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{=0A= document.writeln('

3D"Click

');=0A= }=0A= =0A= function get_text_link(url, linktext)=0A= {=0A= document.writeln('' + = linktext + '');=0A= }=0A= =0A= function get_htmlftext_link(a, b) {=0A= document.writeln("" + = b + ", ");=0A= }=0A= =0A= ------=_NextPart_000_0000_01C9FA4E.A4778860 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://download.interscience.wiley.com/freeflow/js/personalisation.js /*=0A= * Project : Interscience Redesign=0A= * File : personalisation.js=0A= * Creation Date : 25th March 2003=0A= * Author : Jonathan Sugar=0A= *=0A= * Various functions to deliver personalisation functionality.=0A= */=0A= =0A= // Pre-declare userName so it's available when we need to test if the = page=0A= // assembler ran OK=0A= var userName =3D null;=0A= var shcrtCookie =3D null;=0A= =0A= // Browser detect globals:=0A= var uaStr =3D navigator.userAgent.toLowerCase();=0A= var uaVer =3D parseInt(navigator.appVersion);=0A= // for detecting netscape 4=0A= var netscape =3D (uaStr.indexOf("mozilla") > -1);=0A= var netscape4 =3D (netscape && uaVer < 5);=0A= =0A= // Factory Methods=0A= =0A= // Simple wraper object to encapsulate the data for a co-branding item.=0A= function coBrandingItem(image, imageAltText, href)=0A= {=0A= //alert("Making new coBrandingItem:\nImage: " + image + = "\nimageAltText" + imageAltText + "\nhref: " + href);=0A= this.image =3D image;=0A= this.imageAltText =3D imageAltText;=0A= this.href =3D href;=0A= }=0A= =0A= /*=0A= * Insert the 'Customer co-branding' section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= *=0A= * 1. Insert customer co branding. Loop through 'customerCoBranding' array=0A= * inserting XHTML where needed.=0A= *=0A= * NOTE: the array contains ONLY the resource location (the location of a = gif=0A= * on the file system), the required XHTML is then added where needed. = This way=0A= * we maintain the seperation between presentation and content.=0A= */=0A= function insertCustomerCoBranding(maxBranding)=0A= {=0A= if( customerCoBranding[0].image !=3D "none")=0A= {=0A= document.writeln('

');=0A= document.writeln('

');=0A= document.writeln('

' + imageAltText + '
' + imageAltText + = '
More Providers

');=0A= document.writeln('

');=0A= document.writeln('

3D""

');=0A= }=0A= }=0A= =0A= /*=0A= * Insert the 'My Area' section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= * Updated: Ben Marvell, April 2006=0A= *=0A= * My profile link absolute as this file isnt only run from w3 anymore.=0A= */=0A= function insertMyArea(userdata)=0A= {=0A= // just in case the page assembler isn't running.=0A= =0A= =0A= if (userName !=3D null)=0A= {=0A= document.writeln("

" + = userName.substring(0,33) + "..., access your
" + userName + = ", access your

My Profile"); =0A= } =0A= document.writeln(getLoginOutLink());=0A= //CR 3652 getAthenStatus() as added=0A= document.writeln(getAthenStatus());=0A= document.writeln("

");=0A= } else {=0A= if(typeof(environment)!=3D'undefined' && = environment=3D=3D'PRODUCTION') {=0A= document.writeln("

Log Out");=0A= document.writeln("

"); =0A= }=0A= }=0A= if (menuloadedflag){=0A= wisMenu();=0A= }=0A= }=0A= =0A= /*=0A= * Insert the Customer Admin 'Login/Logout' link=0A= * -----------------------------=0A= *=0A= * Author: Bobby Jack, December 2004.=0A= *=0A= */=0A= function insertAdminLink(page)=0A= {=0A= val =3D getCookie("AID");=0A= =0A= if (val && val !=3D "-1")=0A= {=0A= document.writeln('

Logout');=0A= }=0A= else=0A= {=0A= document.writeln('

');=0A= }=0A= }=0A= =0A= /*=0A= * Insert the username section.=0A= * -----------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= *=0A= * 1. Insert the username.=0A= */=0A= function insertUserName()=0A= {=0A= document.write(userName);=0A= }=0A= =0A= /*=0A= * Return the appropriate link to the login/logout cgi=0A= * ---------------------------------------------------=0A= *=0A= * Author: Jonathan Sugar, March 2003.=0A= * Updated: Ben Marvell, April 2006=0A= * Had to change the links absolute as this file isnt only run from w3 = anymore.=0A= */=0A= function getLoginOutLink()=0A= {=0A= if(userName !=3D "")=0A= {=0A= return "

";=0A= }else=0A= {=0A= return "

";=0A= }=0A= }=0A= =0A= /*=0A= * Return the appropriate link to the shopping cart content page=0A= * ---------------------------------------------------=0A= *=0A= * Author: Zhiming & Warrell June 2007=0A= */=0A= function getShCrtLink(logged)=0A= {=0A= if(logged =3D=3D true )=0A= return "

";=0A= else=0A= return "

";=0A= }=0A= =0A= function toggleShCrtLink()=0A= {=0A= shcrtCookie =3D readCookie("SHCRT");=0A= if(shcrtCookie !=3D null)=0A= {=0A= if(document.all)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= document.getElementById("shcrt_id").style.display =3D "block";=0A= }=0A= }=0A= else=0A= {=0A= if(document.all)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= document.getElementById("shcrt_id").style.display =3D "none";=0A= }=0A= }=0A= }=0A= =0A= =0A= =0A= function readCookie(name)=0A= {=0A= var nameEQ =3D name + "=3D";=0A= var ca =3D document.cookie.split(';');=0A= for(var i=3D0; iYou are logged in = to Athens';=0A= }=0A= else=0A= {=0A= return "

