From: Subject: Radiation dose and cancer risk among pediatric patients undergoing interventional neuroradiology procedures Date: Fri, 29 May 2009 18:24:08 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C9E08A.A7DC6F80" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C9E08A.A7DC6F80 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2663652 =EF=BB=BF Radiation dose and cancer risk among pediatric = patients undergoing interventional neuroradiology procedures
<= /TABLE>
3D"Journal
Pediatric Radiology
Springer-Verlag
Journal=20 List > Spri= nger=20 Open Choice
Abstract
"=20 = src=3D"http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif">= Full=20 Text
PDF=20 (147K)

PubMed articles by:
Thierry-Chef,=20 I.
Simon,=20 S.
Miller,=20 D.
Pediatr Radiol. = 2006 September; = 36(Suppl=20 2): 159=E2=80=93162. =
Published online 2006 = July 22.=20 doi:=20 10.1007/s00247-006-0206-2.
PMCID:=20 PMC2663652
Copyright<= /A>=20 =C2=A9 Springer-Verlag 2006
Radiation dose and cancer risk among = pediatric=20 patients undergoing interventional neuroradiology procedures
Isabelle = Thierry-Chef,1,4=20 Steven L. Simon,1 and Donald L. = Miller2
1Radiation Epidemiology Branch, = Division of=20 Epidemiology and Genetics, National Cancer Institute, Rockville, = MD 20892=20 USA
2Department of Radiology and = Radiological=20 Sciences, Uniformed Services University, Bethesda, MD 20814 USA =
3Department of Radiology, Albert = Einstein=20 Medical Center, Philadelphia, PA 19141 USA
418 Domaine de la c=C3=B4te, 69530 = Brignais,=20 France
Isabelle = Thierry-Chef,=20 Phone: +33-6-83830994, Email: thierrychef/at/hotmail.com .
3D"correspondingCorresponding=20 author.
"=20 = src=3D"http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif">= Abstract
Abstract
Background
During interventional=20 neuroradiology procedures, patients can be exposed to moderate to = high=20 levels of radiation. Special considerations are required to = protect=20 children, who are generally more sensitive to the short- and = long-term=20 detrimental effects of radiation exposure. Estimates of dose to = the skin=20 of children from certain interventional procedures have been = published=20 elsewhere, but we are not aware of data on dose to the brain or on = the=20 long-term risk of cancer from brain radiation.
Objectives
Our goals were to = estimate=20 radiation doses to the brain in 50 pediatric patients who had = undergone=20 cerebral embolization and to assess their lifetime risks of = developing=20 radiation-related brain cancer.
Materials and methods
Entrance-peak skin = dose and=20 various assumptions on conditions of exposure were used as input = for=20 dosimetric calculations to estimate the spatial pattern of dose = within the=20 brain and the average dose to the whole brain for each child. The = average=20 dose and the age of the child at time of exposure were used to = estimate=20 the lifetime risk of developing radiation-related brain=20 cancer.
Results
Among the 50 patients, = average=20 radiation doses to the brain were estimated to vary from 100 mGy = to 1,300=20 mGy if exposed to non-collimated fields and from 20 mGy to 160 mGy = for=20 collimated, moving fields. The lifetime risk of developing brain = cancer=20 was estimated to be increased by 2% to 80% as a result of the = exposure.=20 Given the very small lifetime background risk of brain tumor, the = excess=20 number of cases will be small even though the relative increase = might be=20 as high as 80%.
Conclusion
ALARA principles of = collimation=20 and dose optimization are the most effective means to minimize the = risk of=20 future radiation-related cancer.
Keywords: Brain radiation exposure, Neurointerventional = procedures,=20 Lifetime risk radiation-induced = carcinogenesis
"=20 = src=3D"http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif">= Introduction
Introduction
Interventional radiology = procedures are=20 potentially life-saving and often necessary to correct certain = medical=20 conditions. Compared to conventional surgery, interventional = procedures=20 have certain benefits to patients, primarily decreased morbidity = and=20 quicker recovery times, since incisions are usually small and = tissue=20 injury is limited.
