Identification of human immunodeficiency virus type 1 non-B subtypes and antiretroviral drug-resistant strains in United States blood donors

BACKGROUND: In this study, human immunodeficiency virus type 1 (HIV‐1)‐infected blood donors were evaluated for genetic subtype and drug resistance to determine the prevalence of divergent HIV strains in the US donor population. STUDY DESIGN AND METHODS: Subtype was determined by phylogenetic analys...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Transfusion (Philadelphia, Pa.) Pa.), 2009-01, Vol.49 (1), p.125-133
Hauptverfasser: Brennan, Catherine A., Stramer, Susan L., Holzmayer, Vera, Yamaguchi, Julie, Foster, Greg A., Notari IV, Edward P., Schochetman, Gerald, Devare, Sushil G.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 133
container_issue 1
container_start_page 125
container_title Transfusion (Philadelphia, Pa.)
container_volume 49
creator Brennan, Catherine A.
Stramer, Susan L.
Holzmayer, Vera
Yamaguchi, Julie
Foster, Greg A.
Notari IV, Edward P.
Schochetman, Gerald
Devare, Sushil G.
description BACKGROUND: In this study, human immunodeficiency virus type 1 (HIV‐1)‐infected blood donors were evaluated for genetic subtype and drug resistance to determine the prevalence of divergent HIV strains in the US donor population. STUDY DESIGN AND METHODS: Subtype was determined by phylogenetic analysis of viral sequences amplified by reverse transcription‐polymerase chain reaction. The drug resistance profile of the protease and reverse transcriptase (RT) genes was determined using an HIV‐1 genotyping system (ViroSeq). RESULTS: From 1999 through 2005, 26 recently infected donors, defined as HIV‐1 RNA–positive, antibody‐negative (RNA+/Ab−), were identified (yield, 1:1.61 million). Over the same period, the frequency of anti‐HIV–positive donors was 1:34,700. Twenty RNA+/Ab− specimens were evaluated; all were infected with HIV‐1 subtype B. Drug resistance profiles obtained for 18 donors identified one strain with protease mutation L90M that confers resistance to nelfinavir and one with RT mutation Y188H that confers resistance to nevirapine. Genetic subtype was determined for 44 of 46 HIV antibody–reactive and confirmed‐positive (Ab+) specimens. Three infections (6.8%) were due to circulating recombinant forms: 2 CRF01_AE and 1 CRF02_AG. In the Ab+ group, one strain was resistant to all nucleoside RT inhibitors and one had mutations that confer resistance to protease inhibitors. CONCLUSION: The data show that antiretroviral drug–resistant HIV strains are being transmitted in the United States. Overall 6.5 percent (4 of 62) of HIV‐1–infected donors harbored drug‐resistant strains. HIV‐1 non‐B strains accounted for 4.7 percent (3 of 64) of the infections in donors. HIV‐1 subtype B is still the predominant strain in the United States; however, non‐B strains are increasing.
