||void 0===e||e.listenForEvents(),this.adblock=new Adblock,yield this.adblock.inject(),this.google=Google.build(this.findDomainResponse,this.parkResponse,this.adblock,buildSignature({context:this.context,callbacks:null===(t=this.google)||void 0===t?void 0:t.callbacks},"click")),this.google.injectTagManager();const i=Parking.build(this.findDomainResponse,this.google);Render.prerender(i);const s=(null===(n=this.findDomainResponse)||void 0===n?void 0:n.referral)?AFD_REFERRAL_CHEQ_LOAD_PERCENTAGE:AFD_ORGANIC_CHEQ_LOAD_PERCENTAGE;this.cheq=new Cheq(s),this.cheq.inject(this.parkResponse.uuid,this.findDomainResponse.userId),this.cookieConsentManager=new CookieConsentManager,yield this.cookieConsentManager.inject();let a=Failed.cannotPark(this.findDomainResponse);if(a)return void(yield this.transitionToFailed(a,i));yield this.google.injectAds();let o=Disabled.build(this.findDomainResponse,this.adblock.state);if(o)return void(yield this.transitionToDisabled(o,i));const r=this.adblock.hasAdblocker();r&&this.adblock.handleAdblocked();const d=Sales.build(this.findDomainResponse);if(d)return void(yield this.transitionToSales(d));this.eligibleForZeroClick&&(this.zeroClickResponse=yield getZeroClick(this.context));const c=Redirect.build(this.findDomainResponse,this.zeroClickResponse,this.google);if(c)yield this.transitionToRedirect(c);else{if(r)return o=Disabled.build(this.findDomainResponse,this.adblock.state),void(yield this.transitionToDisabled(o,i));a=Failed.noSponsors(this.google),a?yield this.transitionToFailed(a,i):yield this.transitionToParking(i)}}))}transitionToParking(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.template(e),Render.revealPage(),yield this.google.waitForBlocks(),yield this.track()}))}transitionToRedirect(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e;const t=this.track();Render.revealPage(),yield waiter(e.delay,(e=>Render.loading(e))),yield t,window.location.href=e.url,log(`➡ Redirecting [${e.url}]`)}))}transitionToFailed(e,t){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.message(e.message),Render.injectJS(t.javascript),Render.revealPage(),yield this.track()}))}transitionToSales(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,e.init(this.context),yield this.track()}))}transitionToDisabled(e,t){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.message(e.message),Render.injectJS(t.javascript),"adblocker"===e.reason&&t.bannerAdblockerOnly&&Render.revealSalesBanner(),Render.revealPage(),yield this.track()}))}track(){var e;return __awaiter(this,void 0,void 0,(function*(){if(!this.state.track)return Promise.resolve();try{const t=this.state.trackingType;return null===(e=this.pixels)||void 0===e||e.dispatchEvent({type:t}),trackVisit({context:this.context,callbacks:this.google.callbacks},t)}catch(e){return}}))}get eligibleForZeroClick(){const{cannotPark:e,canZeroClick:t,zeroClick:n}=this.findDomainResponse,{cannotLoadAds:i,wantsToServeAds:s}=this.google;return this.adblock.state!==Blocking.BLOCKED&&(!!t&&(!!e||(!(!i||s)||!!(null==n?void 0:n.reason))))}get context(){var e,t,n,i;const s=this.findDomainResponse,a=this.parkResponse,o=null===(e=this.state)||void 0===e?void 0:e.toContext(),r=null===(t=this.adblock)||void 0===t?void 0:t.toContext(),d=null===(n=this.google)||void 0===n?void 0:n.toContext(),c=browserState(),l=Object.assign(Object.assign({},null===(i=this.findDomainResponse)||void 0===i?void 0:i.zeroClick),this.zeroClickResponse);return Object.assign(Object.assign(Object.assign(Object.assign(Object.assign(Object.assign(Object.assign({app_version:APP_VERSION},s),a),r),d),o),c),{zeroClick:l})}init(){return __awaiter(this,void 0,void 0,(function*(){try{window.__parkour=this,yield this.main()}catch(e){console.error("app",e);const t=Failed.fromError(e);this.state=t,Render.message(t.message),Render.revealPage()}}))}}(new App).init(),exports.App=App}));
Skip to toolbar