Show simple item record

dc.contributor.authorNandi, M
dc.contributor.authorJackson, SK
dc.contributor.authorMacrae, D
dc.contributor.authorShankar-Hari, M
dc.contributor.authorTremoleda, JL
dc.contributor.authorLilley, E
dc.date.accessioned2021-10-15T12:51:58Z
dc.date.issued2020-07
dc.identifier.issn0143-5221
dc.identifier.issn1470-8736
dc.identifier.urihttp://hdl.handle.net/10026.1/18076
dc.description.abstract

<jats:title>Abstract</jats:title> <jats:p>Sepsis is a major worldwide healthcare issue with unmet clinical need. Despite extensive animal research in this area, successful clinical translation has been largely unsuccessful.</jats:p> <jats:p>We propose one reason for this is that, sometimes, the experimental question is misdirected or unrealistic expectations are being made of the animal model.</jats:p> <jats:p>As sepsis models can lead to a rapid and substantial suffering – it is essential that we continually review experimental approaches and undertake a full harm:benefit impact assessment for each study. In some instances, this may require refinement of existing sepsis models. In other cases, it may be replacement to a different experimental system altogether, answering a mechanistic question whilst aligning with the principles of reduction, refinement and replacement (3Rs).</jats:p> <jats:p>We discuss making better use of patient data to identify potentially useful therapeutic targets which can subsequently be validated in preclinical systems. This may be achieved through greater use of construct validity models, from which mechanistic conclusions are drawn. We argue that such models could provide equally useful scientific data as face validity models, but with an improved 3Rs impact. Indeed, construct validity models may not require sepsis to be modelled, per se. We propose that approaches that could support and refine clinical translation of research findings, whilst reducing the overall welfare burden on research animals.</jats:p>

dc.format.extent1715-1734
dc.format.mediumPrint
dc.languageen
dc.language.isoen
dc.publisherPortland Press
dc.subject3Rs
dc.subjectClinical translation
dc.subjectconstruct validity
dc.subjectmechanistic
dc.subjectresearch animals
dc.subjectsepsis
dc.subjectAnimals
dc.subjectClinical Trials as Topic
dc.subjectDisease Models, Animal
dc.subjectHumans
dc.subjectSepsis
dc.subjectTranslational Research, Biomedical
dc.titleRethinking animal models of sepsis – working towards improved clinical translation whilst integrating the 3Rs
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
dc.typeReview
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000596759100005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue13
plymouth.volume134
plymouth.publication-statusPublished
plymouth.journalClinical Science
dc.identifier.doi10.1042/cs20200679
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
plymouth.organisational-group/Plymouth/Users by role/Researchers in ResearchFish submission
dc.publisher.placeEngland
dcterms.dateAccepted2020-06-25
dc.rights.embargodate2021-12-8
dc.identifier.eissn1470-8736
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1042/cs20200679
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-07
rioxxterms.typeJournal Article/Review


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record


All items in PEARL are protected by copyright law.
Author manuscripts deposited to comply with open access mandates are made available in accordance with publisher policies. Please cite only the published version using the details provided on the item record or document. In the absence of an open licence (e.g. Creative Commons), permissions for further reuse of content should be sought from the publisher or author.
Theme by 
Atmire NV