Most interventional procedures are = performed in=20 the heart, but the number of complex procedures performed on other = organs=20 has increased in recent years. Complex interventions often lead to = higher=20 radiation exposures. The medical and radiation protection = communities have=20 been concerned about the level of dose to the skin and organs of = patients=20 and the associated risk of developing radiation-related cancer at = a later=20 date. For that reason, the RAD-IR study [1=E2=80=933] was carried out between 1998 and 2001 in seven = medical=20 centers in the US to assess doses to the skin of patients involved = in=20 interventional procedures. Out of more than 2,000 procedures = evaluated, 85=20 (4% of the total) were carried out on children between birth and = 18 years=20 of age. Among those, a group of 50 patients underwent = interventional=20 neuroradiology procedures to embolize intracranial aneurysms,=20 arteriovenous malformations, or tumors.
Because interventional = neuroradiology=20 procedures are rarely carried out on pediatric patients, there is = little=20 information on doses to the brain from these procedures in = children. Thus,=20 estimating radiation dose was one important objective of the = present=20 study. Because children are more sensitive to the harmful effects = of=20 radiation and because they have a longer remaining lifespan during = which=20 time radiation-related cancer might develop, we also estimated the = lifetime risk of developing radiation-related brain cancer for = each child=20 in our cohort.
"=20 = src=3D"http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif">= Materials=20 and methods
Materials and = methods
Our calculation of dose to = the brain=20 was based on estimating the amount of absorbed energy from X-rays = within a=20 mathematical model of the brain. The brain model, developed by the = Medical=20 Internal Radiation Dose Committee, is a mathematical description = of the=20 size, composition, and density of the cranium and brain. For each = age (0,=20 1, 5, 10 and 15 years, and adult), Bouchet et al. [4] and Bouchet [5] provide the dimensions and characteristics of = the cranium=20 and the brain, which is considered as two half-ellipsoids. The = caudal=20 layers of the brain model are truncated to simulate the brain stem = and=20 cerebellum. For the purpose of our calculations, the brain was = divided=20 into 1-cm thick layers, each composed of 1 cm3 cubic = volumes.=20 The radiation dose absorbed within each volume of tissue was = estimated=20 based on the attenuation of X-radiation from the surface of the = head to=20 the depth of each volume. From those calculations, the approximate = spatial=20 pattern of absorbed dose was determined, from which the average = dose to=20 the entire brain was estimated (see Fig. 1).=20 Additional details on the dose calculation model will be described = in a=20 subsequent publication.
Fig.=20 1
Model = used for dose=20 = calculation
Information necessary for these = calculations=20 included the age of the patients (because cranium thickness and = density as=20 well as brain size are a function of age), entrance dose (or peak = skin=20 dose) and characteristics of the radiation fields (energy and = geometry of=20 irradiation). Some of this information was available from a review = of the=20 literature. Patient-specific data from the RAD-IR database were = also used;=20 these data were stripped of protected health information and the = research=20 was conducted with the approval of our Institutional Review = Board.
Typical devices used for = interventional=20 fluoroscopy procedures have two C-shape arms, each with an X-ray = tube and=20 image receptor, that can move and rotate about the patient. The = proportion=20 of exposure coming from each X-ray tube has been investigated; in = our=20 dataset, we estimate that about 60% of the exposure is from the = tube below=20 the patient and 40% from the lateral tube. The distribution of = X-ray=20 energies generated by the fluoroscopy machines is determined by = settings=20 of potential (voltage) and filtration. Peak potential is set = automatically=20 by modern fluoroscopic machines based on patient thickness and is = not=20 recorded. From special measurements conducted on a RANDO phantom, = it was=20 assumed that for pediatric examinations, peak potentials would = rarely be=20 greater than 90 kVp. Based on our review of the literature [6, 7], we found that in the range of peak potentials = usually=20 involved, the attenuation of the broad X-ray spectrum can be = reasonably=20 simulated by a single energy at 30 keV.
Information on field size and = location in the=20 brain was not available for individual cases. We simulated a = variety of=20 fields of a size and orientation characteristic of typical = pediatric=20 neuroradiologic examinations. In one scenario we considered the = head=20 irradiated by two uniform fields as large as the entire brain, = with the=20 radiation directed from the X-ray tube below the table (PA = geometry) and=20 from the lateral plane. This extreme case is unlikely. In most = clinical=20 procedures, the radiation field is focused on the diseased part of = the=20 brain, and the entire brain is not irradiated uniformly throughout = the=20 procedure. Examination fields are usually not static; they are = moved in=20 real-time to track the movement of the catheter within blood = vessels.=20 Taking into account these possibilities, a variety of possible = field sizes=20 and orientations were investigated, including large and small = static and=20 moving fields as well as combinations.
