Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia

Background:  Time‐frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated ma...

Full description

Saved in:
Bibliographic Details
Published in:Acta anaesthesiologica Scandinavica 2004-02, Vol.48 (2), p.145-153
Main Authors: Vakkuri, A., Yli-Hankala, A., Talja, P., Mustola, S., Tolvanen-Laakso, H., Sampson, T., Viertiö-Oja, H.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Anesthesia
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Anesthetics - pharmacology
Biological and medical sciences
desflurane
Electroencephalography - drug effects
Electromyography - drug effects
Entropy
general anesthesia
Humans
Medical sciences
Methyl Ethers - pharmacology
Middle Aged
propofol
Propofol - pharmacology
Sensitivity and Specificity
Sevoflurane
thiopental
Thiopental - pharmacology
Time Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c4983-5daad5682ea778dec417f4a5e96c204c7d61a54208a86a903f2306a132e8e4193
cites cdi_FETCH-LOGICAL-c4983-5daad5682ea778dec417f4a5e96c204c7d61a54208a86a903f2306a132e8e4193
container_end_page 153
container_issue 2
container_start_page 145
container_title Acta anaesthesiologica Scandinavica
container_volume 48
creator Vakkuri, A.
Yli-Hankala, A.
Talja, P.
Mustola, S.
Tolvanen-Laakso, H.
Sampson, T.
Viertiö-Oja, H.
description Background:  Time‐frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. Methods:  Response entropy, SE [S/5™ Entropy Module, M‐ENTROPY (later in text: Entropy), Datex‐Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A‐2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg−1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg−1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. Results:  Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 ± 22%, 75 ± 26%, and 59 ± 18% (mean ± SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86±21%, 88 ± 13%, and 63 ± 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P 
doi_str_mv 10.1111/j.0001-5172.2004.00323.x
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71699959</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71699959</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4983-5daad5682ea778dec417f4a5e96c204c7d61a54208a86a903f2306a132e8e4193</originalsourceid><addsrcrecordid>eNqNkd1uEzEQhS0EoiHwCsg3cNUN_tn1riVuoghSRFWQKELixnK949Zh_2rvluRx-qZMmqi9xTfjkc43Hp9DCOVswfF82CwYYzwreCkWgrEcWynkYvuMzLjUOlNFqZ6T2aPohLxKaYOtzLV-SU44lkLLYkbuL0MLmY9wO0HndvTKNrZzUNM0gBujbSh0Y-yHHbWJWtqCTVME2ntqO0jjDYzB0TpO1xS8R4KGjro9gmQH8a6fEk27NEJL6ymG7pomuOt9M0XkT-mAo3vfN6c4rqbjTegHhJE9Tk_BviYvvG0SvDnWOfn5-dPl6iw7_7b-slqeZy7XlcyK2tq6UJUAW5ZVDS7npc9tAVo5wXJX1orbIhesspWymkkvJFOWSwEV5FzLOXl_mIs7oRlpNG1IDhr0A_AXpuRKP7g2J9VB6GKfUgRvhhhaG3eGM7OPx2zM3nmzd97s4zEP8Zgtom-Pb0xXLdRP4DEPFLw7CmxytvHokgvpSVdUWuSVQN3Hg-5vaGD33wuY5fIHXhDPDnjAZLaPuI1_jCplWZhfF2ujfl-sV0J9Nd_lP4a9vYc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71699959</pqid></control><display><type>article</type><title>Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia</title><source>Wiley-Blackwell Read &amp; Publish Collection</source><creator>Vakkuri, A. ; Yli-Hankala, A. ; Talja, P. ; Mustola, S. ; Tolvanen-Laakso, H. ; Sampson, T. ; Viertiö-Oja, H.</creator><creatorcontrib>Vakkuri, A. ; Yli-Hankala, A. ; Talja, P. ; Mustola, S. ; Tolvanen-Laakso, H. ; Sampson, T. ; Viertiö-Oja, H.</creatorcontrib><description>Background:  Time‐frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. Methods:  Response entropy, SE [S/5™ Entropy Module, M‐ENTROPY (later in text: Entropy), Datex‐Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A‐2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg−1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg−1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. Results:  Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 ± 22%, 75 ± 26%, and 59 ± 18% (mean ± SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86±21%, 88 ± 13%, and 63 ± 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P &lt; 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. Conclusions:  All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.</description><identifier>ISSN: 0001-5172</identifier><identifier>EISSN: 1399-6576</identifier><identifier>DOI: 10.1111/j.0001-5172.2004.00323.x</identifier><identifier>PMID: 14995935</identifier><identifier>CODEN: AANEAB</identifier><language>eng</language><publisher>Oxford, UK; Malden , USA: Munksgaard International Publishers</publisher><subject>Adolescent ; Adult ; Aged ; Anesthesia ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Anesthetics - pharmacology ; Biological and medical sciences ; desflurane ; Electroencephalography - drug effects ; Electromyography - drug effects ; Entropy ; general anesthesia ; Humans ; Medical sciences ; Methyl Ethers - pharmacology ; Middle Aged ; propofol ; Propofol - pharmacology ; Sensitivity and Specificity ; Sevoflurane ; thiopental ; Thiopental - pharmacology ; Time Factors</subject><ispartof>Acta anaesthesiologica Scandinavica, 2004-02, Vol.48 (2), p.145-153</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4983-5daad5682ea778dec417f4a5e96c204c7d61a54208a86a903f2306a132e8e4193</citedby><cites>FETCH-LOGICAL-c4983-5daad5682ea778dec417f4a5e96c204c7d61a54208a86a903f2306a132e8e4193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=15892482$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14995935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vakkuri, A.