21,782 results on '"Newcastle University [Newcastle]"'
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2. How do we assess pain in rodents in veterinary practice, what do we know and why it is important?
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MALIK, ANEESA and Leach Member of Pain & Animal Welfare Science (PAWS) Group, School of Agriculture, Food & Rural Development, Agriculture Building, Newcastle University, Newcastle upon Tyne NE1 7RU, Matt
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VETERINARY medicine , *PAIN in animals , *EFFECT of stress on animals - Abstract
Without the ability to effectively recognise pain and assess its severity in animals, there is no way of assessing the efficacy of analgesia administered. Therefore, we have no way of ensuring that pain is adequately managed. Despite the extensive use of rodents in medical research that often involves the assessment of pain and distress, translation of this knowledge to veterinary medicine has been relatively neglected, and original veterinary research in pain assessment in rodents is lacking. This article aims to provide a broad overview of common behaviours that could be used to assess pain in rodents. [ABSTRACT FROM AUTHOR]
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- 2017
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3. Looking beyond Virus Detection in RNA Sequencing Data: Lessons Learned from a Community-Based Effort to Detect Cellular Plant Pathogens and Pests
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Annelies Haegeman, Yoika Foucart, Kris De Jonghe, Thomas Goedefroit, Maher Al Rwahnih, Neil Boonham, Thierry Candresse, Yahya Z. A. Gaafar, Oscar P. Hurtado-Gonzales, Zala Kogej Zwitter, Denis Kutnjak, Janja Lamovšek, Marie Lefebvre, Martha Malapi, Irena Mavrič Pleško, Serkan Önder, Jean-Sébastien Reynard, Ferran Salavert Pamblanco, Olivier Schumpp, Kristian Stevens, Chandan Pal, Lucie Tamisier, Çiğdem Ulubaş Serçe, Inge van Duivenbode, David W. Waite, Xiaojun Hu, Heiko Ziebell, Sébastien Massart, Research Institute for Agricultural, Fisheries and Food (ILVO), University of California [Davis] (UC Davis), University of California (UC), Newcastle University [Newcastle], Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Julius Kühn-Institut (JKI), USDA-APHIS PPQ, National Institute of Biology [Ljubljana] (NIB), Jozef Stefan International Postgraduate School [Ljubljana, Slovenia], Agricultural Institute of Slovenia, USDA-Animal and Plant Health Inspection Service (USDA-APHIS), United States Department of Agriculture (USDA), Department of Plant Protection, Agroscope, Chemistry, School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK, Zespri International Limited, Génétique et Amélioration des Fruits et Légumes (GAFL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Pathologie Végétale (PV), Niğde Ömer Halisdemir University, Dutch General Inspection Service for Agricultural Seed and Seed Potatoes, Plant Health and Environment Laboratory, Ministry for Primary Industries, Julius Kühn-Institut - Federal Research Centre for Cultivated Plants (JKI), Gembloux Agro-Bio Tech, University of Liege, Belgian Federal Public Service of Health, Food Chain Safety and Environment (FPS Health) through the contract 'RI 18_A-289'., Euphresco project 'Plant Health Bioinformatics Network' (PHBN) (2018-A-289)., Slovenian Research Agency (project and core financing grants No. P4-0072, L7-2632 and P4-0165), and European Project: 2018-A-289,PHBN
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metagenomics ,metatranscriptomics ,Ecology ,Prevention ,plant pathogen ,diagnostics ,high-throughput sequencing ,RNA-seq ,Plant Science ,[SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy ,Vaccine Related ,Emerging Infectious Diseases ,Infectious Diseases ,Biodefense ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Genetics ,Infection ,Ecology, Evolution, Behavior and Systematics - Abstract
International audience; High-throughput sequencing (HTS), more specifically RNA sequencing of plant tissues, has become an indispensable tool for plant virologists to detect and identify plant viruses. During the data analysis step, plant virologists typically compare the obtained sequences to reference virus databases. In this way, they are neglecting sequences without homologies to viruses, which usually represent the majority of sequencing reads. We hypothesized that traces of other pathogens might be detected in this unused sequence data. In the present study, our goal was to investigate whether total RNA-seq data, as generated for plant virus detection, is also suitable for the detection of other plant pathogens and pests. As proof of concept, we first analyzed RNA-seq datasets of plant materials with confirmed infections by cellular pathogens in order to check whether these non-viral pathogens could be easily detected in the data. Next, we set up a community effort to re-analyze existing Illumina RNA-seq datasets used for virus detection to check for the potential presence of non-viral pathogens or pests. In total, 101 datasets from 15 participants derived from 51 different plant species were re-analyzed, of which 37 were selected for subsequent in-depth analyses. In 29 of the 37 selected samples (78%), we found convincing traces of non-viral plant pathogens or pests. The organisms most frequently detected in this way were fungi (15/37 datasets), followed by insects (13/37) and mites (9/37). The presence of some of the detected pathogens was confirmed by independent (q)PCRs analyses. After communicating the results, 6 out of the 15 participants indicated that they were unaware of the possible presence of these pathogens in their sample(s). All participants indicated that they would broaden the scope of their bioinformatic analyses in future studies and thus check for the presence of non-viral pathogens. In conclusion, we show that it is possible to detect non-viral pathogens or pests from total RNA-seq datasets, in this case primarily fungi, insects, and mites. With this study, we hope to raise awareness among plant virologists that their data might be useful for fellow plant pathologists in other disciplines (mycology, entomology, bacteriology) as well.
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- 2023
4. Comment des classes spécifiques de cellules rétiniennes contribuent à la vision : un modèle computationnel
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Kartsaki, Evgenia, Biologically plausible Integrative mOdels of the Visual system : towards synergIstic Solutions for visually-Impaired people and artificial visiON (BIOVISION), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Côte d'Azur (UCA), Newcastle University [Newcastle], Université Côte d'Azur, Newcastle University (Newcastle upon Tyne, Royaume-Uni), Bruno Cessac, Evelyne Sernagor, and Gerrit Hilgen
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Simulations ,Connectivity ,Connectivité ,Rétine ,Modélisation ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Retina ,Modelling - Abstract
The human brain can recreate images by combining parallel streams of information emitted by about one million retinal ganglion cells (RGCs). RGCs exhibit an astonishing functional,anatomical, and molecular diversity and their preference for particular features of the visual scene(contrast, motion, etc.) can be attributed to synaptic connectivity patterns from upstream retinal circuits as well as intrinsic characteristics (such as gene expression, morphological features,membrane properties). However, how these different attributes give rise to distinct functional groups is still largely unknown. In this thesis, we investigated the functional properties of specific RGCs subgroups, sharing gene expression, by applying experimental and theoretical approaches to control their neuronal activity using pharmacogenetics. We hypothesised that modifying their activity may not only affect their individual response but also their concerted activity, thereby elucidating their role in population encoding of visual scenes.To explore this hypothesis, we worked on three main axes:1.General response characterisation of RGCs in control condition and when their activity is altered through pharmacogenetics.2.Development of a mathematical model, constrained by empirical data, to unravel the circuit wiring underlying functional diversity.3.Large-scale simulations of the model on Macular, a novel simulation platform, to explore retinal behaviour to complex stimuli.In this context, we analysed light responses recorded from mouse RGCs and we identified distinct cell types that respond in diverse patterns when their activity is pharmacologically modified. We hypothesised that these various response patterns may arise from lateral interactions between the different RGC types. We tested this hypothesis by means of model definition,mathematical analysis, and numerical simulations and illustrated the role of connectivity patterns in the behaviour of the system. Taken together, our work suggests possible physiological mechanisms underlying the variability of RGCs responses with an emphasis on the role of lateral connectivity on the retinal response.; Le cerveau humain peut recréer des images en combinant des flux parallèles d'informations émis par environ un million de cellules ganglionnaires rétiniennes (RGCs). Les RGCs présentent une étonnante diversité fonctionnelle, anatomique et moléculaire et leurs préférences pour des caractéristiques particulières d'une scène visuelle (contraste, mouvement, etc.) peuvent être attribuées aux modèles de connectivité synaptique des circuits rétiniens amont ainsi que des caractéristiques intrinsèques (telles que l'expression des gènes, les caractéristiques morphologiques, les propriétés membranaires). Cependant, la manière dont ces différents attributs donnent naissance à des groupes fonctionnels distincts est encore largement inconnue. Dans cette thèse,nous avons étudié les propriétés fonctionnelles de sous-groupes spécifiques de RGCs, partageant l'expression de certains gènes, en appliquant des approches expérimentales et théoriques pour contrôler leur activité neuronale en utilisant la pharmacogénétique. Nous avons émis l'hypothèse que la modification de leur activité peut non seulement affecter leur réponse mais aussi leur activité collective, soulignant ainsi leur rôle dans le codage de scènes visuelles effectué au niveau de populations neuronales.Pour explorer cette hypothèse, nous avons travaillé sur trois axes principaux :1.Caractérisation générale de la réponse des RGCs en condition de contrôle et lorsque leur activité est altérée par la pharmacogénétique.2.Développement d'un modèle mathématique, contraint par des données empiriques, pour explorer la structure des circuits sous-tendant la diversité fonctionnelle.3.Simulations à grande échelle du modèle sur Macular, une nouvelle plate-forme, dont le but est d'explorer le comportement rétinien à travers des stimulations visuelles complexes.Dans ce contexte, nous avons analysé les réponses lumineuses enregistrées à partir des RGCs de souris et nous avons identifié des cellules des types distincts qui répondent de diverses manières lorsque leur activité est pharmacologiquement modifiée. Nous avons émis l'hypothèse que ces divers modèles de réponse peuvent résulter d'interactions latérales entre les différents types de RGCs. Nous avons testé cette hypothèse au moyen de la définition du modèle, de l'analyse mathématique, et des simulations numériques et avons illustré le rôle des modèles de connectivité dans le comportement du système. Nos travaux suggèrent des mécanismes physiologiques possibles sous-tendant la variabilité des réponses des RGC en mettant l'accent sur le rôle de la connectivité latérale sur la réponse rétinienne.
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- 2022
5. Impact of dams and climate change on suspended sediment flux to the Mekong delta
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Gianbattista Bussi, Li Jin, Craig W. Hutton, Tristan Berchoux, Daniel R. Parsons, Christopher Hackney, Simon Dadson, Hal Voepel, Paul Whitehead, Grigorios Vasilopoulos, Stephen E. Darby, Andrew Nicholas, School of Geography and the Environment [Oxford] (SoGE), University of Oxford [Oxford], School of Geography and Environmental Sciences, University of Southampton, Geology Department, Suny Cortland, Partenaires INRAE-Partenaires INRAE, Energy and Environment Institute, University of Hull [United Kingdom], School of Geography, Politics and Sociology, Newcastle University, Newcastle upon Tyne, UK., Newcastle University [Newcastle], Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM), Territoires, Environnement, Télédétection et Information Spatiale (UMR TETIS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Exeter University - Department of geography, University of Exeter, and Biotechnology and Biological Sciences Research Council (BBSRC)NERC Natural Environment Research Council
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Delta ,ASIE DU SUD EST ,Environmental Engineering ,010504 meteorology & atmospheric sciences ,CLIMATIC CHANGE ,MODELS ,Drainage basin ,Fluvial ,Climate change ,010501 environmental sciences ,01 natural sciences ,[SHS]Humanities and Social Sciences ,MODELE ,DELTAS ,BARRAGE ,Environmental Chemistry ,SOIL FERTILITY ,14. Life underwater ,Waste Management and Disposal ,SEDIMENTATION ,DAMS ,0105 earth and related environmental sciences ,Hydrology ,geography ,geography.geographical_feature_category ,DELTA ,FERTILITE DU SOL ,Sediment ,[SDV.SA.AEP]Life Sciences [q-bio]/Agricultural sciences/Agriculture, economy and politics ,15. Life on land ,Pollution ,6. Clean water ,Current (stream) ,BASSIN VERSANT ,WATERSHEDS ,13. Climate action ,CHANGEMENT CLIMATIQUE ,Environmental science ,Climate model ,SOUTH EAST ASIA ,Sediment transport - Abstract
International audience; The livelihoods of millions of people living in the world's deltas are deeply interconnected with the sediment dynamics of these deltas. In particular a sustainable supply of fluvial sediments from upstream is critical for ensuring the fertility of delta soils and for promoting sediment deposition that can offset rising sea levels. Yet, in many large river catchments this supply of sediment is being threatened by the planned construction of large dams. In this study, we apply the INCA hydrological and sediment model to the Mekong River catchment in South East Asia. The aim is to assess the impact of several large dams (both existing and planned) on the suspended sediment fluxes of the river. We force the INCA model with a climate model to assess the interplay of changing climate and sediment trapping caused by dam construction. The results show that historical sediment flux declines are mostly caused by dams built in PR China and that sediment trapping will increase in the future due to the construction of new dams in PDR Lao and Cambodia. If all dams that are currently planned for the next two decades are built, they will induce a decline of suspended sediment flux of 50% (47–53% 90% confidence interval (90%CI)) compared to current levels (99 Mt/year at the delta apex), with potentially damaging consequences for local livelihoods and ecosystems.
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- 2020
6. Molards, a landform to track permafrost degradation in Iceland, Greenland and around the globe
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Costanza Morino, Susan Conway, Philip Deline, Kristian Svennevig, Antoine Lucas, Stuart Dunning, Morino, Costanza, Les molards, marqueurs de l'évolution de la dégradation du pergélisol de montagne - - Permolards2019 - ANR-19-CE01-0010 - AAPG2019 - VALID, Environnements, Dynamiques et Territoires de la Montagne (EDYTEM), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire de Planétologie et Géodynamique [UMR 6112] (LPG), Université d'Angers (UA)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Geological Survey of Denmark and Greenland (GEUS), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), School of Geography, Politics and Sociology, Newcastle University, Newcastle upon Tyne, UK., Newcastle University [Newcastle], and ANR-19-CE01-0010,Permolards,Les molards, marqueurs de l'évolution de la dégradation du pergélisol de montagne(2019)
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[SDU.STU.GM] Sciences of the Universe [physics]/Earth Sciences/Geomorphology ,[SDU.STU.GM]Sciences of the Universe [physics]/Earth Sciences/Geomorphology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2020
7. A meta-analysis of genome-wide association studies identifies multiple longevity genes
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Jerome I. Rotter, Rachel Duncan, Lenore J. Launer, Iris E. Jansen, Sarah Cubaynes, Nir Barzilai, Elizabeth J. Becker, Wiesje M. van der Flier, Joris Deelen, Sharon L.R. Kardia, Birgit Debrabant, Wanlin Zheng, Michael A. Province, Janina Dose, Anne B. Newman, Vilmundur Gudnason, Carol Jagger, Kenny Ye, Gil Atzmon, Carmen Martin-Ruiz, Kathryn L. Lunetta, Claudio Franceschi, Marianne Nygaard, Diana van Heemst, Najaf Amin, P. Eline Slagboom, Thomas B. L. Kirkwood, Ilkka Seppälä, Chloé Sarnowski, Heather J. Cordell, Terho Lehtimäki, Jennifer A. Smith, Cornelia M. van Duijn, Marja Jylhä, Dan E. Arking, Hélène Blanché, Jessica D. Faul, Yi Zeng, Henne Holstege, Kent D. Taylor, Junxia Min, Alice M. Arnold, Kristin L. Ayers, Mika Kähönen, Olli T. Raitakari, Pilar Galan, Mary K. Wojczynski, Jean-Marie Robine, Lene Christiansen, David R. Weir, Karen Davies, J. Collerton, Kaare Christensen, Douglas P. Kiel, Niccolò Tesi, Andrew Kingston, Bruce M. Psaty, Joanne M. Murabito, Marcel J. T. Reinders, Albert V. Smith, Xiaomin Liu, Leo-Pekka Lyytikäinen, Mary L. Biggs, Almut Nebel, Sven J. van der Lee, Mikko Hurme, David Karasik, Jean-François Deleuze, Thomas T. Perls, Erin B. Ware, Martijn Huisman, Marian Beekman, Chao Nie, Tamara B. Harris, Ellen A. Nohr, Eric S. Orwoll, Steven R. Cummings, Paola Sebastiani, James W. Vaupel, Wolfgang Lieb, Daniel S. Evans, Thorkild I. A. Sørensen, André G. Uitterlinden, Ashley van der Spek, Max planck Institute for Biology of Ageing [Cologne], Leiden University Medical Center (LUMC), California Pacific Medical Center Research Institute, Johns Hopkins University School of Medicine [Baltimore], McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Department of Clinical Genetics (Academic Medical Center, University of Amsterdam), VU University Medical Center [Amsterdam], Delft Bioinformatics Lab [Delft], Delft University of Technology (TU Delft), University of Southern Denmark (SDU), Beijing Genomics Institute [Shenzhen] (BGI), China National GeneBank, Division of Statistical Genomics, Washington University School of Medicine, Department of Biostatistics, University of Washington [Seattle], Department of Medicine, Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Medicine [Bronx, NY, USA], Albert Einstein College of Medicine [New York], Department of Biology, Faculty of Sciences and Science Education, Haifa University, University of Haifa [Haifa], Institute for Social Research, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Biostatistics [Boston, MA, USA], Harvard T.H. Chan School of Public Health, Icelandic Heart Association [Kopavogur, Iceland] (IHA), Department of Clinical Chemistry, Tempere University, Institute of Genetic Medicine [Newcastle], Newcastle University [Newcastle], Institute of Clinical Molecular Biology, Kiel University, SEMA4, Department of Biostatistics, University of Washington, Boston University [Boston] (BU), Fondation Jean Dausset CEPH, Odense University Hospital, Odense, Copenhagen University Hospital, Institute of Health and Society, Mécanismes moléculaires dans les démences neurodégénératives (MMDN), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institute of Neuroscience [Newcastle] (ION), Institute of Clinical Research, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institute of Ageing and Health, Newcastle University, Newcastle Upon Tyne, Department of Applied Mathematics and Centre of Bioinformatics, Lobachevsky State University [Nizhni Novgorod], Institute of Neurological Sciences of Bologna IRCCS, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Department of Clinical Epidemiology and Biostatistics, VU Medical Centre, Amsterdam, Amsterdam Public Health Research Institute [The Netherlands], Department of Microbiology and Immunology, University of Tampere [Finland], Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, Institute of Health & Society, Department of Complex Trait Genetics, Vrije Universiteit Amsterdam [Amsterdam] (VU), Tampere University Hospital, School of Public Health, University of Michigan [Dearborn], Faculty of Medicine and Life Sciences [Tampere], Institute of Epidemiology and Biobank PopGen, Faculty of Medicine and Health Technology [Tampere, Finland], Zhejiang University School of Medicine [China], University of Pittsburgh Graduate School of Public Health, Oregon Health & Sciences University, Oregon Health and Science University [Portland] (OHSU), Boston University School of Medicine (BUSM), Department of Medicine, University of Washington, Department of Epidemiology, University of Washington, Kaiser Permanente Washington Health Research Institute [Seattle] (KPWHRI), Turku University Hospital (TYKS), University of Turku, School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), UCLA Medical Center, University of Michigan System, University of Copenhage, Faculty of Health and Medical Sciences, MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), University of Bristol [Bristol], Los Angeles Biomedical Research Institute (LA BioMed), Harbor UCLA Medical Center [Torrance, Ca.], Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Department of Internal Medicine (ROTTERDAM - Med Int), Maasstad Ziekenhuis = Maasstad Hospital, Alzheimercentre, department of Neurology, VU University Medical Center, Nuffield Department of Population Health [Oxford], University of Oxford, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, Beijing Forestry University, Medical School of Duke University, Hinda and Arthur Marcus Institute for Aging Research,Hebrew SeniorLife, Harvard Medical School [Boston] (HMS), Broad Institute of MIT & Harvard, AUDOUX, Michèle, Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), University of California-University of California, Maasstad Hospital, University of Oxford [Oxford], Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Neurology, Amsterdam Neuroscience - Complex Trait Genetics, Human genetics, APH - Personalized Medicine, APH - Methodology, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Epidemiology, Internal Medicine, Universiteit Leiden, and École Pratique des Hautes Études (EPHE)
