Prognostic value of suPAR and hs-CRP on cardiovascular disease
Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased pre...
Gespeichert in:
| Veröffentlicht in: | Atherosclerosis 2018-04, Vol.271, p.245-251 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 251 |
|---|---|
| container_issue | |
| container_start_page | 245 |
| container_title | Atherosclerosis |
| container_volume | 271 |
| creator | Diederichsen, Marie Zöga Diederichsen, Søren Zöga Mickley, Hans Steffensen, Flemming Hald Lambrechtsen, Jess Sand, Niels Peter Rønnow Christensen, Kent Lodberg Olsen, Michael Hecht Diederichsen, Axel Grønhøj, Mette Hjortdal |
| description | Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score.
A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROCAUC models.
1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01–1.34) and 1.04 (95% CI 1.01–1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45–2.84) and 60-year-old subjects (1.44; 95% CI 1.09–1.90). By ROCAUC, neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32).
Adjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction.
•In adjusted Cox analysis, suPAR and CRP were significantly associated with cardiovascular events.•suPAR was particular promising among women and persons at age 60.•CPR was of importance among persons at age 60.•Neither suPAR nor CRP improved area under the curve in the entire population.•Inflammatory markers may supplement risk stratification after adjustment for CAC. |
| doi_str_mv | 10.1016/j.atherosclerosis.2018.01.029 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1995151403</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021915018300303</els_id><sourcerecordid>1995151403</sourcerecordid><originalsourceid>FETCH-LOGICAL-c389t-82b420daa13263560aa99408ac64825f075f74f101e652f2356f1377c8e3bf4c3</originalsourceid><addsrcrecordid>eNqNkD1v2zAQhokiQeOk_QuFlgJZpN5RlEQNDWAYzQcQoEbQzgRNHWsasuiQkoH8-9KwkyFTlrvlee_jYew7QoGA9Y9Nocc1BR9Nf6guFhxQFoAF8PYTm6Fs2hyFFGdsBsAxb7GCC3YZ4wYARIPyM7vgrQAuQMzYzTL4f4OPozPZXvcTZd5mcVrOnzI9dNk65ounZeaHzOjQOb_X0Uy9DlnnIulIX9i51X2kr6d-xf7e_vqzuM8ff989LOaPuSllO-aSrwSHTmsseV1WNWjdphOkNrWQvLLQVLYRNj1IdcUtT4jFsmmMpHJlhSmv2PVx7i7454niqLYuGup7PZCfosK2rbBCAWVCfx5Rk_TEQFbtgtvq8KIQ1EGh2qh3CtVBoQJUSWHKfzutmlZb6t7Sr84ScHcEKD28dxRUNI4GQ50LZEbVeffBVf8BNtGKZw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1995151403</pqid></control><display><type>article</type><title>Prognostic value of suPAR and hs-CRP on cardiovascular disease</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Diederichsen, Marie Zöga ; Diederichsen, Søren Zöga ; Mickley, Hans ; Steffensen, Flemming Hald ; Lambrechtsen, Jess ; Sand, Niels Peter Rønnow ; Christensen, Kent Lodberg ; Olsen, Michael Hecht ; Diederichsen, Axel ; Grønhøj, Mette Hjortdal</creator><creatorcontrib>Diederichsen, Marie Zöga ; Diederichsen, Søren Zöga ; Mickley, Hans ; Steffensen, Flemming Hald ; Lambrechtsen, Jess ; Sand, Niels Peter Rønnow ; Christensen, Kent Lodberg ; Olsen, Michael Hecht ; Diederichsen, Axel ; Grønhøj, Mette Hjortdal</creatorcontrib><description>Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score.
A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROCAUC models.
1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01–1.34) and 1.04 (95% CI 1.01–1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45–2.84) and 60-year-old subjects (1.44; 95% CI 1.09–1.90). By ROCAUC, neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32).
Adjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction.
