Serveur d'exploration sur les relations entre la France et l'Australie

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The effect of increased genetic risk for Alzheimer’s disease on hippocampal and amygdala volume

Identifieur interne : 001585 ( Main/Exploration ); précédent : 001584; suivant : 001586

The effect of increased genetic risk for Alzheimer’s disease on hippocampal and amygdala volume

Auteurs : Michelle K. Lupton [Australie] ; Lachlan Strike [Australie] ; Narelle K. Hansell [Australie] ; Wei Wen [Australie] ; Karen A. Mather [Australie] ; Nicola J. Armstrong [Australie] ; Anbupalam Thalamuthu [Australie] ; Katie L. Mcmahon [Australie] ; Greig I. De Zubicaray [Australie] ; Amelia A. Assareh [Australie] ; Andrew Simmons [Royaume-Uni] ; Petroula Proitsi [Royaume-Uni] ; John F. Powell [Royaume-Uni] ; Grant W. Montgomery [Australie] ; Derrek P. Hibar [États-Unis] ; Eric Westman [Suède] ; Magda Tsolaki [Grèce] ; Iwona Kloszewska [Pologne] ; Hilkka Soininen [Finlande] ; Patrizia Mecocci [Italie] ; Bruno Velas [France] ; Simon Lovestone [Royaume-Uni] ; Henry Brodaty [Australie] ; David Ames [Australie] ; Julian N. Trollor [Australie] ; Nicholas G. Martin [Australie] ; Paul M. Thompson [États-Unis] ; Perminder S. Sachdev [Australie] ; Margaret J. Wright [Australie]

Source :

RBID : PMC:4883003

Descripteurs français

English descriptors

Abstract

Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer’s disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16–30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ɛ4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults.


Url:
DOI: 10.1016/j.neurobiolaging.2015.12.023
PubMed: 26973105
PubMed Central: 4883003


