Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol
The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose...
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| creator | Horwell, C.J. Baxter, P.J. Hillman, S.E. Calkins, J.A. Damby, D.E. Delmelle, P. Donaldson, K. Dunster, C. Fubini, B. Kelly, F.J. Le Blond, J.S. Livi, K.J.T. Murphy, F. Nattrass, C. Sweeney, S. Tetley, T.D. Thordarson, T. Tomatis, M. |
| description | The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995.
For Eyjafjallajökull, the grain size distributions were variable: 2–13vol% of the bulk samples were |
| doi_str_mv | 10.1016/j.envres.2013.08.011 |
| format | Article |
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For Eyjafjallajökull, the grain size distributions were variable: 2–13vol% of the bulk samples were <4µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5vol%<4µm material). Surface area ranged from 0.3 to 7.7m2g−1 for Eyjafjallajökull but was very low for Grímsvötn (<0.6m2g−1). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles.
The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted.
•Eyjafjallajökull and Grímsvötn volcanic ash fell on Iceland in 2010 and 2011.•The respiratory hazard was investigated in 2 rapid, multi-disciplinary lab. studies.•Up to 13vol% of the Eyjafjallajökull ash was respirable (<4µm diameter).•Crystalline silica in the samples was negligible and few fibrous particles were observed.•Both ash types showed positive chronic pro-inflammatory responses.</description><identifier>ISSN: 0013-9351</identifier><identifier>EISSN: 1096-0953</identifier><identifier>DOI: 10.1016/j.envres.2013.08.011</identifier><identifier>PMID: 24267795</identifier><identifier>CODEN: ENVRAL</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Air ; Air Pollutants - toxicity ; Ashes ; Biological and medical sciences ; Cell Line - drug effects ; Cellular ; Depletion ; Deposition ; Environmental pollutants toxicology ; Epithelial Cells - drug effects ; Eyjafjallajökull ; Grímsvötn ; Humans ; Hydroxyl Radical - metabolism ; Hydroxyl radicals ; Iceland ; In vitro testing ; Inflammation - chemically induced ; Inflammation - metabolism ; Inflammation Mediators - metabolism ; Lung - drug effects ; Lung - physiopathology ; Medical sciences ; Minerals - analysis ; Particle Size ; Respiratory health ; Risk Assessment ; Silicon Dioxide ; Toxicity Tests ; Toxicology ; Volcanic ash ; Volcanic Eruptions - analysis ; Volcano ; Volcanoes</subject><ispartof>Environmental research, 2013-11, Vol.127, p.63-73</ispartof><rights>2013 The Authors</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-7720b91ea3d01c275b033e515c180657c7e3e0d148772fb9fcbbba1dffe8c4903</citedby><cites>FETCH-LOGICAL-c504t-7720b91ea3d01c275b033e515c180657c7e3e0d148772fb9fcbbba1dffe8c4903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0013935113001539$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28024148$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24267795$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Horwell, C.J.</creatorcontrib><creatorcontrib>Baxter, P.J.</creatorcontrib><creatorcontrib>Hillman, S.E.</creatorcontrib><creatorcontrib>Calkins, J.A.</creatorcontrib><creatorcontrib>Damby, D.E.</creatorcontrib><creatorcontrib>Delmelle, P.</creatorcontrib><creatorcontrib>Donaldson, K.</creatorcontrib><creatorcontrib>Dunster, C.</creatorcontrib><creatorcontrib>Fubini, B.</creatorcontrib><creatorcontrib>Kelly, F.J.</creatorcontrib><creatorcontrib>Le Blond, J.S.</creatorcontrib><creatorcontrib>Livi, K.J.T.</creatorcontrib><creatorcontrib>Murphy, F.</creatorcontrib><creatorcontrib>Nattrass, C.</creatorcontrib><creatorcontrib>Sweeney, S.</creatorcontrib><creatorcontrib>Tetley, T.D.</creatorcontrib><creatorcontrib>Thordarson, T.</creatorcontrib><creatorcontrib>Tomatis, M.</creatorcontrib><title>Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol</title><title>Environmental research</title><addtitle>Environ Res</addtitle><description>The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995.
For Eyjafjallajökull, the grain size distributions were variable: 2–13vol% of the bulk samples were <4µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5vol%<4µm material). Surface area ranged from 0.3 to 7.7m2g−1 for Eyjafjallajökull but was very low for Grímsvötn (<0.6m2g−1). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles.
The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted.