";=0A= }=0A= =0A= } ------=_NextPart_000_0000_01C9FA4E.A4778860 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://download.interscience.wiley.com/freeflow/js/site.js /************************************************************************= ***************************=0A= FILE: site.js=0A= AUTHOR: Jonathan Sugar, Chris Neatby-Smith and Digital Pulp. July = 2003.=0A= =0A= DESCRIPTION: Javascript relating to site wide functionality across =0A= InterScience.=0A= =0A= INCLUDES FUNCTIONS=0A= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=0A= =0A= Search Functions=0A= ----------------=0A= =0A= selectAndSubmit() - for deciding where to submit a query based on the = state of the form.=0A= processallContentSearch() - for validating form input for an all = content search.=0A= processTitleSearch() - for validating form input for a Title search.=0A= checkCitationSearch() - for validating the citation search form.=0A= selectAll() - check all the checkboxes in a form.=0A= do_popup() - stasa Acronym Finder window popup function.=0A= =0A= =0A= Other Functions=0A= ---------------=0A= =0A= fixInlineLists() - fix netscape 4.x bug where

tags with images = display both an image and=0A= the default bullet. =0A= =0A= = *************************************************************************= **************************/=0A= =0A= var http =3D false;=0A= if(navigator.appName =3D=3D "Microsoft Internet Explorer") {=0A= http =3D new ActiveXObject("Microsoft.XMLHTTP");=0A= } else {=0A= http =3D new XMLHttpRequest();=0A= } =0A= =0A= // Global Variables=0A= var debug =3D false;=0A= var first =3D true;=0A= =0A= // Browser detect globals:=0A= var uaStr =3D navigator.userAgent.toLowerCase();=0A= var uaVer =3D parseInt(navigator.appVersion);=0A= // for detecting netscape 4=0A= var netscape =3D (uaStr.indexOf("mozilla") > -1);=0A= var netscape4 =3D (netscape && uaVer < 5);=0A= =0A= /*=0A= * Used to switch search mode between APS and TitleFinder on quicksearch = boxes=0A= * = -------------------------------------------------------------------------= --=0A= *=0A= * 1. Decides which search is required based on the value of the radio = buttons=0A= * in 'document.formSelector.whichForm'.=0A= *=0A= * 2. Calls individual functions to process the forms and submit them.=0A= *=0A= */=0A= function selectAndSubmit()=0A= {=0A= var formSelection;=0A= =0A= // find out which form we need to process.=0A= var selector =3D document.formSelector.whichForm;=0A= for (var i =3D 0; i < selector.length; i++){=0A= if (selector[i].checked){=0A= formSelection =3D selector[i].value;=0A= }=0A= }=0A= =0A= // Call the relevent function to process the required form.=0A= if(formSelection =3D=3D "allContentSearch"){=0A= processallContentSearch(document.allContentSearchForm, = document.formSelector)=0A= }=0A= else if(formSelection =3D=3D "searchTitles"){=0A= processTitleSearch(document.searchTitles, document.formSelector)=0A= }=0A= else{=0A= return false;=0A= }=0A= =0A= //@@@DM It was anoying me this error =0A= return false;=0A= }=0A= =0A= /*=0A= *Process the ADS search form=0A= *=0A= */=0A= function trim(str)=0A= {=0A= return str.replace(/(^\s*)|(\s*$)/g,"");=0A= }=0A= =0A= function ADSquery(t) {=0A= var keyword =3D trim(t.getElementsByTagName("input")[0].value);=0A= if (keyword!=3D"") {=0A= = window.open("","popup","toolbar=3Dyes,location=3Dyes,status=3Dyes,menubar= =3Dno,scrollbars=3Dyes,resizable=3Dyes,width=3D800,height=3D500");=0A= t.target=3D"popup";=0A= t.qsearch.value=3Dkeyword;=0A= return true;=0A= = //processADSSearch(document.ADSSearchForm,document.ADSQueryForm,keyword);=0A= } else {=0A= alert("Please input a keyword for ADS searching before clicking go");=0A= return false;=0A= }=0A= }=0A= /*=0A= function processADSSearch(hiddenForm ,queryForm , str) {=0A= var terms =3D str;=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= formToSubmit.qsearch.value =3D terms;=0A= = window.open("","popup","toolbar=3Dyes,location=3Dyes,status=3Dyes,menubar= =3Dno,scrollbars=3Dyes,resizable=3Dyes,width=3D800,height=3D500");=0A= formToSubmit.action =3D = "http://adsabs.harvard.edu/cgi-bin/nph-basic_connect"=0A= formToSubmit.target =3D "popup";=0A= formToSubmit.submit();=0A= }=0A= */=0A= =0A= /*=0A= * Process the allContentSearch form=0A= * ---------------------------------=0A= * 1. Perform form validation, checking for empty fields.=0A= * Give the user a relevent message if required.=0A= *=0A= * 2. Process/Assign the appropriate form elements and submit the form.=0A= */=0A= function processallContentSearch(hiddenForm, queryForm)=0A= {=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= =0A= // Do some basic form validation=0A= if(formToProcess.terms.value !=3D "")=0A= {=0A= formToSubmit.WISsearch1.value =3D formToProcess.terms.value;=0A= formToSubmit.submit(); =0A= }=0A= else=0A= {=0A= alert("You must enter a search term in the text box before you click = go.");=0A= }=0A= }=0A= =0A= /*=0A= * Process the Title Search form=0A= * -----------------------------=0A= * 1. Perform form validation, checking for empty fields.