Loading…

Characterization of Cerebral Aneurysms for Assessing Risk of Rupture By Using Patient-Specific Computational Hemodynamics Models

Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. This report describes a pilot clinical study of the association between intra-aneurysmal hemodynamic characteristics from computational fluid dynamic models and the rupture of cere...

Full description

Saved in:
Bibliographic Details
Published in:American Journal of Neuroradiology 2005-11, Vol.26 (10), p.2550-2559
Main Authors: Cebral, Juan R, Castro, Marcelo A, Burgess, James E, Pergolizzi, Richard S, Sheridan, Michael J, Putman, Christopher M
Format: Article
Language:English
Subjects:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page 2559
container_issue 10
container_start_page 2550
container_title American Journal of Neuroradiology
container_volume 26
creator Cebral, Juan R
Castro, Marcelo A
Burgess, James E
Pergolizzi, Richard S
Sheridan, Michael J
Putman, Christopher M
description Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. This report describes a pilot clinical study of the association between intra-aneurysmal hemodynamic characteristics from computational fluid dynamic models and the rupture of cerebral aneurysms. A total of 62 patient-specific models of cerebral aneurysms were constructed from 3D angiography images. Computational fluid dynamics simulations were performed under pulsatile flow conditions measured on a normal subject. The aneurysms were classified into different categories, depending on the complexity and stability of the flow pattern, the location and size of the flow impingement region, and the size of the inflow jet. The 62 models consisted of 25 ruptured and 34 unruptured aneurysms and 3 cases with unknown histories of hemorrhage. The hemodynamic features were analyzed for associations with history of rupture. A large variety of flow patterns was observed: 72% of ruptured aneurysms had complex or unstable flow patterns, 80% had small impingement regions, and 76% had small jet sizes. By contrast, unruptured aneurysms accounted for 73%, 82%, and 75% of aneurysms with simple stable flow patterns, large impingement regions, and large jet sizes, respectively. Aneurysms with small impingement sizes were 6.3 times more likely to have experienced rupture than those with large impingement sizes (P = .01). Image-based patient-specific numeric models can be constructed in an efficient manner that allows clinical studies of intra-aneurysmal hemodynamics. A simple flow characterization system was proposed, and interesting trends in the association between hemodynamic features and aneurysmal rupture were found. Simple stable patterns, large impingement regions, and jet sizes were more commonly seen with unruptured aneurysms. By contrast, ruptured aneurysms were more likely to have disturbed flow patterns, small impingement regions, and narrow jets.
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7976176</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68797593</sourcerecordid><originalsourceid>FETCH-LOGICAL-h357t-2b7c6eae1b339a69bd343fbf9d33943975efa909c77a19b391ebc19c5c5500743</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhiNERbeFv4B8AU6R7HhtZy5IS1RapCJQoRI3y3EmG0MSBzvpanvip9e0y9eJ08iaR4_e8fsoWzHgMgcBXx5nK8pA5JLR8jg7ifErpVSAKp5kx0wWpVxTusp-VJ0Jxs4Y3K2ZnR-Jb0mFAetgerIZcQn7OETS-kA2MWKMbtySKxe__QSvlmleApI3e3J9v_iYHDjO-acJrWudJZUfpmW-NyffBQ6-2Y9mcDaS977BPj7NjlrTR3x2mKfZ9duzz9VFfvnh_F21ucw7LtScF7WyEg2ymnMwEuqGr3lbt9Ck95qDEtgaoGCVMgxqDgxry8AKKwSlas1Ps9cP3mmpB2xsSpku1FNwgwl77Y3T_25G1-mtv9EKlGRKJsHLgyD47wvGWQ8uWux7M6JfopZlIgXw_4KpobJMPSTw-d-Rfmf51U4CXhwAE63p22BG6-IfThXAoWSJe_XAdW7b7VxAHQfT90nL9G63K6RmVBfpI_gdAjqqnQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>19388972</pqid></control><display><type>article</type><title>Characterization of Cerebral Aneurysms for Assessing Risk of Rupture By Using Patient-Specific Computational Hemodynamics Models</title><source>Open Access: PubMed Central</source><source>Springer