Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.
Identifieur interne : 001A80 ( PubMed/Checkpoint ); précédent : 001A79; suivant : 001A81Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.
Auteurs : Ruth Keogh [Royaume-Uni] ; Chris Frost [Royaume-Uni] ; Gail Owen [Royaume-Uni] ; Rhian M. Daniel [Royaume-Uni] ; Doug R. Langbehn [États-Unis] ; Blair Leavitt [Canada] ; Alexandra Durr [France] ; Raymund A C. Roos [Pays-Bas] ; G Bernhard Landwehrmeyer [Allemagne] ; Ralf Reilmann [Allemagne] ; Beth Borowsky [États-Unis] ; Julie Stout [Australie] ; David Craufurd [Royaume-Uni] ; Sarah J. Tabrizi [Royaume-Uni]Source :
- PLoS currents [ 2157-3999 ] ; 2016.
Abstract
Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.
DOI: 10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb
PubMed: 26819833
Affiliations:
- Allemagne, Australie, Canada, France, Pays-Bas, Royaume-Uni, États-Unis
- Angleterre, Bade-Wurtemberg, District de Münster, District de Tübingen, Grand Londres, Grand Manchester, Hollande-Méridionale, Iowa, New Jersey, Rhénanie-du-Nord-Westphalie, Île-de-France
- Iowa City, Leyde, Londres, Manchester, Münster, Paris, Ulm
- University College de Londres, Université de l'Iowa
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Roos</name><affiliation wicri:level="3"><nlm:affiliation>Neurology, Leiden University Medical Centre, Leiden, Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Neurology, Leiden University Medical Centre, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Landwehrmeyer, G Bernhard" sort="Landwehrmeyer, G Bernhard" uniqKey="Landwehrmeyer G" first="G Bernhard" last="Landwehrmeyer">G Bernhard Landwehrmeyer</name><affiliation wicri:level="3"><nlm:affiliation>Neurology, Ulm University, Ulm, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Neurology, Ulm University, Ulm</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author><author><name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name><affiliation wicri:level="3"><nlm:affiliation>George-Huntington-Institute, Neurology, University of Münster, Münster, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>George-Huntington-Institute, Neurology, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Borowsky, Beth" sort="Borowsky, Beth" uniqKey="Borowsky B" first="Beth" last="Borowsky">Beth Borowsky</name><affiliation wicri:level="2"><nlm:affiliation>CHDI Management/CHDI Foundation, Princeton, NJ, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>CHDI Management/CHDI Foundation, Princeton, NJ</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Stout, Julie" sort="Stout, Julie" uniqKey="Stout J" first="Julie" last="Stout">Julie Stout</name><affiliation wicri:level="1"><nlm:affiliation>School of Psychological Sciences, Monash University, VIC, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Psychological Sciences, Monash University, VIC</wicri:regionArea><wicri:noRegion>VIC</wicri:noRegion></affiliation></author><author><name sortKey="Craufurd, David" sort="Craufurd, David" uniqKey="Craufurd D" first="David" last="Craufurd">David Craufurd</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester</wicri:regionArea><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J" last="Tabrizi">Sarah J. 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Daniel</name><affiliation wicri:level="3"><nlm:affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Statistics, London School of Hygiene and Tropical Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Langbehn, Doug R" sort="Langbehn, Doug R" uniqKey="Langbehn D" first="Doug R" last="Langbehn">Doug R. Langbehn</name><affiliation wicri:level="4"><nlm:affiliation>Psychiatry, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Psychiatry, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Leavitt, Blair" sort="Leavitt, Blair" uniqKey="Leavitt B" first="Blair" last="Leavitt">Blair Leavitt</name><affiliation wicri:level="1"><nlm:affiliation>Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Medical Genetics, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name><affiliation wicri:level="3"><nlm:affiliation>Genetics, APHP- Groupe Hospitalier Pitié-Salpêtrière, Paris, France; INSERM U1127, CNRS UMR7225, UPMC University Paris VI UMR_S1127, Institut du Cerveau et de la Moelle, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Genetics, APHP- Groupe Hospitalier Pitié-Salpêtrière, Paris, France; INSERM U1127, CNRS UMR7225, UPMC University Paris VI UMR_S1127, Institut du Cerveau et de la Moelle, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Roos, Raymund