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0301 basic medicine ,Percentile ,Aging ,Apolipoprotein E2 ,media_common.quotation_subject ,Science ,[SDV]Life Sciences [q-bio] ,Longevity ,Apolipoprotein E4 ,Áhættuþættir ,General Physics and Astronomy ,Genome-wide association study ,Diseases ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Biology ,Genetic correlation ,Genome-wide association studies ,Article ,General Biochemistry, Genetics and Molecular Biology ,Odds ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Humans ,lcsh:Science ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,media_common ,Genetic association ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Multidisciplinary ,Öldrun ,Sjúkdómar ,Human Genome ,General Chemistry ,Genetic architecture ,[SDV] Life Sciences [q-bio] ,Ageing ,030104 developmental biology ,Risk factors ,Meta-analysis ,lcsh:Q ,Erfðarannsóknir ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Publisher's version (útgefin grein)., Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity., Alexander von Humboldt-Stiftung
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- 2019
8. The diagnostic performance of a simplified blood test (SteatoTest-2) for the prediction of liver steatosis
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Olivier Deckmyn, Frédéric Charlotte, R. Myers, Philippe Mathurin, Hugo Perazzo, Mona Munteanu, An Ngo, Raluca Pais, Valentina Peta, Thierry Poynard, Rohit Loomba, Vlad Ratziu, Yen Ngo, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), BioPredictive [Paris], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Gilead Sciences, Inc. [Foster City, CA, USA], Department of Medicine [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, University of California, The research leading to these results has received funding from the European Community’s Seventh Framework Program (FP7/2007–2013) under grant agreement HEALTHF2–2009–241762 for the project FLIP., The FLIP partners’ consortium Vlad Ratziu, Thierry Poynard: Assistance Publique Hopitaux de Paris, Groupe Hospitalier Pitie Salpetriere, Sorbonne University, Paris, France, Jean-Marie Castille, Yen Ngo: Biopredictive SAS, Paris, France, Tania Langon: Alma Consulting Group SAS,Paris, France, Chris Day, Dina Tiniakos: University of Newcastle, Newcastle, UK, Debbie Lawlor: University of Bristol, Bristol, UK, Giulio Marchesini: Universita di Bologna, Bologna, Italy, Fabio Marra: University di Firenze, Firenze, Italy, Elisabetta Bugianesi: Universita degli studi di Torino, Torino, Italy, Stefano Bellentani: Universita di Modena e Reggio Emilia, Modena, Italy, Jean-Francois Dufour: Universit_ e de Berne, Berne, Switzerland, Manuel Romero Gomez: Servicio Andaluz de Salud, Spain, Thorkild Sørensen: Bispebjerg hospital, Region Hovedstaden, Bispebjerg, Dutch, Claudio Tribelli: Fondazione Italiana Fegato-Fonlus, Milano, Italy, Samuele De Minicis: Universita di Ancona, Ancona,Italy, Michael Trauner: Medizinischen Universitaet, Wien, Austria, Claudia Oliveira: University of S~ ao Paulo School of Medicine, S~ ao Paulo, Brazil. The FLIP pathology consortium Pierre Bedossa: Assistance Publique-Hopitaux de Paris, hopital Beaujon, University Paris- Diderot, Paris, France, Alastair D. Burt: School of Medicine, University of Adelaide Adelaide, Australia, Annette S.H. Gouw: Department of Pathology & Medical Biology, University Medical Center Groningen, Groningen, The Netherlands, Carolin Lackner: Institute of Pathology, Medical University of Graz, Graz, Austria, Peter Schirmacher: Institut Fur Pathologie, Universit€ atsklinikum Heidelberg, Heidelberg, Germany, Luigi Terracciano: Institute of Pathology, University Hospital, Basel, Switzerland, DinaTiniakos: Medical School, National and Kapodistrian University of Athens, Greece and Medical School, Newcastle University, Newcastle-upon-Tyne, UK, J. Brain: Medical School, Newcastle University, Newcastle-upon-Tyne, UK, Yvonne Bury: Royal Victoria Infi rmary, Hospitals Foundation Trust, Newcastle upon Tyne, UK, Daniela Cabibi: University of Palermo, Palermo, Italy, Frederic Charlotte: Assistance Publique Hopitaux de Paris, Groupe Hospitalier Pitie- Salpetriere, Universite university of Torino, Ospedale Molinette, Torino, Italy, Luisa Losi: Modena University Hospital, Modena, Italy, Matteo Montani: Institute of Pathology, University of Bern, Bern, Switzerland, Marı a Jesus Pareja: Hospital Universitario de Valme, Sevilla, Spain, Dominique Wendum: Assistance Publique-Hopitaux de Paris, Hopital St Antoine Sorbonne University, Fritz Wrba: Medical University of Vienna, Vienna, Austria, Marianne Ziol: Assistance Publique-Hôpitaux de Paris, Hopital Jean Verdier, Universite Paris 13, Bobigny, France, Vlad Ratziu: Assistance Publique Hopitaux de Paris, Hopital Pitie Salpetriere, Sorbonne University, Paris,France. The FibroFrance group Thierry Poynard, Vlad Ratziu, Dominique Thabut, Joseph Moussalli, Pascal Lebray, Marika Rudler, Francoise Imbert Bismuth, Frederic Charlotte, Olivier Rosmorduc, Yvon Calmus: Anti- Fibrosis Center, Assistance Publique Hopitaux de Paris, Groupe Hospitalier Pitie-Salpetriere, Sorbonne University, Paris, France, Agnes Hartemann, Sophie Jacqueminet: Diabetes Center, Assistance Publique Hopitaux de Paris, Groupe Hospitalier Pitie-Salpetriere, Sorbonne University, Paris, France, Eric Bruckert, Philippe Giral: Lipid Center, Assistance Publique Hopitaux de Paris, Groupe Hospitalier Pitie-Salpetriere, Sorbonne University, Paris, France, Sylvie Naveau, Gabriel Perlemuter: Alcoholic liver Disease Center, Assistance Publique Hopitaux de Paris, Antoine Beclere Hospital, Clamart, France, Brigitte Varsat: Prevention Centers of Caisse Primaire Assurance Maladie, Paris, France, Anne Mercadier: Transfusion Unit, Assistance Publique Hopitaux de Paris, Groupe Hospitalier Pitie-Salpetriere, Sorbonne University, Paris, France Selonsertib group Study investigators in United States: Manal Abdelmalek, Hays Arnold, Kiran Bambha, Jaideep Behari, Stephen Caldwell, Naga Chalasani, Michael Charlton, James Cooper, Bradley Freilich, Reem Ghalib, Bilal Hameed, Kris V. Kowdley, Michelle Lai, Eric Lawitz, Rohit Loomba, Parvez Mantry, Mary Rinella, Arun Sanyal, Mitchell L. Shiffman, Paul Thuluvath, and Dawn Torres, in Canada : Saumya Jayakumar, and Magdy Elkhashab., European Project: 241762,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,FLIP(2010), Gestionnaire, Hal Sorbonne Université, Fatty liver: Inhibition of Progression - FLIP - - EC:FP7:HEALTH2010-01-01 - 2013-06-30 - 241762 - VALID, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Department of Medicine [Univ California San Diego] (MED - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), and University of California (UC)
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Adult ,Male ,medicine.medical_specialty ,Concordance ,Biopsy ,SteatoTest ,false-positive steatosis test ,Gastroenterology ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Sex Factors ,Predictive Value of Tests ,Internal medicine ,Original Articles: Hepatology ,medicine ,Prevalence ,Blood test ,Humans ,control group for steatosis test ,Prospective cohort study ,Retrospective Studies ,Hepatology ,Receiver operating characteristic ,medicine.diagnostic_test ,business.industry ,Age Factors ,Reproducibility of Results ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Retrospective cohort study ,Middle Aged ,medicine.disease ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Confidence interval ,3. Good health ,Fatty Liver ,030220 oncology & carcinogenesis ,Predictive value of tests ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,false-negative steatosis test ,Feasibility Studies ,030211 gastroenterology & hepatology ,Female ,Steatosis ,business ,noninvasive diagnosis ,Biomarkers - Abstract
Supplemental Digital Content is available in the text., Background Serum biomarkers of steatosis such as the SteatoTest are recommended for large-scale screening studies, because imaging is less accessible and more expensive. Aims The primary aim of this retrospective analysis of prospective studies was to construct a new SteatoTest-2 that was not inferior to the reference first-generation SteatoTest, but that did not include BMI or bilirubin, as these two components can increase test variability because of the assessment of weight and height and in case of Gilbert syndrome or hemolysis, respectively. Patients and methods Five different subsets of 2997 patients with biopsies were evaluated for test construction and validation, and four to assess the prevalence of steatosis in target populations with increasing risks of steatosis. The performance of the SteatoTest-2 was compared with the reference test, using the noninferiority test (0.10 margin) and the Lin concordance coefficient. Results Areas under the receiver operating characteristic curve of the SteatoTest-2 were noninferior to the reference test (P
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- 2018
9. Review article: The need for more efficient and patient‐oriented drug development pathways in NASH—setting the scene for platform trials
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Di Prospero, Nicholas A., Anstee, Quentin M., Mesenbrinck, Peter, Kjær, Mette S, Rivera-Esteban, Jesús, Sena, Elena, Genesca, Joan, Pericas, Juan M, Manzano-Nunez, Ramiro, Institut Català de la Salut, [Pericàs JM, Rivera-Esteban J, Sena E, Manzano R, Genescà J] Unitat Hepàtica, Servei de Medicina Interna, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Di Prospero NA] Janssen Research and Development, Raritan, New Jersey, USA. [Anstee QM] Liver Unit, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. [Mesenbrinck P] Analytics Department, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. [Kjaer MS] Novo Nordisk A/S, Bagsværd, Denmark, and Vall d'Hebron Barcelona Hospital Campus
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Medicaments - Desenvolupament ,enfermedades del sistema digestivo::enfermedades hepáticas::hígado graso::esteatosis hepática no alcohólica [ENFERMEDADES] ,Esteatosi hepàtica - Tractament ,Hepatology ,técnicas de investigación::desarrollo de medicamentos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Gastroenterology ,Digestive System Diseases::Liver Diseases::Fatty Liver::Non-alcoholic Fatty Liver Disease [DISEASES] ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Pharmacology (medical) ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Investigative Techniques::Drug Development [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] - Abstract
Drug development; Non-alcoholic steatohepatitis; Study designs Desenvolupament de fàrmacs; Esteatohepatitis no alcohòlica; Dissenys d'estudi Desarrollo de fármacos; Esteatohepatitis no alcohólica; Diseños de estudio Background and Aims Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. Platform trials (PT) might help accelerate drug development while lowering overall costs and creating a more patient-centric environment. This review provides a comprehensive and nuanced assessment of the NASH clinical development landscape. Methods Narrative review and expert opinion with insight gained during the EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. Results Although NASH represents an opportunity to use adaptive trial designs, including master protocols for PT, there are barriers that might be encountered owing to distinct and sometimes opposing priorities held by these stakeholders and potential ways to overcome them. The following aspects are critical for the feasibility of a future PT in NASH: readiness of the drug pipeline, mainly from large drug companies, while there is not yet an FDA/EMA-approved treatment; the most suitable design (trial Phase and type of population, e.g., Phase 2b for non-cirrhotic NASH patients); the operational requirements such as the scope of the clinical network, the use of concurrent versus non-concurrent control arms, or the re-allocation of participants upon trial adaptations; the methodological appraisal (i.e. Bayesian vs. frequentist approach); patients' needs and patient-centred outcomes; main regulatory considerations and the funding and sustainability scenarios. Conclusions PT represent a promising avenue in NASH but there are a number of conundrums that need addressing. It is likely that before a global NASH PT becomes a reality, ‘proof-of-platform’ at a smaller scale needs to be provided. JMP reports having received consulting fees from Boehringer-Ingelheim, MSD and Novo Nordisk. He has received speaking fees from Gilead, Intercept, and Novo Nordisk, and travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk. He has received educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD. Funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898. NAdP works for Janssen. QMA is Coordinator of the EU IMI-2 LITMUS consortium, which is funded by the EU Horizon 2020 programme and EFPIA. This multistakeholder consortium includes industry partners. He reports research Grant Funding: Allergan/Tobira, AstraZeneca, Boehringer-Ingelheim, Glaxo SmithKline, Glympse Bio, Intercept, Novartis Pharma AG, Pfizer Ltd. Consultancy: 89Bio, Abbvie/Allergan, Akero, Altimentiv, Altimmune, AstraZeneca, Axcella, Blade, BMS, BNN Cardio, Boehringer-Ingelheim, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly & Company Ltd., Galmed, Genentech, Genfit SA, Gilead, Grunthal, HistoIndex, Indalo, Intercept Pharma Europe Ltd., Inventiva, IQVIA, Janssen, Johnson & Johnson, Madrigal, MedImmune, Medpace, Merck, Metacrine, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, PathAI, Pfizer Ltd., Poxel, ProSciento, Raptor Pharma, Roche, Servier, Shionogi, Terns, The Medicines Company, Viking Therapeutics. Speaker: Abbott Laboratories, Allergan/Tobira, BMS, Clinical Care Options, Falk, Fishawack, Genfit SA, Gilead, Integritas Communications, Kenes, Medscape. Royalties: Elsevier Ltd. PM works for Novartis. MSK is an employee of and a shareholder in Novo Nordisk A/S. JG has received consulting fees from Boehringer-Ingelheim, speaking fees from Echosens and travel expenses from Gilead and Abbie. Funds from ISCIII PI18/00947 and PI21/00691. JRE has received speaking fees from Gilead. FT lab’ work has been supported by the German Research Foundation (DFG, CRC/TR 362) and research grants from Gilead, Allergan, Bristol-Myers Squibb and Inventiva. VR consults for and Intercept, Novo Nordisk, Galmed, Poxel, NGM, Madrigal, Enyo, Sagimet, 89 Bio, Prosciento, Terns, and Theratechnologies, and received grants from Intercept and Gilead.
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- 2023
10. Platform trials to overcome major shortcomings of traditional clinical trials in non-alcoholic steatohepatitis? Pros and cons
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Juan M. Pericàs, Frank Tacke, Quentin M. Anstee, Nicholas A. Di Prospero, Mette Skalshøj Kjær, Peter Mesenbrink, Franz Koenig, Joan Genescà, Vlad Ratziu, Institut Català de la Salut, [Pericàs JM, Genescà J] Unitat Hepàtica, Servei de Medicina Interna, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Centros de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. [Tacke F] Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany. [Anstee QM] Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle NIHR Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK. [Di Prospero NA] Janssen Research and Development, Raritan, New Jersey, USA. [Kjær MS] Novo Nordisk, Bagsværd, Denmark. [Mesenbrink P] Analytics Department, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. [Koenig F] Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria. [Ratziu V] Department of Hepatology, Pitié-Salpêtrière Hospital, France, and Vall d'Hebron Barcelona Hospital Campus
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Medicaments - Desenvolupament ,enfermedades del sistema digestivo::enfermedades hepáticas::hígado graso::esteatosis hepática no alcohólica [ENFERMEDADES] ,Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores] ,Hepatology ,técnicas de investigación::desarrollo de medicamentos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Digestive System Diseases::Liver Diseases::Fatty Liver::Non-alcoholic Fatty Liver Disease [DISEASES] ,Esteatosi hepàtica - Complicacions ,Other subheadings::Other subheadings::/complications [Other subheadings] ,Investigative Techniques::Drug Development [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] - Abstract
Non-alcoholic steatohepatitis; Drug development; Non-invasive biomarkers Esteatohepatitis no alcohólica; Desarrollo de fármacos; Biomarcadores no invasivos Esteatohepatitis no alcohòlica; Desenvolupament de medicaments; Biomarcadors no invasius Non-alcoholic fatty liver disease is a condition that affects 25% of the population. Non-alcoholic steatohepatitis (NASH) is a progressive form of the disease that can lead to severe complications such as cirrhosis and hepatocellular carcinoma. Despite its high prevalence, no drugs are currently approved for the treatment of NASH. The drug development pipeline in NASH is very active, yet most assets do not progress to phase III trials and those that do reach phase III often fail to achieve the endpoints necessary for approval by regulatory agencies. Amongst other reasons, the methodological and operational features of traditional clinical trials in NASH might impede optimal drug development. In this regard, platform trials might be an attractive complement or alternative to conventional clinical trials. Platform trials use a master protocol which enables evaluation of multiple investigational medicinal products concurrently or sequentially with a single, shared control arm. Through Bayesian interim analyses, these trials allow for early exit of drugs from the trial based on success or futility, while providing participants better chances of receiving active compounds through adaptive randomisation. Overall, platform trials represent an alternative for patients, pharmaceutical companies, and clinicians in the quest to accelerate the approval of pharmacologic treatments for NASH. EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Children’s Tumor Foundation, Global Alliance for TB Drug Development Non-profit Organisation, Springworks Therapeutics Inc.