•In adjusted Cox analysis, suPAR and CRP were significantly associated with cardiovascular events.•suPAR was particular promising among women and persons at age 60.•CPR was of importance among persons at age 60.•Neither suPAR nor CRP improved area under the curve in the entire population.•Inflammatory markers may supplement risk stratification after adjustment for CAC.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2018.01.029</identifier><identifier>PMID: 29402404</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Atherosclerosis ; Biomarkers - blood ; C-Reactive Protein - analysis ; Cardiovascular disease ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - diagnostic imaging ; Cardiovascular Diseases - epidemiology ; Cardiovascular risk factors ; Computed Tomography Angiography ; Coronary Angiography - methods ; Coronary artery calcification ; Denmark - epidemiology ; Female ; High-sensitive C-reactive-protein ; Humans ; Inflammation Mediators - blood ; Inflammatory markers ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Receptors, Urokinase Plasminogen Activator - blood ; Registries ; Risk Assessment ; Risk Factors ; Soluble urokinase plasminogen activator receptor ; Time Factors</subject><ispartof>Atherosclerosis, 2018-04, Vol.271, p.245-251</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-82b420daa13263560aa99408ac64825f075f74f101e652f2356f1377c8e3bf4c3</citedby><cites>FETCH-LOGICAL-c389t-82b420daa13263560aa99408ac64825f075f74f101e652f2356f1377c8e3bf4c3</cites><orcidid>0000-0003-0252-6631 ; 0000-0002-1285-4826</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.atherosclerosis.2018.01.029$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3541,27915,27916,45986</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29402404$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Diederichsen, Marie Zöga</creatorcontrib><creatorcontrib>Diederichsen, Søren Zöga</creatorcontrib><creatorcontrib>Mickley, Hans</creatorcontrib><creatorcontrib>Steffensen, Flemming Hald</creatorcontrib><creatorcontrib>Lambrechtsen, Jess</creatorcontrib><creatorcontrib>Sand, Niels Peter Rønnow</creatorcontrib><creatorcontrib>Christensen, Kent Lodberg</creatorcontrib><creatorcontrib>Olsen, Michael Hecht</creatorcontrib><creatorcontrib>Diederichsen, Axel</creatorcontrib><creatorcontrib>Grønhøj, Mette Hjortdal</creatorcontrib><title>Prognostic value of suPAR and hs-CRP on cardiovascular disease</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score.
A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROCAUC models.
1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01–1.34) and 1.04 (95% CI 1.01–1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45–2.84) and 60-year-old subjects (1.44; 95% CI 1.09–1.90). By ROCAUC, neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32).
Adjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction.
•In adjusted Cox analysis, suPAR and CRP were significantly associated with cardiovascular events.•suPAR was particular promising among women and persons at age 60.•CPR was of importance among persons at age 60.•Neither suPAR nor CRP improved area under the curve in the entire population.•Inflammatory markers may supplement risk stratification after adjustment for CAC.</description><subject>Atherosclerosis</subject><subject>Biomarkers - blood</subject><subject>C-Reactive Protein - analysis</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - blood</subject><subject>Cardiovascular Diseases - diagnostic imaging</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Cardiovascular risk factors</subject><subject>Computed Tomography Angiography</subject><subject>Coronary Angiography - methods</subject><subject>Coronary artery calcification</subject><subject>Denmark - epidemiology</subject><subject>Female</subject><subject>High-sensitive C-reactive-protein</subject><subject>Humans</subject><subject>Inflammation Mediators - blood</subject><subject>Inflammatory markers</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Receptors, Urokinase Plasminogen Activator - blood</subject><subject>Registries</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Soluble urokinase plasminogen activator receptor</subject><subject>Time Factors</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkD1v2zAQhokiQeOk_QuFlgJZpN5RlEQNDWAYzQcQoEbQzgRNHWsasuiQkoH8-9KwkyFTlrvlee_jYew7QoGA9Y9Nocc1BR9Nf6guFhxQFoAF8PYTm6Fs2hyFFGdsBsAxb7GCC3YZ4wYARIPyM7vgrQAuQMzYzTL4f4OPozPZXvcTZd5mcVrOnzI9dNk65ounZeaHzOjQOb_X0Uy9DlnnIulIX9i51X2kr6d-xf7e_vqzuM8ff989LOaPuSllO-aSrwSHTmsseV1WNWjdphOkNrWQvLLQVLYRNj1IdcUtT4jFsmmMpHJlhSmv2PVx7i7454niqLYuGup7PZCfosK2rbBCAWVCfx5Rk_TEQFbtgtvq8KIQ1EGh2qh3CtVBoQJUSWHKfzutmlZb6t7Sr84ScHcEKD28dxRUNI4GQ50LZEbVeffBVf8BNtGKZw</recordid><startdate>201804</startdate><enddate>201804</enddate><creator>Diederichsen, Marie Zöga</creator><creator>Diederichsen, Søren Zöga</creator><creator>Mickley, Hans</creator><creator>Steffensen, Flemming Hald</creator><creator>Lambrechtsen, Jess</creator><creator>Sand, Niels Peter Rønnow</creator><creator>Christensen, Kent Lodberg</creator><creator>Olsen, Michael Hecht</creator><creator>Diederichsen, Axel</creator><creator>Grønhøj, Mette Hjortdal</creator><general>Elsevier B.V</general><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><orcidid>https://orcid.org/0000-0003-0252-6631</orcidid><orcidid>https://orcid.org/0000-0002-1285-4826</orcidid></search><sort><creationdate>201804</creationdate><title>Prognostic