A C" sort="Roos, Raymund A C" uniqKey="Roos R" first="Raymund A C" last="Roos">Raymund A C. Roos</name><affiliation wicri:level="3"><nlm:affiliation>Neurology, Leiden University Medical Centre, Leiden, Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Neurology, Leiden University Medical Centre, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Landwehrmeyer, G Bernhard" sort="Landwehrmeyer, G Bernhard" uniqKey="Landwehrmeyer G" first="G Bernhard" last="Landwehrmeyer">G Bernhard Landwehrmeyer</name><affiliation wicri:level="3"><nlm:affiliation>Neurology, Ulm University, Ulm, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Neurology, Ulm University, Ulm</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author><author><name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name><affiliation wicri:level="3"><nlm:affiliation>George-Huntington-Institute, Neurology, University of Münster, Münster, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>George-Huntington-Institute, Neurology, University of Münster, Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Borowsky, Beth" sort="Borowsky, Beth" uniqKey="Borowsky B" first="Beth" last="Borowsky">Beth Borowsky</name><affiliation wicri:level="2"><nlm:affiliation>CHDI Management/CHDI Foundation, Princeton, NJ, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>CHDI Management/CHDI Foundation, Princeton, NJ</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Stout, Julie" sort="Stout, Julie" uniqKey="Stout J" first="Julie" last="Stout">Julie Stout</name><affiliation wicri:level="1"><nlm:affiliation>School of Psychological Sciences, Monash University, VIC, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Psychological Sciences, Monash University, VIC</wicri:regionArea><wicri:noRegion>VIC</wicri:noRegion></affiliation></author><author><name sortKey="Craufurd, David" sort="Craufurd, David" uniqKey="Craufurd D" first="David" last="Craufurd">David Craufurd</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester</wicri:regionArea><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region></placeName></affiliation></author><author><name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J" last="Tabrizi">Sarah J. Tabrizi</name><affiliation wicri:level="3"><nlm:affiliation>Neurodegenerative Disease, UCL Institute of Neurology, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Neurodegenerative Disease, UCL Institute of Neurology, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">PLoS currents</title><idno type="eISSN">2157-3999</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">26819833</PMID><DateCreated><Year>2016</Year><Month>01</Month><Day>28</Day></DateCreated><DateCompleted><Year>2016</Year><Month>01</Month><Day>28</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2157-3999</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><PubDate><Year>2016</Year><Month>Jan</Month><Day>11</Day></PubDate></JournalIssue><Title>PLoS currents</Title><ISOAbbreviation>PLoS Curr</ISOAbbreviation></Journal><ArticleTitle>Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb</ELocationID><ELocationID EIdType="pii" ValidYN="Y">ecurrents.hd.8060298fac1801b01ccea6acc00f97cb</ELocationID><Abstract><AbstractText> Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Keogh</LastName><ForeName>Ruth</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frost</LastName><ForeName>Chris</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Owen</LastName><ForeName>Gail</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>UCL Institute of Neurology, University College London, Queen Square, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Daniel</LastName><ForeName>Rhian M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Langbehn</LastName><ForeName>Doug R</ForeName><Initials>DR</Initials><AffiliationInfo><Affiliation>Psychiatry, University of Iowa, Iowa City, Iowa, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leavitt</LastName><ForeName>Blair</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Durr</LastName><ForeName>Alexandra</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Genetics, APHP- Groupe Hospitalier Pitié-Salpêtrière, Paris, France; INSERM U1127, CNRS UMR7225, UPMC University Paris VI UMR_S1127, Institut du Cerveau et de la Moelle, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roos</LastName><ForeName>Raymund A C</ForeName><Initials>RA</Initials><AffiliationInfo><Affiliation>Neurology, Leiden University Medical