Nature</source><creator>Cebral, Juan R ; Castro, Marcelo A ; Burgess, James E ; Pergolizzi, Richard S ; Sheridan, Michael J ; Putman, Christopher M</creator><creatorcontrib>Cebral, Juan R ; Castro, Marcelo A ; Burgess, James E ; Pergolizzi, Richard S ; Sheridan, Michael J ; Putman, Christopher M</creatorcontrib><description>Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. This report describes a pilot clinical study of the association between intra-aneurysmal hemodynamic characteristics from computational fluid dynamic models and the rupture of cerebral aneurysms. A total of 62 patient-specific models of cerebral aneurysms were constructed from 3D angiography images. Computational fluid dynamics simulations were performed under pulsatile flow conditions measured on a normal subject. The aneurysms were classified into different categories, depending on the complexity and stability of the flow pattern, the location and size of the flow impingement region, and the size of the inflow jet. The 62 models consisted of 25 ruptured and 34 unruptured aneurysms and 3 cases with unknown histories of hemorrhage. The hemodynamic features were analyzed for associations with history of rupture. A large variety of flow patterns was observed: 72% of ruptured aneurysms had complex or unstable flow patterns, 80% had small impingement regions, and 76% had small jet sizes. By contrast, unruptured aneurysms accounted for 73%, 82%, and 75% of aneurysms with simple stable flow patterns, large impingement regions, and large jet sizes, respectively. Aneurysms with small impingement sizes were 6.3 times more likely to have experienced rupture than those with large impingement sizes (P = .01). Image-based patient-specific numeric models can be constructed in an efficient manner that allows clinical studies of intra-aneurysmal hemodynamics. A simple flow characterization system was proposed, and interesting trends in the association between hemodynamic features and aneurysmal rupture were found. Simple stable patterns, large impingement regions, and jet sizes were more commonly seen with unruptured aneurysms. By contrast, ruptured aneurysms were more likely to have disturbed flow patterns, small impingement regions, and narrow jets.</description><identifier>ISSN: 0195-6108</identifier><identifier>EISSN: 1936-959X</identifier><identifier>EISSN: 1432-1920</identifier><identifier>PMID: 16286400</identifier><identifier>CODEN: AAJNDL</identifier><language>eng</language><publisher>Oak Brook, IL: Am Soc Neuroradiology</publisher><subject>Adult ; Adult and adolescent clinical studies ; Aged ; Aged, 80 and over ; Aneurysm, Ruptured - classification ; Aneurysm, Ruptured - physiopathology ; Biological and medical sciences ; Carotid Artery, Internal - diagnostic imaging ; Carotid Artery, Internal - physiology ; Cerebral Angiography ; Cerebrovascular Circulation - physiology ; Female ; Hemodynamics - physiology ; Human viral diseases ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Infectious diseases ; Interventional ; Intracranial Aneurysm - classification ; Intracranial Aneurysm - physiopathology ; Investigative techniques, diagnostic techniques (general aspects) ; Logistic Models ; Male ; Medical sciences ; Middle Aged ; Middle Cerebral Artery - diagnostic imaging ; Middle Cerebral Artery - physiology ; Miscellaneous ; Mood disorders ; Nervous system ; Pilot Projects ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Radiodiagnosis. Nmr imagery. Nmr spectrometry ; Radiographic Image Interpretation, Computer-Assisted ; Regional Blood Flow - physiology ; Risk Factors ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids</subject><ispartof>American Journal of Neuroradiology, 2005-11, Vol.26 (10), p.2550-2559</ispartof><rights>2006 INIST-CNRS</rights><rights>Copyright © American Society of Neuroradiology 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976176/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976176/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=17293981$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16286400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cebral, Juan