From: Subject: A case report of pseudoprogression followed by complete remission after proton-beam irradiation for a low-grade glioma in a teenager: the value of dynamic contrast-enhanced MRI Date: Sat, 3 Apr 2010 11:43:53 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01CAD322.EF64A620" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01CAD322.EF64A620 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829589/ =EF=BB=BF A case = report of pseudoprogression followed by complete remission after = proton-beam irradiation for a low-grade glioma in a teenager: the value = of dynamic contrast-enhanced MRI
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Radiat Oncol. 2010; 5: 9.=20
Published online 2010 = February 4.=20 doi:=20 10.1186/1748-717X-5-9.
PMCID:=20 = PMC2829589
Copyright=20 =C2=A92010 Meyzer et al; licensee BioMed Central Ltd.
A case report of pseudoprogression followed = by=20 complete remission after proton-beam irradiation for a low-grade = glioma in=20 a teenager: the value of dynamic contrast-enhanced MRI
Candice Meyzer,1 = Fr=C3=A9d=C3=A9ric=20 Dhermain,2,3 Denis Ducreux,3 = Jean-Louis=20 Habrand,2,4 Pascale Varlet,5 = Christian=20 Sainte-Rose,6 Christelle Dufour,1 and = Jacques=20 Grill3D"corresponding1
1Department of Pediatric and = Adolescent=20 Oncology, Gustave Roussy Institute, 39 Rue Camille Desmoulins, = 94805=20 Villejuif, France
2Department of Radiation Therapy, = Gustave=20 Roussy Institute, Villejuif, France
3LIMEC, INSERM UMR 788, University = Hospital,=20 Kremlin-Bic=C3=AAtre, France
4Centre de Protonth=C3=A9rapie, = Orsay,=20 France
5Department of Neuropathology, = Sainte-Anne=20 Hospital, Paris, France
6Depatment of Neurosurgery, Necker = Sick=20 Children's Hospital, Paris, France
3D"correspondingCorresponding=20 author.
Candice Meyzer:=20 candicemeyzer/at/free.fr ; Fr=C3=A9d=C3=A9ric = Dhermain: dhermain/at/igr.fr ; Denis Ducreux: denis.ducreux/at/bct.aphp.fr ; Jean-Louis Habrand: = habrand/at/igr.fr ; Pascale Varlet: p.varlet/at/ch-sainte-anne.fr ; Christian = Sainte-Rose: christian.sanite-rose/at/nck.aphp.fr ; Christelle Dufour: = dufour/at/igr.fr ; Jacques Grill: grill/at/igr.fr
Received October 15, 2009; Accepted = February 4,=20 2010.
This is an Open Access article = distributed under=20 the terms of the Creative Commons Attribution License (http://creativecommons.org/lic= enses/by/2.0),=20 which permits unrestricted use, distribution, and reproduction in = any=20 medium, provided the original work is properly cited.
Abstract
A fourteen = years-old boy was=20 treated post-operatively with proton therapy for a recurrent = low-grade=20 oligodendroglioma located in the tectal region. Six months after = the end=20 of irradiation (RT), a new enhancing lesion appeared within the = radiation=20 fields. To differentiate disease progression from = radiation-induced=20 changes, dynamic susceptibility contrast-enhanced (DSCE) MRI was = used with=20 a T2* sequence to study perfusion and permeability characteristics = simultaneously. Typically, the lesion showed hypoperfusion and=20 hyperpermeability compared to the controlateral normal brain. = Without=20 additional treatment but a short course of steroids, the image = disappeared=20 over a six months period allowing us to conclude for a = pseudo-progression.=20 The patient is alive in complete remission more than 2 years=20 post-RT.
Background
The occurrence of new = contrast=20 enhancing lesions on routine MRI follow-up after radiation therapy = (RT)=20 for brain gliomas was observed more than ten years ago but remains = problematic because standard MR imaging techniques do not allow a = clear=20 distinction between recurrent tumour and radiation-induced lesions = [1,2]. Recently, "pseudo-progression" was defined as=20 conventional MR images compatible with progression, occurring = shortly=20 after concomitant radio-chemotherapy (CRC), as a transient = phenomenon with=20 spontaneous improvement or stabilization after several months [3-5]. This was mainly described in adult and = paediatric=20 populations with high-grade gliomas whose new standard of care is = CRC=20 followed by adjuvant chemotherapy [6,7].
We report here a clinical = case=20 showing a new contrast-enhancing lesion discovered on a systematic = MRI=20 proposed to a fourteen years-old boy treated six months before for = a=20 recurrent low-grade glioma by surgery and proton-therapy. Dynamic=20 Susceptibility Contrast (DSC) MR imaging and planned follow-up = lead to the=20 diagnosis of pseudo-progression. This phenomenon has rarely been = described=20 in children with supra-tentorial low-grade gliomas after proton = beam RT,=20 particularly with this type of advanced MR = technique.