</creatorcontrib><creatorcontrib>Yli-Hankala, A.</creatorcontrib><creatorcontrib>Talja, P.</creatorcontrib><creatorcontrib>Mustola, S.</creatorcontrib><creatorcontrib>Tolvanen-Laakso, H.</creatorcontrib><creatorcontrib>Sampson, T.</creatorcontrib><creatorcontrib>Viertiö-Oja, H.</creatorcontrib><title>Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia</title><title>Acta anaesthesiologica Scandinavica</title><addtitle>Acta Anaesthesiol Scand</addtitle><description>Background:  Time‐frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. Methods:  Response entropy, SE [S/5™ Entropy Module, M‐ENTROPY (later in text: Entropy), Datex‐Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A‐2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg−1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg−1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. Results:  Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 ± 22%, 75 ± 26%, and 59 ± 18% (mean ± SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86±21%, 88 ± 13%, and 63 ± 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P &lt; 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. Conclusions:  All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Anesthesia</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Anesthetics - pharmacology</subject><subject>Biological and medical sciences</subject><subject>desflurane</subject><subject>Electroencephalography - drug effects</subject><subject>Electromyography - drug effects</subject><subject>Entropy</subject><subject>general anesthesia</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Methyl Ethers - pharmacology</subject><subject>Middle Aged</subject><subject>propofol</subject><subject>Propofol - pharmacology</subject><subject>Sensitivity and Specificity</subject><subject>Sevoflurane</subject><subject>thiopental</subject><subject>Thiopental - pharmacology</subject><subject>Time Factors</subject><issn>0001-5172</issn><issn>1399-6576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqNkd1uEzEQhS0EoiHwCsg3cNUN_tn1riVuoghSRFWQKELixnK949Zh_2rvluRx-qZMmqi9xTfjkc43Hp9DCOVswfF82CwYYzwreCkWgrEcWynkYvuMzLjUOlNFqZ6T2aPohLxKaYOtzLV-SU44lkLLYkbuL0MLmY9wO0HndvTKNrZzUNM0gBujbSh0Y-yHHbWJWtqCTVME2ntqO0jjDYzB0TpO1xS8R4KGjro9gmQH8a6fEk27NEJL6ymG7pomuOt9M0XkT-mAo3vfN6c4rqbjTegHhJE9Tk_BviYvvG0SvDnWOfn5-dPl6iw7_7b-slqeZy7XlcyK2tq6UJUAW5ZVDS7npc9tAVo5wXJX1orbIhesspWymkkvJFOWSwEV5FzLOXl_mIs7oRlpNG1IDhr0A_AXpuRKP7g2J9VB6GKfUgRvhhhaG3eGM7OPx2zM3nmzd97s4zEP8Zgtom-Pb0xXLdRP4DEPFLw7CmxytvHokgvpSVdUWuSVQN3Hg-5vaGD33wuY5fIHXhDPDnjAZLaPuI1_jCplWZhfF2ujfl-sV0J9Nd_lP4a9vYc</recordid><startdate>200402</startdate><enddate>200402</enddate><creator>Vakkuri, A.</creator><creator>Yli-Hankala, A.</creator><creator>Talja, P.</creator><creator>Mustola, S.</creator><creator>Tolvanen-Laakso, H.</creator><creator>Sampson, T.</creator><creator>Viertiö-Oja, H.</creator><general>Munksgaard International Publishers</general><general>Blackwell</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>200402</creationdate><title>Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia</title><author>Vakkuri, A. ; Yli-Hankala, A. ; Talja, P. ; Mustola, S. ; Tolvanen-Laakso, H. ; Sampson, T. ; Viertiö-Oja, H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4983-5daad5682ea778dec417f4a5e96c204c7d61a54208a86a903f2306a132e8e4193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Anesthesia</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Anesthetics - pharmacology</topic><topic>Biological and medical sciences</topic><topic>desflurane</topic><topic>Electroencephalography - drug effects</topic><topic>Electromyography - drug effects</topic><topic>Entropy</topic><topic>general anesthesia</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Methyl Ethers - pharmacology</topic><topic>Middle Aged</topic><topic>propofol</topic><topic>Propofol - pharmacology</topic><topic>Sensitivity and Specificity</topic><topic>Sevoflurane</topic><topic>thiopental</topic><topic>Thiopental - pharmacology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vakkuri, A.</creatorcontrib><creatorcontrib>Yli-Hankala, A.</creatorcontrib><creatorcontrib>Talja, P.</creatorcontrib><creatorcontrib>Mustola, S.</creatorcontrib><creatorcontrib>Tolvanen-Laakso, H.