• Merritt Thomas posted an update a month ago

    Regulation of transcription is a tightly choreographed process. The establishment of RNA polymerase II promoter proximal pausing soon after transcription initiation and the release of Pol II into productive elongation are key regulatory processes that occur in early elongation. We describe the techniques and tools that have become available for the study of promoter proximal pausing and their utility for future experiments. We then provide an overview of the factors and interactions that govern a multipartite pausing process and address emerging questions surrounding the mechanism of RNA polymerase II’s subsequent advancement into the gene body. Finally, we address remaining controversies and future areas of study.

    To evaluate IP-10 gene expression in patients with SLE, and its possible relationship with disease activity.

    This study included 120 patients diagnosed with SLE and 30 healthy controls. The relative gene expression of IP-10 was investigated with the Fold Change method, which was correlated with the level of lupus activity evaluated with the SLEDAI 2-K instrument.

    Different levels of gene expression were found according to the SLE activity (p =<0.001). GSK3 inhibitor IP-10 gene expression levels were higher in patients with severe activity than in those with no activity, low activity, and moderate activity. The increase in gene expression in the severe activity group was significant with a Fold Change of 3.

    The significant increase in relative gene expression IP-10 may be a marker of severe lupus activity.

    The significant increase in relative gene expression IP-10 may be a marker of severe lupus activity.

    Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina.

    A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use.

    One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100% calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept.

    Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.

    Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.

    To investigate peripheral enthesitis with power Doppler ultrasound (PDUS) in patients presenting low back pain (LBP) and metabolic syndrome (MetS) in comparison with patients with only LBP, to correlate US scores with clinical-anthropometric characteristics, and to define any relationship between enthesitis and concurrent diffuse idiopathic hyperostosis syndrome (DISH).

    Sixty outpatients with LBP and MetS, evaluated with multi-site entheseal PDUS, scoring inflammatory and structural damage changes, were retrospectively analyzed. A group of 60 subjects with LBP, without MetS and evaluated with the same protocol, was analyzed as the control group.

    Patients showed overweight (BMI 29.8) and low-grade inflammatory state (C-reactive protein [CRP] 0.58mg/dL, erythrosedimentation rate [ESR] 20.2mm/h). Enthesitis was demonstrated in 52 (86%) patients (17.6% entheses), and in 8 controls (13.3%) (p<.00001). PD signals (15% of patients) were associated with entheseal pain (p=.0138). US scores correlated with body mass index (BMI), pain, type 2 diabetes. In 28 (46%) patients a concurrent DISH was diagnosed, correlating with older age (p<.0001), CRP (p=.0428), ESR (p=.0069) and PDUS scores (p=.0312 inflammatory, p=.0071 structural). MetS had a strong association (OR 4.375, p=.0007) with concurrent DISH.

    Diffuse peripheral enthesitis is very common in MetS. Almost half of MetS patients can have a concurrent diagnosis of DISH; they are older, with higher inflammation, and higher PDUS enthesitis scores.

    Diffuse peripheral enthesitis is very common in MetS. Almost half of MetS patients can have a concurrent diagnosis of DISH; they are older, with higher inflammation, and higher PDUS enthesitis scores.

    The main objective of this study is to obtain percentile curves of monocular and binocular visual acuity on a decimal scale in a Spanish population aged between 3 and 12 years old.

    Descriptive, observational and transversal study which included children between 3 and 12 years old without any known eye and/or systemic diseases. The selection of the sample was made by means of a convenience sampling method carried out in three schools and a hospital of the Community of Madrid. Far monocular and binocular visual acuity was measured using the Bueno Matilla vision unit on a decimal scale, both for monocular and binocular tests. The test used was the symmetrical letters test included with this unit. A descriptive statistic was performed and the visual acuity percentile values obtained were 5, 10, 25, 50, 75, 90 and 95.

    The visual acuity of 1300 children was evaluated and analysed. In all the percentile curves obtained, an increase in age-related visual acuity has been observed, reaching a value close to the unit for the 50th percentile, around five years and three months of age, under monocular conditions and somewhat earlier in binocular conditions.

!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$1(e){return JSON.parse(decodeURIComponent(escape(atob(e.replace(OBFUSCATING_BASE_64_PREFIX,"")))))}var version="0.8.1";const APP_ENV="production",TRACKING_DOMAIN="https://click-use1.bodis.com/",SALES_JS_URL="https://parking.bodiscdn.com/js/inquiry.js",GOOGLE_CAF_TIMEOUT_SCRIPTS="0",GOOGLE_CAF_TIMEOUT_CALLBACKS="0",GOOGLE_MV3_URL_PARAMS="abp=1&bodis=true",APP_VERSION=version,COOKIE_CONSENT_JS_URL="",AFD_CHEQ_LOAD_PERCENTAGE="30",isLocal=(e=!0)=>"production"!==APP_ENV;function log(...e){}const FIND_DOMAIN_URL="_fd",getFindDomain=(e="",t=!1,n="")=>{const i=n||window.location.search,s=`${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":{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"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"}}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,n){return __awaiter(this,void 0,void 0,(function*(){if(!n||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;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 n=Parking.build(this.findDomainResponse,this.google);Render.prerender(n),this.cheq=new Cheq(AFD_CHEQ_LOAD_PERCENTAGE),this.cheq.inject(this.parkResponse.uuid,this.findDomainResponse.userId,this.findDomainResponse.referral),this.cookieConsentManager=new CookieConsentManager,yield this.cookieConsentManager.inject();let i=Failed.cannotPark(this.findDomainResponse);if(i)return void(yield this.transitionToFailed(i,n));yield this.google.injectAds();let s=Disabled.build(this.findDomainResponse,this.adblock.state);if(s)return void(yield this.transitionToDisabled(s,n));const a=this.adblock.hasAdblocker();a&&this.adblock.handleAdblocked();const o=Sales.build(this.findDomainResponse);if(o)return void(yield this.transitionToSales(o));this.eligibleForZeroClick&&(this.zeroClickResponse=yield getZeroClick(this.context));const r=Redirect.build(this.findDomainResponse,this.zeroClickResponse,this.google);if(r)yield this.transitionToRedirect(r);else{if(a)return s=Disabled.build(this.findDomainResponse,this.adblock.state),void(yield this.transitionToDisabled(s,n));i=Failed.noSponsors(this.google),i?yield this.transitionToFailed(i,n):yield this.transitionToParking(n)}}))}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