Case Presentation
Initial presentation and = conventional MRI=20 description
A healthy ten = year-old boy with=20 tinnitus and bilateral papillary oedema underwent a brain MRI = showing a=20 small tumour of the tectal plate. The lesion presented a signal of = low=20 intensity on T1-weighted and a high signal on T2-weighted = sequences. No=20 contrast enhancement was visible. The process was responsible for=20 triventricular hydrocephalus by aqueduct compression. The first = treatment=20 was a ventriculocysternostomy followed, fifteen months later, by a = partial=20 resection when the lesion increased in size. Histopathological = diagnosis=20 was a grade II oligodendroglioma (WHO classification), with a=20 proliferation index (MIB 1) of 5%. Three years after the first = surgery, a=20 systematic follow-up MRI revealed a recurrence localized on the=20 quadrigeminal plate, close to the left thalami and the third = ventricle,=20 again without gadolinium enhancement. A second surgery was = attempted,=20 showing the same histology, but a tumour residue was left on the = left=20 thalamus (Figure <= SPAN=20 style=3D"POSITION: relative; TEXT-DECORATION: none">=E2=80=8B(Figure1).13D"Figure= ).=20 Treatment was completed six weeks later by RT using proton beams,=20 delivering 54 Gy in 30 fractions of 1.8 Gy. Radiation fields = encompassed=20 the medial parts of the thalami (Figure <= SPAN=20 style=3D"TEXT-DECORATION: underline">1C, D3D"Figure= ).=20 Radiological and clinical data were then evaluated every 3 months=20 thereafter. Six months after RT, systematic MRI found obvious = development=20 of a new lesion with an important contrast enhancement and mass = effect on=20 the third ventricle (Figure <= SPAN=20 style=3D"POSITION: relative; TEXT-DECORATION: none">=E2=80=8B(Figure2),23D"Figure= ),=20 however the patient remained asymptomatic.
3D"Figure=
<= STRONG>Figure=20 1 Conventional MR=20 imaging, Target volume and Dosimetry of a Low-grade = Glioma.=20 A left thalamic low-grade oligodendroglioma in a 10 year-old = boy=20 after partial resection, without contrast enhancement. [A]=20 T1-weighted transaxial MR image after = administration = (more ...)
Conventional and Dynamic MRI = with=20 Permeability visualization and Perfusion estimate
In order to more = accurately=20 differentiate tumour recurrence from radiation-induced changes, a = DSC-MRI=20 was performed as described previously [8,9]. The T2* sequence was used in order to assess=20 simultaneously perfusion and permeability characteristics, as = recently=20 proposed for predicting risk of recurrence in adult low-grade = gliomas [10]. In this case, the typical combination of a = focused area=20 of high permeability strictly superimposed on the contrast = enhancing=20 lesion combined with the absence of high perfusion estimate in the = same=20 region (Figure <= SPAN=20 style=3D"POSITION: relative; TEXT-DECORATION: none">=E2=80=8B(Figure3)33D"Figure= )=20 was compatible with post-radiation modifications, as recently = suggested by=20 Hu et al. They found a direct correlation between image-guided = tissue=20 histopathology and localized DSC perfusion MR imaging measurements = in a=20 series of adult high-grade gliomas [11]. Consequently, we favoured the hypothesis of a = delayed=20 radiation injury and began a treatment with oral steroids = (prednisone) at=20 one mg/kg/d for one month before clinical and radiological = reappraisal.=20 After one month, decrease in size of contrast enhancement became=20 significant while the patient remained asymptomatic. Steroids were = therefore discontinued. Gradual improvement continued on = conventional MRI=20 and disappearance of both contrast enhancement and high = permeability area=20 strongly suggested a pseudo-progression rather than recurrent = disease.=20 Follow-up MRI at nine months post-RT showed a complete resolution = of the=20 gadolinium uptake and no detectable microvascular leakage (Figure = <= SPAN=20 style=3D"POSITION: relative; TEXT-DECORATION: none">=E2=80=8B(Figure4).43D"Figure= ).=20 At last follow-up, patient is still in complete remission, more = than two=20 years post-RT.
3D"Figure=
<= STRONG>Figure=20 2 Conventional MR=20 imaging before and six months after exclusive Proton=20 therapy. [A] T1-weighted transaxial MR image after=20 administration of intravenous (iv) Gd-DTPA, one week before=20 radiation. [B] The same sequence, six months after the end = of=20 irradiation = (more ...)
3D"Figure=
<= STRONG>Figure=20 3
Six months=20 after irradiation: superimposed MR images with T1-weighted = sequence=20 after iv Gadolinium injection and co-registered Perfusion = (left) and=20 Permability maps (right). [A] Gradient-echo axial = image=20 with color overlay map showing no focus of = hyperperfusion = (more ...)