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- 2023
11. Mixed coagulant-flocculant optimization for pharmaceutical effluent pretreatment using response surface methodology and Gaussian process regression
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Tahraoui, H., Belhadj, A.-E., Triki, Z., Boudellal, N.R., Seder, S., Amrane, A., Zhang, J., Moula, N, Tifoura, A., Ferhat, R., Bousselma, A., Mihoubi, N., Université Salah Boubnider Constantine 3, Université Yahia Fares de Médéa, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Faculty of Veterinary Medicine - Faculteit Diergeneeskunde [UGhent, Belgium], Universiteit Gent = Ghent University (UGENT), and University of Batna Hadj Lakhder [Algeria]
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Multi-objective optimization ,Pharmaceutical effluent ,Environmental Engineering ,Response surface methodology ,General Chemical Engineering ,[CHIM]Chemical Sciences ,Environmental Chemistry ,Safety, Risk, Reliability and Quality ,Gaussian process regression ,Coagulation-flocculation - Abstract
International audience; Wastewater from the Antibiotical-Saidal pharmaceutical plant (Medéa) was pretreated by coagulation-flocculation using copper sulfate (CuSO4), iron chloride (FeCl3), and mixture of the two salts combined in a 1:1 (v/v) ratio in the present study. Response surface methodology (RSM) was used to optimize pH and coagulant dosage as independent variables, while dissolved organic carbon (DOC), absorbance at 254 nm (UV 254), and turbidity were provided as dependent variables in the central composite design (CCD). Then, the databases of the three treatments were combined in a single database to create a general model valid for the three treatments at the same time, and to predict the reduction rates of DOC, UV254, and turbidity, using the Gaussian process regression coupled with the dragonfly optimization algorithm (GPR-DA). To have the best model obtained between RMS and GPR-DA, an experimental validation was carried out after having had the optimal conditions of each type of coagulant, using the multi-objective optimization technique. The results of the experimental validation show the superiority of the GPR-DA model compared to the RSM model. Also, the results show that the mixed coagulant (CuSO4 + FeCl3) obtain better results than CuSO4 or FeCl3 alone with a treatment efficiency equal to 92.68% at pH = 5 and dosage = 600 mg/L, and the reductions in DOC, UV 254 and turbidity are 97.32%, 82.90% and 96.47%, respectively. © 2022 The Institution of Chemical Engineers
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- 2023
12. The 1905 Chamonix earthquakes: active tectonics in the Mont Blanc and Aiguilles Rouges massifs
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Cara, Michel, Van Der Woerd, Jerome, Alasset, Pierre-Jean, Benjumea, Juan, Meriaux, Anne-Sophie, Sismologie (IPGS) (IPGS-Sismologie), Institut de physique du globe de Strasbourg (IPGS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), School of Geography, Politics and Sociology, Newcastle University, Newcastle upon Tyne, UK., Newcastle University [Newcastle], Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)
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[SDU.STU.TE]Sciences of the Universe [physics]/Earth Sciences/Tectonics ,[SDU.STU.GP]Sciences of the Universe [physics]/Earth Sciences/Geophysics [physics.geo-ph] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2017
13. Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
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Geraldine Dawson, Sven Sandin, Frederico Duque, Peter Holmans, Marion Leboyer, Aarno Palotie, Fritz Poustka, Richard Delorme, Stephen Sanders, Alistair T. Pagnamenta, Lonnie Zwaigenbaum, Bridget A. Fernandez, A. Jeremy Willsey, Christine M. Freitag, Christa Lese Martin, Elena Maestrini, Elena Bacchelli, Guiomar Oliveira, Jeremy R. Parr, Guy A. Rouleau, Jonas Bybjerg-Grauholm, Joseph Piven, Latha Soorya, Lauren A. Weiss, Jonathan Green, Carsten Bøcker Pedersen, Louise Gallagher, Regina Regan, Stephan Ripke, Thomas Werge, Pat Levitt, Aravinda Chakravarti, Joana Almeida, Kathryn Roeder, Catalina Betancur, Bernie Devlin, Benjamin M. Neale, Gillian Baird, Jakob Grove, Thomas Bourgeron, David H. Ledbetter, Eftichia Duketis, Karola Rehnström, Gerard D. Schellenberg, Jillian P. Casey, Preben Bo Mortensen, Patrick Bolton, Igor Martsenkovsky, Elise Robinson, Hakon Hakonarson, Vanessa H. Bal, Stacy Steinberg, Christopher Gillberg, Kathryn Tsang, Jacob A. S. Vorstman, Verneri Anttila, Suma Jacob, Judith Conroy, J. Haines, William M. McMahon, Edwin H. Cook, Ann P. Thompson, Inês C. Conceição, Mark J. Daly, Arthur P. Goldberg, Sarah E. Medland, Milica Pejovic-Milovancevic, David M. Hougaard, Shrikant Mane, Christina M. Hultman, Susana Mouga, Hreinn Stefansson, Ellen M. Wijsman, Andreas G. Chiocchetti, Ole Mors, Phil Lee, Richard Anney, Astrid M. Vicente, Veronica J. Vieland, K. Stefansson, Stephen W. Scherer, Teimuraz Silagadze, Pall Magnusson, Donna M. Martin, Merete Nordentoft, Peter Szatmari, Patrícia B. S. Celestino-Soper, Ann S Le-Couteur, Cátia Café, Arthur L. Beaudet, Kerstin Wittemeyer, Anders D. Børglum, Joel S. Bader, Christopher S. Poultney, Hailiang Huang, Alexander Kolevzon, Margaret A. Pericak-Vance, Joachim Hallmayer, Rita M. Cantor, Eric Fombonne, Andrew Green, Dan E. Arking, M. Daniele Fallin, Matthew W. State, Christine Ladd-Acosta, Silvia Derubeis, Raphael Bernier, Regina Waltes, David G. Amaral, Manuel Mattheisen, Abraham Reichenberg, Lambertus Klei, Daniel Moreno-De-Luca, Marie Bækvad-Hansen, Maretha V. Dejonge, Susan G. McGrew, Joseph D. Buxbaum, Hilary Coon, Jennifer Reichert, Michael Gill, Herman Vanengeland, Christine Søholm Hansen, Anthony P. Monaco, Nadia Bolshakova, John I. Nurnberger, Nancy J. Minshew, Michael T. Murtha, Thomas H. Wassink, Evald Saemundsen, Simon Wallace, Sean Brennan, Sean Ennis, A. Gulhan Ercan-Sencicek, Sven Bölte, Oscar Svantesson, Susan L. Santangelo, Andrew D. Paterson, Robert L. Hendren, Timothy W. Yu, Dalila Pinto, D.E. Grice, Alison Merikangas, Stephen J. Guter, Anthony J. Bailey, Bernadette Rogé, Christopher A. Walsh, Susan E. Folstein, Wendy Roberts, Sabine M. Klauck, Marianne Giørtz Pedersen, Tiago R. Magalhaes, John R. Gilbert, Irva Hertz-Picciotto, James S. Sutcliffe, Evdokia Anagnostou, Catarina Correia, Eric M. Morrow, Daniel H. Geschwind, Jennifer K. Lowe, Agatino Battaglia, Bozenna Iliadou, Michael L. Cuccaro, Catherine Lord, MRC Centre for Neuropsychiatric Genetics and Genomics [Cardiff, UK], Cardiff University, The Autism Working Group of the Psychiatric Genomics Consortium was supported by National Institutes of Mental Health (NIMH, USA) grant MH109539, MH094432 and MH094421 to M.J.D. The ACE Network was supported by MH081754 and MH100027 to D.H.G. The Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) and was supported by grant MH081810. The Autism Genome Project (AGP) was supported by grants from Autism Speaks, the Canadian Institutes of Health Research (CIHR), Genome Canada, the Health Research Board (Ireland, AUT/ 2006/1, AUT/2006/2, PD/2006/48), the Hilibrand Foundation (USA), the Medical Research Council (UK), the National Institutes of Health (USA, the National Institute of Child Health and Human Development and the National Institute of Mental Health), the Ontario Genomics Institute, and the University of Toronto McLaughlin Centre. The Simons Simplex Collection (SSC) was supported by a grant from the Simons Foundation (SFARI 124827 to the investigators of the Simons Simplex Collection Genetic Consortium), approved researchers can obtain the SSC population dataset described in this study (http://sfari.org/resources/sfari-base) by applying at https://base.sfari.org. The Gene Discovery Project of Johns Hopkins was funded by MH060007, MH081754, and the Simons Foundation. The MonBos Collection study was funded in part through a grant from the Autism Consortium of Boston. Support for the Extreme Discordant Sib-Pair (EDSP) family sample (part of the MonBos collection) was provided by the NLM Family foundation. Support for the Massachusetts General Hospital (MGH)–Finnish collaborative sample was provided by NARSAD. The PAGES collection was funded by NIMH grant MH097849. The collection of data and biomaterials that participated in the NIMH Autism Genetics Initiative has been supported by National Institute of Health grants MH52708, MH39437, MH00219, and MH00980, National Health Medical Research Council grant 0034328, and by grants from the Scottish Rite, the Spunk Fund, Inc., the Rebecca and Solomon Baker Fund, the APEX Foundation, the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD), the endowment fund of the Nancy Pritzker Laboratory (Stanford), and by gifts from the Autism Society of America, the Janet M. Grace Pervasive Developmental Disorders Fund, and families and friends of individuals with autism. The iPSYCH project is funded by The Lundbeck Foundation and the universities and university hospitals of Aarhus and Copenhagen. In addition, the genotyping of iPSYCH samples was supported by grants from the Stanley Foundation, the Simons Foundation (SFARI 311789 to MJD), and NIMH (5U01MH094432-02 to MJD). The Study to Explore Early Development (SEED) was funded by the Centers for Disease Control and Prevention (CDC) grants U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, and U10DD000498. Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003), along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Additional statistical analyses were performed and supported by the Trinity Centre for High Performance Computing (http://www.tchpc.tcd.ie/) funded through Science Foundation Ireland. Computational support for the PAGES collection was provided in part through the computational resources and staff expertise of the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai (https://hpc.mssm.edu). Data QC and statistical analyses of the iPSYCH samples were performed at the high-performance computing cluster GenomeDK (http://genome.au.dk) at the Center for Integrative Sequencing, iSEQ, Aarhus University. iSEQ provided computed time, data storage, and technical support for the study., Richard JL Anney, Email: anneyr@cardiff.ac.uk, Affiliation/s: MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, CF24 4HQ, UK, Department of Psychiatry, Trinity College Dublin, Dublin, D8, Ireland. Stephan Ripke, Email: ripke@atgu.mgh.harvard.edu, Affiliation/s: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA, Stanley Center for Psychiatric Research and Program in Medical and Population Genetic, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin 10117, Germany. Verneri Anttila, Affiliation/s: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA, Stanley Center for Psychiatric Research and Program in Medical and Population Genetic, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Jakob Grove, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, DK-8000, Denmark, Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, DK-8000, Denmark, Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. Peter Holmans, Affiliation/s: MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, CF24 4HQ, UK. Hailiang Huang, Affiliation/s: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA, Stanley Center for Psychiatric Research and Program in Medical and Population Genetic, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Lambertus Klei, Affiliation/s: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Phil H Lee, Affiliation/s: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA, Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA. Sarah E Medland, Affiliation/s: Queensland Institute of Medical Research Brisbane, QLD, 4006, Australia. Benjamin Neale, Affiliation/s: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA, Stanley Center for Psychiatric Research and Program in Medical and Population Genetic, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Elise Robinson, Affiliation/s: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA, Stanley Center for Psychiatric Research and Program in Medical and Population Genetic, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Lauren A Weiss, Affiliation/s: Department of Psychiatry, University of California San Francisco, San Francisco, CA 94143, USA, Inst Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA. Lonnie Zwaigenbaum, Affiliation/s: Department of Pediatrics, University of Alberta, Edmonton, AB, T6G 1C9, Canada. Timothy W Yu, Affiliation/s: Division of Genetics, Children ’ s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. Kerstin Wittemeyer, Affiliation/s: School of Education, University of Birmingham, Birmingham, B15 2TT, UK. A.Jeremy Willsey, Affiliation/s: Department of Psychiatry, University of California San Francisco, San Francisco, CA 94143, USA. Ellen M Wijsman, Affiliation/s: Department of Medicine, University of Washington, Seattle, WA 98195, USA, Department of Biostatistics, University of Washington, Seattle, WA 98195, USA. Thomas Werge, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Institute of Biological Psychiatry, MHC Sct Hans, Mental Health Services Copenhagen, Roskilde, Denmark, Department of Clinical Medicine, University of Copenhagen, Copenhagen, DK-2200, Denmark. Thomas H Wassink, Affiliation/s: Department of Psychiatry, Carver College of Medicine, Iowa City, IA 52242, USA. Regina Waltes, Affiliation/s: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe University Frankfurt, Frankfurt am Main, 60528, Germany. Christopher A Walsh, Affiliation/s: Division of Genetics, Children ’ s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA, Program in Genetics and Genomics, Harvard Medical School, Boston, MA 02115, USA, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA, Simon Wallace, Affiliation/s: Department of Psychiatry, University of Oxford and Warneford Hospital, Oxford, OX3 7JX, UK. Jacob AS Vorstman, Affiliation/s: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands. Veronica J Vieland, Affiliation/s: Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children ’ s Hospital, Columbus, OH 43205, USA. Astrid M Vicente, Affiliation/s: Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa, 1600, Portugal, Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, Lisboa, 1649, Portugal. Herman vanEngeland, Affiliation/s: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands. Kathryn Tsang, Affiliation/s: Department of Psychiatry, University of California San Francisco, San Francisco, CA 94143, USA, Inst Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA. Ann P Thompson, Affiliation/s: Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, L8S 4L8, Canada. Peter Szatmari, Affiliation/s: Department of Psychiatry, University of Toronto, ON, M5T 1R8, Canada. Oscar Svantesson, Affiliation/s: Karolinska Institutet, Solna, SE-171 77, Sweden. Stacy Steinberg, Affiliation/s: deCODE Genetics, Reykjavik, IS-101, Iceland. Kari Stefansson, Affiliation/s: deCODE Genetics, Reykjavik, IS-101, Iceland. Hreinn Stefansson, Affiliation/s: deCODE Genetics, Reykjavik, IS-101, Iceland. Matthew W State, Affiliation/s: Department of Psychiatry, University of California San Francisco, San Francisco, CA 94143, USA. Latha Soorya, Affiliation/s: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Department of Psychiatry, Rush University Medical Center, Chicago, IL 60612, USA. Teimuraz Silagadze, Affiliation/s: Department of Psychiatry and Drug Addiction, Tbilisi State Medical University, Tbilisi, 0186, Georgia. Stephen W Scherer, Affiliation/s: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, M5G 1L4, Canada, McLaughlin Centre, University of Toronto, Toronto, ON, M5G 0A4, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada. Gerard D Schellenberg, Affiliation/s: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19102, USA. Sven Sandin, Affiliation/s: Karolinska Institutet, Solna, SE-171 77, Sweden. Stephan J Sanders, Affiliation/s: Department of Psychiatry, University of California San Francisco, San Francisco, CA 94143, USA. Evald Saemundsen, Affiliation/s: State Diagnostic and Counseling Centre, Kopavogur, IS-201, Iceland. Guy A Rouleau, Affiliation/s: Montreal Neurological Institute, Dept of Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada. Bernadette Rogé, Affiliation/s: Centre d ’ Etudes et de Recherches en Psychopathologie, Toulouse University, Toulouse, 31058, France. Kathryn Roeder, Affiliation/s: Department of Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15213, USA, Department of Statistics, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Wendy Roberts, Affiliation/s: Autism Research Unit, The Hospital for Sick Children, Toronto, ON, M5G 1L4, Canada. Jennifer Reichert, Affiliation/s: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Abraham Reichenberg, Affiliation/s: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Karola Rehnström, Affiliation/s: Sanger Institute, Hinxton, CB10 1SA, UK. Regina Regan, Affiliation/s: National Childrens Research Centre, Our Lady ’ s Hospital Crumlin, Dublin, D12, Ireland, Academic Centre on Rare Diseases, University College Dublin, Dublin, D4, Ireland. Fritz Poustka, Affiliation/s: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe University Frankfurt, Frankfurt am Main, 60528, Germany. Christopher S Poultney, Affiliation/s: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Joseph Piven, Affiliation/s: University of North Carolina, Chapel Hill, NC 27599, USA. Dalila Pinto, Affiliation/s: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Margaret A Pericak-Vance, Affiliation/s: The John P Hussman Institute for Human Genomics, University of Miami, Miami, FL 33101, USA. Milica Pejovic-Milovancevic, Affiliation/s: Institute of Mental Health and Medical Faculty, University of Belgrade, Belgrade, 11 000, Serbia. Marianne Giørtz Pedersen, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark, Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark. Carsten Bøcker Pedersen, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark. Andrew D Paterson, Affiliation/s: Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, M5G 1L4, Canada, Dalla Lana School of Public Health, Toronto, ON, M5T 3M7, Canada. Jeremy R Parr, Affiliation/s: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK, Institue of Health and Science, Newcastle University, Newcastle Upon Tyne, NE2 4AX, UK. Alistair T Pagnamenta, Affiliation/s: Wellcome Trust Centre for Human Genetics, OxfordUniversity,Oxford,OX37BN,UK. Guiomar Oliveira, Affiliation/s: Unidade de Neurodesenvolvimento e Autismo do Serviço do Centro de Desenvolvimento da Criança and Centro de Investigação e Formação Clinica, Pediatric Hospital, Centro Hospitalar e Universitário de Coimbra, Coimbra, 3041-80, Portugal, University Clinic of Pediatrics and Institute for Biomedical Imaging and Life Science, Faculty of Medicine, University of Coimbra, Coimbra, 3041-80, Portugal. John I Nurnberger, Affiliation/s: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA, Program in Medical Neuroscience, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Merete Nordentoft, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark. Michael T Murtha, Affiliation/s: Programs on Neurogenetics, Yale University School of Medicine, New Haven, CT 06520, USA. Susana Mouga, Affiliation/s: Unidade de Neurodesenvolvimento e Autismo do Serviço do Centro de Desenvolvimento da Criança and Centro de Investigação e Formação Clinica, Pediatric Hospital, Centro Hospitalar e Universitário de Coimbra, Coimbra, 3041-80, Portugal, University Clinic of Pediatrics and Institute for Biomedical Imaging and Life Science, Faculty of Medicine, University of Coimbra, Coimbra, 3041-80, Portugal. Preben Bo Mortensen, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Na- tional Centre for Register-based Research, Aarhus University, Aarhus, Denmark, Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark, Ole Mors, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark. Eric M Morrow, Affiliation/s: Department of Psychiatry and Human Behaviour, Brown University, Providence, RI 02912, USA. Daniel Moreno-De-Luca, Affiliation/s: Department of Psychiatry and Hu- man Behaviour, Brown University, Providence, RI 02912, USA. Anthony P Monaco, Affiliation/s: Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, OX3 7BN, UK, Tufts University, Boston, MA 02155?, USA. Nancy Minshew, Affiliation/s: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Alison Merikangas, Affiliation/s: Department of Psychiatry, Trinity College Dublin, Dublin, D8, Ireland. William M McMahon, Affiliation/s: Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA. Susan G McGrew, Affiliation/s: Department of Pediatrics, Vanderbilt University, Nashville, TN 37232, USA. Manuel Mattheisen, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, DK-8000, Denmark. Igor Martsenkovsky, Affiliation/s: Department of Child, Adolescent Psychiatry and Medical-Social Rehabilitation, Ukrainian Research Institute of Social Fo- rensic Psychiatry and Drug Abuse, Kyiv, 04080, Ukraine. Donna M Martin, Affiliation/s: Department of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA. Shrikant M Mane, Affiliation/s: Yale Center for Genomic Analysis, Yale University School of Medicine, New Haven, CT 06516, USA. Pall Magnusson, Affiliation/s: Department of Child and Adolescent Psychiatry, National