doi_str_mv 10.1111/j.1537-2995.2008.01935.x
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66814036</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66814036</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4865-b4663d2c7f84ce53909e26c48b721ef1fbc6df56e3b5e4357021ed10673151843</originalsourceid><addsrcrecordid>eNqNkcuO0zAUhi0EYsrAKyBvYJdgx5ckGySomGGkUZHmIthZTnwCLondsR1o34GHxp1WZYsly5fznd_W_yOEKSlpHu_WJRWsLqq2FWVFSFMS2jJRbp-gxanwFC0I4bSglFVn6EWMa0JI1RL6HJ3RphWcE75Af64MuGQH2-tkvcN-wD_mSTtsp2l23kCuWHD9Dv-yYY447TaAKXbeFR9xnLv9OWLtTJ7JBkjBZ1CP2IT5exEg2phyBccUtHURW4fvnU1g8G3SKbd2o_cGG-98iC_Rs0GPEV4d13N0f_Hpbvm5uP5yebX8cF30vJGi6LiUzFR9PTS8B8Fa0kIlc62rKwoDHbpemkFIYJ0AzkRN8rWhRNaMCtpwdo7eHnQ3wT_MEJOabOxhHLUDP0clZUM5YTKDzQHsg48xwKA2wU467BQlap-EWqu94WpvuNonoR6TUNvc-vr4xtxNYP41Hq3PwJsjoGOvxyFo19t44iqa05I1zdz7A_fbjrD77w-ou5uLx20WKA4COQrYngR0-KmyI7VQX1eXiq1uxepmydU39hfT1bYV</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66814036</pqid></control><display><type>article</type><title>Identification of human immunodeficiency virus type 1 non-B subtypes and antiretroviral drug-resistant strains in United States blood donors</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Brennan, Catherine A. ; Stramer, Susan L. ; Holzmayer, Vera ; Yamaguchi, Julie ; Foster, Greg A. ; Notari IV, Edward P. ; Schochetman, Gerald ; Devare, Sushil G.</creator><creatorcontrib>Brennan, Catherine A. ; Stramer, Susan L. ; Holzmayer, Vera ; Yamaguchi, Julie ; Foster, Greg A. ; Notari IV, Edward P. ; Schochetman, Gerald ; Devare, Sushil G.</creatorcontrib><description>BACKGROUND: In this study, human immunodeficiency virus type 1 (HIV‐1)‐infected blood donors were evaluated for genetic subtype and drug resistance to determine the prevalence of divergent HIV strains in the US donor population. STUDY DESIGN AND METHODS: Subtype was determined by phylogenetic analysis of viral sequences amplified by reverse transcription‐polymerase chain reaction. The drug resistance profile of the protease and reverse transcriptase (RT) genes was determined using an HIV‐1 genotyping system (ViroSeq). RESULTS: From 1999 through 2005, 26 recently infected donors, defined as HIV‐1 RNA–positive, antibody‐negative (RNA+/Ab−), were identified (yield, 1:1.61 million). Over the same period, the frequency of anti‐HIV–positive donors was 1:34,700. Twenty RNA+/Ab− specimens were evaluated; all were infected with HIV‐1 subtype B. Drug resistance profiles obtained for 18 donors identified one strain with protease mutation L90M that confers resistance to nelfinavir and one with RT mutation Y188H that confers resistance to nevirapine. Genetic subtype was determined for 44 of 46 HIV antibody–reactive and confirmed‐positive (Ab+) specimens. Three infections (6.8%) were due to circulating recombinant forms: 2 CRF01_AE and 1 CRF02_AG. In the Ab+ group, one strain was resistant to all nucleoside RT inhibitors and one had mutations that confer resistance to protease inhibitors. CONCLUSION: The data show that antiretroviral drug–resistant HIV strains are being transmitted in the United States. Overall 6.5 percent (4 of 62) of HIV‐1–infected donors harbored drug‐resistant strains. HIV‐1 non‐B strains accounted for 4.7 percent (3 of 64) of the infections in donors. HIV‐1 subtype B is still the predominant strain in the United States; however, non‐B strains are increasing.