Post-treatment modifications, = evolution=20 with time and micro-vascular hypothesis
Subacute = radiation-induced=20 modifications have been described previously in childhood gliomas, = with or=20 without concomitant or sequential use of chemotherapy [1,12-14]. In adults, these changes are more and more = reported=20 after combined radio-chemotherapy [4,5,15]. MRI findings usually consist on new contrast = enhancing=20 mass on T1-weighted imaging with gadolinium, which is = indistinguishable=20 from tumour progression. It occurs usually within the irradiated = tumour=20 volume but radiation-induced lesions could be located less = commonly in the=20 controlateral hemisphere, remotely from the primary tumour site = [6]. To our knowledge, it is the first case of=20 pseudo-progression fully described after exclusive proton RT. = Here, time=20 of occurrence was delayed (6 months) since the typical time frame = is=20 rather within 3 months after chemo-radiation, possibly due to the = absence=20 of concomitant chemotherapy [3,5,6]. Cerebral injury has been classified according = to time to=20 appearance after RT [8] as "acute", with brain oedema occurring during = RT, mostly=20 transient and reversible; subacute or "early delayed" injury, = occurring a=20 few weeks to three months post-RT, improving within six weeks; = late=20 injury, occurring months to years post-RT, including true = radionecrosis.=20 It is often irreversible, progressive, and possibly lethal and = constitutes=20 the major dose-limiting clinical complication of brain = irradiation,=20 particularly in children. Pseudo-progression (PsP) could be = considered as=20 a pathological continuum between acute post-RT reaction and=20 treatment-related necrosis [6]. Mechanisms behind these events are not fully = understood=20 but are probably related to micro-vessels changes. Post-RT brain = injury=20 induces a focal tissue reaction with inflammatory component and = increased=20 capillary permeability, causing fluid transudation into the = interstitial=20 space and brain oedema. Transient alterations in the blood-brain = barrier=20 may be responsible for new or increased contrast enhancement, = falsely=20 suggesting tumour progression, with low perfusion values [11].
Role of PET and advanced MR = techniques in=20 the diagnosis of "pseudo-progresion", clinical implication
This DSC-MR = technique evaluates=20 tissue changes, close to the physiopathology of PsP, whereas = metabolic=20 tools as FDG-PET or MR spectroscopy (MRS) analyse level of glucose = uptake=20 or distribution of metabolites peaks. MRS can distinguish = recurrent true=20 necrosis from active tumour [16-18] but it needs long acquisition time. In=20 18FDG-PET, FDG uptake is not specific of tumour tissue = and=20 false positive can be observed in non malignant inflammatory = processes.=20 The use of aminoacid tracers as 11C-methionine better=20 discriminates post-RT necrosis from tumour recurrence [19] but it is rarely available in daily practice. = Recently,=20 the DSC-MR technique was proposed for adult high-grade gliomas in = this=20 situation [20,21] as an alternative tool. It can be incorporated = in the=20 routine follow-up, within the interval of three to six months = post-RT=20 where PsP can be observed. Importantly, there is a risk of = including=20 children with gliomas in phase II studies for "recurrent disease" = that=20 would be spontaneously reversible, leading to false positive = results,=20 consequently delivering salvage treatments for = "pseudo-progressive"=20 patients who could be, at the contrary, potentially long term = survivors=20 [15].
Conclusion
The lack of typical = clinical=20 symptoms and the limits of anatomical MRI techniques imply that = any=20 subacute change suggesting disease progression may be considered = as=20 possible PsP. Post-RT therapy should not be interrupted too early = [22] and DSC-MRI could help for distinguishing PsP = from real=20 progression.
Consent
Written informed = consent was=20 obtained from the parents and the patient for publication of this = case=20 report and accompagnying images. A copy of the written consent is=20 available for review by the Editor-in-Chief of this=20 journal.
Competing interests
The authors declare = that they=20 have no competing interests.
Authors' contributions
CM collected the = data and wrote=20 the manuscript. FD analysed the imaging studies and contributed to = the=20 legend of figures and correction of the manuscript. DD created and = developed the software used to treat T2* acquisition and produce = the=20 images. JLH supervised the irradiation of the patient. PV analysed = the=20 histology of the tumour. CSR operated the patient. CD was the = treating=20 physician of the patient. JG supervised the manuscript. All = authors read=20 and approved the final manuscript.
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BioMed Central
3D"Figure=
<= STRONG>Figure=20 4
Nine months=20 after irradiation: complete disappearance of the contrast=20 enhancement (left) and no detectable Permeability = (right).=20 [A] T1-weighted transaxial MR image after administration of = iv=20 Gd-DTPA and [B] the superimposed Permeability map, with = no = (more ...)

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  • Meyzer,=20 C.
  • Dhermain,=20 F.
  • Ducreux,=20 D.
  • Grill,=20 J.