University Hospital, Reykjavik, IS-101, Iceland. Tiago Magalhaes, Affiliation/s: National Childrens Research Centre, Our Lady ’ s Hospital Crumlin, Dublin, D12, Ireland, Academic Centre on Rare Diseases, University College Dublin, Dublin, D4, Ireland. Elena Maestrini, Affiliation/s: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy. Jennifer K Lowe, Affiliation/s: Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA, Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA, Center for Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Catherine Lord, Affiliation/s: Department of Psychiatry, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA. Pat Levitt, Affiliation/s: Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA. Christa LeseMartin, Affiliation/s: Autism and Developmental Medicine Institute, Geisinger Health System, Danville, PA 17837, USA. David H Ledbetter, Affiliation/s: Chief Scientific Officer, Geisinger Health System, Danville, PA 17837, USA. Marion Leboyer, Affiliation/s: FondaMental Foundation, Créteil, 94000, France, INSERM U955, Paris, 94010, France, Faculté de Médecine, Université Paris Est, Créteil, 94000, France, Department of Psychiatry, Henri Mondor-Albert Chene- vier Hospital, Assistance Publique – Hôpitaux de Paris, Créteil, 94000, France, Ann S LeCouteur, Affiliation/s: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK, Institue of Health and Science, Newcastle University, Newcastle Upon Tyne, NE2 4AX, UK. Christine Ladd-Acosta, Affiliation/s: Department of Epidemiology, Johns Hop- kins Bloomberg School of Public Health, Baltimore, MD 21205, USA. Alexander Kolevzon, Affiliation/s: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Sabine M Klauck, Affiliation/s: Division of Molecular Genome Analysis and Working Group Cancer Genome Research, Deutsches Krebsforschungszentrum, Heidelberg, D-69120, Germany. Suma Jacob, Affiliation/s: Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA, Institute of Translational Neuroscience and Department of Psychiatry, University of Minnesota, Minneapolis, MN 55454, USA. Bozenna Iliadou, Affiliation/s: Karolinska Institutet, Solna, SE-171 77, Sweden. Christina M Hultman, Affiliation/s: Karolinska Institutet, Solna, SE-171 77, Sweden. David M Hougaard, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, DK-2300, Denmark. Irva Hertz-Picciotto, Affiliation/s: Department of Public Health Sciences, School of Medicine, University of California Davis, Davis, CA 95616, USA, The MIND Institute, School of Medicine, University of California Davis, Davis, CA 95817, USA. Robert Hendren, Affiliation/s: Department of Psychiatry, University of California San Francisco, San Francisco, CA 94143, USA. Christine Søholm Hansen, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, DK-2300, Denmark. Jonathan L Haines, Affiliation/s: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA. Stephen J Guter, Affiliation/s: Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. Dorothy E Grice, Affiliation/s: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Jonathan M Green, Affiliation/s: Manchester Academic Health Sciences Centre, Manchester, M13 9NT, UK, Institute of Brain, Behaviour, and Mental Health, University of Manchester, Manchester, M13 9PT, UK. Andrew Green, Affiliation/s: Academic Centre on Rare Diseases, University College Dublin, Dublin, D4, Ireland, Centre for Medical Genetics, Our Lady ’ s Hospital Crumlin, Dublin, D12, Ireland. Arthur P Goldberg, Affiliation/s: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Christopher Gillberg, Affiliation/s: Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, S-405 30, Sweden. John Gilbert, Affiliation/s: The John P Hussman Institute for Human Genomics, University of Miami, Miami, FL 33101, USA. Louise Gallagher, Affiliation/s: Department of Psychiatry, Trinity College Dublin, Dublin, D8, Ireland. Christine M Freitag, Affiliation/s: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe University Frankfurt, Frankfurt am Main, 60528, Germany. Eric Fombonne, Affiliation/s: Department of Psychiatry and Institute for Development and Disability, Oregon Health and Science University, Portland, OR 97239, USA. Susan E Folstein, Affiliation/s: Division of Child and Adolescent Psychiatry, Department of Psychiatry, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. Bridget Fernandez, Affiliation/s: Memorial University of Newfoundland, St John ’ s, NL, A1B 3X9, Canada. M.Daniele Fallin, Affiliation/s: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. A.Gulhan Ercan-Sencicek, Affiliation/s: Programs on Neurogenetics, Yale Uni- versity School of Medicine, New Haven, CT 06520, USA. Sean Ennis, Affiliation/s: Academic Centre on Rare Diseases, University College Dublin, Dublin, D4, Ireland, Centre for Medical Genetics, Our Lady ’ s Hospital Crumlin, Dublin, D12, Ireland. Frederico Duque, Affiliation/s: Unidade de Neurodesenvolvimento e Autismo do Serviço do Centro de Desenvolvimento da Criança and Centro de Investigação e Formação Clinica, Pediatric Hospital, Centro Hospitalar e Universitário de Coimbra, Coimbra, 3041-80, Portugal, University Clinic of Pediatrics and Institute for Biomedical Imaging and Life Science, Faculty of Medicine, University of Coimbra, Coimbra, 3041-80, Portugal. Eftichia Duketis, Affiliation/s: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe University Frankfurt, Frankfurt am Main, 60528, Germany. Richard Delorme, Affiliation/s: FondaMental Foundation, Créteil, 94000, France, Human Genetics and Cognitive Functions Unit, Institut Pasteur, Paris, 75015, France, Centre National de la Recherche Scientifique URA 2182 Institut Pasteur, Paris, 75724, France, Department of Child and Adolescent Psychiatry, Robert Debré Hospital, Assistance Publique – Hôpitaux de Paris, Paris, 75019, France, Silvia DeRubeis, Affiliation/s: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Maretha V DeJonge, Affiliation/s: Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands. Geraldine Dawson, Affiliation/s: Duke Center for Autism and Brain Developments, Duke University School of Medicine, Durham, NC 27705, USA, Duke Institute for Brain Sciences, Duke University School of Medicine, Durham, NC 27708, USA. Michael L Cuccaro, Affiliation/s: The John P Hussman Institute for Human Genomics, University of Miami, Miami, FL 33101, USA. Catarina T Correia, Affiliation/s: Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa, 1600, Portugal, Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, Lisboa, 1649, Portugal. Judith Conroy, Affiliation/s: Academic Centre on Rare Diseases, University College Dublin, Dublin, D4, Ireland, Temple Street Children ’ s University Hospital, Dublin, D1, Ireland. Ines C Conceição, Affiliation/s: Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa, 1600, Portugal, Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, Lisboa, 1649, Portugal. Andreas G Chiocchetti, Affiliation/s: Depar tment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goe the University Frankfurt, Frankfurt am Main, 60528, Germany. Patrícia BS Celestino-Soper, Affiliation/s: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indian- apolis, IN 46202, USA. Jillian Casey, Affiliation/s: Temple Street Children ’ s University Hospital, Dublin, D1, Ireland, Academic Centre on Rare Diseases, University College Dublin, Dublin, D4, Ireland. Rita M Cantor, Affiliation/s: Department of Psychiatry, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA, Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA. Cátia Café, Affiliation/s: Unidade de Neurodesenvolvimento e Autismo do Serviço do Centro de Desenvolvimento da Criança and Centro de Investigação e Formação Clinica, Pediatric Hospital, Centro Hospitalar e Universitário de Coimbra, Coimbra, 3041-80, Portugal. Jonas Bybjerg-Grauholm, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, DK-2300, Denmark. Sean Brennan, Affiliation/s: Department of Psychiatry, Trinity College Dublin, Dublin, D8, Ireland. Thomas Bourgeron, Affiliation/s: FondaMental Foundation, Créteil, 94000, France, University Paris Diderot, Sorbonne Paris Cité, Paris, 75013, France, Patrick F Bolton, Affiliation/s: Institute of Psychiatry, Kings College London, London, SE5 8AF, UK, South London and Maudsley Biomedical Research Centre for Mental Health, London, SE5 8AF, UK. Sven Bölte, Affiliation/s: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JW Goethe University Frankfurt, Frankfurt am Main, 60528, Germany, Department of Women ’ s and Children ’ s Health, Center of Neurodevelopmental Disorders, Karolinska Institutet, Stockholm, SE- 113 30, Sweden, Child and Adolescent Psychiatry, Center for Psychiatry Re- search, Stockholm County Council, Stockholm, SE-171 77, Sweden. Nadia Bolshakova, Affiliation/s: Department of Psychiatry, Trinity College Dublin, Dublin, D8, Ireland. Catalina Betancur, Affiliation/s: INSERM U1130, Paris, 75005, France, CNRS UMR 8246, Paris, 75005, France, Sorbonne Universités, UPMC Univ Paris 6, Neuroscience Paris Seine, Paris, 75005, France. Raphael Bernier, Affiliation/s: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, USA. Arthur L Beaudet, Affiliation/s: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Agatino Battaglia, Affiliation/s: Stella Maris Institute for Child and Adolescent Neuropsychiatr, Pisa, 56018, Italy. Vanessa H Bal, Affiliation/s: Department of Psychiatry, University of California San Francisco, San Francisco, CA 94143, USA. Gillian Baird, Affiliation/s: Paediatric Neurodisability, King ’ s Health Partners, Kings College London, London, SE1 7EH, UK. Anthony J Bailey, Affiliation/s: Department of Psychiatry, University of Oxford and Warneford Hospital, Oxford, OX3 7JX, UK, Mental Health and Addictions Research Unit, University of British Colombia, Vancouver, BC, V5Z 4H4, Canada. Marie Bækvad-Hansen, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, DK-2300, Denmark. Joel S Bader, Affiliation/s: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21218, USA. Elena Bacchelli, Affiliation/s: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, 40126, Italy. Evdokia Anagnostou, Affiliation/s: Bloorview Research Institute, University of Toronto, Toronto, ON, M4G 1R8, Canada. David Amaral, Affiliation/s: The MIND Institute, School of Medicine, University of California Davis, Davis, CA 95817, USA, Department of Psychiatry, School of Medicine, University of California Davis, Davis, CA 95817, USA, Department of Behavioural Sciences, School of Medicine, University of California Davis, Davis, CA 95817, USA. Joana Almeida, Affiliation/s: Unidade de Neurodesenvolvimento e Autismo do Serviço do Centro de Desenvolvimento da Criança and Centro de Investigação e Formação Clinica, Pediatric Hospital, Centro Hospitalar e Universitário de Coimbra, Coimbra, 3041-80, Portugal. Anders D Børglum, Affiliation/s: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, DK-8000, Denmark. Joseph D Buxbaum, Affiliation/s: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Aravinda Chakravarti, Affiliation/s: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21218, USA. Edwin H Cook, Affiliation/s: Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. Hilary Coon, Affiliation/s: Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA. Daniel H Geschwind, Affiliation/s: Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA, Center for Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA, Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA, Michael Gill, Affiliation/s: Department of Psychiatry, Trinity College Dublin, Dublin, D8, Ireland. Hakon Hakonarson, Affiliation/s: The Center for Applied Genomics and Division of Human Genetics, Children ’ s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA, Dept of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104, USA. Joachim Hallmayer, Affiliation/s: Department of Psychiatry, Stanford University, Stanford, CA 94305, USA. Aarno Palotie, Affiliation/s: Sanger Institute, Hinxton, CB10 1SA, UK., Anney, Richard J. L., Ripke, Stephan, Anttila, Verneri, Grove, Jakob, Holmans, Peter, Huang, Hailiang, Klei, Lambertu, Lee, Phil H., Medland, Sarah E., Neale, Benjamin, Robinson, Elise, Weiss, Lauren A., Zwaigenbaum, Lonnie, Yu, Timothy W., Wittemeyer, Kerstin, Willsey, A. Jeremy, Wijsman, Ellen M., Werge, Thoma, Wassink, Thomas H., Waltes, Regina, Walsh, Christopher A., Wallace, Simon, Vorstman, Jacob A. S., Vieland, Veronica J., Vicente, Astrid M., Vanengeland, Herman, Tsang, Kathryn, Thompson, Ann P., Szatmari, Peter, Svantesson, Oscar, Steinberg, Stacy, Stefansson, Kari, Stefansson, Hreinn, State, Matthew W., Soorya, Latha, Silagadze, Teimuraz, Scherer, Stephen W., Schellenberg, Gerard D., Sandin, Sven, Sanders, Stephan J., Saemundsen, Evald, Rouleau, Guy A., Rogã©, Bernadette, Roeder, Kathryn, Roberts, Wendy, Reichert, Jennifer, Reichenberg, Abraham, Rehnstrã¶m, Karola, Regan, Regina, Poustka, Fritz, Poultney, Christopher S., Piven, Joseph, Pinto, Dalila, Pericak-Vance, Margaret A., Pejovic-Milovancevic, Milica, Pedersen, Marianne Giørtz, Pedersen, Carsten Bøcker, Paterson, Andrew D., Parr, Jeremy R., Pagnamenta, Alistair T., Oliveira, Guiomar, Nurnberger, John I., Nordentoft, Merete, Murtha, Michael T., Mouga, Susana, Mortensen, Preben Bo, Mors, Ole, Morrow, Eric M., Moreno-De-Luca, Daniel, Monaco, Anthony P., Minshew, Nancy, Merikangas, Alison, Mcmahon, William M., Mcgrew, Susan G., Mattheisen, Manuel, Martsenkovsky, Igor, Martin, Donna M., Mane, Shrikant M., Magnusson, Pall, Magalhaes, Tiago, Maestrini, Elena, Lowe, Jennifer K., Lord, Catherine, Levitt, Pat, Martin, Christa Lese, Ledbetter, David H., Leboyer, Marion, Lecouteur, Ann S., Ladd-Acosta, Christine, Kolevzon, Alexander, Klauck, Sabine M., Jacob, Suma, Iliadou, Bozenna, Hultman, Christina M., Hougaard, David M., Hertz-Picciotto, Irva, Hendren, Robert, Hansen, Christine Søholm, Haines, Jonathan L., Guter, Stephen J., Grice, Dorothy E., Green, Jonathan M., Green, Andrew, Goldberg, Arthur P., Gillberg, Christopher, Gilbert, John, Gallagher, Louise, Freitag, Christine M., Fombonne, Eric, Folstein, Susan E., Fernandez, Bridget, Fallin, M. Daniele, Ercan-Sencicek, A. Gulhan, Ennis, Sean, Duque, Frederico, Duketis, Eftichia, Delorme, Richard, Derubeis, Silvia, Dejonge, Maretha V., Dawson, Geraldine, Cuccaro, Michael L., Correia, Catarina T., Conroy, Judith, Conceiã§ã£o, Ines C., Chiocchetti, Andreas G., Celestino-Soper, PatrÃcia B. S., Casey, Jillian, Cantor, Rita M., Cafã©, Cã¡tia, Bybjerg-Grauholm, Jona, Brennan, Sean, Bourgeron, Thoma, Bolton, Patrick F., Bã¶lte, Sven, Bolshakova, Nadia, Betancur, Catalina, Bernier, Raphael, Beaudet, Arthur L., Battaglia, Agatino, Bal, Vanessa H., Baird, Gillian, Bailey, Anthony J., Bækvad-Hansen, Marie, Bader, Joel S., Bacchelli, Elena, Anagnostou, Evdokia, Amaral, David, Almeida, Joana, Bã¸rglum, Anders D., Buxbaum, Joseph D., Chakravarti, Aravinda, Cook, Edwin H., Coon, Hilary, Geschwind, Daniel H., Gill, Michael, Hallmayer, Joachim, Palotie, Aarno, Santangelo, Susan, Sutcliffe, James S., Arking, Dan E., Devlin, Bernie, Daly, Mark J., Hakonarson, Hakon, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Fondation FondaMental [Créteil], Génétique de l'autisme = Genetics of Autism (NPS-01), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Male ,INTELLECTUAL DISABILITY ,Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium ,Autism ,Neurodevelopment ,Gene Expression ,Genome-wide association study ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,lcsh:RC346-429 ,0302 clinical medicine ,2.1 Biological and endogenous factors ,Pair 10 ,Copy-number variation ,Aetiology ,Autism spectrum disorder ,Genetics ,Adaptor Proteins ,Forkhead Transcription Factors ,Serious Mental Illness ,3. Good health ,Mental Health ,Psychiatry and Mental Health ,Meta-analysis ,Female ,Biotechnology ,Human ,Autismo ,Genetic correlation ,Intellectual and Developmental Disabilities (IDD) ,Clinical Sciences ,Gene-set analysi ,Genomics ,Locus (genetics) ,FOXP1 ,Biology ,Chromosomes ,Heritability ,03 medical and health sciences ,Plasma Membrane Calcium-Transporting ATPases ,Developmental Neuroscience ,REVEALS ,mental disorders ,LINKAGE ,medicine ,Journal Article ,Humans ,Genetic Predisposition to Disease ,Meta-analysi ,GENOME-WIDE ASSOCIATION ,COMMON ,Genotyping ,Molecular Biology ,lcsh:Neurology. Diseases of the nervous system ,COPY NUMBER VARIATION ,Genetic association ,Adaptor Proteins, Signal Transducing ,Homeodomain Proteins ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Chromosomes, Human, Pair 10 ,Research ,Human Genome ,Signal Transducing ,Neurosciences ,Membrane Proteins ,medicine.disease ,RISK LOCI ,R1 ,Brain Disorders ,Repressor Proteins ,030104 developmental biology ,Genetic Loci ,Case-Control Studies ,Perturbações do Desenvolvimento Infantil e Saúde Mental ,Schizophrenia ,Carrier Proteins ,Gene-set analysis ,MENTAL-RETARDATION ,SCAN ,030217 neurology & neurosurgery ,Transcription Factors ,Developmental Biology - Abstract
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium - Collaborators (162): Anney RJL, Ripke S, Anttila V, Grove J, Holmans P, Huang H, Klei L, Lee PH, Medland SE, Neale B, Robinson E, Weiss LA, Zwaigenbaum L, Yu TW, Wittemeyer K, Willsey AJ, Wijsman EM, Werge T, Wassink TH, Waltes R, Walsh CA, Wallace S, Vorstman JAS, Vieland VJ, Vicente AM, vanEngeland H, Tsang K, Thompson AP, Szatmari P, Svantesson O, Steinberg S, Stefansson K, Stefansson H, State MW, Soorya L, Silagadze T, Scherer SW, Schellenberg GD, Sandin S, Sanders SJ, Saemundsen E, Rouleau GA, Rogé B, Roeder K, Roberts W, Reichert J, Reichenberg A, Rehnström K, Regan R, Poustka F, Poultney CS, Piven J, Pinto D, Pericak-Vance MA, Pejovic-Milovancevic M, Pedersen MG, Pedersen CB, Paterson AD, Parr JR, Pagnamenta AT, Oliveira G, Nurnberger JI, Nordentoft M, Murtha MT, Mouga S, Mortensen PB, Mors O, Morrow EM, Moreno-De-Luca D, Monaco AP, Minshew N, Merikangas A, McMahon WM, McGrew SG, Mattheisen M, Martsenkovsky I, Martin DM, Mane SM, Magnusson P, Magalhaes T, Maestrini E, Lowe JK, Lord C, Levitt P, Martin CL, Ledbetter DH, Leboyer M, LeCouteur AS, Ladd-Acosta C, Kolevzon A, Klauck SM, Jacob S, Iliadou B, Hultman CM, Hougaard DM, Hertz-Picciotto I, Hendren R, Hansen CS, Haines JL, Guter SJ, Grice DE, Green JM, Green A, Goldberg AP, Gillberg C, Gilbert J, Gallagher L, Freitag CM, Fombonne E, Folstein SE, Fernandez B, Fallin MD, Ercan-Sencicek AG, Ennis S, Duque F, Duketis E, Delorme R, DeRubeis S, DeJonge MV, Dawson G, Cuccaro ML, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Celestino-Soper PBS, Casey J, Cantor RM, Café C, Bybjerg-Grauholm J, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bolshakova N, Betancur C, Bernier R, Beaudet AL, Battaglia A, Bal VH, Baird G, Bailey AJ, Bækvad-Hansen M, Bader JS, Bacchelli E, Anagnostou E, Amaral D, Almeida J, Børglum AD, Buxbaum JD, Chakravarti A, Cook EH, Coon H, Geschwind DH, Gill M, Hallmayer J, Palotie A, Santangelo S, Sutcliffe JS, Arking DE, Devlin B, Daly MJ. Astrid M. Vicente .- Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis do INSA. PMS free full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441062/ Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR)
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- 2017
14. Breakdown of Kolmogorov's first similarity hypothesis in grid turbulence
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Lyazid Djenidi, Luminita Danaila, Sedat F. Tardu, R. A. Antonia, Discipline of Mechanical Engineering, Newcastle University [Newcastle]-Faculty of Engineering & Built Environment-School of Engineering, Laboratoire des Écoulements Géophysiques et Industriels [Grenoble] (LEGI), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Department of Mechanical Engineering (DEPARTMENT OF MECHANICAL ENGINEERING), Newcastle University [Newcastle], Complexe de recherche interprofessionnel en aérothermochimie (CORIA), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
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Physics ,Turbulence ,K-epsilon turbulence model ,Computational Mechanics ,Direct numerical simulation ,Kolmogorov microscales ,General Physics and Astronomy ,Reynolds number ,Reynolds stress equation model ,Condensed Matter Physics ,[SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph] ,Physics::Fluid Dynamics ,symbols.namesake ,Mechanics of Materials ,Reynolds decomposition ,symbols ,Statistical physics ,ComputingMilieux_MISCELLANEOUS ,Taylor microscale - Abstract
Kolmogorov's first similarity hypothesis (or KSH1) stipulates that two-point statistics have a universal form which depends on two parameters, the kinematic viscosity ν and the mean energy dissipation rate ⟨e⟩. KSH1 is underpinned by two assumptions: the Reynolds number is very large and local isotropy holds. To disentangle the intricacies of these two requirements, we assess the validity of KSH1 in a flow where local isotropy is a priori tenable, i.e. decaying grid turbulence. The main question we address is how large should the Reynolds number be for KSH1 to be valid over a range of scales wider than, say, five Kolmogorov scales. To this end, direct numerical simulations based on the lattice Boltzmann method are carried out in low Reynolds number grid turbulence. The results show that when the Taylor microscale Reynolds number Rλ drops below about 20, the Kolmogorov normalised spectra deviate from those at higher Rλ; the deviation increases with decreasing Rλ. It is shown that at Rλ ≃ 20, the contributi...