=0A= * Give the user a relevent message if required.=0A= *=0A= * 2. Process/Assign the appropriate form elements and submit the form.=0A= */=0A= =0A= function processTitleSearch(hiddenForm, queryForm)=0A= {=0A= var formToSubmit =3D hiddenForm;=0A= var formToProcess =3D queryForm;=0A= =0A= // Do some basic form validation=0A= if(formToProcess.terms.value !=3D "")=0A= {=0A= formToSubmit.query.value =3D formToProcess.terms.value;=0A= formToSubmit.submit();=0A= }=0A= else=0A= {=0A= alert("You must enter a search term in the text box before you click = go.");=0A= }=0A= }=0A= =0A= function doCitationSearch()=0A= {=0A= var form =3D document.citsearchform;=0A= if(checkCitationSearch())=0A= {=0A= form.action =3D "/search/allsearch";=0A= form.submit();=0A= }=0A= }=0A= =0A= // Preprocesses the arguments sent to CitationSearch and checks validity = of user inputs.=0A= function checkCitationSearch()=0A= {=0A= var supplementFound =3D 0; //increment if found;=0A= var hyphenFound =3D 0; //increment if found;=0A= var fm =3D document.citsearchform;=0A= var errmsg =3D "Please use the valid digits '0' to '9'";=0A= // remove all spaces=0A= fm.volume.value =3D fm.volume.value.replace(/ /g, "");=0A= fm.issue.value =3D fm.issue.value.replace(/ /g, "");=0A= fm.pages.value =3D fm.pages.value.replace(/ /g, "");=0A= =0A= if (fm.issn.value.length > 0 && fm.volume.value.length > 0 && = fm.pages.value.length > 0)=0A= {=0A= // check page range=0A= var pageRange =3D fm.pages.value;=0A= var volume =3D fm.volume.value;=0A= var issue =3D fm.issue.value;=0A= var continueFlag =3D 0;=0A= //check the volume=0A= // if (isNaN(volume))=0A= // {=0A= // // volume failed checking=0A= // alert("Volume is invalid. "+errmsg+".");=0A= // return false;=0A= // }=0A= //check the issue=0A= if ((issue.length !=3D 0) && isNaN(issue))=0A= {=0A= // issue failed checking=0A= alert("Issue is invalid. "+errmsg+" or leave blank.");=0A= return false;=0A= }=0A= //check the page range=0A= if (isNaN(pageRange))=0A= {=0A= var isValid =3D false;=0A= // check for hyphen=0A= var hyphenIndex =3D pageRange.indexOf("-");=0A= if ((hyphenIndex !=3D -1) && (hyphenIndex =3D=3D = pageRange.lastIndexOf("-")))=0A= {=0A= // we have only one hyphen, so extract each number=0A= var firstNum =3D pageRange.substring(0, hyphenIndex);=0A= var secondNum =3D pageRange.substring(hyphenIndex + 1);=0A= // check for S=0A= var firstS =3D firstNum.indexOf("S");=0A= var secondS =3D secondNum.indexOf("S");=0A= if (firstS =3D=3D secondS)=0A= {=0A= if ((firstS =3D=3D -1) && isNum(firstNum) && isNum(secondNum) && = (firstNum.length > 0) && (secondNum.length > 0))=0A= isValid =3D true; // both inputs are digits=0A= else if (firstS =3D=3D 0)=0A= {=0A= var firstNumNoS =3D firstNum.substring(1);=0A= var secondNumNoS =3D secondNum.substring(1);=0A= if (isNum(firstNumNoS) && isNum(secondNumNoS) && = (firstNumNoS.length > 0) && (secondNumNoS.length > 0))=0A= isValid =3D true; // both inputs are Sdigits=0A= }=0A= =0A= }=0A= }=0A= if (isValid)=0A= {=0A= return true;=0A= }=0A= else=0A= {=0A= alert("The page range is invalid. "+errmsg+" and a hyphen '-' if = required.");=0A= return false;=0A= }=0A= }=0A= return true;=0A= }=0A= else=0A= {=0A= alert("Volume and pages are required fields. Please make sure data has = been entered for both fields.");=0A= return false;=0A= }=0A= }=0A= =0A= // returns true if a is an Integer.=0A= function isNum(a)=0A= { return !(isNaN(a)); }=0A= =0A= function fixInlineLists() {=0A= if (!document.getElementById) return;=0A= var allLIs =3D document.getElementsByTagName('li');=0A= var bulletNode =3D document.createElement('img');=0A= bulletNode.src = =3D"http://download.interscience.wiley.com/images/icon.bullet.gif";=0A= =0A= for (var i=3D0; iAbstract | References';=0A= }=0A= //alert("URL: " + loc + "\nStart Index: " + startIndex + "\nEnd Index: = " + endIndex + "\nPage: " + page + "\nLink Text: " + links);=0A= return links;=0A= }=0A= =0A= =0A= function selectAll(fm)=0A= {=0A= //var fm =3D document.viewSelectedForm;=0A= =0A= for (var i =3D 0; i < fm.elements.length; i++)=0A= {=0A= if (fm.elements[i].type =3D=3D 'checkbox' /*&& fm.elements[i].name = =3D=3D 'ID'*/)=0A= {=0A= fm.elements[i].checked =3D true;=0A= }=0A= }=0A= }=0A= =0A= =0A= function do_popup(file)=0A= {=0A= var w =3D window.open(file, 'popWin', = 'width=3D350,height=3D500,scrollbars=3Dyes');=0A= =0A= }=0A= =0A= =0A= function mailTool(itemID, useurl, skin)=0A= {=0A= //var url =3D "/cgi-bin/mailform?item=3D"+itemID;=0A= var url =3D "/cgi-bin/mailform?item=3D" + itemID + "&skin=3D" + skin;=0A= var parameters =3D = 'status=3Dno,scrollbars=3Dno,resizable=3Dyes,width=3D400,height=3D475';=0A= =0A= if (useurl !=3D "")=0A= {=0A= url +=3D "&useurl=3D"+useurl;=0A= }=0A= =0A= if ((isNaN(parseInt(itemID))=3D=3Dtrue)||(arguments.length >=3D 4 && = arguments[3] =3D=3D 'cluster'))=0A= {=0A= url +=3D '&type=3Dcluster';=0A= }=0A= =0A= //check whether the last 2 arguments is used for urllink.