</description><identifier>ISSN: 0041-1132</identifier><identifier>EISSN: 1537-2995</identifier><identifier>DOI: 10.1111/j.1537-2995.2008.01935.x</identifier><identifier>PMID: 18954404</identifier><identifier>CODEN: TRANAT</identifier><language>eng</language><publisher>Malden, USA: Blackwell Publishing Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Anti-Retroviral Agents ; Base Sequence ; Biological and medical sciences ; Blood Donors ; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis ; Drug Resistance, Viral - genetics ; Female ; HIV Infections - blood ; HIV Infections - epidemiology ; HIV Infections - genetics ; HIV-1 - genetics ; Human viral diseases ; Humans ; Infectious diseases ; Male ; Medical sciences ; Miscellaneous ; Molecular Sequence Data ; Mutation ; Red Cross ; Retrospective Studies ; RNA, Viral - blood ; RNA, Viral - genetics ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; United States ; Viral diseases</subject><ispartof>Transfusion (Philadelphia, Pa.), 2009-01, Vol.49 (1), p.125-133</ispartof><rights>2008 American Association of Blood Banks</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4865-b4663d2c7f84ce53909e26c48b721ef1fbc6df56e3b5e4357021ed10673151843</citedby><cites>FETCH-LOGICAL-c4865-b4663d2c7f84ce53909e26c48b721ef1fbc6df56e3b5e4357021ed10673151843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1537-2995.2008.01935.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1537-2995.2008.01935.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,4025,27927,27928,27929,45578,45579</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=21002671$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18954404$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brennan, Catherine A.</creatorcontrib><creatorcontrib>Stramer, Susan L.</creatorcontrib><creatorcontrib>Holzmayer, Vera</creatorcontrib><creatorcontrib>Yamaguchi, Julie</creatorcontrib><creatorcontrib>Foster, Greg A.</creatorcontrib><creatorcontrib>Notari IV, Edward P.</creatorcontrib><creatorcontrib>Schochetman, Gerald</creatorcontrib><creatorcontrib>Devare, Sushil G.</creatorcontrib><title>Identification of human immunodeficiency virus type 1 non-B subtypes and antiretroviral drug-resistant strains in United States blood donors</title><title>Transfusion (Philadelphia, Pa.)</title><addtitle>Transfusion</addtitle><description>BACKGROUND: In this study, human immunodeficiency virus type 1 (HIV‐1)‐infected blood donors were evaluated for genetic subtype and drug resistance to determine the prevalence of divergent HIV strains in the US donor population. STUDY DESIGN AND METHODS: Subtype was determined by phylogenetic analysis of viral sequences amplified by reverse transcription‐polymerase chain reaction. The drug resistance profile of the protease and reverse transcriptase (RT) genes was determined using an HIV‐1 genotyping system (ViroSeq). RESULTS: From 1999 through 2005, 26 recently infected donors, defined as HIV‐1 RNA–positive, antibody‐negative (RNA+/Ab−), were identified (yield, 1:1.61 million). Over the same period, the frequency of anti‐HIV–positive donors was 1:34,700. Twenty RNA+/Ab− specimens were evaluated; all were infected with HIV‐1 subtype B. Drug resistance profiles obtained for 18 donors identified one strain with protease mutation L90M that confers resistance to nelfinavir and one with RT mutation Y188H that confers resistance to nevirapine. Genetic subtype was determined for 44 of 46 HIV antibody–reactive and confirmed‐positive (Ab+) specimens. Three infections (6.8%) were due to circulating recombinant forms: 2 CRF01_AE and 1 CRF02_AG. In the Ab+ group, one strain was resistant to all nucleoside RT inhibitors and one had mutations that confer resistance to protease inhibitors. CONCLUSION: The data show that antiretroviral drug–resistant HIV strains are being transmitted in the United States. Overall 6.5 percent (4 of 62) of HIV‐1–infected donors harbored drug‐resistant strains. HIV‐1 non‐B strains accounted for 4.7 percent (3 of 64) of the infections in donors. HIV‐1 subtype B is still the predominant strain in the United States; however, non‐B strains are increasing.