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- 2014
15. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders
- Author
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Joana Almeida, Christian R. Marshall, Hakon Hakonarson, Bárbara Oliveira, Anthony J. Griswold, Jacob A. S. Vorstman, Bhooma Thiruvahindrapuram, Suma Jacob, Judith Conroy, Alistair T. Pagnamenta, Christelle Cabrol, Jeremy R. Parr, Daniel H. Geschwind, Nancy J. Minshew, Xiao Xu, Richard Anney, Sven Bölte, Zhuozhi Wang, Emily L. Crawford, Elsa Delaby, Margaret A. Pericak-Vance, Joachim Hallmayer, Jonathan L. Haines, Dalila Pinto, Susana Mouga, Alexander Kolevzon, Elena Bacchelli, Frederico Duque, Bernie Devlin, Latha Soorya, Cátia Café, Kirsty Wing, Jennifer K. Lowe, Ana Tryfon, Stephen J. Guter, Geraldine Dawson, Tiago R. Magalhaes, Anthony J. Bailey, Michael Gill, Peter Szatmari, Steven Gallinger, Marion Pilorge, James S. Sutcliffe, Bridget A. Fernandez, Herman van Engeland, Catalina Betancur, Guiomar Oliveira, Andrew Green, Eftichia Duketis, Bernadette Rogé, Ann Le Couteur, Evdokia Anagnostou, Michelle Cotterchio, Daniele Merico, Giovanna Pellecchia, Jonathan Green, Regina Regan, Jillian P. Casey, Guiqing Cai, Gerard D. Schellenberg, Jennifer L. Howe, Elena Maestrini, Andrew D. Paterson, L. Alison McInnes, Patrick Bolton, Edwin H. Cook, Richard Delorme, Lambertus Klei, Thomas Bourgeron, Gillian Baird, Christine M. Freitag, Beth A. Dombroski, Andreas G. Chiocchetti, Sabine M. Klauck, Susan E. Folstein, Mafalda Barbosa, Anthony P. Monaco, Marion Leboyer, Nadia Bolshakova, Fritz Poustka, Richard Holt, Kerstin Wittemeyer, Wendy Roberts, Lonnie Zwaigenbaum, Louise Gallagher, Susan G. McGrew, Joseph D. Buxbaum, Graham Casey, Simon Wallace, Catherine Lord, Sean Brennan, Robert Ziman, Alison K. Merikangas, John I. Nurnberger, Christopher Gillberg, Ellen M. Wijsman, Astrid M. Vicente, Inȇs C. Conceição, Sean Ennis, Patricia Jiménez González, Hilary Coon, Raphael Bernier, John R. Gilbert, Ann P. Thompson, Susanne Thomson, Agatino Battaglia, Maretha de Jonge, Michael L. Cuccaro, Catarina Correia, Veronica J. Vieland, Stephen W. Scherer, Pauline Chaste, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Friedman Brain Institute, The Mindich Child Health and Development Institute, The Icahn Institute for Genomics and Multiscale Biology, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Trinity College Dublin-St. James's Hospital, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), McLaughlin Centre, University of Toronto, BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Department of Neurology, University of California [Los Angeles] (UCLA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Department of Pathology, Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Prevention & Cancer Control, Cancer Care Ontario, Department of Preventive Medicine, University of Southern California (USC), Department of Pediatrics, University of Alberta, School of Education, University of Birmingham [Birmingham], University of Oxford [Oxford]-Warneford Hospital, Octogone Unité de Recherche Interdisciplinaire (Octogone), Université Toulouse - Jean Jaurès (UT2J), Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Institute for Biomedical Imaging and Life Science, University of Coimbra [Portugal] (UC), Vanderbilt University [Nashville], Center for Autism and the Developing Brain (CADB), Weill Medical College of Cornell University [New York], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institute of Health and Society, Newcastle University [Newcastle], Department of Child and Adolescent Psychiatry, Newcastle University [Newcastle]-Institute of Health & Society (Child & Adolescent Psychiatry), Child Developmental and Behavioral Unit, Hospital Nacional de Niños Dr Sáenz Herrera, Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Manchester Academic Health Sciences Centre, Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Institute of Child Health, University College of London [London] (UCL), Memorial University of Newfoundland [St. John's], Disciplines of Genetics and Medicine, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Institute of Psychiatry, King‘s College London, Institute of psychiatry, University of Washington [Seattle], Paediatric Neurodisability, King‘s College London-King's Health Partners, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, University of British Columbia (UBC), Bloorview Research Institute, Division of Medical Genetics [Seattle], Departments of Biostatistics and Medicine, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Institute of Neuroscience [Newcastle] (ION), Institutes of Neuroscience and Health and Society, Indiana University School of Medicine, Indiana University System-Indiana University System, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Utah Autism Research Program, University of Utah Psychiatry Department, University of Miami School of Medicine, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford School of Medicine [Stanford], Institute for Juvenile Research, University of Illinois [Chicago] (UIC), Department of Neuroscience, Main funders of the Autism Genome Project: Autism Speaks (USA), the Health Research Board (Ireland, AUT/2006/1, AUT/2006/2, PD/2006/48), the Medical Research Council (UK), the Hilibrand Foundation (USA), Genome Canada, the Ontario Genomics Institute, and the Canadian Institutes of Health Research (CIHR), Autism Genome Project Consortium, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), University of Pennsylvania, University of Oxford-Warneford Hospital, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Betancur, Catalina, Instituto Nacional de Saude Dr Ricardo Jorge, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement (LAMBE - UMR 8587), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Università di Bologna [Bologna] (UNIBO), Mount Sinai Hospital (MSH), University of Toronto-The Hospital for Sick Children, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Gillberg Neuropsychiatry Centre, University of Gothenburg (GU), Stanford University Medical School, Stanford University School of Medicine [Stanford], Stanford University [Stanford], Université de Toulouse (UT)-Université de Toulouse (UT), Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Casey JP, Cai G, Cabrol C, Bolshakova N, Bacchelli E, Anney R, Gallinger S, Cotterchio M, Casey G, Zwaigenbaum L, Wittemeyer K, Wing K, Wallace S, van Engeland H, Tryfon A, Thomson S, Soorya L, Rogé B, Roberts W, Poustka F, Mouga S, Minshew N, McInnes LA, McGrew SG, Lord C, Leboyer M, Le Couteur AS, Kolevzon A, Jiménez González P, Jacob S, Holt R, Guter S, Green J, Green A, Gillberg C, Fernandez BA, Duque F, Delorme R, Dawson G, Chaste P, Café C, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bernier R, Baird G, Bailey AJ, Anagnostou E, Almeida J, Wijsman EM, Vieland VJ, Vicente AM, Schellenberg GD, Pericak-Vance M, Paterson AD, Parr JR, Oliveira G, Nurnberger JI, Monaco AP, Maestrini E, Klauck SM, Hakonarson H, Haines JL, Geschwind DH, Freitag CM, Folstein SE, Ennis S, Coon H, Battaglia A, Szatmari P, Sutcliffe JS, Hallmayer J, Gill M, Cook EH, Buxbaum JD, Devlin B, Gallagher L, Betancur C, and Scherer SW.
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Male ,INTELLECTUAL DISABILITY ,pathways ,Genome-wide association study ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Bioinformatics ,DUPLICATIONS ,Intellectual disability ,Gene Regulatory Networks ,Genetics(clinical) ,Copy-number variation ,10. No inequality ,Child ,GDI1 ,Genetics (clinical) ,Sequence Deletion ,COPY NUMBER VARIANTS ,Genetics ,gene networks ,Copy Number Variation ,3. Good health ,Pedigree ,Fragile X syndrome ,Multigene Family ,Female ,Metabolic Networks and Pathways ,de novo ,DNA Copy Number Variations ,autism ,Biology ,rare CNV ,PHENOTYPE ONTOLOGY ,Article ,Structural variation ,mental disorders ,medicine ,Humans ,ddc:610 ,FRAGILE-X-SYNDROME ,GENOME-WIDE ASSOCIATION ,Gene ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,HDAC4 ,SETD5 ,medicine.disease ,CHD2 ,inherited ,STRUCTURAL VARIATION ,DELETIONS ,DE-NOVO MUTATIONS ,Child Development Disorders, Pervasive ,Autism - Abstract
International audience; Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
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- 2014
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16. No chromosome arm unturned: in memory of Roland Berger 1934–2012
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M Le Coniat-Busson, Anne Hagemeijer, H. Van den Berghe, Alain Bernheim, M Gautier, Florence Nguyen-Khac, Serge Romana, Nicole Dastugue, Janet D. Rowley, Philippe Jonveaux, Christine J. Harrison, M Martineau, Olivier Bernard, Leukaemia Research Cytogenetics Group [Northern Institute for Cancer Research - Newcastle University], Northern Institute for Cancer Research [Newcastle] (NICR), Newcastle University [Newcastle]-Newcastle University [Newcastle], Section of Hematology/Oncology [Chicago], The University of Chicago Medicine, Center for the Biology of Disease, and KU Leuven (VIB), Génétique des tumeurs (U985), Institut Gustave Roussy (IGR)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Sciences Unit, Faculty of Medicine, University of Southampton, UK, Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie biologique [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique et d'Embryologie Médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]
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Chromosome Aberrations ,0303 health sciences ,Cancer Research ,Leukemia ,business.industry ,[SDV]Life Sciences [q-bio] ,Hematology ,History, 20th Century ,History, 21st Century ,Pediatrics ,Genealogy ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Physicians ,030220 oncology & carcinogenesis ,Chromosome Arm ,Medicine ,France ,business ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology - Abstract
International audience
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- 2014
17. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
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William E R Ollier, Gillian A. Wallis, Unnur Styrkarsdottir, Nicholas G. Martin, P. Eline Slagboom, Mike R. Reed, Helgi Jonsson, J. Mark Wilkinson, John P. A. Ioannidis, Aime Keis, Yolande F. M. Ramos, Daniel S. Evans, Penelope A. Lind, Stuart H. Ralston, Thorvaldur Ingvarsson, Andrew McCaskie, Konstantinos K. Tsilidis, Evangelos Evangelou, Kay Chapman, Tim D. Spector, Aaron G. Day-Williams, L. Stefan Lohmander, Aspasia Tsezou, Ashok Rai, Rob G H H Nelissen, Kari Stefansson, Cristina Rodriguez-Fontenla, Sarah Metrustry, Andres Metspalu, Kalliope Panoutsopoulou, Albert Hofman, Hanneke J. M. Kerkhof, John Loughlin, Panos Deloukas, Joyce B. J. van Meurs, Ana M. Valdes, Evangelia E. Ntzani, Lorraine Southam, José A. Riancho, J. Christiaan Keurentjes, Francisco J. Blanco, Gudmar Thorleifsson, Peter M. Nilsson, Ingrid Meulenbelt, Lili Milani, Fernando Rivadeneira, Michael C. Nevitt, Nicholas Bellamy, Nancy E Lane, Unnur Thorsteinsdottir, Grant W. Montgomery, Michael Doherty, Tõnu Esko, Ingileif Jonsdottir, Nigel K Arden, Hafdis T. Helgadottir, André G. Uitterlinden, Antonio Gonzalez, Steffan D. Bos, Margreet Kloppenburg, Andrew Carr, Eleftheria Zeggini, Gunnar Engström, N Aslam, Fraser Birrell, Neeta Parimi, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece Department of Twin Research & Genetic Epidemiology, King's College London, London, UK. 2Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. 3Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland. 4Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece. 5Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands Netherlands Consortium for Healthy Ageing, The Netherlands. 6Estonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. 7California Pacific Medical Center Research Institute, San Francisco, USA. 8Department of Twin Research & Genetic Epidemiology, King's College London, London, UK. 9Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. 10Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. 11NIHR Biomedical Research Unit and ARUK Centre of excellence for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK MRC Epidemiology Resource Centre, University of Southampton, Southampton, UK. 12Worcestershire Royal Hospital, Worcestershire Acute Hospitals NHS Trust, Worcester, UK. 13Centre of National Research on Disability and Rehabilitation Medicine, The University of Queensland, Brisbane, Australia. 14Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK Wansbeck General Hospital, Northumbria Healthcare NHS Foundation Trust, Ashington, UK. 15Rheumatology Division, Instituto de Investigación Biomédica-Hospital Universitario A Coruña, A Corunna, Spain. 16NIHR Biomedical Research Unit and ARUK Centre of excellence for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK. 17Department of Academic Rheumatology, University of Nottingham, Nottingham, UK. 18Department of Clinical Sciences Malmo, Lund University, Malmo, Sweden. 19Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. 20Department of Orthopedic Surgery, Akureyri Hospital, Akureyri, Iceland School of Health Sciences, University of Akureyri, Akureyri, Iceland. 21Department of Medicine, The National University Hospital of Iceland, Reykjavik, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 22Department of Public Health, University of Tartu, Tartu, Estonia Orthopedic Surgeons, Elva Hospital, Elva, Estonia. 23Department of Orthopedics, Leiden University Medical Center, Leiden, The Netherlands. 24Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. 25Department of Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia. 26Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. 27Department of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia. 28Estonian Genome Center, University of Tartu, Tartu, Estonia. 29Department of Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia. 30Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. 31Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK. 32Worcestershire Acute Hospitals NHS Trust, Worcester, UK. 33Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. 34Wansbeck General Hospital, Northumbria Healthcare NHS Foundation Trust, Ashington, UK. 35Department of Internal Medicine, Hospital U.M. Valdecilla-IFIMAV, University of Cantabria, Santander, Spain. 36Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. 37Laboratorio Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain. 38Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland Department of Medicine, The National University Hospital of Iceland, Reykjavik, Iceland. 39Department of Biology, University of Thessaly, Medical School, Larissa, Greece. 40Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK. 41Department of Human Metabolism, University of Sheffield, Sheffield, UK. 42Department of Medicine, University of California at Davis, Sacramento, USA. 43Research Unit for Musculoskeletal Function and Physiotherapy, and Department of Orthopedics and Traumatology, University of Southern Denmark, Odense, Denmark Department of Clinical Sciences Lund, Lund University, Lund, Sweden. 44Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 45Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, USA. 46Department of Twin Research & Genetic Epidemiology, King's College London, London, UK Department of Academic Rheumatology, University of Nottingham, Nottingham, UK., arcOGEN Consortium, Universidad de Cantabria, Medical Oncology, Epidemiology, and Internal Medicine
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Male ,Aging ,Epidemiology ,Genome-wide association study ,Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics ,Bioinformatics ,Osteoarthritis, Hip ,Nuclear Receptor Coactivator 3 ,Gene Frequency ,Grupo de Ascendencia Continental Europea ,Immunology and Allergy ,Medicine ,2.1 Biological and endogenous factors ,Osteoarthritis, Hip/genetics ,Aetiology ,European Continental Ancestry Group/genetics ,Gene polymorphism ,Single Nucleotide ,Protein-Tyrosine Kinases ,Protein-Serine-Threonine Kinases ,3. Good health ,Slitgigt ,1117 Public Health And Health Services ,1107 Immunology ,Nuclear Receptor Coactivator 3/genetics ,Female ,arcOGEN Consortium ,Frecuencia de los Genes ,Protein-Serine-Threonine Kinases/genetics ,Clinical Sciences ,Immunology ,European Continental Ancestry Group ,Predisposición Genética a la Enfermedad ,Single-nucleotide polymorphism ,Locus (genetics) ,Protein Serine-Threonine Kinases ,Public Health And Health Services ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Immediate early protein ,White People ,Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina ,Estudio de Asociación del Genoma Completo ,Immediate-Early Proteins ,Sex Factors ,Rheumatology ,Gene Polymorphism ,Osteoarthritis ,Genetics ,Humans ,Genetic Predisposition to Disease ,Polymorphism ,Allele frequency ,Genetic association ,Rheumatology and Autoimmunity ,Homeodomain Proteins ,Hip ,Protein-Tyrosine Kinases/genetics ,business.industry ,Whites ,Arthritis ,Prevention ,Human Genome ,1103 Clinical Sciences ,Clinical and Epidemiological Research ,Arfgengi ,Immediate-Early Proteins/genetics ,Arthritis & Rheumatology ,Minor allele frequency ,Musculoskeletal ,Mjaðmir ,HMGN Proteins ,Osteoartritis de la Cadera ,Homeodomain Proteins/genetics ,business ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,HMGN Proteins/genetics ,Genome-Wide Association Study - Abstract
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. We performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. We accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis). Novel genetic loci for hip OA were found in this meta-analysis of GWAS. info:eu-repo/grantAgreement/EC/FP7/200800 info:eu-repo/grantAgreement/EC/FP7/286213
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- 2014
18. Associations of early-life pet ownership with asthma and allergic sensitization: A meta-analysis of more than 77,000 children from the EU Child Cohort Network
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Angela Pinot de Moira, Katrine Strandberg-Larsen, Tom Bishop, Marie Pedersen, Demetris Avraam, Tim Cadman, Lucinda Calas, Maribel Casas, Blandine de Lauzon Guillain, Ahmed Elhakeem, Ana Esplugues, Marisa Estarlich, Rachel E. Foong, Sido Haakma, Jennifer R. Harris, Rae-Chi Huang, Hazel Inskip, Aitana Lertxundi, Sara M. Mensink-Bout, Johanna L.T. Nader, Costanza Pizzi, Maja Popovic, Theodosia Salika, Jordi Sunyer, Evelien R. Van Meel, Morris A. Swertz, Vincent W.V. Jaddoe, Paul Burton, Liesbeth Duijts, Anne-Marie Nybo Andersen, Pediatrics, Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), University of Cambridge [UK] (CAM), Newcastle University [Newcastle], Bristol Medical School, University of Bristol [Bristol], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Erasmus University Medical Center [Rotterdam] (Erasmus MC), European Project: 733206,H2020,H2020-SC1-2016-RTD,LIFECYCLE(2017), Department of Public Health, University of Copenhagen, Copenhagen, Denmark, parent, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
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FAIR (findableaccessibleinteroperableand reusable) ,Immunology ,FAIR (findable ,cat ,ownership ,allergic sensitization ,Cat ,accessible ,allergic sensitisation ,asthma ,birth cohort ,children ,dog ,exposure ,interoperable and reusable) ,lifecourse epidemiology ,meta-analysis ,birth cohortlife course epidemiology ,Cohort Studies ,Dogs ,interoperable ,Odds Ratio ,Animals ,Humans ,Immunology and Allergy ,and reusable) ,Child ,ComputingMilieux_MISCELLANEOUS ,Environmental Exposure ,Allergens ,life course epidemiology ,Child, Preschool ,Cats ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
Background: studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure.Objective: our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization.Methods: we used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis.Results: the prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization.Conclusion: our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age asthma, but they do suggest that ownership may potentially exacerbate the risks associated with cat- and dog-specific allergic sensitization.
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- 2022
19. Managing the deluge of newly discovered plant viruses and viroids: an optimized scientific and regulatory framework for their characterization and risk analysis
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Nuria Fontdevila Pareta, Maryam Khalili, Ayoub Maachi, Mark Paul S. Rivarez, Johan Rollin, Ferran Salavert, Coline Temple, Miguel A. Aranda, Neil Boonham, Marleen Botermans, Thierry Candresse, Adrian Fox, Yolanda Hernando, Denis Kutnjak, Armelle Marais, Françoise Petter, Maja Ravnikar, Ilhem Selmi, Rachid Tahzima, Charlotte Trontin, Thierry Wetzel, Sebastien Massart, Gembloux Agro-Bio Tech [Gembloux], Université de Liège, Biologie du fruit et pathologie (BFP), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecophysiologie et Génomique Fonctionnelle de la Vigne (UMR EGFV), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Abiopep S.L., National Institute of Biology [Ljubljana] (NIB), Caraga State University, DNAVision, Newcastle University [Newcastle], Spanish National Research Council (CSIC), Netherlands Institute for Vectors, Invasive Plants and Plant Health (NIVIP), European and Mediterranean Plant Protection Organization - Organisation Européenne et Méditerranéenne pour la Protection des Plantes (EPPO), Research Institute for Agricultural, Fisheries and Food (ILVO), Bioversity International [Montpellier], Bioversity International [Rome], Consultative Group on International Agricultural Research [CGIAR] (CGIAR)-Consultative Group on International Agricultural Research [CGIAR] (CGIAR), This work was supported by the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 773139 (VALITEST) and under the Marie Skłodowska-Curie grant agreement no. 813542 (INEXTVIR), by the CGIAR Genbank platform and by the Germplasm Health Unit (GHU) improvement initiative., European Project: 773139,VALITEST, and European Project: 813542,INEXTVIR
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Microbiology (medical) ,high throughput sequencing (HTS) ,regulatory agencies ,biological characterization ,[SDV]Life Sciences [q-bio] ,plant viruses and viroids ,Pest Risk Analysis (PRA) ,plant health ,virus disease ,Microbiology ,[SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy - Abstract
International audience; The advances in high-throughput sequencing (HTS) technologies and bioinformatic tools have provided new opportunities for virus and viroid discovery and diagnostics. Hence, new sequences of viral origin are being discovered and published at a previously unseen rate. Therefore, a collective effort was undertaken to write and propose a framework for prioritizing the biological characterization steps needed after discovering a new plant virus to evaluate its impact at different levels. Even though the proposed approach was widely used, a revision of these guidelines was prepared to consider virus discovery and characterization trends and integrate novel approaches and tools recently published or under development. This updated framework is more adapted to the current rate of virus discovery and provides an improved prioritization for filling knowledge and data gaps. It consists of four distinct steps adapted to include a multi-stakeholder feedback loop. Key improvements include better prioritization and organization of the various steps, earlier data sharing among researchers and involved stakeholders, public database screening, and exploitation of genomic information to predict biological properties.