=0A= // urllink is needed to open up mail form for mrw pages on tomcat = port=0A= if (arguments.length>=3D5 && = arguments[arguments.length-2]=3D=3D'urllink' && = arguments[arguments.length-1]!=3D'')=0A= {=0A= url =3D arguments[arguments.length-1] + url;=0A= }=0A= =0A= if (arguments.length>=3D5 && arguments[3]=3D=3D'currentlink' && = arguments[4]!=3D'')=0A= {=0A= url =3D url + '¤tLink=3D' + arguments[4];=0A= =0A= //processing specific cases=0A= if (arguments[4]=3D=3D'jcatalogjsphdr')=0A= {=0A= //get the issn and pass it the next stage for processing=0A= var currloc =3D location.href;=0A= var issnloc =3D currloc.indexOf("&issn=3D");=0A= if (issnloc !=3D -1)=0A= {=0A= url =3D url + '¤tISSN=3D' + = currloc.substring(issnloc+6);=0A= }=0A= }=0A= // issn is needed for cocoon rendered mrw to form the final url.=0A= else if ( (arguments[4]=3D=3D'cocoonmrwhome') || = (arguments[4]=3D=3D'cocoonmrwarticle') )=0A= {=0A= if (arguments.length>=3D7 && arguments[5]=3D=3D'issn' && = arguments[6]!=3D'')=0A= {=0A= url =3D url + '¤tISSN=3D' + arguments[6];=0A= }=0A= //getting the parameters of the currently shown mrw from the = url=0A= //the method used here is a little crude, it extracts the = values from the current url of the page the user is in =0A= //to pass it to the background program to reconstruct the = requred url=0A= if (arguments[4]=3D=3D'cocoonmrwhome')=0A= {=0A= var currloc =3D location.href;=0A= var mrwParamArr =3D currloc.split("/");=0A= if (mrwParamArr.length >=3D 7)=0A= {=0A= url =3D url + '&mrwPath=3D' + mrwParamArr[5];=0A= var mrwFileParam =3D mrwParamArr[6];=0A= var seploc =3D mrwFileParam.indexOf("#");=0A= if (seploc !=3D -1)=0A= {=0A= url =3D url + '&mrwSection=3D' + = mrwFileParam.substring(seploc+1);=0A= mrwFileParam =3D = mrwFileParam.substring(0,seploc);=0A= }=0A= seploc =3D mrwFileParam.indexOf("?");=0A= if (seploc !=3D -1)=0A= {=0A= url =3D url + '&mrwUrlParam=3D' + = mrwFileParam.substring(seploc+1);=0A= url =3D url + '&mrwDocType=3D' + = mrwFileParam.substring(0,seploc);=0A= }=0A= else=0A= {=0A= url =3D url + '&mrwDocType=3D' + mrwFileParam;=0A= }=0A= }=0A= =0A= }=0A= else if (arguments[4]=3D=3D'cocoonmrwarticle')=0A= {=0A= var currloc =3D location.href;=0A= var mrwParamArr =3D currloc.split("/");=0A= if (mrwParamArr.length >=3D 7)=0A= {=0A= url =3D url + '&mrwPath=3D' + mrwParamArr[5];=0A= url =3D url + '&mrwAid=3D' + mrwParamArr[7];=0A= url =3D url + '&mrwVersion=3D' + mrwParamArr[8];=0A= var mrwFileParam =3D mrwParamArr[9];=0A= var seploc =3D mrwFileParam.indexOf("#");=0A= if (seploc !=3D -1)=0A= {=0A= url =3D url + '&mrwSection=3D' + = mrwFileParam.substring(seploc+1);=0A= url =3D url + '&mrwDocType=3D' + = mrwFileParam.substring(0,seploc);=0A= }=0A= else=0A= {=0A= url =3D url + '&mrwDocType=3D' + mrwFileParam;=0A= }=0A= }=0A= }=0A= }=0A= }=0A= =0A= //checking if a html file exists in the url=0A= var tmpfname =3D location.href;=0A= var loc =3D tmpfname.indexOf("?");=0A= if (loc !=3D -1)=0A= {=0A= tmpfname =3D tmpfname.substring(0,loc);=0A= }=0A= loc =3D tmpfname.indexOf(".html");=0A= if (loc !=3D -1)=0A= {=0A= loc =3D tmpfname.lastIndexOf("/");=0A= if (loc !=3D -1)=0A= {=0A= tmpfname =3D tmpfname.substring(loc+1);=0A= url =3D url + '¤tFile=3D' + tmpfname;=0A= }=0A= }=0A= =0A= if (arguments.length>=3D7 && arguments[5]=3D=3D'currentyear' && = arguments[6]!=3D'')=0A= {=0A= url =3D url + '¤tYear=3D' + arguments[6];=0A= }=0A= =0A= eval("wileyMailTool =3D = window.open('"+url+"','MailTool','"+parameters+"')");=0A= =0A= // If object exists ensure has focus=0A= if (eval("wileyMailTool") && window.focus)=0A= eval("wileyMailTool").focus();=0A= }=0A= =0A= =0A= /*=0A= * 1. Find the links we need to alter.=0A= * 2. For each link apply the new styles we need.=0A= */=0A= function fixAbsRefRendering()=0A= { =0A= var table =3D document.getElementById('prerendered');=0A= var anchors =3D table.getElementsByTagName('a');=0A= for (var i =3D 1; i < anchors.length; i++)=0A= {=0A= if(anchors[i].href !=3D"") =0A= { =0A= applyAbsRefStyleCorrection(anchors[i]);=0A= =0A= }=0A= }=0A= }=0A= =0A= function applyAbsRefStyleCorrection(currentLink)=0A= {=0A= currentLink.style["color"] =3D "#369";=0A= currentLink.style["fontWeight"] =3D "normal";=0A= currentLink.style["marginLeft"] =3D "3px";=0A= currentLink.style["marginRight"] =3D "5px";=0A= }=0A= =0A= function populatePage(formName)=0A= {=0A= if (formName.Page.value =3D=3D '')=0A= {=0A= formName.Page.value =3D document.location;=0A= }=0A= }=0A= =0A= function equalizeColumnWidth(numFeatures)=0A= {=0A= var numberOfFeatures =3D numFeatures; =0A= // Percentage width of table to use for each column.=0A= var percentPerFeature =3D Math.floor(100 / numberOfFeatures); =0A= // Number of columns in total. Content cols + seperators. =0A= =0A= document.writeln("");=0A= for(var i =3D 0; i < numberOfFeatures; i++)=0A= { =0A= document.writeln(' 3D"blank"