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url(../../img/oldentrez/panel/tool-sprites.gif) } .x-panel-ghost { BACKGROUND: #e0e0e0 } .x-panel-ghost UL { BORDER-LEFT-COLOR: #b0b0b0; BORDER-BOTTOM-COLOR: #b0b0b0; = BORDER-TOP-COLOR: #b0b0b0; BORDER-RIGHT-COLOR: #b0b0b0 } .x-grid-panel .x-panel-mc .x-panel-body { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: #d0d0d0 1px solid } .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/button/btn-sprite.gif) } .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/button/btn-sprite.gif) } .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/button/btn-sprite.gif) } .x-border-layout-ct { BACKGROUND: #f0f0f0 } .x-accordion-hd { BACKGROUND-IMAGE: url(../../img/oldentrez/panel/light-hd.gif) } .x-layout-collapsed { BORDER-LEFT-COLOR: #e0e0e0; BORDER-BOTTOM-COLOR: #e0e0e0; = BORDER-TOP-COLOR: #e0e0e0; BACKGROUND-COLOR: #eee; BORDER-RIGHT-COLOR: = #e0e0e0 } .x-layout-collapsed-over { BACKGROUND-COLOR: #fbfbfb } .x-tip .x-tip-top { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-left { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-right { BACKGROUND-IMAGE: url(../../img/oldentrez/qtip/tip-sprite.gif) } .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(../../img/oldentrez/toolbar/bg.gif) #f0f4f5 repeat-x left top; = BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-toolbar BUTTON { COLOR: #444 } .x-toolbar .x-btn-menu-arrow-wrap .x-btn-center BUTTON { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-text-icon .x-btn-menu-arrow-wrap .x-btn-center BUTTON = { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-over .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over BUTTON { COLOR: #111 } .x-toolbar .x-btn-click .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-left { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-right { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-center { BACKGROUND-IMAGE: url(../../img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .ytb-sep { BACKGROUND-IMAGE: url(../images/default/grid/grid-split.gif) } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-top { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(../../img/oldentrez/tabs/tab-strip-bg.gif) #dbdbdb repeat-x left = top; BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = PADDING-TOP: 2px; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-bottom { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(../../img/oldentrez/tabs/tab-strip-btm-bg.gif); BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-strip SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-over SPAN.x-tab-strip-text { COLOR: #111 } .x-tab-strip-active SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-disabled .x-tabs-text { COLOR: #aaaaaa } 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url(../../img/oldentrez/tabs/tab-close.gif) } .x-tab-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #fff; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-bbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-header-plain .x-tab-strip-spacer { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-scroller-left { BORDER-LEFT-COLOR: #aeaeae; BACKGROUND-IMAGE: = url(../../img/oldentrez/tabs/scroll-left.gif); BORDER-BOTTOM-COLOR: = #aeaeae; BORDER-TOP-COLOR: #aeaeae; BORDER-RIGHT-COLOR: #aeaeae } .x-tab-scroller-right { BORDER-LEFT-COLOR: #aeaeae; BACKGROUND-IMAGE: = url(../../img/oldentrez/tabs/scroll-right.gif); BORDER-BOTTOM-COLOR: = #aeaeae; BORDER-TOP-COLOR: #aeaeae; BORDER-RIGHT-COLOR: #aeaeae } .x-window-proxy { BORDER-LEFT-COLOR: #b0b0b0; BACKGROUND: #e0e0e0; BORDER-BOTTOM-COLOR: = #b0b0b0; BORDER-TOP-COLOR: #b0b0b0; BORDER-RIGHT-COLOR: #b0b0b0 } .x-window-tl .x-window-header { COLOR: #555 } .x-window-tc { BACKGROUND-IMAGE: url(../../img/oldentrez/window/top-bottom.png) } .x-window-tl { BACKGROUND-IMAGE: url(../../img/oldentrez/window/left-corners.png) } .x-window-tr { BACKGROUND-IMAGE: url(../../img/oldentrez/window/right-corners.png) } .x-window-bc { BACKGROUND-IMAGE: url(../../img/oldentrez/window/top-bottom.png) } .x-window-bl { BACKGROUND-IMAGE: url(../../img/oldentrez/window/left-corners.png) } .x-window-br { BACKGROUND-IMAGE: url(../../img/oldentrez/window/right-corners.png) } .x-window-mc { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BACKGROUND: #e8e8e8; BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: = #d0d0d0 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BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tl .x-panel-header { COLOR: #333 } .x-panel-tc { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/top-bottom.gif) } .x-panel-tl { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif); = BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-panel-tr { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-bc { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/top-bottom.gif) } .x-panel-bl { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-br { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/corners-sprite.gif) } .x-panel-mc { BACKGROUND: #f1f1f1 } .x-panel-mc .x-panel-body { BORDER-RIGHT: 0px; BORDER-TOP: 0px; BACKGROUND: none transparent scroll = repeat 0% 0%; BORDER-LEFT: 0px; BORDER-BOTTOM: 0px } .x-panel-ml { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/left-right.gif) } .x-panel-mr { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/left-right.gif) } .x-tool { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/tool-sprites.gif) } .x-panel-ghost { BACKGROUND: #e0e0e0 } .x-panel-ghost UL { BORDER-LEFT-COLOR: #b0b0b0; BORDER-BOTTOM-COLOR: #b0b0b0; = BORDER-TOP-COLOR: #b0b0b0; BORDER-RIGHT-COLOR: #b0b0b0 } .x-grid-panel .x-panel-mc .x-panel-body { BORDER-RIGHT: #d0d0d0 1px solid; BORDER-TOP: #d0d0d0 1px solid; = BORDER-LEFT: #d0d0d0 1px solid; BORDER-BOTTOM: #d0d0d0 1px solid } .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/button/btn-sprite.gif) } .x-border-layout-ct { BACKGROUND: #f0f0f0 } .x-accordion-hd { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/panel/light-hd.gif) } .x-layout-collapsed { BORDER-LEFT-COLOR: #e0e0e0; BORDER-BOTTOM-COLOR: #e0e0e0; = BORDER-TOP-COLOR: #e0e0e0; BACKGROUND-COLOR: #eee; BORDER-RIGHT-COLOR: = #e0e0e0 } .x-layout-collapsed-over { BACKGROUND-COLOR: #fbfbfb } .x-tip .x-tip-top { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-top-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-ft-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-tip .x-tip-bd-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/qtip/tip-sprite.gif) } .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/bg.gif) #f0f4f5 repeat-x left = top; BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-toolbar BUTTON { COLOR: #444 } .x-toolbar .x-btn-menu-arrow-wrap .x-btn-center BUTTON { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-text-icon .x-btn-menu-arrow-wrap .x-btn-center BUTTON = { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/btn-arrow.gif) } .x-toolbar .x-btn-over .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-over BUTTON { COLOR: #111 } .x-toolbar .x-btn-click .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-click .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-pressed .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .x-btn-menu-active .x-btn-center { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/toolbar/tb-btn-sprite.gif) } .x-toolbar .ytb-sep { BACKGROUND-IMAGE: = url(/core/extjs/ext-2.1/resources/images/default/grid/grid-split.gif) } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-header { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-footer { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-top { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-strip-bg.gif) #dbdbdb = repeat-x left top; BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: = #d0d0d0; PADDING-TOP: 2px; BORDER-RIGHT-COLOR: #d0d0d0 } UL.x-tab-strip-bottom { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-strip-btm-bg.gif); = BORDER-BOTTOM-COLOR: #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; = BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-strip SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-over SPAN.x-tab-strip-text { COLOR: #111 } .x-tab-strip-active SPAN.x-tab-strip-text { COLOR: #333 } .x-tab-strip-disabled .x-tabs-text { COLOR: #aaaaaa } .x-tab-strip-top .x-tab-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-top .x-tab-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-top .x-tab-strip-inner { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tabs-sprite.gif) } .x-tab-strip-bottom .x-tab-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-btm-inactive-right-bg.gif) } .x-tab-strip-bottom .x-tab-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-btm-inactive-left-bg.gif) } .x-tab-strip-bottom .x-tab-strip-active .x-tab-right { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-btm-right-bg.gif) } .x-tab-strip-bottom .x-tab-strip-active .x-tab-left { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-btm-left-bg.gif) } .x-tab-strip .x-tab-strip-closable A.x-tab-strip-close { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-close.gif) } .x-tab-strip .x-tab-strip-closable A.x-tab-strip-close:hover { BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/tab-close.gif) } .x-tab-panel-body { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #fff; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-bbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-tbar .x-toolbar { BORDER-LEFT-COLOR: #d0d0d0; BORDER-BOTTOM-COLOR: #d0d0d0; = BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-panel-header-plain .x-tab-strip-spacer { BORDER-LEFT-COLOR: #d0d0d0; BACKGROUND: #eaeaea; BORDER-BOTTOM-COLOR: = #d0d0d0; BORDER-TOP-COLOR: #d0d0d0; BORDER-RIGHT-COLOR: #d0d0d0 } .x-tab-scroller-left { BORDER-LEFT-COLOR: #aeaeae; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/scroll-left.gif); = BORDER-BOTTOM-COLOR: #aeaeae; BORDER-TOP-COLOR: #aeaeae; = BORDER-RIGHT-COLOR: #aeaeae } .x-tab-scroller-right { BORDER-LEFT-COLOR: #aeaeae; BACKGROUND-IMAGE: = url(/core/ext.ncbi/1/img/oldentrez/tabs/scroll-right.gif); = BORDER-BOTTOM-COLOR: #aeaeae; BORDER-TOP-COLOR: #aeaeae; = BORDER-RIGHT-COLOR: #aeaeae } .x-window-proxy { BORDER-LEFT-COLOR: 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1.1.2+=0A= * =0A= *=0A= */=0A= /*=0A= * modified on 2009.07.01 by Andrey Kolotev=0A= * to support "onclick" event.