R</creatorcontrib><creatorcontrib>Castro, Marcelo A</creatorcontrib><creatorcontrib>Burgess, James E</creatorcontrib><creatorcontrib>Pergolizzi, Richard S</creatorcontrib><creatorcontrib>Sheridan, Michael J</creatorcontrib><creatorcontrib>Putman, Christopher M</creatorcontrib><title>Characterization of Cerebral Aneurysms for Assessing Risk of Rupture By Using Patient-Specific Computational Hemodynamics Models</title><title>American Journal of Neuroradiology</title><addtitle>AJNR Am J Neuroradiol</addtitle><description>Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. This report describes a pilot clinical study of the association between intra-aneurysmal hemodynamic characteristics from computational fluid dynamic models and the rupture of cerebral aneurysms. A total of 62 patient-specific models of cerebral aneurysms were constructed from 3D angiography images. Computational fluid dynamics simulations were performed under pulsatile flow conditions measured on a normal subject. The aneurysms were classified into different categories, depending on the complexity and stability of the flow pattern, the location and size of the flow impingement region, and the size of the inflow jet. The 62 models consisted of 25 ruptured and 34 unruptured aneurysms and 3 cases with unknown histories of hemorrhage. The hemodynamic features were analyzed for associations with history of rupture. A large variety of flow patterns was observed: 72% of ruptured aneurysms had complex or unstable flow patterns, 80% had small impingement regions, and 76% had small jet sizes. By contrast, unruptured aneurysms accounted for 73%, 82%, and 75% of aneurysms with simple stable flow patterns, large impingement regions, and large jet sizes, respectively. Aneurysms with small impingement sizes were 6.3 times more likely to have experienced rupture than those with large impingement sizes (P = .01). Image-based patient-specific numeric models can be constructed in an efficient manner that allows clinical studies of intra-aneurysmal hemodynamics. A simple flow characterization system was proposed, and interesting trends in the association between hemodynamic features and aneurysmal rupture were found. Simple stable patterns, large impingement regions, and jet sizes were more commonly seen with unruptured aneurysms. By contrast, ruptured aneurysms were more likely to have disturbed flow patterns, small impingement regions, and narrow jets.</description><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aneurysm, Ruptured - classification</subject><subject>Aneurysm, Ruptured - physiopathology</subject><subject>Biological and medical sciences</subject><subject>Carotid Artery, Internal - diagnostic imaging</subject><subject>Carotid Artery, Internal - physiology</subject><subject>Cerebral Angiography</subject><subject>Cerebrovascular Circulation - physiology</subject><subject>Female</subject><subject>Hemodynamics - physiology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Image Processing, Computer-Assisted</subject><subject>Imaging, Three-Dimensional</subject><subject>Infectious diseases</subject><subject>Interventional</subject><subject>Intracranial Aneurysm - classification</subject><subject>Intracranial Aneurysm - physiopathology</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Middle Cerebral Artery - diagnostic imaging</subject><subject>Middle Cerebral Artery - physiology</subject><subject>Miscellaneous</subject><subject>Mood disorders</subject><subject>Nervous system</subject><subject>Pilot Projects</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Radiodiagnosis. Nmr imagery. Nmr spectrometry</subject><subject>Radiographic Image Interpretation, Computer-Assisted</subject><subject>Regional Blood Flow - physiology</subject><subject>Risk