Centre, Leiden, Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Landwehrmeyer</LastName><ForeName>G Bernhard</ForeName><Initials>GB</Initials><AffiliationInfo><Affiliation>Neurology, Ulm University, Ulm, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reilmann</LastName><ForeName>Ralf</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>George-Huntington-Institute, Neurology, University of Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Borowsky</LastName><ForeName>Beth</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>CHDI Management/CHDI Foundation, Princeton, NJ, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stout</LastName><ForeName>Julie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>School of Psychological Sciences, Monash University, VIC, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Craufurd</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tabrizi</LastName><ForeName>Sarah J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Neurodegenerative Disease, UCL Institute of Neurology, London, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MR/L012936/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS Curr</MedlineTA><NlmUniqueID>101515638</NlmUniqueID><ISSNLinking>2157-3999</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Stat Med. 2002 Jun 30;21(12):1689-709</RefSource><PMID Version="1">12111906</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurol Neurosurg Psychiatry. 1997 Jul;63(1):35-9</RefSource><PMID Version="1">9221965</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Neurol. 2013 Jul;12(7):637-49</RefSource><PMID Version="1">23664844</PMID></CommentsCorrections><CommentsCorrections 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PubStatus="medline"><Year>2016</Year><Month>1</Month><Day>29</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26819833</ArticleId><ArticleId IdType="doi">10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb</ArticleId><ArticleId IdType="pmc">PMC4718719</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Canada</li><li>France</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Bade-Wurtemberg</li><li>District de Münster</li><li>District de Tübingen</li><li>Grand Londres</li><li>Grand Manchester</li><li>Hollande-Méridionale</li><li>Iowa</li><li>New Jersey</li><li>Rhénanie-du-Nord-Westphalie</li><li>Île-de-France</li></region><settlement><li>Iowa City</li><li>Leyde</li><li>Londres</li><li>Manchester</li><li>Münster</li><li>Paris</li><li>Ulm</li></settlement><orgName><li>University College de Londres</li><li>Université de l'Iowa</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Keogh, Ruth" sort="Keogh, Ruth" uniqKey="Keogh R" first="Ruth" last="Keogh">Ruth Keogh</name></region><name sortKey="Craufurd, David" sort="Craufurd, David" uniqKey="Craufurd D" first="David" last="Craufurd">David Craufurd</name><name sortKey="Daniel, Rhian M" sort="Daniel, Rhian M" uniqKey="Daniel R" first="Rhian M" last="Daniel">Rhian M. Daniel</name><name sortKey="Frost, Chris" sort="Frost, Chris" uniqKey="Frost C" first="Chris" last="Frost">Chris Frost</name><name sortKey="Owen, Gail" sort="Owen, Gail" uniqKey="Owen G" first="Gail" last="Owen">Gail Owen</name><name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J" last="Tabrizi">Sarah J. Tabrizi</name></country><country name="États-Unis"><region name="Iowa"><name sortKey="Langbehn, Doug R" sort="Langbehn, Doug R" uniqKey="Langbehn D" first="Doug R" last="Langbehn">Doug R. Langbehn</name></region><name sortKey="Borowsky, Beth" sort="Borowsky, Beth" uniqKey="Borowsky B" first="Beth" last="Borowsky">Beth Borowsky</name></country><country name="Canada"><noRegion><name sortKey="Leavitt, Blair" sort="Leavitt, Blair" uniqKey="Leavitt B" first="Blair" last="Leavitt">Blair Leavitt</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name></region></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Roos, Raymund A C" sort="Roos, Raymund A C" uniqKey="Roos R" first="Raymund A C" last="Roos">Raymund A C. Roos</name></region></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Landwehrmeyer, G Bernhard" sort="Landwehrmeyer, G Bernhard" uniqKey="Landwehrmeyer G" first="G Bernhard" last="Landwehrmeyer">G Bernhard Landwehrmeyer</name></region><name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name></country><country name="Australie"><noRegion><name sortKey="Stout, Julie" sort="Stout, Julie" uniqKey="Stout J" first="Julie" last="Stout">Julie Stout</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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