</creatorcontrib><creatorcontrib>Sampson, T.</creatorcontrib><creatorcontrib>Viertiö-Oja, H.</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>Acta anaesthesiologica Scandinavica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vakkuri, A.</au><au>Yli-Hankala, A.</au><au>Talja, P.</au><au>Mustola, S.</au><au>Tolvanen-Laakso, H.</au><au>Sampson, T.</au><au>Viertiö-Oja, H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia</atitle><jtitle>Acta anaesthesiologica Scandinavica</jtitle><addtitle>Acta Anaesthesiol Scand</addtitle><date>2004-02</date><risdate>2004</risdate><volume>48</volume><issue>2</issue><spage>145</spage><epage>153</epage><pages>145-153</pages><issn>0001-5172</issn><eissn>1399-6576</eissn><coden>AANEAB</coden><abstract>Background:  Time‐frequency balanced spectral entropy of electroencephalogram (EEG) and frontal electromyogram (FEMG) is a novel measure of hypnosis during anesthesia. Two Entropy parameters are described: Response entropy (RE) is calculated from EEG and FEMG; and State Entropy (SE) is calculated mainly from EEG. This study was performed to validate their performance during transition from consciousness to unconsciousness under different anesthetic agents. Methods:  Response entropy, SE [S/5™ Entropy Module, M‐ENTROPY (later in text: Entropy), Datex‐Ohmeda Division, Instrumentarium Corp., Helsinki, Finland] and BIS (BIS XP, A‐2000, Aspect Medical Systems, Newton, MA) data were collected from 70 patients; 30 anesthetized with propofol 2 mg kg−1, 20 with sevoflurane inhalation, and 20 with thiopental 5 mg kg−1. Loss and regaining of consciousness (LOC, ROC) was tested every 10 s, and sensitivity, specificity, and prediction probability (Pk) were calculated. Behavior of the indices was studied. Results:  Sensitivity, specificity, and Pk values for consciousness were high and similar for all indices. During regaining of consciousness after propofol bolus, RE, SE, and BIS values recovered by 81 ± 22%, 75 ± 26%, and 59 ± 18% (mean ± SD), respectively, from the minimum relative to their baseline. After thiopental bolus, RE, SE, and BIS values recovered by 86±21%, 88 ± 13%, and 63 ± 14%, respectively. The relative rise was higher in RE and SE compared with BIS (P &lt; 0.01). During deep levels of hypnosis, RE and SE decreased monotonously as a function of burst suppression ratio, while BIS showed biphasic behavior. On average, RE indicated emergence from anesthesia 11 s earlier than SE, and 12.4 s earlier than BIS. Conclusions:  All indices, RE, SE, and BIS, distinguished excellently between conscious and unconscious states during propofol, sevoflurane, and thiopental anesthesia. During burst suppression, Entropy parameters RE and SE, but not BIS, behave monotonously. During regaining of consciousness after a thiopental or propofol bolus, RE and SE values recovered significantly closer to their baseline values than did BIS. Response entropy indicates emergence from anesthesia earlier than SE or BIS.</abstract><cop>Oxford, UK; Malden , USA</cop><pub>Munksgaard International Publishers</pub><pmid>14995935</pmid><doi>10.1111/j.0001-5172.2004.00323.x</doi><tpages>9</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0001-5172
ispartof Acta anaesthesiologica Scandinavica, 2004-02, Vol.48 (2), p.145-153
issn 0001-5172
1399-6576
language eng
recordid cdi_proquest_miscellaneous_71699959
source Wiley-Blackwell Read & Publish Collection
subjects Adolescent
Adult
Aged
Anesthesia
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Anesthetics - pharmacology
Biological and medical sciences
desflurane
Electroencephalography - drug effects
Electromyography - drug effects
Entropy
general anesthesia
Humans
Medical sciences
Methyl Ethers - pharmacology
Middle Aged
propofol
Propofol - pharmacology
Sensitivity and Specificity
Sevoflurane
thiopental
Thiopental - pharmacology
Time Factors
title Time-frequency balanced spectral entropy as a measure of anesthetic drug effect in central nervous system during sevoflurane, propofol, and thiopental anesthesia
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T21%3A33%3A57IST&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=Time-frequency%20balanced%20spectral%20entropy%20as%20a%20measure%20of%20anesthetic%20drug%20effect%20in%20central%20nervous%20system%20during%20sevoflurane,%20propofol,%20and%20thiopental%20anesthesia&rft.jtitle=Acta%20anaesthesiologica%20Scandinavica&rft.au=Vakkuri,%20A.&rft.date=2004-02&rft.volume=48&rft.issue=2&rft.spage=145&rft.epage=153&rft.pages=145-153&rft.issn=0001-5172&rft.eissn=1399-6576&rft.coden=AANEAB&rft_id=info:doi/10.1111/j.0001-5172.2004.00323.x&rft_dat=%3Cproquest_cross%3E71699959%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4983-5daad5682ea778dec417f4a5e96c204c7d61a54208a86a903f2306a132e8e4193%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=71699959&rft_id=info:pmid/14995935&rfr_iscdi=true