Factors</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>0195-6108</issn><issn>1936-959X</issn><issn>1432-1920</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAQhiNERbeFv4B8AU6R7HhtZy5IS1RapCJQoRI3y3EmG0MSBzvpanvip9e0y9eJ08iaR4_e8fsoWzHgMgcBXx5nK8pA5JLR8jg7ifErpVSAKp5kx0wWpVxTusp-VJ0Jxs4Y3K2ZnR-Jb0mFAetgerIZcQn7OETS-kA2MWKMbtySKxe__QSvlmleApI3e3J9v_iYHDjO-acJrWudJZUfpmW-NyffBQ6-2Y9mcDaS977BPj7NjlrTR3x2mKfZ9duzz9VFfvnh_F21ucw7LtScF7WyEg2ymnMwEuqGr3lbt9Ck95qDEtgaoGCVMgxqDgxry8AKKwSlas1Ps9cP3mmpB2xsSpku1FNwgwl77Y3T_25G1-mtv9EKlGRKJsHLgyD47wvGWQ8uWux7M6JfopZlIgXw_4KpobJMPSTw-d-Rfmf51U4CXhwAE63p22BG6-IfThXAoWSJe_XAdW7b7VxAHQfT90nL9G63K6RmVBfpI_gdAjqqnQ</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>Cebral, Juan R</creator><creator>Castro, Marcelo A</creator><creator>Burgess, James E</creator><creator>Pergolizzi, Richard S</creator><creator>Sheridan, Michael J</creator><creator>Putman, Christopher M</creator><general>Am Soc Neuroradiology</general><general>American Society of Neuroradiology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20051101</creationdate><title>Characterization of Cerebral Aneurysms for Assessing Risk of Rupture By Using Patient-Specific Computational Hemodynamics Models</title><author>Cebral, Juan R ; Castro, Marcelo A ; Burgess, James E ; Pergolizzi, Richard S ; Sheridan, Michael J ; Putman, Christopher M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h357t-2b7c6eae1b339a69bd343fbf9d33943975efa909c77a19b391ebc19c5c5500743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aneurysm, Ruptured - classification</topic><topic>Aneurysm, Ruptured - physiopathology</topic><topic>Biological and medical sciences</topic><topic>Carotid Artery, Internal - diagnostic imaging</topic><topic>Carotid Artery, Internal - physiology</topic><topic>Cerebral Angiography</topic><topic>Cerebrovascular Circulation - physiology</topic><topic>Female</topic><topic>Hemodynamics - physiology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Image Processing, Computer-Assisted</topic><topic>Imaging, Three-Dimensional</topic><topic>Infectious diseases</topic><topic>Interventional</topic><topic>Intracranial Aneurysm - classification</topic><topic>Intracranial Aneurysm - physiopathology</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Middle Cerebral Artery - diagnostic imaging</topic><topic>Middle Cerebral Artery - physiology</topic><topic>Miscellaneous</topic><topic>Mood disorders</topic><topic>Nervous system</topic><topic>Pilot Projects</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Radiodiagnosis. Nmr imagery. Nmr spectrometry</topic><topic>Radiographic Image Interpretation, Computer-Assisted</topic><topic>Regional Blood Flow - physiology</topic><topic>Risk Factors</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cebral, Juan R</creatorcontrib><creatorcontrib>Castro, Marcelo A</creatorcontrib><creatorcontrib>Burgess, James E</creatorcontrib><creatorcontrib>Pergolizzi, Richard S</creatorcontrib><creatorcontrib>Sheridan, Michael J</creatorcontrib><creatorcontrib>Putman, Christopher M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American Journal of Neuroradiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cebral, Juan R</au><au>Castro, Marcelo A</au><au>Burgess, James E</au><au>Pergolizzi, Richard S</au><au>Sheridan, Michael J</au><au>Putman, Christopher M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of Cerebral Aneurysms for Assessing Risk of Rupture By Using Patient-Specific Computational Hemodynamics Models</atitle><jtitle>American Journal of Neuroradiology</jtitle><addtitle>AJNR Am J Neuroradiol</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>26</volume><issue>10</issue><spage>2550</spage><epage>2559</epage><pages>2550-2559</pages><issn>0195-6108</issn><eissn>1936-959X</eissn><eissn>1432-1920</eissn><coden>AAJNDL</coden><abstract>Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. This report describes a pilot clinical study of the association between intra-aneurysmal hemodynamic characteristics from computational fluid dynamic models and the rupture of cerebral aneurysms. A total of 62 patient-specific