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<name sortKey="De Zubicaray, Greig I" sort="De Zubicaray, Greig I" uniqKey="De Zubicaray G" first="Greig I." last="De Zubicaray">Greig I. De Zubicaray</name>
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<name sortKey="Kloszewska, Iwona" sort="Kloszewska, Iwona" uniqKey="Kloszewska I" first="Iwona" last="Kloszewska">Iwona Kloszewska</name>
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<name sortKey="Mecocci, Patrizia" sort="Mecocci, Patrizia" uniqKey="Mecocci P" first="Patrizia" last="Mecocci">Patrizia Mecocci</name>
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<name sortKey="Lovestone, Simon" sort="Lovestone, Simon" uniqKey="Lovestone S" first="Simon" last="Lovestone">Simon Lovestone</name>
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<name sortKey="Brodaty, Henry" sort="Brodaty, Henry" uniqKey="Brodaty H" first="Henry" last="Brodaty">Henry Brodaty</name>
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<name sortKey="Ames, David" sort="Ames, David" uniqKey="Ames D" first="David" last="Ames">David Ames</name>
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<nlm:aff id="A17">Academic Unit for Psychiatry of Old Age, University of Melbourne, Kew, Victoria, Australia</nlm:aff>
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<name sortKey="Trollor, Julian N" sort="Trollor, Julian N" uniqKey="Trollor J" first="Julian N." last="Trollor">Julian N. Trollor</name>
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<name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G." last="Martin">Nicholas G. Martin</name>
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<name sortKey="Sachdev, Perminder S" sort="Sachdev, Perminder S" uniqKey="Sachdev P" first="Perminder S." last="Sachdev">Perminder S. Sachdev</name>
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<name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J." last="Wright">Margaret J. Wright</name>
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<nlm:aff id="A18">The Centre for Advanced Imaging, The University of Queensland, St Lucia, Queensland, Australia</nlm:aff>
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<nlm:aff id="A3">Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia</nlm:aff>
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<name sortKey="Mcmahon, Katie L" sort="Mcmahon, Katie L" uniqKey="Mcmahon K" first="Katie L." last="Mcmahon">Katie L. Mcmahon</name>
<affiliation wicri:level="1">
<nlm:aff id="A5">Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia</nlm:aff>
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<name sortKey="De Zubicaray, Greig I" sort="De Zubicaray, Greig I" uniqKey="De Zubicaray G" first="Greig I." last="De Zubicaray">Greig I. De Zubicaray</name>
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<author>
<name sortKey="Assareh, Amelia A" sort="Assareh, Amelia A" uniqKey="Assareh A" first="Amelia A." last="Assareh">Amelia A. Assareh</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia</nlm:aff>
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<name sortKey="Proitsi, Petroula" sort="Proitsi, Petroula" uniqKey="Proitsi P" first="Petroula" last="Proitsi">Petroula Proitsi</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London</wicri:regionArea>
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<name sortKey="Hibar, Derrek P" sort="Hibar, Derrek P" uniqKey="Hibar D" first="Derrek P." last="Hibar">Derrek P. Hibar</name>
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<nlm:aff id="A8">Imaging Genetics Center, Keck School of Medicine, University of Southern California, Marina del Ray, CA, USA</nlm:aff>
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<name sortKey="Soininen, Hilkka" sort="Soininen, Hilkka" uniqKey="Soininen H" first="Hilkka" last="Soininen">Hilkka Soininen</name>
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<name sortKey="Mecocci, Patrizia" sort="Mecocci, Patrizia" uniqKey="Mecocci P" first="Patrizia" last="Mecocci">Patrizia Mecocci</name>
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<nlm:aff id="A13">Section of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy</nlm:aff>
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<name sortKey="Velas, Bruno" sort="Velas, Bruno" uniqKey="Velas B" first="Bruno" last="Velas">Bruno Velas</name>
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<nlm:aff id="A14">Gerontopole, CHU, UMR INSERM 1027, University of Toulouse, France</nlm:aff>
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<nlm:aff id="A3">Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<nlm:aff id="A16">National Ageing Research Institute, Parkville, Victoria, Australia</nlm:aff>
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<wicri:regionArea>Academic Unit for Psychiatry of Old Age, University of Melbourne, Kew, Victoria</wicri:regionArea>