');=0A= }=0A= document.writeln("");=0A= }=0A= =0A= function old_equalizeColumnWidth(numFeatures)=0A= {=0A= var numberOfFeatures =3D numFeatures; =0A= // Percentage width of table to use for each column.=0A= var percentPerFeature =3D Math.floor(100 / numberOfFeatures); =0A= // Number of columns in total. Content cols + seperators. =0A= =0A= if(debug)=0A= {=0A= alert("Number of feature boxes: " + numberOfFeatures + "\nPercent per = feature: " + percentPerFeature);=0A= }=0A= =0A= document.writeln("");=0A= for(var i =3D 0; i < numberOfFeatures; i++)=0A= { =0A= if (netscape4 =3D=3D false)=0A= {=0A= document.writeln(' 3D"blank"

'); =0A= }=0A= }=0A= document.writeln("");=0A= }=0A= =0A= function writeFBoxCell()=0A= {=0A= if(first)=0A= {=0A= document.write('');=0A= }else=0A= {=0A= document.write('');=0A= }=0A= numFeatures ++;=0A= }=0A= =0A= =0A= //=0A= // escape apostrophe characters within a string=0A= //=0A= function encode(str)=0A= {=0A= out =3D '';=0A= =0A= for (a =3D 0; a < str.length; a++)=0A= {=0A= c =3D str.charAt(a);=0A= =0A= if (c =3D=3D "'")=0A= {=0A= out +=3D '\\';=0A= }=0A= =0A= out +=3D c;=0A= }=0A= =0A= return out;=0A= }=0A= =0A= =0A= //=0A= //=0A= //=0A= function escapeEntities(str)=0A= {=0A= while (str.indexOf("'") > -1)=0A= {=0A= pos =3D str.indexOf("'");=0A= str =3D str.substr(0, pos) + '\\\'' + str.substr(pos + 6);=0A= }=0A= =0A= return str;=0A= }=0A= =0A= =0A= // new popup function less intrusive just uses the DOM to pickup links = with an exwin class.=0A= // currently implemented for Figure popups on D&T homepage.=0A= =0A= function exLinks()=0A= {=0A= if (document.getElementById)=0A= {=0A= var aObject =3D document.getElementsByTagName("a");=0A= for (var x=3D0; x" + = liels[j].innerHTML + "

You do not have = anything saved in this menu.

";=0A= else=0A= tmpinnerhtml +=3D "

" = + liels[j].innerHTML + "

"; =0A= } =0A= } else {=0A= //setup var to see if more is required=0A= var more =3D (subnodeslength < lilength) ? true : = false; =0A= var flag =3D true;=0A= for (var j=3D0; j" + liels[j].innerHTML + = "";=0A= } else if (j > lilength-3){=0A= if (j =3D=3D lilength-2){=0A= var url =3D liels[j].innerHTML.split('"')[1];=0A= tmpinnerhtml +=3D "

" + liels[j].innerHTML + "

";=0A= } else {=0A= tmpinnerhtml +=3D "

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European Journal of Neurology

ISSN: 1468-1331 (Online)

ISSN: 1351-5101 (Print)

Volume 16, Issue 7, 2009.

Pages: 874=96878

Top of Page
Abstract
Introduction
Methods
Results
Discussion
References

Tables: 1, 2, 3

List of=20 Images

Abstract=20 Only

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Online ISSN: = 1096-9896 Print ISSN: 0022-3417
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Copyright =C2=A9 2007 Pathological Society of Great = Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Copyright Journal compilation = © 2009 European Federation of Neurological Societies

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3D""=20

Peritumoral edema on MRI at initial = diagnosis:=20 an independent prognostic factor for glioblastoma?

K.=20 Schoenegger = ^a,*,=20 S. Oberndorfer = ^e,*, B. Wuschitz ^e , = W. Struhal ^e , = J. Hainfellner ^b = , D. Prayer ^c , = H. Heinzl ^d , = H. Lahrmann ^e , = C. Marosi ^a and = W. Grisold ^e

^a Clinical Division = of=20 Oncology, Department of Medicine I, General Hospital, All Medical=20 University of Vienna, W=E4hringer G=FCrtel ; ^b Institute of = Neurology,=20 General Hospital, All Medical University of Vienna, W=E4hringer=20 G=FCrtel ; =20 ^c Department = of=20 Radiology, General Hospital, All Medical University of Vienna, = W=E4hringer=20 G=FCrtel ; =20 ^d Core Unit = for Medical=20 Statistics and Informatics, General Hospital, All Medical = University of=20 Vienna, W=E4hringer G=FCrtel ; and ^e LBI Neurooncology, = KFJ-Hospital, Kundratstr, Vienna, Austria

Correspondence to Stefan = Oberndorfer,=20 MD, Department Neurology, LBI Neurooncology, KFJ-Hospital, = Kundratstr. 3,=20 1100 Vienna, Austria (tel.: 00431601919992042; fax: = 00431601912009;=20 e-mail: stefan.oberndorfer@wienkav.= at).