•Eyjafjallajökull and Grímsvötn volcanic ash fell on Iceland in 2010 and 2011.•The respiratory hazard was investigated in 2 rapid, multi-disciplinary lab. studies.•Up to 13vol% of the Eyjafjallajökull ash was respirable (<4µm diameter).•Crystalline silica in the samples was negligible and few fibrous particles were observed.•Both ash types showed positive chronic pro-inflammatory responses.</description><subject>Air</subject><subject>Air Pollutants - toxicity</subject><subject>Ashes</subject><subject>Biological and medical sciences</subject><subject>Cell Line - drug effects</subject><subject>Cellular</subject><subject>Depletion</subject><subject>Deposition</subject><subject>Environmental pollutants toxicology</subject><subject>Epithelial Cells - drug effects</subject><subject>Eyjafjallajökull</subject><subject>Grímsvötn</subject><subject>Humans</subject><subject>Hydroxyl Radical - metabolism</subject><subject>Hydroxyl radicals</subject><subject>Iceland</subject><subject>In vitro testing</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - metabolism</subject><subject>Inflammation Mediators - metabolism</subject><subject>Lung - drug effects</subject><subject>Lung - physiopathology</subject><subject>Medical sciences</subject><subject>Minerals - analysis</subject><subject>Particle Size</subject><subject>Respiratory health</subject><subject>Risk Assessment</subject><subject>Silicon Dioxide</subject><subject>Toxicity Tests</subject><subject>Toxicology</subject><subject>Volcanic ash</subject><subject>Volcanic Eruptions - analysis</subject><subject>Volcano</subject><subject>Volcanoes</subject><issn>0013-9351</issn><issn>1096-0953</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxiMEokvhDRDyBYlDE8b5nwtSVbWlUiU4wNlynHHjkMSLJ1mxvBPXnpH2xXCaBW6Ik-3xb-b77C8IXnKIOPD8bRfhuHNIUQw8iaCMgPNHwYZDlYdQZcnjYAP-JqySjJ8Ez4g6f-RZAk-DkziN86Kosk3w82O7J6OsanEwSvZMjg2b7Ddf6u3dQ2XrrDa9Ge-Y1UxSy7SzA5taZF4ZHhr8hjN083YydqSFu9x3Uney72V3uP8y9-vga3f4MdDucD-NbGd7JUeLdMZuFPbL9UyLimRObk3D_Nu2xsnJuj1r5XfpGq9OSDTgOC2uJutNPg-eaNkTvjiup8Hnq8tPF-_D2w_XNxfnt6HKIJ3CooihrjjKpAGu4iKrIUkw45niJeRZoQpMEBqelp7UdaVVXdeSN1pjqdIKktPgzTrXC3-dkSYxGPK-vXG0Mwme51VZQlmV_4OmvMrjYpmarqhylsihFltnBun2goNYYhadWGMWS8wCSuG_2re9OirM9YDNn6bfuXrg9RGQ5DPUTo7K0F-uhDj1b_Xcu5VD_3U7g06QMjgqbIxDNYnGmn87-QXUm81M</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Horwell, C.J.</creator><creator>Baxter, P.J.</creator><creator>Hillman, S.E.</creator><creator>Calkins, J.A.</creator><creator>Damby, D.E.</creator><creator>Delmelle, P.</creator><creator>Donaldson, K.</creator><creator>Dunster, C.</creator><creator>Fubini, B.</creator><creator>Kelly, F.J.</creator><creator>Le Blond, J.S.</creator><creator>Livi, K.J.T.</creator><creator>Murphy, F.</creator><creator>Nattrass, C.</creator><creator>Sweeney, S.</creator><creator>Tetley, T.D.</creator><creator>Thordarson, T.</creator><creator>Tomatis, M.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>7ST</scope><scope>7T2</scope><scope>7U1</scope><scope>7U2</scope><scope>C1K</scope><scope>SOI</scope><scope>8FD</scope><scope>FR3</scope><scope>KR7</scope></search><sort><creationdate>20131101</creationdate><title>Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol</title><author>Horwell, C.J. ; Baxter, P.J. ; Hillman, S.E. ; Calkins, J.A. ; Damby, D.E. ; Delmelle, P. ; Donaldson, K. ; Dunster, C. ; Fubini, B. ; Kelly, F.J. ; Le Blond, J.S. ; Livi, K.J.T. ; Murphy, F. ; Nattrass, C. ; Sweeney, S. ; Tetley, T.D. ; Thordarson, T. ; Tomatis, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-7720b91ea3d01c275b033e515c180657c7e3e0d148772fb9fcbbba1dffe8c4903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Air</topic><topic>Air Pollutants - toxicity</topic><topic>Ashes</topic><topic>Biological and medical sciences</topic><topic>Cell Line - drug effects</topic><topic>Cellular</topic><topic>Depletion</topic><topic>Deposition</topic><topic>Environmental pollutants toxicology</topic><topic>Epithelial Cells - drug effects</topic><topic>Eyjafjallajökull</topic><topic>Grímsvötn</topic><topic>Humans</topic><topic>Hydroxyl Radical - metabolism</topic><topic>Hydroxyl radicals</topic><topic>Iceland</topic><topic>In vitro testing</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - metabolism</topic><topic>Inflammation Mediators - metabolism</topic><topic>Lung - drug effects</topic><topic>Lung - physiopathology</topic><topic>Medical sciences</topic><topic>Minerals - analysis</topic><topic>Particle Size</topic><topic>Respiratory health</topic><topic>Risk Assessment</topic><topic>Silicon Dioxide</topic><topic>Toxicity Tests</topic><topic>Toxicology</topic><topic>Volcanic ash</topic><topic>Volcanic Eruptions - analysis</topic><topic>Volcano</topic><topic>Volcanoes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Horwell, C.J.