=0A= * When this event is taking place, the tooltip will be automatically=0A= * hidden after preset timeout, the way it is if=0A= * the mouse moved out of the hovered object.=0A= */=0A= (function(a){a.fn.hoverIntent=3Dfunction(k,j){var = l=3D{sensitivity:7,interval:100,timeout:0};l=3Da.extend(l,j?{over:k,out:j= }:k);var n,m,h,d;var e=3Dfunction(f){n=3Df.pageX;m=3Df.pageY};var = c=3Dfunction(g,f){f.hoverIntent_t=3DclearTimeout(f.hoverIntent_t);if((Mat= h.abs(h-n)+Math.abs(d-m))=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 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//=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=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= =0A= if (report_url && typeof jQuery !=3D 'undefined')=0A= jQuery(document).click(function(e) {=0A= =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= var href =3D target.attr("href")=0A= =0A= // special processing of href element for pubmed's authors=0A= if (typeof (href) !=3D 'undefined' && = href.indexOf('sites/entrez') && href.indexOf('%5Bauth%5D'))=0A= {=0A= var newHref =3D replacePubMedUnsupportedChars(href);=0A= if (newHref !=3D href)=0A= target.attr("href", newHref)=0A= }=0A= =0A= // append ref with value of href if 'redirect-to-url' is = missing in ref.=0A= if (typeof (ref) !=3D 'undefined' && = ref.indexOf('redirect-to-url') =3D=3D -1)=0A= {=0A= ref =3D ref + '&redirect-to-url=3D' + = encodeURIComponent(href)=0A= //=0A= jQuery.ajax({=0A= type: "HEAD",=0A= url: report_url + '?' + ref,=0A= timeout: 1000,=0A= async: false=0A= });=0A= }=0A= =0A= return true;=0A= });=0A= };=0A= =0A= // function to replace unsupported charachters in author names to be = searchable in PubMed database.=0A= function replacePubMedUnsupportedChars (str)=0A= {=0A= // replace low 128 chars automatically=0A= str =3D str.replace(/%26%23(x000[0-7][0-9a-f])%3b/ig,=0A= function($0, $1){=0A= return (String.fromCharCode('0' + $1))=0A= }=0A= )=0A= // replace others based on map and if it is not in the map replace = with empty string.=0A= str =3D = str.replace(/%26%23(x[0-9a-f][0-9a-f][0-9a-f][0-9a-f][0-9a-f])%3b/ig,=0A= function($0, $1){=0A= return (pubmedUnsupportedCharMap[$1] ? = pubmedUnsupportedCharMap[$1] : '')=0A= }=0A= )=0A= return str;=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.$$handleEvent(event) =3D=3D=3D false) {=0A= returnValue =3D false;=0A= }=0A= }=0A= return returnValue;=0A= };=0A= =0A= function fixEvent(event) {=0A= // add W3C standard event methods=0A= event.preventDefault =3D fixEvent.preventDefault;=0A= event.stopPropagation =3D fixEvent.stopPropagation;=0A= return event;=0A= };=0A= =0A= fixEvent.preventDefault =3D function() {=0A= this.returnValue =3D false;=0A= };=0A= =0A= fixEvent.stopPropagation =3D function() {=0A= this.cancelBubble =3D true;=0A= };=0A= },=0A= =0A= // a counter used to create unique IDs=0A= addEvent_guid: 1,=0A= =0A= removeEvent: function(element, type, handler) {=0A= // delete the event handler from the hash table=0A= if (element.events && element.events[type]) {=0A= delete element.events[type][handler.$$guid];=0A= }=0A= }=0A= }=0A= =0A= =0A= // = *************************************************************************= ***=0A= // implementation of figure's popup using jQuery and = jQuery.fn.hoverIntent lib=0A= // it set appropriate handlers for all "a" elements with "figpopup" = class name.=0A= // = *************************************************************************= ***=0A= if (typeof jQuery !=3D 'undefined' && typeof jQuery.fn.hoverIntent !=3D = 'undefined') {=0A= (function($j) {=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 hoverHandlers = =3D=3D=3D=3D=3D=3D=3D=3D=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= var hoverHandlers =3D function (opts) {=0A= this.config =3D {}=0A= this.self =3D this;=0A= this.__init(opts)=0A= }=0A= =0A= $j.fn.extend(hoverHandlers.prototype, {=0A= //=0A= __init: function(opts) {=0A= $j.fn.extend(this.config, opts)=0A= },=0A= //=0A= over: function (el) {=0A= var canvas =3D $j('.large-thumb-canvas', el)=0A= var prnt =3D canvas.parent();=0A= var win =3D $j(window)=0A= =0A= //=0A= if (canvas && prnt && win)=0A= {=0A= =0A= // collect necessary coordinates from all = intresting objects=0A= canvas.coords =3D this._x_coords(canvas, = 'canvas')=0A= prnt.coords =3D this._x_coords(prnt, = 'parent')=0A= win.coords =3D this._x_coords(win, = 'window')=0A= =0A= // replace @src with value of @hires, because = href hold high resolution image and src low one.