=20 *Both authors; contributed equally to = the=20 present investigation.

Copyright Journal compilation =A9 2009 = European=20 Federation of Neurological Societies

KEYWORDS

glioblastoma =95 MRI =95 overall survival = =95 peritumoral=20 brain edema =95 prognostic factor

ABSTRACT

3DAbstract=20

Background: Peritumoral=20 brain edema in glioblastoma patients is a frequently encountered=20 phenomenon that strongly contributes to neurological signs and = symptoms.=20 The role of peritumoral edema as a prognostic factor is = controversial.

Materials and=20 Methods: This multi-centre clinical retrospective = study=20 included 110 patients with histologically proven glioblastoma. The = prognostic impact on overall survival of pre-treatment peritumoral = edema=20 detected on MRI-scans was evaluated. All patients had preoperative = MRI,=20 surgery, histology, and received standard treatment regimens. = Edema on=20 MRI-scans was classified as minor (<1 cm), and major=20 (>1 cm).

Results: Our = results=20 confirm that peritumoral edema on preoperative MRI is an = independent=20 prognostic factor in addition to postoperative Karnofsky = performance score=20 (KPS), age, and type of tumor resection. Patients with major edema = had=20 significant shorter overall survival compared to patients with = minor=20 edema.

Conclusion: This easily=20 applicable early radiological characterization may contribute to a = more=20 subgroup oriented treatment in glioblastoma patients for future = trials, as=20 well as in clinical routine.

Received 9 September 2008 Accepted 18 February=20 2009

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1468-1331.2009.02613.x About=20 DOI

=20

=20

=20

Introduction

Glioblastoma is the most common malignant primary = brain=20 tumor in adults. Prognosis of glioblastoma patients is dismal with = a=20 median survival of approximately 1 year [1,2].=20 However, patient outcome is variable with a small fraction of = long-term=20 survivors [3,4].=20 To evaluate predictors of individual outcome in glioblastoma = patients,=20 several clinical, radiological, molecular, and histological = factors have=20 been identified. Important factors are age, KPS (Karnofsky = performance=20 score), extent of tumor resection, radio-chemotherapy, and = corticosteroid=20 use [5=969].=20 Molecular alterations, such as EGFR and MGMT promoter status are = under=20 investigation [10=9612].

Peritumoral brain edema in glioblastoma patients = is a=20 frequently encountered phenomenon. It is considered as vasogenic; = however,=20 mechanisms of tumor related brain edema are complex and probably = because=20 of several cellular mechanisms [13].

Its prognostic value at diagnosis, as well as in = the course=20 of disease is still a matter of discussion. Peritumoral edema may = cause=20 severe neurological signs and symptoms, and remains a challenge in = the=20 treatment of glioblastoma patients. Some studies report that the = severity=20 of brain edema at diagnosis is a negative prognostic factor [14,15].=20 Other studies show no prognostic impact [7].=20 However, there is no agreement on how peritumoral edema should be = measured=20 or classified on MRI-scans.

The purpose of this study was to evaluate the = degree of=20 peritumoral edema as prognostic factor for survival in = glioblastoma=20 patients. The peritumoral edema was measured on first diagnostic = MRI with=20 an easy applicable and simple technique. Moreover, results from = Pope et al. [15],=20 using a similar radiological technique for the measurement of = peritumoral=20 edema, are re-evaluated.

=20

=20

Methods

This multi-centre retrospective study included 110 = patients=20 with primary glioblastoma. All patients underwent initial = neurosurgical=20 tumor intervention between 1995 and 2005. Surgery was categorized = as=20 total, subtotal, or biopsy. All tumor specimens were = histologically=20 confirmed as glioblastomas according to the WHO classification [1,2].

Postoperative KPS was assessed 10=9614 days = after surgery=20 [16].=20 Patients underwent standard treatment with radio-chemotherapy.

The preoperative MRI-studies were performed at = different=20 institutions. MRI scans had different slice thicknesses and slice=20 distances. However, minimum protocol included axial T1-weighted = sequences=20 with and without contrast enhancement, and a T2-weighted or flair = sequence=20 for the assessment of edema and vascularity. Peritumoral edema was = defined=20 as a region of increased T2 signal intensity on the tumor margin. = In most=20 of the patients, axial scans were available, some also had = additional=20 coronal sequences. If this was the case, both axial and coronal = sequences=20 were analyzed. Measurement was performed at the maximum extent of = the=20 peritumoral edema evaluable on the MRI scans.

Edema extending <1 cm from the tumor = margin was=20 defined as minor, and edema extending more than 1 cm from the = tumor=20 margin as major (Fig. 1).

=20

= Figure 1=20 Measurement of peritumoral edema by means of = MRI T2=20 (coronal/axial) weighted images. (a) Coronal T2-weighted = images=20 showing peritumoral edema extending less than 1 cm from = the=20 tumor margin, which was defined as minor edema. (b) Axial=20 T2-weighted images showing peritumoral edema extending more = than=20 1 cm from the tumor margin as major, which was defined = as major=20 edema.

[Normal View=20 ]

Tumor size was measured as unidimensional largest = diameter=20 in cm on T2-weighted images. Two groups were defined, using the = mean value=20 of 4.3 cm as cut-off point (tumors ≤4 cm and = tumors=20 >4 cm). Contrast enhancement =96 grading was not possible = because of=20 the retrospective character of this study and the availability of = mostly=20 hard copies. Moreover, different MRI machines, contrast media, as = well as=20 application schedules were applied.