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Anti-Retroviral Agents</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blood Donors</subject><subject>Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis</subject><subject>Drug Resistance, Viral - genetics</subject><subject>Female</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - epidemiology</subject><subject>HIV Infections - genetics</subject><subject>HIV-1 - genetics</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Red Cross</subject><subject>Retrospective Studies</subject><subject>RNA, Viral - blood</subject><subject>RNA, Viral - genetics</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>United States</subject><subject>Viral diseases</subject><issn>0041-1132</issn><issn>1537-2995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcuO0zAUhi0EYsrAKyBvYJdgx5ckGySomGGkUZHmIthZTnwCLondsR1o34GHxp1WZYsly5fznd_W_yOEKSlpHu_WJRWsLqq2FWVFSFMS2jJRbp-gxanwFC0I4bSglFVn6EWMa0JI1RL6HJ3RphWcE75Af64MuGQH2-tkvcN-wD_mSTtsp2l23kCuWHD9Dv-yYY447TaAKXbeFR9xnLv9OWLtTJ7JBkjBZ1CP2IT5exEg2phyBccUtHURW4fvnU1g8G3SKbd2o_cGG-98iC_Rs0GPEV4d13N0f_Hpbvm5uP5yebX8cF30vJGi6LiUzFR9PTS8B8Fa0kIlc62rKwoDHbpemkFIYJ0AzkRN8rWhRNaMCtpwdo7eHnQ3wT_MEJOabOxhHLUDP0clZUM5YTKDzQHsg48xwKA2wU467BQlap-EWqu94WpvuNonoR6TUNvc-vr4xtxNYP41Hq3PwJsjoGOvxyFo19t44iqa05I1zdz7A_fbjrD77w-ou5uLx20WKA4COQrYngR0-KmyI7VQX1eXiq1uxepmydU39hfT1bYV</recordid><startdate>200901</startdate><enddate>200901</enddate><creator>Brennan, Catherine A.</creator><creator>Stramer, Susan L.</creator><creator>Holzmayer, Vera</creator><creator>Yamaguchi, Julie</creator><creator>Foster, Greg A.</creator><creator>Notari IV, Edward P.</creator><creator>Schochetman, Gerald</creator><creator>Devare, Sushil G.</creator><general>Blackwell Publishing Inc</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200901</creationdate><title>Identification of human immunodeficiency virus type 1 non-B subtypes and antiretroviral drug-resistant strains in United States blood donors</title><author>Brennan, Catherine A. ; Stramer, Susan L. ; Holzmayer, Vera ; Yamaguchi, Julie ; Foster, Greg A. ; Notari IV, Edward P. ; Schochetman, Gerald ; Devare, Sushil G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4865-b4663d2c7f84ce53909e26c48b721ef1fbc6df56e3b5e4357021ed10673151843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Anti-Retroviral Agents</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blood Donors</topic><topic>Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis</topic><topic>Drug Resistance, Viral - genetics</topic><topic>Female</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - epidemiology</topic><topic>HIV Infections - genetics</topic><topic>HIV-1 - genetics</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Red Cross</topic><topic>Retrospective Studies</topic><topic>RNA, Viral - blood</topic><topic>RNA, Viral - genetics</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>United States</topic><topic>Viral diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brennan, Catherine A.</creatorcontrib><creatorcontrib>Stramer, Susan L.</creatorcontrib><creatorcontrib>Holzmayer, Vera</creatorcontrib><creatorcontrib>Yamaguchi, Julie</creatorcontrib><creatorcontrib>Foster, Greg A.</creatorcontrib><creatorcontrib>Notari IV, Edward P.</creatorcontrib><creatorcontrib>Schochetman, Gerald</creatorcontrib><creatorcontrib>Devare, Sushil G.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Transfusion (Philadelphia, Pa.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brennan, Catherine A.</au><au>Stramer, Susan L.</au><au>Holzmayer, Vera</au><au>Yamaguchi, Julie</au><au>Foster, Greg A.</au><au>Notari IV, Edward P.</au><au>Schochetman, Gerald</au><au>Devare, Sushil G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of human immunodeficiency virus type 1 non-B subtypes and antiretroviral drug-resistant strains in United States blood donors</atitle><jtitle>Transfusion (Philadelphia, Pa.)