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- 2023
20. Evolution of anelloviruses from a circovirus-like ancestor through gradual augmentation of the jelly-roll capsid protein
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Anamarija Butkovic, Simona Kraberger, Zoe Smeele, Darren P Martin, Kara Schmidlin, Rafaela S Fontenele, Michelle R Shero, Roxanne S Beltran, Amy L Kirkham, Maketalena Aleamotu’a, Jennifer M Burns, Eugene V Koonin, Arvind Varsani, Mart Krupovic, Virologie des archées - Archaeal Virology, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Arizona State University [Tempe] (ASU), University of Cape Town, Woods Hole Oceanographic Institution (WHOI), University of California [Santa Cruz] (UC Santa Cruz), University of California (UC), US Fish and Wildlife Service, Newcastle University [Newcastle], Texas Tech University [Lubbock] (TTU), National Center for Biotechnology Information (NCBI), A.B. was supported by a post-doctoral fellowship from Foundation pour la Recherche Mèdicale (grant number SPF202110014092). M.K. was supported by a grant from the l’Agence Nationale de la Recherche (ANR-20-CE20-0009-02). A.L.K. and R.S.B. were supported by Institutional Development Awards (IDeA) Networks of Biomedical Research Excellence Assistantships (grant number P20GM103395) from the National Institute of General Medical Sciences of the National Institutes of Health (NIH). E.V.K. was supported by the Intramural Research Program of the NIH (National Library of Medicine).Weddell seal samples were collected under National Marine Fisheries Service Marine Mammal permit #17411, Antarctic Conservation Act permit #2014-003, and the University of Alaska Anchorage and University of Alaska Fairbanks’s Institutional Animal Care and Use Committee approvals #419971 and #854089, with funding from the National Science Foundation grant ANT-1246463 to J.M.B.The molecular work described in this study is supported by the Center of Evolution and Medicine Venture Fund (Center of Evolution and Medicine, Arizona State University, USA) grant awarded to A.V., and ANR-20-CE20-0009,VIROMET,Devoiler le virome des archées methanogenes(2020)
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virus evolution ,Commensaviricota ,jelly-roll fold ,Virology ,structural modelling ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,taxonomy and classification ,Anellovirus ,Microbiology ,capsid proteins - Abstract
Anelloviruses are highly prevalent in diverse mammals, including humans, but so far have not been linked to any disease and are considered to be part of the ‘healthy virome’. These viruses have small circular single-stranded DNA (ssDNA) genomes and encode several proteins with no detectable sequence similarity to proteins of other known viruses. Thus, anelloviruses are the only family of eukaryotic ssDNA viruses currently not included in the realm Monodnaviria. To gain insights into the provenance of these enigmatic viruses, we sequenced more than 250 complete genomes of anelloviruses from nasal and vaginal swab samples of Weddell seal (Leptonychotes weddellii) from Antarctica and a fecal sample of grizzly bear (Ursus arctos horribilis) from USA, and performed a comprehensive family-wide analysis of the signature anellovirus protein, ORF1. Using state-of-the-art remote sequence similarity detection approaches and structural modeling with AlphaFold2, we show that ORF1 orthologs from all Anelloviridae genera adopt a jelly-roll fold typical of viral capsid proteins, establishing an evolutionary link to other eukaryotic ssDNA viruses, specifically, circoviruses. However, unlike capsid proteins of other ssDNA viruses, ORF1 encoded by anelloviruses from different genera display remarkable variation in size, due to insertions into the jelly-roll domain. In particular, the insertion between β-strands H and I forms a projection domain predicted to face away from the capsid surface and function at the interface of virus-host interactions. Consistent with this prediction and supported by recent experimental evidence, the outermost region of the projection domain is a mutational hotspot, where rapid evolution was likely precipitated by the host immune system. Collectively, our findings further expand the known diversity of anelloviruses and explain how anellovirus ORF1 proteins likely diverged from canonical jelly-roll capsid proteins through gradual augmentation of the projection domain. We suggest assigning Anelloviridae to a new phylum, ‘Commensaviricota’, and including it into kingdom Shotokuvirae (realm Monodnaviria), alongside Cressdnaviricota and Cossaviricota.
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- 2023
21. Instruction Giving in Online Language Lessons: A Multimodal (Inter)action Analysis
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Satar, Müge, Wigham, Ciara R., Newcastle University [Newcastle], Activité, Connaissance, Transmission, éducation (ACTé ), Université Clermont Auvergne (UCA), and Newcastle University (Faculty of Humanities and Social Sciences Research Fund,2018 Spring call) and Université Clermont Auvergne (Foreign researchers – short research visit, 2018 call) 'An Examination of Experienced Online Language Teachers’ Multimodal Instruction-Giving Practices'.
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videoconferencing ,instruction giving ,[SHS.LANGUE]Humanities and Social Sciences/Linguistics ,multimodal (inter)action analysis ,language learning ,multimodality - Abstract
International audience; This concise volume calls attention to the instruction-giving practices of language teachers in online environments, in particular videoconferencing, employing a Multimodal (Inter)action Analysis approach to explore the challenges, affordances, and pedagogical implications of teaching in these settings.The book examines the unique competences necessary for language teachers in multimodal synchronous online environments, which require mediating a mix of modes, including spoken language gaze, gesture, posture, and textual elements. Satar and Wighamʼs innovative approach draws on Sigrid Norrisʼs work on Multimodal (Inter)action Analysis to examine variance in practices, combining in-depth micro-analytic analysis of mediation with a consideration of the modal density and complexity in the act of giving instructions. The volume shows how studying instruction giving can offer a better understanding of how online teachers mediate learning multimodally in electronic environments but also research-informed guidance for practical implementation in the classroom.This book is a valuable resource for scholars in applied linguistics, language education, and language learning and teaching as well as practicing online language teachers.Full-size versions of all Figures, Extracts, and Tables are available in colour at https://doi.org/10.25405/data.ncl.20315142
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- 2023
22. Designing an Efficient Surfactant–Polymer–Oil–Electrolyte System: A Multi-Objective Optimization Study
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Mohammed Nedjhioui, Noureddine Nasrallah, Mohammed Kebir, Hichem Tahraoui, Rachida Bouallouche, Aymen Amin Assadi, Abdeltif Amrane, Bassem Jaouadi, Jie Zhang, Lotfi Mouni, Université Yahia Fares de Médéa, Université des Sciences et de la Technologie Houari Boumediene = University of Sciences and Technology Houari Boumediene [Alger] (USTHB), Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques (CRAPC), Université Ferhat-Abbas Sétif 1 [Sétif] (UFAS1), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Université de Sfax, Université de Sfax - University of Sfax, Newcastle University [Newcastle], Université Mohamed Akli Ouelhadj de Bouira (UMAOB), and None
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Process Chemistry and Technology ,polymer ,viscosity ,Chemical Engineering (miscellaneous) ,[CHIM]Chemical Sciences ,Bioengineering ,full factorial design ,interfacial tension ,conductivity ,turbidity - Abstract
International audience; This research aimed to study the effects of individual components on the physicochemical properties of systems composed of surfactants, polymers, oils, and electrolytes in order to maximize the recovery efficiency of kerosene while minimizing the impact on the environment and human health. Four independent factors, namely anionic surfactant sodium dodecylbenzene sulfonate (X1) (SDBS), oil (X2) (kerosene), water-soluble polymer poly(ethylene glycol) (X3) (PEG), and sodium chloride (X4) (NaCl), were studied using the full factorial design (FFD) model. Four output variables, namely conductivity (Y1), turbidity (Y2), viscosity (Y3), and interfacial tension (IFT) (Y4), were taken as the response variables. All four FFD models have high coefficients of determination and low errors. The developed models were used in a multi-objective optimization (MOO) framework to determine the optimal conditions. The obtained optimal conditions are X1 = 0.01, X2 = 50, X3 = 5, and X4 = 0.1, with an error of 0.9414 between the predicted and experimental objective function values. This result shows the efficiency of the model developed and the system used for the recovery of kerosene, while also having a positive effect on the protection of the environment. © 2023 by the authors.
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- 2023
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23. Reversible Pressure-Magnetic Modulation in a Tetrathiafulvalene-Based Dyad Piezochromic Dysprosium Single-Molecule Magnet
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Fabrice Pointillart, Jessica Flores Gonzalez, Haiet Douib, Vincent Montigaud, Charles J. McMonagle, Boris Le Guennic, Olivier Cador, Dawid Pinkowicz, Michael R. Probert, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), This work was supported by the CNRS, Université de Rennes 1 and the European Commission through the ERC-CoG 725184 MULTIPROSMM (project n. 725184). B.L.G. and V.M. thank the French GENCI/IDRIS-CINES centres for high-performance computing resources., and European Project: 725184,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),MULTIPROSMM(2017)
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Isotopes ,Single-Molecule Magnet ,Organic Chemistry ,Pressure ,Tetrathiafulvalene ,[CHIM]Chemical Sciences ,dysprosium ,General Chemistry ,Catalysis - Abstract
International audience; The extreme sensitivity of trivalent lanthanide ions to crystal field variations led to the emergence of single-molecule magnetic switching under various stimuli. The use of pressure as an external stimulus instead of classic light irradiation, oxidation or any chemical reactions allows a fine tuning of the magnetic modulation. Here the well-known pure isotopically enriched [162Dy(tta)3(L)]⋅C6H14 ( 162Dy) Single-Molecule Magnet (SMM) (tta- = 2-2-thenoyltrifluoroacetonate and L = 4,5-bis(propylthio)-tetrathiafulvalene-2-(2-pyridyl)benzimidazole-methyl-2-pyridine) was experimentally investigated by single-crystal diffraction and squid magnetometry under high applied pressures. Both reversible piezochromic properties and pressure modulation of the SMM behavior were demonstrated and supported by ab initio calculations. The magnetic study of the diluted sample [162Dy0.05Y0.95(tta)3(L)]⋅C6H14 ( 162Dy@Y) indicated that variations in the electronic structure have both intra- and inter-molecular origins. Quantitative magnetic interpretation concludes to a deterioration of the Orbach process for the benefit of both Raman and QTM mechanisms under applied pressure.
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- 2023
24. Evaluation of Physicochemical and Amphiphilic Properties of New Xanthan Gum Hydrophobically Functionalized Derivatives
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Madiha Melha Yahoum, Selma Toumi, Hichem Tahraoui, Sonia Lefnaoui, Abdelkader Hadjsadok, Abdeltif Amrane, Mohammed Kebir, Jie Zhang, Aymen Amine Assadi, Lotfi Mouni, Université Yahia Fares de Médéa, Université Ferhat-Abbas Sétif 1 [Sétif] (UFAS1), Université Saâd Dahlab Blida 1 (UB1), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques (CRAPC), Newcastle University [Newcastle], and Université Mohamed Akli Ouelhadj de Bouira (UMAOB)
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amphiphilic polysaccharides ,Renewable Energy, Sustainability and the Environment ,benzyl chloride ,xanthan gum ,Geography, Planning and Development ,[CHIM]Chemical Sciences ,Williamson synthesis ,benzyl xanthan gum ,oil in water emulsions ,Building and Construction ,Management, Monitoring, Policy and Law - Abstract
International audience; This research aimed to develop new hydrophobic and potentially amphiphilic benzyl xanthan gum (BXG) derivatives using a Williamson synthesis. This modification consists of an etherification reaction between xanthan gum (XG) and benzyl chloride (BC) under microwave heating. The effects of the molar ratio (R = XG/CLB, with R equal to 2 or 4) on the amphiphilic character and the degree of substitution (DS) were studied. The two benzyl xanthan gum derivatives (BXG1 and BXG2) were subsequently subjected to various physicochemical and rheological characterization techniques. The obtained results of FTIR and H-1-NMR spectroscopy showed the effectiveness of the grafting of aromatic moieties onto the XG molecule with DS values of 0.59 for BXG1 and 0.7 for BXG2. The XRD analysis revealed slight modifications in the xanthan crystallinity after etherification, where the degree of crystallinity (DOC) values were 8.46%, 10.18%, and 14.67% for XG, BXG1, and BXG2, respectively. Additionally, conductivity measurements showed that the BXG derivatives exhibit higher values than native XG, due to the inter- and intra-molecular associations following the grafting of aromatic groups. Moreover, the critical aggregation concentration (CAC) was detected at 0.32% for BXG1 and 0.28% for BXG2. The rheological study confirmed that XG and its BXG derivatives exhibited a shear-thinning pseudoplastic behavior and that the viscosity increases when the DS increases. The emulsifying power test of the BXGs compared to the native XG confirmed the amphiphilic properties of the new benzylated derivatives, where the stabilizing capacity increases with increased DS.
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- 2023
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25. Clinical activity of <scp>CC‐90011</scp> , an oral, potent, and reversible <scp>LSD1</scp> inhibitor, in advanced malignancies
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Antoine Hollebecque, Stefania Salvagni, Ruth Plummer, Patricia Niccoli, Jaume Capdevila, Giuseppe Curigliano, Victor Moreno, Filippo de Braud, Sonia Gonzalez de Villambrosia, Patricia Martin‐Romano, Eric Baudin, Marina Arias, Juan de Alvaro, Josep L. Parra‐Palau, Tania Sánchez‐Pérez, Ida Aronchik, Ellen H. Filvaroff, Manisha Lamba, Zariana Nikolova, Johann S. de Bono, Institut Català de la Salut, [Hollebecque A] Gustave Roussy, Département d’innovation thérapeutique et essais précoces, Villejuif, France. [Salvagni S] S. Orsola Polyclinic, Malpighi University Hospital, Bologna, Italy. [Plummer R] Clinical and Translational Research Institute Northern, Newcastle University, Newcastle, UK. [Niccoli P] Department of Medical Oncology, ENETS Center of Excellence, IPC NET Center, Institut Paoli-Calmettes, Marseille, France. [Capdevila J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. IOB-Teknon, Barcelona, Spain. [Curigliano G] European Institute of Oncology, IRCCS, University of Milan, Milan, Italy, and Vall d'Hebron Barcelona Hospital Campus
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enzimas y coenzimas::enzimas::oxidorreductasas::oxidorreductasas que actúan sobre donantes de grupos CH-NH::oxidorreductasas N-desmetilantes::histona desmetilasas [COMPUESTOS QUÍMICOS Y DROGAS] ,Histone Demethylases ,Cancer Research ,Maximum Tolerated Dose ,Càncer - Tractament ,Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH Group Donors::Oxidoreductases, N-Demethylating::Histone Demethylases [CHEMICALS AND DRUGS] ,Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, B-Cell, Marginal Zone [DISEASES] ,neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B de la zona marginal [ENFERMEDADES] ,Investigative Techniques::Toxicity Tests::Maximum Tolerated Dose [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Lymphoma, B-Cell, Marginal Zone ,Posologia ,Neoplasms [DISEASES] ,neoplasias [ENFERMEDADES] ,Oncology ,Neoplasms ,Medicaments - Eficàcia ,técnicas de investigación::pruebas de toxicidad::dosis máxima tolerada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Humans ,Organic Chemicals - Abstract
Lysine-specific demethylase 1 (LSD1) inhibitor; Neuroendocrine tumor; Non-Hodgkin lymphoma Tumor neuroendocrino; Linfoma no Hodgkin; Inhibidores de desmetilasa-1 específica a lisina Tumor neuroendocrí; Limfoma no Hodgkin; Inhibidor de la desmetilasa-1 específica a la lisina Background CC-90011 is an oral, potent, selective, reversible inhibitor of lysine-specific demethylase 1 (LSD1) that was well tolerated, with encouraging activity in patients who had advanced solid tumors or relapsed/refractory marginal zone lymphoma. The authors present long-term safety and efficacy and novel pharmacodynamic and pharmacokinetic data from the first-in-human study of CC-90011. Methods CC-90011-ST-001 (ClincalTrials.gov identifier NCT02875223; Eudract number 2015–005243-13) is a phase 1, multicenter study in which patients received CC-90011 once per week in 28-day cycles. The objectives were to determine the safety, maximum tolerated dose, and/or recommended phase 2 dose (primary) and to evaluate preliminary efficacy and pharmacokinetics (secondary). Results Sixty-nine patients were enrolled, including 50 in the dose-escalation arm and 19 in the dose-expansion arm. Thrombocytopenia was the most common treatment-related adverse event and was successfully managed with dose modifications. Clinical activity with prolonged, durable responses were observed, particularly in patients who had neuroendocrine neoplasms. In the dose-escalation arm, one patient with relapsed/refractory marginal zone lymphoma achieved a complete response (ongoing in cycle 58). In the dose-expansion arm, three patients with neuroendocrine neoplasms had stable disease after nine or more cycles, including one patient who was in cycle 46 of ongoing treatment. CC-90011 decreased levels of secreted neuroendocrine peptides chromogranin A, progastrin-releasing peptide, and RNA expression of the blood pharmacodynamic marker monocyte-to-macrophage differentiation–associated. Conclusions The safety profile of CC-90011 suggested that its reversible mechanism of action may provide an advantage over other irreversible LSD1 inhibitors. The favorable tolerability profile, clinical activity, durable responses, and once-per-week dosing support further exploration of CC-90011 as monotherapy and in combination with other treatments for patients with advanced solid tumors and other malignancies. This study was supported by Bristol Myers Squibb, Princeton, New Jersey, USA. Writing and editorial assistance was provided by Bio Connections, LLC, funded by Bristol Myers Squibb.
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- 2022
26. A network analysis of rest-activity rhythms in young people with emerging bipolar disorders
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Jan, Scott, Bruno, Etain, Ashlee, Grierson, Sharon, Naismith, Elizabeth, Scott, Ian, Hickie, Newcastle University [Newcastle], The University of Sydney, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), St. Vincent's Hospital, Sydney, and Etain, Bruno
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Male ,Sleep Wake Disorders ,Bipolar Disorder ,Youth ,MESH: Actigraphy ,Adolescent ,MESH: Sleep ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,MESH: Bipolar Disorder ,Bipolar disorders ,Humans ,MESH: Circadian Rhythm ,Aged ,MESH: Adolescent ,MESH: Aged ,MESH: Humans ,Circadian ,Actigraphy ,MESH: Sleep Wake Disorders ,MESH: Male ,Circadian Rhythm ,Psychiatry and Mental health ,Clinical Psychology ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,MESH: Biomarkers ,Female ,Network analysis ,Sleep ,MESH: Female ,Biomarkers - Abstract
International audience; Aims: Actigraphy studies of individuals with bipolar disorders (BD) suggest that illness progression may be associated with a range of progressive disruptions in 24-hour rest-activity rhythms (RAR). However, those longitudinal studies were undertaken in older adults with extended histories or illness and treatment rather than young people with emerging BD. To our knowledge, this is the first study to use network modelling to examine the statistical associations between clinical phenotypes of BD and different subsets of RAR markers.Methods: This study of adolescents and young adults (mean age 22 years; 69% female) uses network modelling to examine which self-rated or actigraphic markers of RAR are more strongly associated with full threshold BD (referred to as Stage 2; N = 15) compared with BD-at risk syndromes (subthreshold presentations referred to as Stage 1; N = 25).Results: Network analysis demonstrated that some RAR are associated with both stage of BD and a family history of BD (such as longer sleep duration and higher levels of daytime impairment). Markers of circadian rhythmicity indicated that regulation of this system is weaker in Stage 2 compared with Stage 1 of BD.Limitations: The small subgroup samples may have undermined the ability to detect some associations between phenotypes and RAR.Conclusions: Network modelling may offer a useful strategy for visualizing and analysing patterns of association between RAR and clinical phenotypes defined by stage of illness, familial loading or symptom profile. This could prove useful in understanding the underlying pathophysiology of sleep-wake cycle and circadian rhythm disturbances in BD.