Only treatment naive patients, with respect to = anti-tumor=20 and anti-edema therapy, were included. Steroid use before first=20 radiological diagnosis in a single patient cannot be ruled out, = but was=20 not documented and seems improbably prior to MRI confirmation of a = cerebral tumor mass.

The end-point of the study was overall survival, = which was=20 measured from the day of surgery (equivalent to the day of = diagnosis)=20 until death of the patient. Survival beyond the end of the = observational=20 period (last follow-up visit) was considered as censored = observation.

Kaplan=96Meier method was used to generate = survival plots. The=20 prognostic value of the factors of interest was assessed with Cox=20 proportional hazards regression models [17].=20 Overall and partial measures of dependence (R-squared=20 values) were computed according to Kent and O'Quigley [18,19].

All reported P-values are = results of=20 two-sided tests. P-values ≤0.05 were = considered=20 statistically significant. All statistical analyses were performed = using=20 spss (SPSS Inc., Chicago, IL, = USA) or=20 sas (SAS Institute Inc., Cary, = NC,=20 USA).

=20

=20

Results

The main characteristics of the patients are = summarized in=20 Table 1.=20 Out of 110 patients, 71 (64.5%) were male and 39 (35.5%) were = female=20 (gender ratio: 1.8). Fifty-three (48.2%) patients were = ≤60 years and=20 57 (51.8%) were >60 years (median age 60.1 years; = range:=20 27.3=9684 years). During the observation period, 92 patients = died=20 whilst 18 patients were still alive (follow up time minimum = 5 days,=20 maximum 1354 days, median 293 days). Median = postoperative KPS=20 was 90% (range 50=96100%). Eighty-three (85%) patients had a KPS = ≥80 and 15=20 (15%) a KPS <80. In 12 cases, KPS was not estimated. The MRIs = of 24=20 (22%) patients showed minor edema and in 86 (78%) patients, major = edema.=20 Fifteen (14%) patients had biopsy only, 58 (53%) patients had = subtotal,=20 and 36 (33%) had total tumor resection. In 56 patients, tumor size = was=20 measured. Twenty-five (45%) patients had tumors ≤4 cm = and 31 (55%)=20 patients had tumors measuring >4 cm.

=20

Table 1 = Patients=20 characteristics are described with absolute frequencies, = percentages and,=20 if applicable, minimum and maximum values

Factors = of=20 interest	n	%

Age of=20 patient (years) (Range 27.3=9684.0,=20 Median 60.1, Mean 58.7)
≤60	53	48.2
>60	57	51.8
Gender
Female	39	35.5
Male	71	64.5
Karnofsky=20 performance score (n =3D 98) (Range 50=96100, = Median=20 90)
<80	15	15.3
≥80	83	84.7
Edema=20
Minor edema=20 (≤1 cm)	24	21.8
Major edema=20 (>1 cm)	86	78.2
Tumor=20 resection (n =3D 109)
Total	36	33
Subtotal	58	53.2
Biopsy	15	13.8
Tumor size=20 (cm) (n =3D 56) (Range=20 1.0=967.0, Median 5.0, Mean 4.3)
≤4	25	44.6
>4	31	55.4

Eighty-four (77%) patients received radiotherapy = and=20 adjuvant chemotherapy with alkylating agents. Nine (8%) patients = had=20 radiotherapy, and one patient chemotherapy only. Nine (8%) = patients had=20 surgical tumor resection only. Out of these, one patient refused = any=20 further treatment, three died shortly after surgery, and four were = included in the study after tumor resection and had not received = any=20 adjuvant treatment at end-point. Six (5.5%) patients had biopsy = only, and=20 in one case, information on adjuvant radio-chemotherapy was not=20 available.

Looking at the distribution of patient = characteristics in=20 the edema subgroups, patients with minor edema showed larger = percentage of=20 younger age and smaller tumors. The percentage of patients = receiving=20 total, subtotal resection, or biopsy is approximately equal in = both groups=20 (Table 2).=20 Correlation of factors showed a weak correlation between edema = grade and=20 tumor diameter (r =3D −0.33 = P =3D 0.001). Between age-subgroups and = KPS-subgroups, no significant correlation could be found (r =3D −0.159 P =3D 0.117).

=20

Table 2 = Distribution=20 of patient characteristics in edema subgoups (absolute = frequencies,=20 percentages)

Factors = of=20 interest	Minor edema	Major edema

Age of=20 patient (years)
	n =3D 24	n =3D 86
≤60	15 (62.5%)	38 (44.2%)
>60	9 (37.5%)	48 (55.8%)
Gender
	n =3D 24	n =3D 86
Female	12 (50%)	27 (31.4%)
Male	12 (50%)	59 (68.6%)
Karnofsky=20 performance score
	n =3D 19	n =3D 79
<80	2 (10.5%)	13 (16.5%)
≥80	17 (89%)	66 (83.5%)
Tumor=20 resection
	n =3D 24	n =3D 85
Total	8 (33.3%)	28 (32.9%)
Subtotal	12 (50%)	46 (54.1%)
Biopsy	4(16.7%)	11 (12.9%)
Tumor=20 size
	n =3D 13	n =3D 43
≤4	9 (69.2%)	16 (37.2%)
>4	4 (30.8%)	27 = (62.8%)

Univariate analysis revealed that patients with = major edema=20 had significantly shorter survival than patients with minor edema = (P =3D 0.006) (Fig. 2).=20 A high KPS (≥80%) (<0.0001) and younger age = (≤60 years) (P =3D 0.004) were positive clinical = factors,=20 associated with longer survival. Glioblastoma patients with biopsy = only=20 had a significantly worse outcome as compared to patients with=20 total/subtotal resection (P =3D 0.0002).=20 Preoperative tumor size had no significant impact on = survival.