</jtitle><addtitle>Transfusion</addtitle><date>2009-01</date><risdate>2009</risdate><volume>49</volume><issue>1</issue><spage>125</spage><epage>133</epage><pages>125-133</pages><issn>0041-1132</issn><eissn>1537-2995</eissn><coden>TRANAT</coden><abstract>BACKGROUND: In this study, human immunodeficiency virus type 1 (HIV‐1)‐infected blood donors were evaluated for genetic subtype and drug resistance to determine the prevalence of divergent HIV strains in the US donor population. STUDY DESIGN AND METHODS: Subtype was determined by phylogenetic analysis of viral sequences amplified by reverse transcription‐polymerase chain reaction. The drug resistance profile of the protease and reverse transcriptase (RT) genes was determined using an HIV‐1 genotyping system (ViroSeq). RESULTS: From 1999 through 2005, 26 recently infected donors, defined as HIV‐1 RNA–positive, antibody‐negative (RNA+/Ab−), were identified (yield, 1:1.61 million). Over the same period, the frequency of anti‐HIV–positive donors was 1:34,700. Twenty RNA+/Ab− specimens were evaluated; all were infected with HIV‐1 subtype B. Drug resistance profiles obtained for 18 donors identified one strain with protease mutation L90M that confers resistance to nelfinavir and one with RT mutation Y188H that confers resistance to nevirapine. Genetic subtype was determined for 44 of 46 HIV antibody–reactive and confirmed‐positive (Ab+) specimens. Three infections (6.8%) were due to circulating recombinant forms: 2 CRF01_AE and 1 CRF02_AG. In the Ab+ group, one strain was resistant to all nucleoside RT inhibitors and one had mutations that confer resistance to protease inhibitors. CONCLUSION: The data show that antiretroviral drug–resistant HIV strains are being transmitted in the United States. Overall 6.5 percent (4 of 62) of HIV‐1–infected donors harbored drug‐resistant strains. HIV‐1 non‐B strains accounted for 4.7 percent (3 of 64) of the infections in donors. HIV‐1 subtype B is still the predominant strain in the United States; however, non‐B strains are increasing.</abstract><cop>Malden, USA</cop><pub>Blackwell Publishing Inc</pub><pmid>18954404</pmid><doi>10.1111/j.1537-2995.2008.01935.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0041-1132
ispartof Transfusion (Philadelphia, Pa.), 2009-01, Vol.49 (1), p.125-133
issn 0041-1132
1537-2995
language eng
recordid cdi_proquest_miscellaneous_66814036
source MEDLINE; Access via Wiley Online Library
subjects Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Anti-Retroviral Agents
Base Sequence
Biological and medical sciences
Blood Donors
Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis
Drug Resistance, Viral - genetics
Female
HIV Infections - blood
HIV Infections - epidemiology
HIV Infections - genetics
HIV-1 - genetics
Human viral diseases
Humans
Infectious diseases
Male
Medical sciences
Miscellaneous
Molecular Sequence Data
Mutation
Red Cross
Retrospective Studies
RNA, Viral - blood
RNA, Viral - genetics
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
United States
Viral diseases
title Identification of human immunodeficiency virus type 1 non-B subtypes and antiretroviral drug-resistant strains in United States blood donors
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T10%3A07%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Identification%20of%20human%20immunodeficiency%20virus%20type%201%20non-B%20subtypes%20and%20antiretroviral%20drug-resistant%20strains%20in%20United%20States%20blood%20donors&rft.jtitle=Transfusion%20(Philadelphia,%20Pa.)&rft.au=Brennan,%20Catherine%20A.&rft.date=2009-01&rft.volume=49&rft.issue=1&rft.spage=125&rft.epage=133&rft.pages=125-133&rft.issn=0041-1132&rft.eissn=1537-2995&rft.coden=TRANAT&rft_id=info:doi/10.1111/j.1537-2995.2008.01935.x&rft_dat=%3Cproquest_cross%3E66814036%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=66814036&rft_id=info:pmid/18954404&rfr_iscdi=true