Early-life hepatitis e infection in pigs: the importance of maternally-derived antibodies
Passive immunity (PI), acquired through colostrum intake, is essential for piglet protection against pathogens. Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals. Only...
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| description | Passive immunity (PI), acquired through colostrum intake, is essential for piglet protection against pathogens. Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals. Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission. In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI. This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake. A Bayesian approach (Metropolis-Hastings algorithm) was used for parameter estimation. The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms. A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5-21). Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd. Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake. These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices. The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents. |
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Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals. Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission. In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI. This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake. A Bayesian approach (Metropolis-Hastings algorithm) was used for parameter estimation. The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms. A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5-21). Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd. Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake. These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices. The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0105527</identifier><identifier>PMID: 25144763</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Age Factors ; Algorithms ; Analysis ; Animal biology ; Animal husbandry ; Animals ; Antibodies ; Antibodies, Viral - immunology ; Bayesian analysis ; Biology and Life Sciences ; Colostrum ; Disease ; Epidemiology ; Farms ; Hepatitis ; Hepatitis E ; Hepatitis E - veterinary ; Hogs ; Host-Pathogen Interactions ; Hygiene ; Immunity ; Immunity (passive) ; Immunity, Maternally-Acquired ; Immunoglobulins ; Infections ; Infectious diseases ; Life Sciences ; Mathematical models ; Maximum likelihood method ; Medicine and Health Sciences ; Models, Biological ; Parameter estimation ; Pathogens ; Random variables ; Seroepidemiologic Studies ; Swine ; Swine Diseases - epidemiology ; Swine Diseases - immunology ; Swine Diseases - transmission ; Veterinary medicine and animal Health ; Virology ; Viruses ; Weaning ; Zoonoses</subject><ispartof>PloS one, 2014-08, Vol.9 (8), p.e105527-e105527</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Andraud et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2014 Andraud et al 2014 Andraud et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c726t-8fd9943a20161e9b69d8469b8f40ccdcf64fec9beb129643691d8c5cb4fc85a13</citedby><cites>FETCH-LOGICAL-c726t-8fd9943a20161e9b69d8469b8f40ccdcf64fec9beb129643691d8c5cb4fc85a13</cites><orcidid>0000-0003-2891-2901 ; 0000-0001-8789-2395 ; 0000-0003-1327-621X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140806/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140806/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25144763$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.inrae.fr/hal-02637873$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Andraud, Mathieu</creatorcontrib><creatorcontrib>Casas, Maribel</creatorcontrib><creatorcontrib>Pavio, Nicole</creatorcontrib><creatorcontrib>Rose, Nicolas</creatorcontrib><title>Early-life hepatitis e infection in pigs: the importance of maternally-derived antibodies</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Passive immunity (PI), acquired through colostrum intake, is essential for piglet protection against pathogens. Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals. Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission. In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI. This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake. A Bayesian approach (Metropolis-Hastings algorithm) was used for parameter estimation. The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms. A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5-21). Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd. Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake. These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices. The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents.</description><subject>Age</subject><subject>Age Factors</subject><subject>Algorithms</subject><subject>Analysis</subject><subject>Animal biology</subject><subject>Animal husbandry</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Viral - immunology</subject><subject>Bayesian analysis</subject><subject>Biology and Life Sciences</subject><subject>Colostrum</subject><subject>Disease</subject><subject>Epidemiology</subject><subject>Farms</subject><subject>Hepatitis</subject><subject>Hepatitis E</subject><subject>Hepatitis E - veterinary</subject><subject>Hogs</subject><subject>Host-Pathogen Interactions</subject><subject>Hygiene</subject><subject>Immunity</subject><subject>Immunity (passive)</subject><subject>Immunity, Maternally-Acquired</subject><subject>Immunoglobulins</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Life Sciences</subject><subject>Mathematical models</subject><subject>Maximum likelihood method</subject><subject>Medicine and Health Sciences</subject><subject>Models, Biological</subject><subject>Parameter estimation</subject><subject>Pathogens</subject><subject>Random variables</subject><subject>Seroepidemiologic Studies</subject><subject>Swine</subject><subject>Swine Diseases - epidemiology</subject><subject>Swine Diseases - immunology</subject><subject>Swine Diseases - transmission</subject><subject>Veterinary medicine and animal