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<settlement type="city">Melbourne</settlement>
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<name sortKey="Trollor, Julian N" sort="Trollor, Julian N" uniqKey="Trollor J" first="Julian N." last="Trollor">Julian N. Trollor</name>
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<nlm:aff id="A3">Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales</wicri:regionArea>
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<name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G." last="Martin">Nicholas G. Martin</name>
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<nlm:aff id="A1">Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff>
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<name sortKey="Thompson, Paul M" sort="Thompson, Paul M" uniqKey="Thompson P" first="Paul M." last="Thompson">Paul M. Thompson</name>
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<nlm:aff id="A8">Imaging Genetics Center, Keck School of Medicine, University of Southern California, Marina del Ray, CA, USA</nlm:aff>
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<name sortKey="Sachdev, Perminder S" sort="Sachdev, Perminder S" uniqKey="Sachdev P" first="Perminder S." last="Sachdev">Perminder S. Sachdev</name>
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<nlm:aff id="A3">Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
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<name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J." last="Wright">Margaret J. Wright</name>
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<nlm:aff id="A1">Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff>
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<title level="j">Neurobiology of aging</title>
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<term>Adolescent</term>
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<term>Aged, 80 and over</term>
<term>Alzheimer Disease (diagnostic imaging)</term>
<term>Alzheimer Disease (genetics)</term>
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<term>Cognitive Dysfunction (diagnostic imaging)</term>
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<term>Genetic Association Studies</term>
<term>Hippocampus (diagnostic imaging)</term>
<term>Hippocampus (pathology)</term>
<term>Humans</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Middle Aged</term>
<term>Receptors, Immunologic (genetics)</term>
<term>Risk</term>
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<term>Adolescent</term>
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<term>Dysfonctionnement cognitif</term>
<term>Hippocampe</term>
<term>Maladie d'Alzheimer</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Alzheimer Disease</term>
<term>Amygdala</term>
<term>Cognitive Dysfunction</term>
<term>Hippocampus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Case-Control Studies</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Genetic Association Studies</term>
<term>Humans</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Risk</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Femelle</term>
<term>Humains</term>
<term>Imagerie par résonance magnétique</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Risque</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Études cas-témoins</term>
<term>Études d'associations génétiques</term>
<term>Études de cohortes</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="P1">Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer’s disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16–30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (
<italic>APOE</italic>
), and a single nucleotide polymorphism in
<italic>TREM2</italic>
, were both associated with reduced hippocampal volume in healthy older adults and those with MCI.
<italic>APOE</italic>
ɛ4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults.</p>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>Finlande</li>
<li>France</li>
<li>Grèce</li>
<li>Italie</li>
<li>Pologne</li>
<li>Royaume-Uni</li>
<li>Suède</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Californie</li>
<li>Grand Londres</li>
<li>Oxfordshire</li>
<li>Svealand</li>
<li>Victoria (État)</li>
</region>
<settlement>
<li>Londres</li>
<li>Los Angeles</li>
<li>Melbourne</li>
<li>Oxford</li>
<li>Stockholm</li>
</settlement>
<orgName>
<li>Université d'Oxford</li>
<li>Université de Californie du Sud</li>
<li>Université de Melbourne</li>
</orgName>
</list>
<tree>
<country name="Australie">
<noRegion>
<name sortKey="Lupton, Michelle K" sort="Lupton, Michelle K" uniqKey="Lupton M" first="Michelle K." last="Lupton">Michelle K. Lupton</name>
</noRegion>
<name sortKey="Ames, David" sort="Ames, David" uniqKey="Ames D" first="David" last="Ames">David Ames</name>