value of suPAR and hs-CRP on cardiovascular disease</title><author>Diederichsen, Marie Zöga ; Diederichsen, Søren Zöga ; Mickley, Hans ; Steffensen, Flemming Hald ; Lambrechtsen, Jess ; Sand, Niels Peter Rønnow ; Christensen, Kent Lodberg ; Olsen, Michael Hecht ; Diederichsen, Axel ; Grønhøj, Mette Hjortdal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-82b420daa13263560aa99408ac64825f075f74f101e652f2356f1377c8e3bf4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Atherosclerosis</topic><topic>Biomarkers - blood</topic><topic>C-Reactive Protein - analysis</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases - blood</topic><topic>Cardiovascular Diseases - diagnostic imaging</topic><topic>Cardiovascular Diseases - epidemiology</topic><topic>Cardiovascular risk factors</topic><topic>Computed Tomography Angiography</topic><topic>Coronary Angiography - methods</topic><topic>Coronary artery calcification</topic><topic>Denmark - epidemiology</topic><topic>Female</topic><topic>High-sensitive C-reactive-protein</topic><topic>Humans</topic><topic>Inflammation Mediators - blood</topic><topic>Inflammatory markers</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Receptors, Urokinase Plasminogen Activator - blood</topic><topic>Registries</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Soluble urokinase plasminogen activator receptor</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Diederichsen, Marie Zöga</creatorcontrib><creatorcontrib>Diederichsen, Søren Zöga</creatorcontrib><creatorcontrib>Mickley, Hans</creatorcontrib><creatorcontrib>Steffensen, Flemming Hald</creatorcontrib><creatorcontrib>Lambrechtsen, Jess</creatorcontrib><creatorcontrib>Sand, Niels Peter Rønnow</creatorcontrib><creatorcontrib>Christensen, Kent Lodberg</creatorcontrib><creatorcontrib>Olsen, Michael Hecht</creatorcontrib><creatorcontrib>Diederichsen, Axel</creatorcontrib><creatorcontrib>Grønhøj, Mette Hjortdal</creatorcontrib><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>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Diederichsen, Marie Zöga</au><au>Diederichsen, Søren Zöga</au><au>Mickley, Hans</au><au>Steffensen, Flemming Hald</au><au>Lambrechtsen, Jess</au><au>Sand, Niels Peter Rønnow</au><au>Christensen, Kent Lodberg</au><au>Olsen, Michael Hecht</au><au>Diederichsen, Axel</au><au>Grønhøj, Mette Hjortdal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic value of suPAR and hs-CRP on cardiovascular disease</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2018-04</date><risdate>2018</risdate><volume>271</volume><spage>245</spage><epage>251</epage><pages>245-251</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score.
A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROCAUC models.
1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01–1.34) and 1.04 (95% CI 1.01–1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45–2.84) and 60-year-old subjects (1.44; 95% CI 1.09–1.90). By ROCAUC, neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32).
Adjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction.
•In adjusted Cox analysis, suPAR and CRP were significantly associated with cardiovascular events.•suPAR was particular promising among women and persons at age 60.•CPR was of importance among persons at age 60.•Neither suPAR nor CRP improved area under the curve in the entire population.•Inflammatory markers may supplement risk stratification after adjustment for CAC.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>29402404</pmid><doi>10.1016/j.atherosclerosis.2018.01.029</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-0252-6631</orcidid><orcidid>https://orcid.org/0000-0002-1285-4826</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9150 |
| ispartof | Atherosclerosis, 2018-04, Vol.271, p.245-251 |
| issn | 0021-9150 1879-1484 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1995151403 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Atherosclerosis Biomarkers - blood C-Reactive Protein - analysis Cardiovascular disease Cardiovascular Diseases - blood Cardiovascular Diseases - diagnostic imaging Cardiovascular Diseases - epidemiology Cardiovascular risk factors Computed Tomography Angiography Coronary Angiography - methods Coronary artery calcification Denmark - epidemiology Female High-sensitive C-reactive-protein Humans Inflammation Mediators - blood Inflammatory markers Male Middle Aged Predictive Value of Tests Prognosis Prospective Studies Receptors, Urokinase Plasminogen Activator - blood Registries Risk Assessment Risk Factors Soluble urokinase plasminogen activator receptor Time Factors |
| title | Prognostic value of suPAR and hs-CRP on cardiovascular disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T05%3A48%3A30IST&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=Prognostic%20value%20of%20suPAR%20and%20hs-CRP%20on%20cardiovascular%20disease&rft.jtitle=Atherosclerosis&rft.au=Diederichsen,%20Marie%20Z%C3%B6ga&rft.date=2018-04&rft.volume=271&rft.spage=245&rft.epage=251&rft.pages=245-251&rft.issn=0021-9150&rft.eissn=1879-1484&rft_id=info:doi/10.1016/j.atherosclerosis.2018.01.029&rft_dat=%3Cproquest_cross%3E1995151403%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=1995151403&rft_id=info:pmid/29402404&rft_els_id=S0021915018300303&rfr_iscdi=true |