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- 2022
27. <scp>ROBITT</scp> : A tool for assessing the risk‐of‐bias in studies of temporal trends in ecology
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Robin J. Boyd, Gary D. Powney, Fiona Burns, Alain Danet, François Duchenne, Matthew J. Grainger, Susan G. Jarvis, Gabrielle Martin, Erlend B. Nilsen, Emmanuelle Porcher, Gavin B. Stewart, Oliver J. Wilson, Oliver L. Pescott, UK Centre for Ecology & Hydrology, Natural Environment Research Council (NERC), RSPB Centre for Conservation Science, Royal Society for the Protection of Birds, Centre d'Ecologie et des Sciences de la COnservation (CESCO), Muséum national d'Histoire naturelle (MNHN)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Swiss Federal Institute for Forest, Snow and Landscape Research WSL, Norwegian Institute for Nature Research (NINA), Evolution et Diversité Biologique (EDB), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Faculty of Biosciences and Aquaculture [Bodø], University of Nordland, School of Natural and Environmental Sciences, Newcastle University [Newcastle], and Plantlife
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[SDV.EE]Life Sciences [q-bio]/Ecology, environment ,Ecological Modeling ,risk-of-bias ,[SDV.BID]Life Sciences [q-bio]/Biodiversity ,bepress|Life Sciences|Ecology and Evolutionary Biology ,indicators ,Ecology and Environment ,Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Zoogeografi: 486 [VDP] ,species occurrence data ,temporal trends ,bepress|Life Sciences ,Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Økologi: 488 [VDP] ,Data and Information ,uncertainty ,Essential Biodiversity Variables ,insect declines ,bepress|Life Sciences|Ecology and Evolutionary Biology|Population Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
1. Aggregated species occurrence and abundance data from disparate sources are increasingly accessible to ecologists for the analysis of temporal trends in biodiversity. However, sampling biases relevant to any given research question are often poorly explored and infrequently reported; this can undermine statistical inference. In other disciplines, it is common for researchers to complete “risk-of-bias” assessments to expose and document the potential for biases to undermine conclusions. The huge growth in available data, and recent controversies surrounding their use to infer temporal trends, indicate that similar assessments are urgently needed in ecology. 2. We introduce ROBITT, a structured tool for assessing the “Risk-Of-Bias In studies of Temporal Trends in ecology”. ROBITT has a similar format to its counterparts in other disciplines: it comprises signalling questions designed to elicit information on the potential for bias in key study domains. In answering these, users will define study inferential goal(s) and relevant statistical target populations. This information is used to assess potential sampling biases across domains relevant to the research question (e.g. geography, taxonomy, environment), and how these vary through time. If assessments indicate biases, then usersmust clearly describe them and/or explain what mitigating action will be taken.3. Everything that users need to complete a ROBITT assessment is provided: the tool,a guidance document,and a worked example. Following other disciplines, the tool and guidance document were developed through a consensus-forming process across experts working in relevant areas of ecology and evidence synthesis.4. We propose that researchers should be strongly encouraged to include a ROBITT assessment when publishing studies of biodiversitytrends, especially when usingaggregated data. This will help researchers to structure their thinking, clearly acknowledge potential sampling issues,highlight where expert consultation is required, and provides an opportunity to describe data checks that might gounreported. ROBITT will also enable reviewers, editors, and readers to establish how well research conclusions are supported given a dataset combined with some analytical approach. In turn, itshouldstrengthen evidence-based policy and practice, reduce differing interpretations of data, and provide a clearer picture of the uncertainties associated with our understanding of reality. risk-of-bias; speciesoccurrence data; temporal trends; Essential Biodiversity Variables; indicators; uncertainty; insect declines
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- 2022
28. Analysis of Desalination Performance with a Thermal Vapor Compression System
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Zineb Fergani, Zakaria Triki, Rabah Menasri, Hichem Tahraoui, Mohammed Kebir, Abdeltif Amrane, Nassim Moula, Jie Zhang, Lotfi Mouni, Université Yahia Fares de Médéa, Université Ferhat-Abbas Sétif 1 [Sétif] (UFAS1), Research Unit on Analysis and Technological Development in Environment (URADTE-CRAPC), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Liège, Newcastle University [Newcastle], Université Mohamed Akli Ouelhadj de Bouira (UMAOB), and None
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thermal vapor compression ,water desalination ,multi-effect distillation ,Geography, Planning and Development ,exergoeconomic analysis ,[CHIM]Chemical Sciences ,Aquatic Science ,Biochemistry ,total water price ,Water Science and Technology - Abstract
International audience; Multi-effect distillation with thermal vapor compression (MED-TVC) is a highly energy-efficient desalination technology that can provide a reliable and sustainable source of high-quality water, particularly in areas with limited energy infrastructure and water resources. In this study, a numerical model based on exergoeconomic approach is developed to analyze the economic performance of a MED-TVC system for seawater desalination. A parallel/cross feed configuration is considered because of its high energy efficiency. In addition, a parametric study is performed to evaluate the effects of some operational parameters on the total water price, such as the top brine temperature, seawater temperature, motive steam flow rate, and number of effects. The obtained results indicate that the total water price is in the range of 1.73 USD/m(3) for a distilled water production of 55.20 kg/s. Furthermore, the exergy destructions in the effects account for 45.8% of the total exergy destruction. The MED effects are also identified to be the most relevant component from an exergoeconomic viewpoint. Careful attention should be paid to these components. Of the total cost associated with the effects, 75.1% is due to its high thermodynamic inefficiency. Finally, the parametric study indicates that adjusting the top brine temperature, the cooling seawater temperature, the motive steam flow rate, and the number of effects has a significant impact on the TWP, which varies between 1.42 USD/m(3) and 2.85 USD/m(3).
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- 2023
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29. Co-designing implementation strategies to promote remote physical activity programs in frail older community-dwellers
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Lorena Villa-García, Vanessa Davey, Laura M. Peréz, Luis Soto-Bagaria, Ester Risco, Pako Díaz, Kerry Kuluski, Maria Giné-Garriga, Carmina Castellano-Tejedor, Marco Inzitari, Institut Català de la Salut, [Villa-García L] Grup de Recerca en Envelliment, Fragilitat i Transicions a Barcelona, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Parc Sanitari Pere Virgili, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. QIDA, Sabadell, Spain. [Davey V] Grup de Recerca en Envelliment, Fragilitat i Transicions a Barcelona, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Parc Sanitari Pere Virgili, Barcelona, Spain. Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. [Peréz LM, Soto-Bagaria L, Castellano-Tejedor C] Grup de Recerca en Envelliment, Fragilitat i Transicions a Barcelona, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Parc Sanitari Pere Virgili, Barcelona, Spain. [Risco E] Nursing Research Group, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament d’Infermeria, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Díaz P] Centre d'Atenció Primària Bordeta-Magòria, Barcelona, Spain. [Inzitari M] Grup de Recerca en Envelliment, Fragilitat i Transicions a Barcelona, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Parc Sanitari Pere Virgili, Barcelona, Spain. Faculty of Health Sciences, Universitat Oberta de Catalunya (UOC), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Exercici terapèutic ,Aging ,Envelliment ,Persons::Age Groups::Adult::Aged [NAMED GROUPS] ,Therapeutics::Patient Care::Continuity of Patient Care::Aftercare::Rehabilitation::Exercise Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,terapéutica::asistencia al paciente::continuidad de la atención al paciente::asistencia del convaleciente::rehabilitación::tratamiento por actividad física [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Public Health, Environmental and Occupational Health ,Physical fitness ,Older people ,Persones grans ,personas::Grupos de Edad::adulto::anciano [DENOMINACIONES DE GRUPOS] ,Condició física - Abstract
Frailty; Integrated care; Older adults Fragilidad; Atención integrada; Personas mayores Fragilitat; Atenció integrada; Ancians Background: The “AGIL Barcelona (AGILBcn)” community-based integrated care program is a multicomponent healthy aging intervention for frail older adults. In this context, the present study aimed to identify implementation strategies to optimize the accessibility, acceptability, and adaptability of mobile health (mhealth) interventions to enhance physical activity in frail older adults, and to prioritize action points according to their importance and feasibility, through a co-design process. Material and methods: A mixed methods approach was used. In the qualitative phase, a method adapted from the World Café was applied in 6 virtual groups to identify strategies to facilitate the virtual physical activity program. In the quantitative phase, prioritization and feasibility of the strategies was analyzed through surveys. Strategies were ranked based on priority vs. feasibility, revealing if strategies should either be: implemented first; if possible; taken into account for future consideration; or directly disregarded. The convenience sample included older adults (n = 7), community professionals (n = 9) and health professionals (n = 13). Qualitative data were analyzed by summative content analysis and quantitative data by nonparametric descriptive analyses. Results: A total of 27 strategies were identified and grouped into four categories: general strategies for reducing barriers; specific strategies for facilitating the use of a digital application; specific strategies for facilitating participation in virtual exercise groups; and specific strategies for facilitating external support. According to the ranking of strategies, the first ones to be implemented included: digital literacy, digital capability assessment, family technology support, weekly telephone follow-up by professionals, personalizing exercises, and virtual exercises in small groups. Conclusion: The active participation of all stakeholders enabled us to identify potential strategies for implementing person-oriented technology in physical activity programs and for engaging older adults. LV-G was funded by the Industrial Doctorates Program [reference 2020 DI 76], promoted by the Government of Catalonia, Spain. This study received funding by the Barcelona Science Plan of the Cultural Institute of Barcelona-Barcelona City Council and by la Caixa Foundation [19S01576-006].
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- 2023
30. Formulation and Evaluation of Xanthan Gum Microspheres for the Sustained Release of Metformin Hydrochloride
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Madiha Melha Yahoum, Selma Toumi, Hichem Tahraoui, Sonia Lefnaoui, Mohammed Kebir, Abdeltif Amrane, Aymen Amin Assadi, Jie Zhang, Lotfi Mouni, Université Yahia Fares de Médéa, Université Ferhat-Abbas Sétif 1 [Sétif] (UFAS1), Research Unit on Analysis and Technological Development in Environment (URADTE-CRAPC), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Newcastle University [Newcastle], Université Mohamed Akli Ouelhadj de Bouira (UMAOB), and None
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[SPI]Engineering Sciences [physics] ,Control and Systems Engineering ,Mechanical Engineering ,xanthan gum ,encapsulation ,[CHIM]Chemical Sciences ,gelling ,metformin chloride ,extended release ,Electrical and Electronic Engineering - Abstract
International audience; This work aimed to formulate xanthan gum microspheres for the encapsulation of metformin hydrochloride, according to the process of ionotropic gelation. The obtained microparticles, based on various fractions of xanthan gum (0.5–1.25), were subjected to different physico-chemical tests and a drug release study. Microspheres with an average size varying between 110.96 μm and 208.27 μm were obtained. Encapsulation efficiency reached 93.11% at a 1.25% biopolymer concentration. The swelling study showed a swelling rate reaching 29.8% in the gastric medium (pH 1.2) and 360% in the intestinal medium (pH 6.8). The drug release studies showed complete metformin hydrochloride release from the beads, especially those prepared from xanthan gum at the concentration of 1.25%, in intestinal medium at 90.00% after 6 h. However, limited and insignificant drug release was observed within the gastric medium (32.50%). The dissolution profiles showed sustained release kinetics.
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- 2023
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31. Identification of new candidate drugs for primary Sjögren’s syndrome using a drug repurposing transcriptomic approach
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Renaud Felten, Tao Ye, Cedric Schleiss, Benno Schwikowski, Jean Sibilia, Fanny Monneaux, Hélène Dumortier, Roland Jonsson, Christopher Lessard, Fai Ng, Tsutomu Takeuchi, Xavier Mariette, Jacques-Eric Gottenberg, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), CHU Bordeaux [Bordeaux], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomédecine computationelle des systèmes / Computational systems biomedicine, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Bergen (UiB), Oklahoma Medical Research Foundation (OMRF), Newcastle University [Newcastle], Keio University, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and European Project: 806975,NECESSITY
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clue ,Rheumatology ,drug repurposing ,[SDV]Life Sciences [q-bio] ,transcriptomic signature ,therapeutics ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Pharmacology (medical) ,Sjogren syndrome ,histone deacetylase inhibitors ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,IFNs - Abstract
ObjectivesTo date, no immunomodulatory drug has demonstrated its efficacy in primary SS (pSS). We sought to analyse potential commonalities between pSS transcriptomic signatures and signatures of various drugs or specific knock-in or knock-down genes.MethodsGene expression from peripheral blood samples of patients with pSS was compared with that of healthy controls in two cohorts and three public databases. In each of the five datasets, we analysed the 150 most up- and downregulated genes between pSS patients and controls with regard to the differentially expressed genes resulting from the biological action on nine cell lines of 2837 drugs, 2160 knock-in and 3799 knock-down genes in the Connectivity Map database.ResultsWe analysed 1008 peripheral blood transcriptomes from five independent studies (868 patients with pSS and 140 healthy controls). Eleven drugs could represent potential candidate drugs, with histone deacetylases and PI3K inhibitors among the most significantly associated. Twelve knock-in genes were associated with a pSS-like profile and 23 knock-down genes were associated with a pSS-revert profile. Most of those genes (28/35, 80%) were interferon-regulated.ConclusionThis first drug repositioning transcriptomic approach in SS confirms the interest of targeting interferons and identifies histone deacetylases and PI3K inhibitors as potential therapeutic targets.
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- 2023
32. Application of Walnut Shell Biowaste as an Inexpensive Adsorbent for Methylene Blue Dye: Isotherms, Kinetics, Thermodynamics, and Modeling
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Sabrina Farch, Madiha Melha Yahoum, Selma Toumi, Hichem Tahraoui, Sonia Lefnaoui, Mohammed Kebir, Meriem Zamouche, Abdeltif Amrane, Jie Zhang, Amina Hadadi, Lotfi Mouni, Université Yahia Fares de Médéa, Université Djilali Liabès [Sidi-Bel-Abbès], Research Unit on Analysis and Technological Development in Environment (URADTE-CRAPC), Université Salah Boubnider Constantine 3, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Université Mohamed Akli Ouelhadj de Bouira (UMAOB), and None
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[SPI]Engineering Sciences [physics] ,[CHIM]Chemical Sciences ,Filtration and Separation ,walnut shells ,methylene blue ,adsorption ,analytical approaches ,isotherms ,kinetic models ,Analytical Chemistry - Abstract
This research aimed to assess the adsorption properties of raw walnut shell powder (WNSp) for the elimination of methylene blue (MB) from an aqueous medium. The initial MB concentration (2–50 mg/L), the mass of the biomaterial (0.1–1 g/L), the contact time (10–120 min), the medium’s pH (2–12), and the temperature (25–55 °C) were optimized as experimental conditions. A maximum adsorption capacity of 19.99 mg/g was obtained at an MB concentration of 50 mg/L, a medium pH of 6.93 and a temperature of 25 °C, using 0.2 g/L of WNSp. These conditions showed that the MB dye elimination process occurred spontaneously. Different analytical approaches were used to characterize the WNSp biomaterial, including functional groups involved in MB adsorption, the surface characteristics and morphological features of the WNSp before and after MB uptake, and identification of WNSp based on their diffraction pattern. The experimental isotherm data were analyzed by the Langmuir and Freundlich models for the adsorption of MB dye. The corresponding values of parameter RL of Langmuir were between 0.51 and 0.172, which confirmed the WNSp’s favorable MB dye adsorption. The experimental kinetic data were examined, and the pseudo-second-order model was shown to be more suitable for describing the adsorption process, with an excellent determination coefficient (R2 = 0.999). The exchanged standard enthalpy (H° = −22.456 KJ.mol−1) was calculated using the van ‘t Hoff equation, and it was proven that the adsorption process was exothermic. The spontaneous nature and feasibility of the MB dye adsorption process on WNSp were validated by negative standard enthalpy values (G°) ranging from −2.580 to −0.469 at different temperatures. It was established that WNSp may be employed as a novel, effective, low-cost adsorbent for the elimination of methylene blue in aqueous solutions.
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- 2023
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33. Maternal age and the prevalence of congenital heart defects in Europe, 1995-2015: A register-based study
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Chrysovalanto Mamasoula, Theophile Bigirumurame, Thomas Chadwick, Marie‐Claude Addor, Clara Cavero‐Carbonell, Carlos M. Dias, Luis‐Javier Echevarría‐González‐de‐Garibay, Miriam Gatt, Babak Khoshnood, Kari Klungsoyr, Kay Randall, Sylvia Stoianova, Martin Haeusler, Vera Nelen, Amanda J. Neville, Isabelle Perthus, Anna Pierini, Bénédicte Bertaut‐Nativel, Anke Rissmann, Florence Rouget, Bruno Schaub, David Tucker, Diana Wellesley, Natalya Zymak‐Zakutnia, Ingeborg Barisic, Hermien E.K. de Walle, Monica Lanzoni, Gerardine Sayers, Carmel Mullaney, Lindsay Pennington, Judith Rankin, Newcastle University [Newcastle], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), CEMC-Auvergne, Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Agence Régionale de Santé d'Auvergne, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
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Embryology ,MESH: Humans ,MESH: Bayes Theorem ,[SDV]Life Sciences [q-bio] ,Health, Toxicology and Mutagenesis ,prevalence ,MESH: Heart Defects, Congenital ,Toxicology ,register-based study ,European Surveillance of Congenital Anomalies ,maternal age ,Pediatrics, Perinatology and Child Health ,congenital Heart Defects ,MESH: Maternal Age ,MESH: Europe ,MESH: Prevalence ,Developmental Biology - Abstract
Background Evidence on the direction and strength of association between maternal age and the prevalence of congenital heart defects (CHD) in different age group categories is conflicting. Some studies have illustrated different trends with an increase in prevalence in younger and older age groups while other studies have reported a linear relationship. Given the increase in maternal age over recent years, it is important to study the CHD prevalence by maternal age. Objectives To examine the association between maternal age and the prevalence of CHD in Europe between 1995 and 2015 using population-based data from 24 registries belonging to the European Surveillance of Congenital Anomalies (EUROCAT) network. Methods Associations over time of all nonsyndromic CHD according to maternal age category and for three CHD severity groupings (severity group I: very severe; severity group II: severe; severity group III: less severe) were examined using Bayesian multilevel Poisson regression modeling. Further subgroup analyses were undertaken within four maternal age-bands: ≤24, 25–29, 30–34 and 35–44 years. Descriptive summaries are also presented. Results There were 51,608 nonsyndromic CHD cases in Europe over the 20-year study period. Total prevalence for all CHD combined was increased for younger mothers (≤24 years) and for mothers 35–44 years of age when compared with mothers aged 25–29 years (reference group) (IRR: 1.05, 95% CI: 1.02, 1.07). The total prevalence was increased for severity group I (very severe) only for younger mothers compared to those aged 25–29 years (IRR: 1.14, 95% CI: 1.04, 1.23). We found an increased prevalence of the following CHD subtypes: double outlet right ventricle (IRR:1.33, 95% CI: 1.09, 1.60), hypoplastic left heart syndrome (IRR: 1.18, 95% CI: 1.05, 1.32), hypoplastic right heart syndrome (IRR: 1.41, 95% CI: 1.05, 1.84), atrioventricular septal defect (IRR: 1.15, 95% CI: 1.01, 1.32), coarctation of aorta (IRR: 1.15, 95% CI: 1.03, 1.28) and atrial septal defect (IRR: 1.08, 95% CI: 1.02, 1.13). For older mothers (35–44 years) compared to the reference category, we observed an increased risk in the prevalence for severity group II (IRR: 1.09, 95% CI: 1.03, 1.14), severity group III (IRR: 1.05, 95% CI: 1.01, 1.08) and an increased prevalence of the CHD subtypes: Pulmonary valve stenosis (IRR: 1.22, 95% CI: 1.09, 1.34), ASD (IRR: 1.07, 95% CI: 1.02, 1.13), CoA (IRR: 1.18, 95% CI: 1.06, 1.32) and Tetralogy of Fallot (IRR: 1.14, 95% CI: 1.01, 1.28). Finally, for all age categories compared to the reference category, different associations of ASD and an increased prevalence of CoA was also observed. Conclusions Based on data for cases of CHD from 24 European population-based registries, evidence of a positive association between maternal age and the total prevalence of CHD for younger (≤24 years old) and older (35–44 years old) mothers was observed. The results suggest that young maternal age (≤24 years old) is a factor associated with severe CHD phenotypes while a positive association between advanced maternal age (35–44 years old) and mild CHD phenotypes was observed. publishedVersion
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- 2023
34. Jujube stones based highly efficient activated carbon for methylene blue adsorption: Kinetics and isotherms modeling, thermodynamics and mechanism study, optimization via response surface methodology and machine learning approaches
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Nasma Bouchelkia, Hichem Tahraoui, Abdeltif Amrane, Hayet Belkacemi, Jean-Claude Bollinger, Abdelkrim Bouzaza, Abdelhalim Zoukel, Jie Zhang, Lotfi Mouni, Université Abderrahmane Mira [Béjaïa], Université Salah Boubnider Constantine 3, Université Yahia Fares de Médéa, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Eau Environnement Limoges ( E2Lim), Institut Matériaux Procédés Environnement Ouvrages (IMPEO), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université Amar Telidji - Laghouat, Newcastle University [Newcastle], and Université Mohamed Akli Ouelhadj de Bouira (UMAOB)
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Bootstrap Aggregation_Bag ,Environmental Engineering ,Methylene blue adsorption ,General Chemical Engineering ,Activated carbon ,Dragonfly algorithm ,[SDE]Environmental Sciences ,Environmental Chemistry ,Gaussian Process Regression ,[CHIM]Chemical Sciences ,Box-Behnken design ,Safety, Risk, Reliability and Quality - Abstract
International audience; Water contaminated by methylene blue (MB) dye was treated with activated carbon based on locally collected jujube stones. This activated carbon was characterized by physico-chemical methods after preparation and chemical activation. Response surface methodology (RSM) was used to maximize the MB uptake a dependent variable in Box-Behnken Design (BBD) with the initial concentration of methylene blue (400-700 mg/L), adsorbent dosage (0.6-1.6 g/L), contact time (30-540 min), pH (7-11) and temperature (20-50 degrees C) as inde-pendent variables. Then, the database created by BBD was further modeled using Gaussian Process Regression coupled with Bagging (Bootstrap Aggregation_Bag) and Dragonfly optimization algorithm (GPR_DA_Bootstrap). The results of the optimization analysis using the GPR_DA_Bootstrap model are shown to be superior to those of the BBD model. The experimental validation of the optimal conditions of the GPR_DA_Bootstrap model (X1 = 700 mg/L, X2 = 0.6 g/L, X3 = 540 min, X4 = 11, and X5 =50 degrees C) led to an MB uptake (501.01 mg/g) significantly higher than that of BBD (456.00 g/g). In addition, the very low error between the experimental and the predicted values given by the GPR_DA_Bootstrap model (8.64 mg/g) compared to that of the BBD model (22.19 mg/g), should be highlighted. This clearly shows the efficiency and the performance of the GPR_DA_Bootstrap model on the one hand; as well as the effectiveness of activated carbon prepared from jujube stones (PJAC) as a low-cost adsorbent on the other hand.