=0A= $j('img', canvas).attr('src',=0A= function(){=0A= var hires =3D $j(this).attr("hires");=0A= return (typeof (hires) !=3D = 'undefined' && hires !=3D this.src)=0A= ? hires : this.src=0A= }=0A= )=0A= =0A= // make arrangement of canvas in the view port = nearby parent element.=0A= var cnvsRltvToPrnt =3D = this._x_arrange_canvas(canvas.coords, prnt.coords, win.coords)=0A= =0A= // visualize the canvas with images.=0A= canvas.css('top', cnvsRltvToPrnt.top + 'px')=0A= canvas.css('left', cnvsRltvToPrnt.left + 'px')=0A= canvas.css('display', 'block')=0A= } // canvas=0A= }, // over=0A= //=0A= out: function (el) {=0A= var canvas =3D $j('.large-thumb-canvas', el)=0A= canvas.css('display', 'none')=0A= },=0A= //=0A= _x_offset: function(el, elname) {=0A= var c =3D {}=0A= if (el[0] =3D=3D window )=0A= c =3D this._x_scroll(el, elname)=0A= else=0A= c =3D el.offset()=0A= //console.info('%s.offset {top,left} =3D {%s, %s}', = elname, c.top, c.left)=0A= return c=0A= },=0A= _x_scroll: function(el, elname) {=0A= var c =3D {top: el.scrollTop(), left: = el.scrollLeft()}=0A= //console.info('%s.scroll {top,left} =3D {%s, %s}', = elname, c.top, c.left)=0A= return c=0A= },=0A= _x_width: function(el, elname) {=0A= var w =3D el.outerWidth() || el.width()=0A= //console.info('%s.width =3D %s; outerWidth =3D = %s; width =3D %s', elname, w, el.outerWidth(), el.width())=0A= //IE: alert(elname + '.width =3D ' + w + '; = outerWidth =3D ' + el.outerWidth() + 'width =3D ' + el.width())=0A= return w=0A= },=0A= _x_height: function(el, elname) {=0A= var h =3D el.outerHeight() || el.height()=0A= // console.info('%s.height =3D %s', elname, h)=0A= return h=0A= },=0A= _x_coords: function(el, elname) {=0A= var size =3D { width: this._x_width (el, elname), = height: this._x_height(el, elname)}=0A= var coords =3D {=0A= scroll: this._x_scroll(el, elname),=0A= width: size.width,=0A= height: size.height,=0A= offset: this._x_offset(el, elname),=0A= size: size=0A= }=0A= return coords=0A= },=0A= _x_get_rltv_coord: function(trgtObj, baseObj, = label) {=0A= var c =3D {top: trgtObj.top - baseObj.top, left: = trgtObj.left - baseObj.left}=0A= //console.info("%s {top: %s, left: %s}", label, = c.top, c.left)=0A= return c=0A= },=0A= //=0A= _x_get_empty_space: function(objCoords, = objSize, viewPortCoords, viewPortSize, label) {=0A= var objRelToViewPort =3D = this._x_get_rltv_coord(objCoords, viewPortCoords, '_x_get_empty_space: = for ' + label);=0A= var c =3D {above: objRelToViewPort.top,=0A= below: viewPortSize.height - = (objRelToViewPort.top + objSize.height),=0A= left: objRelToViewPort.left,=0A= right: viewPortSize.width - = (objRelToViewPort.left + objSize.width)}=0A= $j.each(c, function(k, v){c[k] =3D (v < 0 ? 0 : v)})=0A= //console.info("%s {above: %s, below: %s, left: %s, = right: %s}", label, c.above, c.below, c.left, c.right)=0A= return c=0A= },=0A= //=0A= _x_get_bigest_space_area_name: function(spaces, label) {=0A= var sArr =3D [];=0A= for (k in spaces){ sArr[sArr.length] =3D {k: k, v: = spaces[k]} }=0A= // sort in reverse order=0A= sArr.sort (function(a,b){return ( a.v < b.v ? 1 : ( = a.v > b.v ? - 1 : 0 ) )})=0A= // console.info('%s: %s', label, sArr[0].k)=0A= return sArr[0].k=0A= },=0A= //=0A= _x_get_space_ratios: function(spaces, = viewPortSize, label) {=0A= var ratios =3D {above: 0, left: 0}=0A= if (viewPortSize.height > 0)=0A= ratios.above =3D spaces.above / = viewPortSize.height=0A= if (viewPortSize.width > 0)=0A= ratios.left =3D spaces.left / viewPortSize.width=0A= // console.info('ratio: %s {above: %s, left: %s}', = label, ratios.above, ratios.left)=0A= return ratios=0A= },=0A= _x_arrange_canvas: function(c_c, prnt_c, = viewp_c) {=0A= // then calculate empty space areas around parent = element of the canvas, which is ususally an anchor ("a" element)=0A= var emptySpacesArndPrntInViewPort =3D = this._x_get_empty_space (prnt_c.offset, prnt_c.size, viewp_c.offset, = viewp_c.size, 'emptySpacesArndPrntInWinPort')=0A= =0A= // get the area name, where the most linear space = avaiable=0A= var areaName =3D = this._x_get_bigest_space_area_name(emptySpacesArndPrntInViewPort, = viewp_c.size, 'spacios areaName')=0A= =0A= // calculate the proportions of area to be taken by = canvas in empty space area=0A= // relativly to the parent element.=0A= var ratios =3D = this._x_get_space_ratios(emptySpacesArndPrntInViewPort, viewp_c.size, = 'ratios')=0A= =0A= // calculate parent's coordinates relative to view = port=0A= var prntRltvToViewPort =3D = this._x_get_rltv_coord(prnt_c.offset, viewp_c.offset, = 'prntRltvToViewPort')=0A= =0A= // declare canvas relative coordinates=0A= var cnvsRltvToPrnt =3D {top: 0, left: 0}=0A= =0A= // choose appropriate location for placing canvas.=0A= // and choose the 1st element of an array as the one = with the biggest area around parent of canvas.