The absorption of energy = decreased with=20 depth in the tissue, resulting in the highest dose either = immediately=20 below the point of entrance or where fields overlapped. The = average brain=20 dose was determined from the dose received within all of the small = volumes=20 defined in the age-dependent brain phantom (Fig. 1).=20 Based on the average dose to the brain, the risk of developing = brain=20 cancer during the remainder of a normal lifespan was estimated for = each=20 case using the Interactive RadioEpidemiological Program [8] developed by the US National Cancer Institute = for=20 estimating the probability of cancer causation following radiation = exposure. IREP calculates Assigned Share, defined as = AS=3DERR/(1+ERR), for a=20 specific age at cancer diagnosis. For the present paper, = age-specific=20 estimates of AS were obtained from IREP for each year of age after = exposure and converted to ERR=3DAS/(1=E2=88=92AS), and a summary = ERR value was=20 computed as a life-table-weighted average of the age-specific=20 values.
"=20 = src=3D"http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif">= Results
Results
Irradiation by two large = uniform=20 fields
Spatial patterns of = absorbed radiation=20 dose in several layers of the brain phantom, from the center slice = to the=20 top of the brain, are shown in Fig. 2=20 for the infant and the adolescent. Dose within each 1 = cm3 cube=20 is shown relative to 1 unit peak skin dose. The highest brain dose = occurred, in general, where frontal and lateral examination fields = overlapped. For the infant, the highest dose in any small volume = in the=20 brain reached 0.7 for each unit peak skin dose. For the = adolescent, the=20 attenuation by the much thicker cranium had a significant effect. = As a=20 result, for 1 unit peak skin dose, the highest dose in any small = volume=20 was only 0.4. When the dose in all of the small volumes of the = phantom was=20 considered, the brain dose was 0.5 per unit of peak skin dose for = the=20 infant and 0.2 for the adolescent.
Fig.=20 2
Comparison of doses=20 from uniform = fields
This scenario of irradiation = of the=20 brain by two large uniform fields during the entire procedure is = an=20 unusual case. Radiologists are trained to collimate the fields in = order to=20 expose the smallest area necessary.
Irradiation by small moving = fields
Through most of the = examination=20 time, the field was collimated on the diseased part of the brain = rather=20 than on the entire organ. Figure 3=20 gives a representation of two possible cases with the pathologic = focus at=20 the center of the brain, or at the edge. As shown in Fig. 3=20 and Table 1,=20 average radiation doses were dramatically reduced when fields were = collimated; reductions by about 70% for the infant and 85% to 95% = for the=20 adolescent were possible, depending on the location of the = pathology=20 within the brain. Note that the dose to small regions of the brain = could=20 still be quite high even if the average organ dose was small. =
Fig.=20 3
Dose in = the=20 infant=E2=80=99s brain=E2=80=94moving=20 fields
Table=20 1
Comparison of=20 average dose to the brain for the infant and the adolescent = (1 unit=20 peak skin = dose)
Lifetime risk of developing=20 radiation-related brain cancer
Based on the estimated = radiation=20 dose to the brain where the brain is irradiated by two large = uniform=20 fields, or by two small fields with the pathologic focus at the = center of=20 the brain, the risk of developing radiation-related brain cancer, = relative=20 to non-exposed children, was estimated for the least-exposed child = in the=20 cohort, a 2-year-old boy, and the most exposed child, a = 14-year-old boy=20 (Table 2).=20 For the least-exposed child, the lifetime risk of developing brain = cancer=20 compared to a non-exposed child of the same age was estimated to = be=20 increased by 2% to 10% (a relative risk of 1.02 to 1.10); that is, = for=20 children exposed similarly, the number of cases of brain cancer to = occur=20 would be increased from 65 per 10,000 (the baseline) [9] to approximately 66 or 71, depending on the = actual=20 conditions of exposure. In contrast, for the most highly exposed = child (14=20 years of age at exposure), the increase in risk ranged from 10% to = 80%,=20 depending on the actual conditions of his exposure, meaning that = for each=20 10,000 children exposed similarly, the number of cases of brain = cancer=20 expected to occur would increase from 65 per 10,000 to = approximately=20 71=E2=80=93117.