</creatorcontrib><creatorcontrib>Baxter, P.J.</creatorcontrib><creatorcontrib>Hillman, S.E.</creatorcontrib><creatorcontrib>Calkins, J.A.</creatorcontrib><creatorcontrib>Damby, D.E.</creatorcontrib><creatorcontrib>Delmelle, P.</creatorcontrib><creatorcontrib>Donaldson, K.</creatorcontrib><creatorcontrib>Dunster, C.</creatorcontrib><creatorcontrib>Fubini, B.</creatorcontrib><creatorcontrib>Kelly, F.J.</creatorcontrib><creatorcontrib>Le Blond, J.S.</creatorcontrib><creatorcontrib>Livi, K.J.T.</creatorcontrib><creatorcontrib>Murphy, F.</creatorcontrib><creatorcontrib>Nattrass, C.</creatorcontrib><creatorcontrib>Sweeney, S.</creatorcontrib><creatorcontrib>Tetley, T.D.</creatorcontrib><creatorcontrib>Thordarson, T.</creatorcontrib><creatorcontrib>Tomatis, M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Environment Abstracts</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Civil Engineering Abstracts</collection><jtitle>Environmental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Horwell, C.J.</au><au>Baxter, P.J.</au><au>Hillman, S.E.</au><au>Calkins, J.A.</au><au>Damby, D.E.</au><au>Delmelle, P.</au><au>Donaldson, K.</au><au>Dunster, C.</au><au>Fubini, B.</au><au>Kelly, F.J.</au><au>Le Blond, J.S.</au><au>Livi, K.J.T.</au><au>Murphy, F.</au><au>Nattrass, C.</au><au>Sweeney, S.</au><au>Tetley, T.D.</au><au>Thordarson, T.</au><au>Tomatis, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol</atitle><jtitle>Environmental research</jtitle><addtitle>Environ Res</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>127</volume><spage>63</spage><epage>73</epage><pages>63-73</pages><issn>0013-9351</issn><eissn>1096-0953</eissn><coden>ENVRAL</coden><abstract>The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995.
For Eyjafjallajökull, the grain size distributions were variable: 2–13vol% of the bulk samples were <4µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5vol%<4µm material). Surface area ranged from 0.3 to 7.7m2g−1 for Eyjafjallajökull but was very low for Grímsvötn (<0.6m2g−1). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles.
The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted.
•Eyjafjallajökull and Grímsvötn volcanic ash fell on Iceland in 2010 and 2011.•The respiratory hazard was investigated in 2 rapid, multi-disciplinary lab. studies.•Up to 13vol% of the Eyjafjallajökull ash was respirable (<4µm diameter).•Crystalline silica in the samples was negligible and few fibrous particles were observed.•Both ash types showed positive chronic pro-inflammatory responses.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>24267795</pmid><doi>10.1016/j.envres.2013.08.011</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Environmental research, 2013-11, Vol.127, p.63-73 |
| issn | 0013-9351 1096-0953 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1669880898 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Air Air Pollutants - toxicity Ashes Biological and medical sciences Cell Line - drug effects Cellular Depletion Deposition Environmental pollutants toxicology Epithelial Cells - drug effects Eyjafjallajökull Grímsvötn Humans Hydroxyl Radical - metabolism Hydroxyl radicals Iceland In vitro testing Inflammation - chemically induced Inflammation - metabolism Inflammation Mediators - metabolism Lung - drug effects Lung - physiopathology Medical sciences Minerals - analysis Particle Size Respiratory health Risk Assessment Silicon Dioxide Toxicity Tests Toxicology Volcanic ash Volcanic Eruptions - analysis Volcano Volcanoes |
| title | Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T22%3A41%3A46IST&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=Physicochemical%20and%20toxicological%20profiling%20of%20ash%20from%20the%202010%20and%202011%20eruptions%20of%20Eyjafjallaj%C3%B6kull%20and%20Gr%C3%ADmsv%C3%B6tn%20volcanoes,%20Iceland%20using%20a%20rapid%20respiratory%20hazard%20assessment%20protocol&rft.jtitle=Environmental%20research&rft.au=Horwell,%20C.J.&rft.date=2013-11-01&rft.volume=127&rft.spage=63&rft.epage=73&rft.pages=63-73&rft.issn=0013-9351&rft.eissn=1096-0953&rft.coden=ENVRAL&rft_id=info:doi/10.1016/j.envres.2013.08.011&rft_dat=%3Cproquest_cross%3E1669880898%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=1664196270&rft_id=info:pmid/24267795&rft_els_id=S0013935113001539&rfr_iscdi=true |