=0A= // console.info ('place it at the %s', = bigestEmptySpaceAreaName)=0A= // calculations are relative to the left corner of = the parent element of canvas. (it has to have the css property = position:relative)=0A= switch (areaName)=0A= {=0A= case 'above':=0A= cnvsRltvToPrnt.top =3D - c_c.height=0A= cnvsRltvToPrnt.left =3D prnt_c.width * 0.5 - = c_c.width * ratios.left=0A= break;=0A= case 'below':=0A= cnvsRltvToPrnt.top =3D prnt_c.height=0A= cnvsRltvToPrnt.left =3D prnt_c.width * 0.5 - = c_c.width * ratios.left=0A= break;=0A= case 'left':=0A= cnvsRltvToPrnt.left =3D - c_c.width=0A= cnvsRltvToPrnt.top =3D prnt_c.height * 0.5 = - c_c.height * ratios.above=0A= break;=0A= case 'right':=0A= cnvsRltvToPrnt.left =3D prnt_c.width=0A= cnvsRltvToPrnt.top =3D prnt_c.height * 0.5 = - c_c.height * ratios.above=0A= break;=0A= }=0A= =0A= // recalculate canvas' coordinates relative to = parent into coordinates relative to view port.=0A= var cnvsRltvToViewPort =3D {=0A= top: prntRltvToViewPort.top + = cnvsRltvToPrnt.top,=0A= left: prntRltvToViewPort.left + = cnvsRltvToPrnt.left=0A= }=0A= //console.info("cnvsRltvToPrnt {top:%s, left: %s}", = cnvsRltvToPrnt.top, cnvsRltvToPrnt.left)=0A= //console.info("cnvsRltvToViewPort {top:%s, left: = %s}", cnvsRltvToViewPort.top, cnvsRltvToViewPort.left)=0A= =0A= // adjust relative position of canvas to the window = if calculated values=0A= // are forcing canvas go out of view port=0A= // next order should be preserved to keep left top = corner visible always=0A= =0A= // adjust right side and move a bit to the left=0A= if (cnvsRltvToViewPort.left + c_c.width > = viewp_c.width)=0A= {=0A= var horAdj =3D c_c.width - (viewp_c.width - = cnvsRltvToViewPort.left)=0A= cnvsRltvToPrnt.left -=3D horAdj=0A= cnvsRltvToViewPort.left -=3D horAdj=0A= //console.log('adjust right side and move to = the left %spx', horizontalAdjustment)=0A= }=0A= =0A= // adjust below side and move to the top=0A= if (cnvsRltvToViewPort.top + c_c.height > = viewp_c.height)=0A= {=0A= var vertAdj =3D c_c.height - (viewp_c.height - = cnvsRltvToViewPort.top)=0A= cnvsRltvToPrnt.top -=3D vertAdj=0A= cnvsRltvToViewPort.top -=3D vertAdj=0A= // console.log('adjust below side and move to = the top %spx', verticalAdjustment)=0A= }=0A= =0A= // adjust left side and move to the right=0A= if (cnvsRltvToViewPort.left < 0)=0A= {=0A= // console.log('adjust left side and move to the = right %spx', -(cnvsLeftRelativeToWindowPort))=0A= cnvsRltvToPrnt.left -=3D = cnvsRltvToViewPort.left=0A= cnvsRltvToViewPort.left =3D 0=0A= }=0A= // adjust above side and move to the bottom=0A= if (cnvsRltvToViewPort.top < 0)=0A= {=0A= // console.log('adjust above side and move to = the bottom %spx', -(cnvsTopRelativeToWindowPort))=0A= cnvsRltvToPrnt.top -=3D = cnvsRltvToViewPort.top=0A= cnvsRltvToViewPort.top =3D 0=0A= }=0A= // console.info("cnvsRltvToPrnt adjusted {top: %s, = left: %s}", cnvsRltvToPrnt.top, cnvsRltvToPrnt.left)=0A= // console.info("cnvsRltvToViewPort adjusted {top: = %s, left: %s}", cnvsRltvToViewPort.top, cnvsRltvToViewPort.left)=0A= return cnvsRltvToPrnt=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 end of hoverHandlers = =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= =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 $j.fn.figPopup = =3D=3D=3D=3D=3D=3D=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 hoverOverHandler () {=0A= var h =3D new hoverHandlers();=0A= h.over(this)=0A= }=0A= =0A= function hoverOutHandler () {=0A= var h =3D new hoverHandlers();=0A= h.out(this)=0A= }=0A= =0A= $j.fn.figPopup =3D function(opts){=0A= var config =3D {=0A= interval: 500,=0A= timeout: 0,=0A= over: hoverOverHandler, // handler onMouseOver=0A= out: hoverOutHandler // handler onMouseOut=0A= }=0A= $j.extend(config, opts)=0A= return config=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 end of $j.fn.figPopup = =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= =0A= }) (jQuery) // end of extention of jQuery with figPopup=0A= =0A= =0A= =0A= jQuery(document).ready( function () {=0A= var fp_cfg =3D new jQuery.fn.figPopup()=0A= jQuery('a.figpopup').hoverIntent(fp_cfg)=0A= });=0A= }=0A= =0A= // end of hoverIntent routines for figures' popups=0A= // = *************************************************************************= ***=0A= // implementation of ....=0A= // = *************************************************************************= ***=0A= ------=_NextPart_000_0000_01CAD322.EF64A620 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.ncbi.nlm.nih.gov/corehtml/pmc/js/noext.menu.js if (typeof(noext) =3D=3D=3D 'undefined') { noext =3D {};=20 } if (typeof jQuery =3D=3D=3D 'undefined') { throw new Error('noext.Menu: jQuery must be present'); } // Constructor noext.Menu =3D function (n, subMenuStyle) { this.n =3D n; this.subMenuStyle =3D (subMenuStyle =3D=3D=3D 'ext') ? 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