Table=20 2
Predicted = relative=20 risk of brain cancer from radiation received during = interventional=20 procedure
"=20 = src=3D"http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif">= Discussion
Discussion
Because no data are = available on=20 doses received to the brain in children undergoing cerebral = embolization=20 procedures, we developed a calculation strategy to estimate the = spatial=20 pattern of dose and average dose to the organ. Our calculations = were=20 applied to a cohort of 50 children who had been treated for = aneurysms,=20 arteriovenous malformations, or tumors in the brain. Because these = interventions are uncommon in children, and radiation dose is = usually not=20 measured, our cohort likely represents the largest set of data = available=20 for which radiation dose and risk can be estimated following such=20 procedures. The main factors influencing dose are patient age (age = is=20 related to density and thickness of a child=E2=80=99s cranium), = duration of=20 fluoroscopy, portion of the brain irradiated, and degree of = overlap of=20 radiation fields. It is apparent that even if the average organ = dose is=20 low, the maximum dose received at localized points can still be = high,=20 particularly where fields overlap. As we have discussed, if = radiation=20 procedures are conducted with the intent of minimizing unnecessary = exposure, i.e., if ALARA principles are followed, the future risk = of=20 developing brain cancer is not greatly enhanced compared to the = risk=20 experienced by non-exposed children. To better understand the = actual doses=20 received and to better estimate the lifetime cancer risks, we = recommend=20 that better and more detailed record-keeping of machine parameters = and=20 specifics of the exposure conditions become standard=20 procedure.
Conclusion
Interventional = radiology=20 procedures are potentially life-saving, and it is widely = understood that=20 the requirement for these procedures often outweighs = considerations for=20 minimizing radiation dose. However, minimizing cancer risk for the = future=20 also serves patients. Applying ALARA principles of collimation and = shortest possible exposure time are the most effective means to = minimize=20 risk of future radiation cancer.
"=20 = src=3D"http://www.pubmedcentral.nih.gov/corehtml/pmc/pmcgifs/square.gif">= References
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Springer
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.scale-pmc A.selected-2:hover { BACKGROUND-POSITION: -37px -77px; CURSOR: default } .scale-pmc A.scale-3 { BACKGROUND-POSITION: 3px -97px } .scale-pmc A.scale-3:hover { BACKGROUND-POSITION: -77px -97px } .scale-pmc A.selected-3 { BACKGROUND-POSITION: -37px -97px; CURSOR: default } .scale-pmc A.selected-3:hover { BACKGROUND-POSITION: -37px -97px; CURSOR: default } .scale-pmc A.scale-4 { BACKGROUND-POSITION: 3px -117px } .scale-pmc A.scale-4:hover { BACKGROUND-POSITION: -77px -117px } .scale-pmc A.selected-4 { BACKGROUND-POSITION: -37px -117px; CURSOR: default } .scale-pmc A.selected-4:hover { BACKGROUND-POSITION: -37px -117px; CURSOR: default } .scale-pmc A.scale-5 { BACKGROUND-POSITION: 3px -137px } .scale-pmc A.scale-5:hover { BACKGROUND-POSITION: -77px -137px } .scale-pmc A.selected-5 { BACKGROUND-POSITION: -37px -137px; CURSOR: default } .scale-pmc A.selected-5:hover { BACKGROUND-POSITION: -37px -137px; CURSOR: default } .scale-pmc A.scale-6 { BACKGROUND-POSITION: 3px -157px } .scale-pmc A.scale-6:hover { BACKGROUND-POSITION: -77px -157px } .scale-pmc A.selected-6 { BACKGROUND-POSITION: -37px -157px; CURSOR: default } .scale-pmc A.selected-6:hover { BACKGROUND-POSITION: -37px -157px; CURSOR: default } .scale-pmc A.scale-7 { BACKGROUND-POSITION: 3px -177px } .scale-pmc A.scale-7:hover { BACKGROUND-POSITION: -77px -177px } .scale-pmc A.selected-7 { BACKGROUND-POSITION: -37px -177px; CURSOR: default } .scale-pmc A.selected-7:hover { BACKGROUND-POSITION: -37px -177px; CURSOR: default } .scale-pmc A.scale-8 { BACKGROUND-POSITION: 3px -207px } .scale-pmc A.scale-8:hover { BACKGROUND-POSITION: -77px -207px } .scale-pmc A.selected-8 { BACKGROUND-POSITION: -37px -207px; CURSOR: default } .scale-pmc A.selected-8:hover { BACKGROUND-POSITION: -37px -207px; CURSOR: default } ------=_NextPart_000_0000_01C9E08A.A7DC6F80 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.pubmedcentral.nih.gov/corehtml/pmc/js/common.js // Called from many places to handle links.=0A= // Params:=0A= // link: URL. 'this' to reuse same window, else ""=0A= // windowname: Reference name for window=0A= // additional: Attributes for window.open, from:=0A= // width, height, resizable, scrollbars, toolbar, location, = directories,=0A= // status, menubar, copyhistory.=0A= // Notes: Book version always provides menubar, toolbar, etc.=0A= //=0A= function startTargetBook(link,windowname,width,height,additional)=0A= {=0A= startTarget(link,windowname,width,height,additional)=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function startTarget(link,windowname,width,height, additional)=0A= {=0A= if(! window.focus)=0A= return;=0A= =0A= var sizestring =3D ",width=3D" + width + ",height=3D" + height;=0A= var opt =3D = "menubar=3Dno,toolbar=3Dno,status=3Dno,scrollbars=3Dyes,resizable=3Dyes,d= ependent=3Dyes,location=3Dno";=0A= var allOptions =3D opt + sizestring;=0A= if (additional) { allOptions =3D allOptions + ',' + additional; }=0A= =0A= windowname =3D String(windowname).replace(/-/g, "_")=0A= var moveToXDefault =3D 75=0A= var moveToYDefault =3D 50=0A= =0A= var moveToX =3D moveToXDefault=0A= var moveToY =3D moveToYDefault=0A= var yAdj =3D 50=0A= var yAdjDelta =3D 25=0A= =0A= var barNames =3D ['menubar', 'toolbar', 'statusbar']=0A= for (var idx in barNames)=0A= {=0A= if (String(allOptions).lastIndexOf(barNames[idx] + '=3Dyes') >=0A= String(allOptions).lastIndexOf(barNames[idx] + '=3Dno'))=0A= yAdj +=3D yAdjDelta=0A= }=0A= =0A= try {=0A= if (window.screen.width && width > 0)=0A= moveToX =3D Math.ceil((window.screen.width - width)) - 15=0A= moveToX =3D (moveToX > 0 ? moveToX : moveToXDefault)=0A= =0A= if (window.screen.height && height > 0)=0A= moveToY =3D Math.ceil((window.screen.height - height)) - yAdj=0A= moveToY =3D (moveToY > 0 ? moveToY : moveToYDefault)=0A= }=0A= catch (e) {}=0A= =0A= var wLeftTopCornerOptions =3D ',left=3D' + moveToX + ',top=3D' + = moveToY + ',screenX=3D' + moveToX + ',screenY=3D' + moveToY=0A= =0A= allOptions =3D allOptions + wLeftTopCornerOptions=0A= =0A= w =3D window.open ("", windowname, allOptions)=0A= w.focus()=0A= =0A= link.target=3Dwindowname=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function focuswin(windowname)=0A= {=0A= windowname =3D String(windowname).replace(/-/g, "_")=0A= w =3D = window.open("",windowname,"menubar=3Dyes,scrollbars=3Dyes,toolbar=3Dyes,l= ocation=3Dyes,status=3Dyes,directories=3Dyes,resizable=3Dyes");=0A= w.focus();=0A= =0A= return true;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseString (inStr)=0A= {=0A= var outStr =3D ''=0A= =0A= for (i =3D0; i <=3D inStr.length; i++)=0A= {=0A= outStr =3D inStr.charAt(i) + outStr=0A= }=0A= =0A= return outStr=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseAndReplaceString (inStr, findStr, newStr)=0A= {=0A= return reverseString(inStr).replace(findStr, newStr)=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function initUnObscureEmail (className, innerHTML)=0A= {=0A= =0A= try{=0A= if (window.addEventListener)=0A= window.addEventListener('load', function() {unObscureEmail = (className, innerHTML)}, false)=0A= else if (window.attachEvent)=0A= window.attachEvent('onload', function() {unObscureEmail = (className, innerHTML)})=0A= }catch(e){=0A= }=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function unObscureEmail (className, innerHTML)=0A= {=0A= try {=0A= if (typeof(unObscuredEmails) =3D=3D 'undefined')=0A= unObscuredEmails =3D new Array()=0A= =0A= if (! unObscuredEmails[className])=0A= {=0A= =0A= var elmnts =3D document.getElementsByTagName("span")=0A= for (var i =3D 0, len =3D elmnts.length; i < len; i++)=0A= {=0A= if (elmnts.item(i).className.indexOf(className, " ") = !