models of cerebral aneurysms were constructed from 3D angiography images. Computational fluid dynamics simulations were performed under pulsatile flow conditions measured on a normal subject. The aneurysms were classified into different categories, depending on the complexity and stability of the flow pattern, the location and size of the flow impingement region, and the size of the inflow jet. The 62 models consisted of 25 ruptured and 34 unruptured aneurysms and 3 cases with unknown histories of hemorrhage. The hemodynamic features were analyzed for associations with history of rupture. A large variety of flow patterns was observed: 72% of ruptured aneurysms had complex or unstable flow patterns, 80% had small impingement regions, and 76% had small jet sizes. By contrast, unruptured aneurysms accounted for 73%, 82%, and 75% of aneurysms with simple stable flow patterns, large impingement regions, and large jet sizes, respectively. Aneurysms with small impingement sizes were 6.3 times more likely to have experienced rupture than those with large impingement sizes (P = .01). Image-based patient-specific numeric models can be constructed in an efficient manner that allows clinical studies of intra-aneurysmal hemodynamics. A simple flow characterization system was proposed, and interesting trends in the association between hemodynamic features and aneurysmal rupture were found. Simple stable patterns, large impingement regions, and jet sizes were more commonly seen with unruptured aneurysms. By contrast, ruptured aneurysms were more likely to have disturbed flow patterns, small impingement regions, and narrow jets.</abstract><cop>Oak Brook, IL</cop><pub>Am Soc Neuroradiology</pub><pmid>16286400</pmid><tpages>10</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0195-6108
ispartof American Journal of Neuroradiology, 2005-11, Vol.26 (10), p.2550-2559
issn 0195-6108
1936-959X
1432-1920
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7976176
source Open Access: PubMed Central; Springer Nature
subjects Adult
Adult and adolescent clinical studies
Aged
Aged, 80 and over
Aneurysm, Ruptured - classification
Aneurysm, Ruptured - physiopathology
Biological and medical sciences
Carotid Artery, Internal - diagnostic imaging
Carotid Artery, Internal - physiology
Cerebral Angiography
Cerebrovascular Circulation - physiology
Female
Hemodynamics - physiology
Human viral diseases
Humans
Image Processing, Computer-Assisted
Imaging, Three-Dimensional
Infectious diseases
Interventional
Intracranial Aneurysm - classification
Intracranial Aneurysm - physiopathology
Investigative techniques, diagnostic techniques (general aspects)
Logistic Models
Male
Medical sciences
Middle Aged
Middle Cerebral Artery - diagnostic imaging
Middle Cerebral Artery - physiology
Miscellaneous
Mood disorders
Nervous system
Pilot Projects
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Radiodiagnosis. Nmr imagery. Nmr spectrometry
Radiographic Image Interpretation, Computer-Assisted
Regional Blood Flow - physiology
Risk Factors
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
title Characterization of Cerebral Aneurysms for Assessing Risk of Rupture By Using Patient-Specific Computational Hemodynamics Models
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T10%3A01%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Characterization%20of%20Cerebral%20Aneurysms%20for%20Assessing%20Risk%20of%20Rupture%20By%20Using%20Patient-Specific%20Computational%20Hemodynamics%20Models&rft.jtitle=American%20Journal%20of%20Neuroradiology&rft.au=Cebral,%20Juan%20R&rft.date=2005-11-01&rft.volume=26&rft.issue=10&rft.spage=2550&rft.epage=2559&rft.pages=2550-2559&rft.issn=0195-6108&rft.eissn=1936-959X&rft.coden=AAJNDL&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E68797593%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-h357t-2b7c6eae1b339a69bd343fbf9d33943975efa909c77a19b391ebc19c5c5500743%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=19388972&rft_id=info:pmid/16286400&rfr_iscdi=true