Health</subject><subject>Virology</subject><subject>Viruses</subject><subject>Weaning</subject><subject>Zoonoses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01r3DAQhk1padK0_6C0hkJpDruVLFm2eigsIW0WFgL9gp6ErI-1FttyJHlp_n3lrhPWIYfig8XomVfvjDRJ8hqCJUQF_Lizg-t4s-xtp5YAgjzPiifJKaQoW5AMoKdH65Pkhfc7AHJUEvI8OclyiHFB0Gny-5K75nbRGK3SWvU8mGB8qlLTaSWCsV1cpb3Z-k9pqGO47a0LvBMqtTpteVCjhygglTN7JVPeBVNZaZR_mTzTvPHq1fQ_S35-ufxxcbXYXH9dX6w2C1FkJCxKLSnFiGcAEqhoRagsMaFVqTEQQgpNcHRCK1XBjBKMCIWyFLmosBZlziE6S94edPvGejZ1xTOYx4aUKM9pJNYHQlq-Y70zLXe3zHLD_gWs2zLughGNYlISwCWGhQQScyp5JpHCWhdltBidRq3P02lD1SopVBccb2ai853O1Gxr9wxDDEpAosD5QaB-kHa12rAxBjKCirJA-7G0D9Nhzt4MygfWGi9U0_BO2eFQY7zerBh9vXuAPt6JidryWGy8Yxs9ilGUrTAsIaIZxJFaPkLFT6rWiPjctInxWcL5LCEyQf0JWz54z9bfv_0_e_1rzr4_YmvFm1B72wzju_RzEB9A4az3Tun7zkLAxmm56wYbp4VN0xLT3hxf5n3S3Xigv6K_Dy0</recordid><startdate>20140821</startdate><enddate>20140821</enddate><creator>Andraud, Mathieu</creator><creator>Casas, Maribel</creator><creator>Pavio, Nicole</creator><creator>Rose, Nicolas</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>COVID</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2891-2901</orcidid><orcidid>https://orcid.org/0000-0001-8789-2395</orcidid><orcidid>https://orcid.org/0000-0003-1327-621X</orcidid></search><sort><creationdate>20140821</creationdate><title>Early-life hepatitis e infection in pigs: the importance of maternally-derived antibodies</title><author>Andraud, Mathieu ; Casas, Maribel ; Pavio, Nicole ; Rose, Nicolas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c726t-8fd9943a20161e9b69d8469b8f40ccdcf64fec9beb129643691d8c5cb4fc85a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Age</topic><topic>Age Factors</topic><topic>Algorithms</topic><topic>Analysis</topic><topic>Animal biology</topic><topic>Animal husbandry</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Viral - immunology</topic><topic>Bayesian analysis</topic><topic>Biology and Life Sciences</topic><topic>Colostrum</topic><topic>Disease</topic><topic>Epidemiology</topic><topic>Farms</topic><topic>Hepatitis</topic><topic>Hepatitis E</topic><topic>Hepatitis E - veterinary</topic><topic>Hogs</topic><topic>Host-Pathogen Interactions</topic><topic>Hygiene</topic><topic>Immunity</topic><topic>Immunity (passive)</topic><topic>Immunity, Maternally-Acquired</topic><topic>Immunoglobulins</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Life Sciences</topic><topic>Mathematical models</topic><topic>Maximum likelihood method</topic><topic>Medicine and Health Sciences</topic><topic>Models, Biological</topic><topic>Parameter estimation</topic><topic>Pathogens</topic><topic>Random variables</topic><topic>Seroepidemiologic Studies</topic><topic>Swine</topic><topic>Swine Diseases - epidemiology</topic><topic>Swine Diseases - immunology</topic><topic>Swine Diseases - transmission</topic><topic>Veterinary medicine and animal Health</topic><topic>Virology</topic><topic>Viruses</topic><topic>Weaning</topic><topic>Zoonoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Andraud, Mathieu</creatorcontrib><creatorcontrib>Casas, Maribel</creatorcontrib><creatorcontrib>Pavio, Nicole</creatorcontrib><creatorcontrib>Rose, Nicolas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Andraud, Mathieu</au><au>Casas, Maribel</au><au>Pavio, Nicole</au><au>Rose, Nicolas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early-life hepatitis e infection in pigs: the importance of maternally-derived antibodies</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-08-21</date><risdate>2014</risdate><volume>9</volume><issue>8</issue><spage>e105527</spage><epage>e105527</epage><pages>e105527-e105527</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Passive immunity (PI), acquired through colostrum intake, is essential for piglet protection against pathogens. Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals. Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission. In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI. This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake. A Bayesian approach (Metropolis-Hastings algorithm) was used for parameter estimation. The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms. A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5-21). Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd. Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake. These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices. The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25144763</pmid><doi>10.1371/journal.pone.0105527</doi><orcidid>https://orcid.org/0000-0003-2891-2901</orcidid><orcidid>https://orcid.org/0000-0001-8789-2395</orcidid><orcidid>https://orcid.org/0000-0003-1327-621X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Age Factors Algorithms Analysis Animal biology Animal husbandry Animals Antibodies Antibodies, Viral - immunology Bayesian analysis Biology and Life Sciences Colostrum Disease Epidemiology Farms Hepatitis Hepatitis E Hepatitis E - veterinary Hogs Host-Pathogen Interactions Hygiene Immunity Immunity (passive) Immunity, Maternally-Acquired Immunoglobulins Infections Infectious diseases Life Sciences Mathematical models Maximum likelihood method Medicine and Health Sciences Models, Biological Parameter estimation Pathogens Random variables Seroepidemiologic Studies Swine Swine Diseases - epidemiology Swine Diseases - immunology Swine Diseases - transmission Veterinary medicine and animal Health Virology Viruses Weaning Zoonoses |
| title | Early-life hepatitis e infection in pigs: the importance of maternally-derived antibodies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T18%3A33%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Early-life%20hepatitis%20e%20infection%20in%20pigs:%20the%20importance%20of%20maternally-derived%20antibodies&rft.jtitle=PloS%20one&rft.au=Andraud,%20Mathieu&rft.date=2014-08-21&rft.volume=9&rft.issue=8&rft.spage=e105527&rft.epage=e105527&rft.pages=e105527-e105527&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0105527&rft_dat=%3Cgale_plos_%3EA418139214%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1555283559&rft_id=info:pmid/25144763&rft_galeid=A418139214&rft_doaj_id=oai_doaj_org_article_dd60ad417d0d4a9da2d3e4ff7843afd9&rfr_iscdi=true |