=20

= Figure 2=20 Kaplan=96Meier estimated survival curves for = the edema=20 subgroups (minor edema <1 cm and major edema=20 >1 cm).

[Normal View=20 ]

Multivariate analysis showed that postoperative = KPS >80,=20 tumor resection, and minor edema on pre-treatment MRI are = independently=20 associated with longer survival.

Adjusted R²=20 measure showed that these four prognostic factors explained 36.8% = of the=20 variability in the overall survival time. The partial adjusted = R² for edema alone after = accounting=20 for the effects of age, KPS, and tumor resection was 11% (Table 3).

=20

Table 3 = Hazard ratios,=20 95% confidence intervals (CI), and P-values = of four=20 univariate and a multiple Cox model are given. Partial adjusted = R² values are added for = the=20 latter

Factors of = interest	Univariate Cox=20 models	Multiple = Cox=20 model

Hazard ratio (95% = CI)	P-value	Hazard ratio (95% = CI)	P-value	Partial R²

Age of = patient
>60/≤60	1.83 (1.21=962.77)	0.004	1.54 (0.986=962.41)	0.058	2.9%
Karnofsky = performance=20 score
<80/≥80	3.26 (1.79=965.92)	<0.0001	2.74 (1.48=965.08)	0.001	7.9%
Peritumoral = edema
Major/minor	2.17 (1.23=963.80)	0.006	2.51 (1.30=964.81)	0.006	11.0%
Tumor = resection
Biopsy/total	2.98 (1.55=965.74)	0.0002	4.90 (2.33=9610.3)	<0.0001	17.6%

Subtotal/total	0.87 (0.54=961.40)	0.87=20 (0.53=961.42)

=20

=20

Discussion

Several studies have elaborated neuroradiological = imaging=20 properties as prognostic factors in glioma patients. Tumor size, = extent of=20 necrosis, extent of peritumoral edema, contrast enhancement, = location, and=20 others have been examined [20,21].=20 In a large series of 416 glioblastoma patients, Lacroix et al. found five independent predictors: = age, KPS,=20 contrast enhancement, extent of necrosis on preoperative MRI, and = extent=20 of resection. Extent of edema was not found to be an independent=20 prognostic factor in multivariate analysis [7].=20 The evaluation of the extent of edema in this series was modified = and=20 based on a study by Hammoud et al. who = introduced three edema grades (grade I =3D amount of = edema is less=20 than tumor volume, grade II =3D amount of edema equal to = tumor=20 volume, grade III =3D amount of edema is larger than = tumor volume)=20 using volumetric data [14].=20 However, Hammoud's study reported brain edema as significant = prognostic=20 factor with the moderate edema group having a significantly better = outcome=20 than the large edema group. In conclusion: these two scoring = systems of=20 peritumoral edema are bound to a time-consuming procedure, and do = not seem=20 to yield data that is reproducible.

In contrast, the evaluation system of peritumoral = edema in=20 our study is measured in centimeter from the outer ring of the = tumor=20 margin, followed by grouping into a minor (<1 cm) and = major=20 (>1 cm) edema. A similar scoring system for preoperative = brain=20 edema in patients with high-grade gliomas was introduced by Pope = et al. They used imaging definitions with a = clear=20 score description (0 =3D no edema, = 1 =3D bright T2 signal=20 intensity with no mass effect and architectural deterioration and = not=20 extending more than 1 cm; 2 =3D edema = >1 cm) [15].=20 In this study, the extent of edema turned out to be an independent = prognostic factor in patients with glioblastoma.

Thus, in the literature, results concerning the = prognostic=20 impact of brain edema in glioblastoma patients have not been = conclusive=20 and uniform. Many different scoring systems make comparison = between=20 studies and validation of results difficult. Our study confirms = the=20 results of Pope et al. applying a = similar=20 scoring system. Both our and Pope et al.`s [15]=20 study establishes that peritumoral edema is an independent = prognostic=20 factor for survival in glioblastoma. The pathophysiological = mechanisms of=20 pre-treatment peritumoral edema leading to a worse prognosis need = to be=20 elucidated in further studies.

Extent of resection has a statistical significant = impact on=20 overall survival. In this sample, we observed that glioblastoma = patients=20 with biopsy had a significantly worse outcome compared to patients = with=20 partial or total resections. Comparing the patient subgroups with = partial=20 and total resections, we did not find a significant difference of = outcome.=20 This observation was previously shared [22],=20 whereas recent studies reported a better outcome for patients with = total=20 resection [7,9].=20 This might be because of recently more accurate pre- and = post-operative=20 tumor volume measurements and documentation.

Tumor size at first radiological diagnosis had no=20 significant impact on survival, as reported by Hammoud et al. [14],=20 and Kreth et al. [22],=20 although they used different measurement techniques. We found that = larger=20 tumors were more probably to have major edema (Table 2).=20 This positive weak correlation seems feasible, but remains=20 pathophysiologically unclear.

For use in everyday clinical setting, selection of = radiological parameters that are easily determined from routine = scans is=20 preferable, whereas volumetric analysis is bound to specific = computer=20 systems, and is a rather time-consuming procedure. In this = respect, we=20 recommend this radiological scoring system for evaluation of the = extent of=20 pre-treatment brain edema in glioblastoma. Our study confirms = peritumoral=20 edema as an independent prognostic factor, as previously published = by Pope=20 et al. [15].=20 This easily applicable early radiological characterization may = contribute=20 to a more subgroup oriented treatment approach in glioblastoma = patients=20 for future trials as well as in clinical = routine.

=20

=20

=20

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