<name sortKey="Ames, David" sort="Ames, David" uniqKey="Ames D" first="David" last="Ames">David Ames</name>
<name sortKey="Armstrong, Nicola J" sort="Armstrong, Nicola J" uniqKey="Armstrong N" first="Nicola J." last="Armstrong">Nicola J. Armstrong</name>
<name sortKey="Assareh, Amelia A" sort="Assareh, Amelia A" uniqKey="Assareh A" first="Amelia A." last="Assareh">Amelia A. Assareh</name>
<name sortKey="Brodaty, Henry" sort="Brodaty, Henry" uniqKey="Brodaty H" first="Henry" last="Brodaty">Henry Brodaty</name>
<name sortKey="De Zubicaray, Greig I" sort="De Zubicaray, Greig I" uniqKey="De Zubicaray G" first="Greig I." last="De Zubicaray">Greig I. De Zubicaray</name>
<name sortKey="Hansell, Narelle K" sort="Hansell, Narelle K" uniqKey="Hansell N" first="Narelle K." last="Hansell">Narelle K. Hansell</name>
<name sortKey="Hansell, Narelle K" sort="Hansell, Narelle K" uniqKey="Hansell N" first="Narelle K." last="Hansell">Narelle K. Hansell</name>
<name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G." last="Martin">Nicholas G. Martin</name>
<name sortKey="Mather, Karen A" sort="Mather, Karen A" uniqKey="Mather K" first="Karen A." last="Mather">Karen A. Mather</name>
<name sortKey="Mcmahon, Katie L" sort="Mcmahon, Katie L" uniqKey="Mcmahon K" first="Katie L." last="Mcmahon">Katie L. Mcmahon</name>
<name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W." last="Montgomery">Grant W. Montgomery</name>
<name sortKey="Sachdev, Perminder S" sort="Sachdev, Perminder S" uniqKey="Sachdev P" first="Perminder S." last="Sachdev">Perminder S. Sachdev</name>
<name sortKey="Strike, Lachlan" sort="Strike, Lachlan" uniqKey="Strike L" first="Lachlan" last="Strike">Lachlan Strike</name>
<name sortKey="Strike, Lachlan" sort="Strike, Lachlan" uniqKey="Strike L" first="Lachlan" last="Strike">Lachlan Strike</name>
<name sortKey="Thalamuthu, Anbupalam" sort="Thalamuthu, Anbupalam" uniqKey="Thalamuthu A" first="Anbupalam" last="Thalamuthu">Anbupalam Thalamuthu</name>
<name sortKey="Trollor, Julian N" sort="Trollor, Julian N" uniqKey="Trollor J" first="Julian N." last="Trollor">Julian N. Trollor</name>
<name sortKey="Wen, Wei" sort="Wen, Wei" uniqKey="Wen W" first="Wei" last="Wen">Wei Wen</name>
<name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J." last="Wright">Margaret J. Wright</name>
<name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J." last="Wright">Margaret J. Wright</name>
<name sortKey="Wright, Margaret J" sort="Wright, Margaret J" uniqKey="Wright M" first="Margaret J." last="Wright">Margaret J. Wright</name>
</country>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Simmons, Andrew" sort="Simmons, Andrew" uniqKey="Simmons A" first="Andrew" last="Simmons">Andrew Simmons</name>
</region>
<name sortKey="Lovestone, Simon" sort="Lovestone, Simon" uniqKey="Lovestone S" first="Simon" last="Lovestone">Simon Lovestone</name>
<name sortKey="Lovestone, Simon" sort="Lovestone, Simon" uniqKey="Lovestone S" first="Simon" last="Lovestone">Simon Lovestone</name>
<name sortKey="Powell, John F" sort="Powell, John F" uniqKey="Powell J" first="John F." last="Powell">John F. Powell</name>
<name sortKey="Proitsi, Petroula" sort="Proitsi, Petroula" uniqKey="Proitsi P" first="Petroula" last="Proitsi">Petroula Proitsi</name>
</country>
<country name="États-Unis">
<region name="Californie">
<name sortKey="Hibar, Derrek P" sort="Hibar, Derrek P" uniqKey="Hibar D" first="Derrek P." last="Hibar">Derrek P. Hibar</name>
</region>
<name sortKey="Thompson, Paul M" sort="Thompson, Paul M" uniqKey="Thompson P" first="Paul M." last="Thompson">Paul M. Thompson</name>
</country>
<country name="Suède">
<region name="Svealand">
<name sortKey="Westman, Eric" sort="Westman, Eric" uniqKey="Westman E" first="Eric" last="Westman">Eric Westman</name>
</region>
</country>
<country name="Grèce">
<noRegion>
<name sortKey="Tsolaki, Magda" sort="Tsolaki, Magda" uniqKey="Tsolaki M" first="Magda" last="Tsolaki">Magda Tsolaki</name>
</noRegion>
</country>
<country name="Pologne">
<noRegion>
<name sortKey="Kloszewska, Iwona" sort="Kloszewska, Iwona" uniqKey="Kloszewska I" first="Iwona" last="Kloszewska">Iwona Kloszewska</name>
</noRegion>
</country>
<country name="Finlande">
<noRegion>
<name sortKey="Soininen, Hilkka" sort="Soininen, Hilkka" uniqKey="Soininen H" first="Hilkka" last="Soininen">Hilkka Soininen</name>
</noRegion>
</country>
<country name="Italie">
<noRegion>
<name sortKey="Mecocci, Patrizia" sort="Mecocci, Patrizia" uniqKey="Mecocci P" first="Patrizia" last="Mecocci">Patrizia Mecocci</name>
</noRegion>
</country>
<country name="France">
<noRegion>
<name sortKey="Velas, Bruno" sort="Velas, Bruno" uniqKey="Velas B" first="Bruno" last="Velas">Bruno Velas</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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