=3D -1)=0A= {=0A= elmnts.item(i).innerHTML =3D innerHTML;=0A= unObscuredEmails[className] =3D true=0A= =0A= }=0A= }=0A= }=0A= }=0A= catch(e){=0A= }=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function pubMedDbLinkSubmit(control) {=0A= try{=0A= if (control.pubmedOption)=0A= control =3D control.pubmedOption=0A= if (control.options)=0A= location.href =3D = control.options[control.options.selectedIndex].value;=0A= }=0A= catch(e){}=0A= return false;=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= // elements "a", "area" with "ref" attribute report to redirect utility = before dereferencing link=0A= //=0A= function initRedirectClicks(report_url) {=0A= if (report_url && jQuery)=0A= jQuery(document).click(function(e) {=0A= //=0A= if (!e) return true;=0A= //=0A= if (e.shiftKey || e.altKey || e.ctrlKey) return true;=0A= //=0A= var target =3D jQuery(e.target).closest("a[ref], area[ref]");=0A= if (!target || target.length =3D=3D 0) return true;=0A= //=0A= var ref =3D target.attr("ref");=0A= // append ref with value of href if 'redirect-to-url' is = missing in ref.=0A= if (ref.indexOf('redirect-to-url') =3D=3D -1)=0A= ref =3D ref + '&redirect-to-url=3D' + = encodeURIComponent(target.attr("href"))=0A= =0A= //=0A= jQuery.ajax({=0A= type: "HEAD",=0A= url: report_url + '?' + ref,=0A= timeout: 1000,=0A= async: false=0A= });=0A= =0A= return true;=0A= });=0A= };=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= // Based on script written by Dean Edwards, 2005=0A= // http://dean.edwards.name/=0A= =0A= var pmc_script =3D {=0A= addEvent: function(element, type, handler) {=0A= // assign each event handler a unique ID=0A= if (!handler.$$guid) handler.$$guid =3D this.addEvent_guid++;=0A= // create a hash table of event types for the element=0A= if (!element.events) element.events =3D {};=0A= // create a hash table of event handlers for each element/event pair=0A= var handlers =3D element.events[type];=0A= if (!handlers) {=0A= handlers =3D element.events[type] =3D {};=0A= // store the existing event handler (if there is one)=0A= if (element["on" + type]) {=0A= handlers[0] =3D element["on" + type];=0A= }=0A= }=0A= // store the event handler in the hash table=0A= handlers[handler.$$guid] =3D handler;=0A= // assign a global event handler to do all the work=0A= element["on" + type] =3D handleEvent;=0A= =0A= =0A= function handleEvent(event) {=0A= var returnValue =3D true;=0A= // grab the event object (IE uses a global event object)=0A= event =3D event || fixEvent(window.event);=0A= // get a reference to the hash table of event handlers=0A= var handlers =3D this.events[event.type];=0A= // execute each event handler=0A= for (var i in handlers) {=0A= this.$$handleEvent =3D handlers[i];=0A= if (this.$$handleEvent(event) =3D=3D=3D false) {=0A= returnValue =3D false;=0A= }=0A= }=0A= return returnValue;=0A= };=0A= =0A= function fixEvent(event) {=0A= // add W3C standard event methods=0A= event.preventDefault =3D fixEvent.preventDefault;=0A= event.stopPropagation =3D fixEvent.stopPropagation;=0A= return event;=0A= };=0A= =0A= fixEvent.preventDefault =3D function() {=0A= this.returnValue =3D false;=0A= };=0A= =0A= fixEvent.stopPropagation =3D function() {=0A= this.cancelBubble =3D true;=0A= };=0A= },=0A= =0A= // a counter 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