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- 2023
35. Energy and Exergy Analysis of Solar Air Gap Membrane Distillation System for Seawater Desalination
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Nawel Mibarki, Zakaria Triki, Abd-Elmouneïm Belhadj, Hichem Tahraoui, Abdeltif Amrane, Sabrina Cheikh, Amina Hadadi, Nasma Bouchelkia, Mohamed Kebir, Jie Zhang, Amine Aymen Assadi, Lotfi Mouni, Université Yahia Fares de Médéa, Université Ferhat-Abbas Sétif 1 [Sétif] (UFAS1), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Mohamed Akli Ouelhadj de Bouira (UMAOB), Newcastle University [Newcastle], DG-RSDT of Algeria, and Biomaterials and Transport Phenomena Laboratory at the University of Medea [303 03-12-2003]
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air gap membrane distillation ,energy analysis ,exergy evaluation ,seawater desalination ,solar energy ,performance ,Geography, Planning and Development ,[CHIM]Chemical Sciences ,Aquatic Science ,Biochemistry ,Water Science and Technology - Abstract
International audience; Air gap membrane distillation (AGMD) is a widely utilized technology for producing drinking water due to its low heat loss, high thermal efficiency, and compatibility with solar energy. The application of the first and second laws of thermodynamics in energy and exergy analyses provides a comprehensive evaluation of the efficiency of thermal processes. This study aims to examine numerically the energy and exergy performance indicators of a solar AGMD system used for seawater desalination. The simulation was carried out using MATLAB 9.7 software. The total thermal efficiency and overall efficiency of each element in the AGMD system were calculated for various solar field energy outputs, and moreover, a parametric study was conducted. The results indicate that the exergetic efficiency of the AGMD system components was the lowest in the solar field, with the concentrator having the lowest energy efficiency. Additionally, the thermal and exergetic efficiency of the entire solar AGMD system decreases along with the raise of ambient temperature. An additional investigation was conducted to better apprehend the sources of exergy destruction in the solar field. The obtained results from this study can be employed as a guide to reduce exergy destruction in the whole solar AGMD desalination system with recognition of the main sources of irreversibility.
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- 2023
36. Optimization of Partially Hydrolyzed Polyacrylamide (HPAM) Utilized in Water-Based Mud While Drilling
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Asma Nour El Houda Sid, Benalia Kouini, Mohammed Amin Bezzekhami, Selma Toumi, Khadidja Ouchak, Sara Benfarhat, Hichem Tahraoui, Mohammed Kebir, Abdeltif Amrane, Aymen Amine Assadi, Jie Zhang, Lotfi Mouni, University of Constantine, Université M'Hamed Bougara Boumerdes (UMBB), Abdelhamid Ibn Badis University, Ministère de l'Enseignement Supérieur et de la Recherche Scientifique [Algérie] (MESRS), Université Yahia Fares de Médéa, Université Ferhat-Abbas Sétif 1 [Sétif] (UFAS1), Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques (CRAPC), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Université Mohamed Akli Ouelhadj de Bouira (UMAOB), and None
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Process Chemistry and Technology ,aging ,drilling mud ,Chemical Engineering (miscellaneous) ,[CHIM]Chemical Sciences ,Bioengineering ,rheology ,thermal aging ,HPAM ,optimization - Abstract
International audience; Water-soluble polymers are becoming increasingly important in various applications, such as stabilizer fluids and drilling muds. These materials are used as viscosifiers and filtration control agents, flocculants, and deflocculants due to their superior properties in increasing viscosity and gelling ability in the presence of crosslinkers. In general, studying the rheological behavior of drilling fluids is of paramount importance to ensure successful well drilling operations. Partially hydrolyzed polyacrylamide is one of the polymers widely used in water-based muds. The main objective of this study is to optimize the rheological properties of drilling muds through a characterization study of various parameters, including rheological behavior, viscosity, temperature (23 degrees C, 40 degrees C, and 60 degrees C), salinity using KCl and NaCl contents, aging, pH, solubility, and structural analysis using infrared of partially hydrolyzed polyacrylamide. The study aims to demonstrate the importance of using polymers in drilling muds. The findings revealed that a rate of 3% of HPAM gave better rheological behavior, the influence of KCl (1.5%, 3%, and 4.5%) was greater than that of NaCl (1.5%, 3%, and 4.5%) on polymers, and the aging test showed that the different formulations are stable and maintain their behavior up to 110 degrees C. The solubility test results confirmed the maximum amount absorbed by polyacrylamide ([C-HPAM] = 66.42 g/L) in order to avoid aggregation, gelification, and enhance the drilling mud by utilizing the prescribed contents.
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- 2023
37. Development of New Alkylated Carrageenan Derivatives: Physicochemical, Rheological, and Emulsification Properties Assessment
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Selma Toumi, Madiha Melha Yahoum, Sonia Lefnaoui, Abdelkader Hadjsadok, Asma Nour El Houda Sid, Amel Hind Hassein-Bey, Abdeltif Amrane, Jie Zhang, Amin Aymen Assadi, Lotfi Mouni, Université Yahia Fares de Médéa, Université Saâd Dahlab Blida 1 (UB1), Université Salah Boubnider Constantine 3, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], and Université Mohamed Akli Ouelhadj de Bouira (UMAOB)
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hydrophobic modification ,kappa-carrageenan ,Renewable Energy, Sustainability and the Environment ,Geography, Planning and Development ,κ-carrageenan ,critical aggregation concentration ,emulsion stability ,rheology ,[CHIM]Chemical Sciences ,Building and Construction ,Management, Monitoring, Policy and Law - Abstract
International audience; In this research, amphiphilic derivatives of kappa carrageenan (KC) were synthesized by hydrophobic modification with an alkyl halide (1-Octyl chloride). Three hydrophobic polymers with different degrees of substitution (DS) were obtained by the Williamson etherification reaction in an alkaline medium. The effect of the molar ratio (R = reagent/polymer) on the DS was investigated at different ratios (1, 2, and 3). The KC derivatives (KCRs) were characterized by different techniques such as FT-IR, H-1-NMR, X-ray Diffraction, Scanning electron microscopy, and a rheological assessment. The FT-IR and (HNMR)-H-1 analyses confirmed the binding of the hydrophobic groups onto the KC molecule. The degrees of substitution calculated by H-1-NMR demonstrated that the derivative KCR3 (0.68) presented a higher degree of substitution compared to KCR1(0.45) and KCR2 (0.53). The XRD and SEM analyses revealed that the alkaline etherification conditions did not alter the morphological and crystallographic properties, as well as the rheological behavior of the obtained derivatives. The amphiphilic character of the KCRs was investigated using a conductivity method which revealed that the molecular aggregation occurred above the critical aggregation concentration (CAC). Decreasing CAC values of 0.15% (KCR1), 0.11% (KCR2) and 0.08% (KCR3)with the degree of substitution (DS) were found. Furthermore, KCR's derivatives greatly improved the stability of oil/water emulsions as the droplet size decreased with increasing DS. The derivative (KCR3) with higher DS, showed a greater amphiphilic character, and improved emulsifying power.
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- 2023
38. Experimental Analysis and Neural Network Modeling of the Rheological Behavior of Xanthan Gum and Its Derivatives
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Madiha Melha Yahoum, Selma Toumi, Salma Hentabli, Hichem Tahraoui, Sonia Lefnaoui, Abdelkader Hadjsadok, Abdeltif Amrane, Mohammed Kebir, Nassim Moula, Amin Aymen Assadi, Jie Zhang, Lotfi Mouni, Université Yahia Fares de Médéa, Université Ferhat-Abbas Sétif 1 [Sétif] (UFAS1), Université Saâd Dahlab Blida 1 (UB1), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Liège, Newcastle University [Newcastle], Université Mohamed Akli Ouelhadj de Bouira (UMAOB), and None
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artificial neural networks ,chemical modification ,rheological behavior ,xanthan gum ,General Materials Science ,[CHIM.MATE]Chemical Sciences/Material chemistry - Abstract
International audience; The main objective of this study was to create a mathematical tool that could be used with experimental data to predict the rheological flow behavior of functionalized xanthan gum according to the types of chemical groups grafted onto its backbone. Different rheological and physicochemical analyses were applied to assess six derivatives synthesized via the etherification of xanthan gum by hydrophobic benzylation with benzyl chloride and carboxymethylation with monochloroacetic acid at three (regent/polymer) ratios R equal to 2.4 and 6. Results from the FTIR study verified that xanthan gum had been modified. The degree of substitution (DS) values varying between 0.2 and 2.9 for carboxymethylxanthan gum derivatives were found to be higher than that of hydrophobically modified benzyl xanthan gum for which the DS ranged from 0.5 to 1. The molecular weights of all the derivatives were found to be less than that of xanthan gum for the two types of derivatives, decreasing further as the degree of substitution (DS) increased. However, the benzyl xanthan gum derivatives presented higher molecular weights varying between 1,373,146 (g/mol) and 1,262,227 (g/mol) than carboxymethylxanthan gum derivatives (1,326,722-1,015,544) (g/mol). A shear-thinning behavior was observed in the derivatives, and the derivatives' viscosity was found to decrease with increasing DS. The second objective of this research was to create an ANN model to predict one of the rheological properties (the apparent viscosity). The significance of the ANN model (R-2 = 0.99998 and MSE = 5.95 x 10(-3)) was validated by comparing experimental results with the predicted ones. The results showed that the model was an efficient tool for predicting rheological flow behavior.
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- 2023
39. Professional's Attitudes Do Not Influence Screening and Brief Interventions Rates for Hazardous and Harmful Drinkers: Results from ODHIN Study
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Myrna Keurhorst, Jorge Palacio, Marcin Wojnar, Artur Mierzecki, Preben Bendtsen, Luiza Słodownik, Colin Drummond, Katarzyna Okulicz-Kozaryn, Ben van Steenkiste, Kathryn Parkinson, Karolina Kłoda, Fredrik, Dorothy Newbury-Birch, Joan Colom, Paul K. Wallace, Ulrika Müssener, Amy Wolstenholme, Krzysztof Brzózka, Miranda Laurant, Antoni Gual, Nadine Karlsson, Peter J. Anderson, Lidia Segura, Eileen Kaner, Gaby Ronda, Begoña Baena, Paolo Deluca, Jillian Reynolds, [Bendsten P] Department of Medical Specialist and Department of Medicine and Health Sciences, Linköping University, Motala, Sweden. [Anderson P] Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK Department of Family Medicine, Maastricht University, School CAPHRI, Maastricht, The Netherlands. [Wojnar M] Department of Psychiatry, Medical University of Warsaw, Warsaw, Poland Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. [Newbury-Birch D] Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK. [Müssener U] Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden. [Colom J, Segura L, Palacio J, Baena B] Programa d’Abús de Substàncies, Agència de Salut Pública de Catalunya, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain, Departament de Salut, Family Medicine, Health promotion, RS: CAPHRI School for Public Health and Primary Care, RS: CAPHRI - R5 - Optimising Patient Care, and RS: CAPHRI - R6 - Promoting Health & Personalised Care
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Male ,medicine.medical_specialty ,Otros calificadores::Otros calificadores::/prevención & control [Otros calificadores] ,Alcohol Drinking ,STRATEGIES ,Cross-sectional study ,Attitude of Health Personnel ,HELPING AGENTS ,Psychological intervention ,Alternative medicine ,PRIMARY-HEALTH-CARE ,CONTROLLED-TRIAL ,law.invention ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Alcoholisme - Prevenció ,Other subheadings::Other subheadings::/prevention & control [Other subheadings] ,Professional Role ,Randomized controlled trial ,Acquired immunodeficiency syndrome (AIDS) ,law ,Surveys and Questionnaires ,trastornos inducidos químicamente::trastornos relacionados con sustancias::trastornos relacionados con el alcohol::alcoholismo [ENFERMEDADES] ,Health care ,GENERAL-PRACTICE ,SUPPORT ,medicine ,MANAGEMENT ,Humans ,Psychiatry ,atención a la salud (salud pública)::niveles de atención a la salud::atención a la salud (salud pública)::atención primaria de la salud [SALUD PÚBLICA] ,Social work ,Primary Health Care ,business.industry ,General Medicine ,medicine.disease ,MANAGING ALCOHOL-PROBLEMS ,Europe ,Cross-Sectional Studies ,Atenció primària ,Health Care (Public Health)::Health Care Levels::Health Care (Public Health)::Primary Health Care [PUBLIC HEALTH] ,PRACTITIONERS ,Psychotherapy, Brief ,Female ,Brief intervention ,Chemically-Induced Disorders::Substance-Related Disorders::Alcohol-Related Disorders::Alcoholism [DISEASES] ,business - Abstract
Detecció d'alcoholèmia; Intervenció breu; Actitud del personal sanitari Detección de alcoholemia; Intervención breve; Actitud del personal sanitario Alcoholism detection; Brief intervention; Attitude of Health Personnel Aims: To determine the relation between existing levels of alcohol screening and brief interventionrates infive European jurisdictions and role security and therapeutic commitment by the participat-ing primary healthcare professionals. Methods: Health care professionals consisting of, 409 GPs, 282 nurses and 55 other staff including psy-chologists, social workers and nurse aids from 120 primary health care centres participated in a cross-sectional 4-week survey. The participants registered all screening and brief intervention activities aspart of their normal routine. The participants also completed the Shortened Alcohol and Alcohol Pro-blems Perception Questionnaire (SAAPPQ), which measure role security and therapeutic commitment. Results: The only significant but small relationship was found between role security and screeningrate in a multilevel logistic regression analysis adjusted for occupation of the provider, number ofeligible patients and the random effects of jurisdictions and primary health care units (PHCU). Nosignificant relationship was found between role security and brief intervention rate nor betweentherapeutic commitment and screening rate/brief intervention rate. The proportion of patientsscreened varied across jurisdictions between 2 and 10%. Conclusion: Thefindings show that the studied factors (role security and therapeutic commitment)are not of great importance for alcohol screening and BI rates. Given the fact that screening and briefintervention implementation rate has not changed much in the last decade in spite of increased pol-icy emphasis, training initiatives and more research being published, this raises a question aboutwhat else is needed to enhance implementation. Radboud university medical centre received co-funding from The NetherlandsOrganization for Health Research and Development (ZonMW, Prevention Pro-gramme), under Grant Agreement n° 200310017—ODHIN—Optimizing de-livery of healthcare interventions in the Netherlands, according to Art.II.17 ofthe FP7 EC Grant Agreement. Pomeranian Medical University in Szczecin re-ceived co-funding regarding presented research from the Polish sciencefinancialresources in the years 2012–2014 allocated to conduct the international co-funded project ODHIN.
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- 2015
40. Reply: Are CHCHD10 mutations indeed associated with familial amyotrophic lateral sclerosis?
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Sylvie Bannwarth, Samira Ait-El-Mkadem, Annabelle Chaussenot, Emmanuelle C. Genin, Sandra Lacas-Gervais, Konstantina Fragaki, Laetitia Berg-Alonso, Yusuke Kageyama, Valérie Serre, David Moore, Annie Verschueren, Cécile Rouzier, Isabelle Le Ber, Gaëlle Augé, Charlotte Cochaud, Françoise Lespinasse, Karine N’Guyen, Anne de Septenville, Alexis Brice, Patrick Yu-Wai-Man, Hiromi Sesaki, Jean Pouget, Véronique Paquis-Flucklinger, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Medical Genetics, National Centre for Mitochondrial Diseases-Nice Teaching Hospital, Joint Centre for Applied Electron Microscopy, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Department of Cell Biology, Baltimore, Johns Hopkins University School of Medicine, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Wellcome Trust Centre for Mitochondrial Research, Newcastle University [Newcastle]-International Centre for Life-Institute of Genetic Medicine, Neuro-Oncologie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE)-Marseille Teaching Hospital, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Newcastle Eye Centre, Royal Victoria Infirmary, Association Française contre les Myopathies (AFM), Fondation pour la Recherche Médicale (FRM), National Institutes of Health (GM089853), program ‘Investissements d’avenir’ ANR-10-IAIHU-06, Programme Hospitalier de Recherche Clinique, 7th framework program of the European Union (FP7, E12009DD, Neuromics), Clinician Scientist Fellowship Award (G1002570), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS)
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Male ,Ataxia ,Mitochondrial Diseases ,Hearing loss ,Pedigree chart ,Disease ,DNA, Mitochondrial ,Mitochondrial Proteins ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Amyotrophic lateral sclerosis ,Myopathy ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Genetics ,0303 health sciences ,Amyotrophic Lateral Sclerosis ,medicine.disease ,Mitochondria ,Frontotemporal Dementia ,Mutation (genetic algorithm) ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neurology (clinical) ,medicine.symptom ,Psychology ,030217 neurology & neurosurgery ,Frontotemporal dementia - Abstract
Sir, A recent study by Bannwarth et al. (2014) in Brain identified a novel mutation (c.176C > T; p.Ser59Leu) in the CHCHD10 gene that segregates in a family presenting with ataxia, myopathy, hearing loss as well as motor neuron disease and frontotemporal dementia (FTD). Furthermore they identified a second family with ALS/FTD harbouring the identical mutation making this a gene of interest in the pathogenesis of ALS/FTD. For this reason we read with great interest the letter by Muller et al. (2014) that describes the identification of two novel variants in CHCHD10 in three pedigrees with familial amyotrophic lateral sclerosis (ALS). The authors state that their findings provide strong support for CHCHD10 being a novel ALS gene. Although their findings are highly interesting and their conclusion is appealing, we feel obliged to make several remarks concerning the genetic evidence provided to support this statement. The definition of genetic evidence, driven by the problem of non-replicating findings, is a matter of concern over the past years and has led to multiple consensus definitions for different study designs (reviewed by Pulit et al. , 2014). A landmark paper published nearly 20 years ago defined segregation of the gene with the studied phenotype within a pedigree resulting in a LOD score ≥ 3 as robust genetic evidence (Lander and Kruglyak, 1995). For …
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- 2014
41. Short communication: Do clinical guidelines for bipolar disorders adequately address sleep, circadian rhythm, activity and lifestyle problems?
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Tibby Flint, Vincent Hennion, Bruno Etain, Jan Scott, University of Bristol [Bristol], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département Médico-Universitaire Neurosciences [Sorbonne Université] (DMU Neurosciences), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fondation FondaMental [Créteil], Newcastle University [Newcastle], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Etain, Bruno
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Bipolar Disorder ,Energy ,MESH: Humans ,MESH: Sleep ,Health Personnel ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Circadian ,MESH: Life Style ,Lifestyle ,Quality ,Practice guidelines ,Circadian Rhythm ,Psychiatry and Mental health ,Clinical Psychology ,MESH: Bipolar Disorder ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Bipolar disorders ,Humans ,MESH: Health Personnel ,MESH: Circadian Rhythm ,Sleep ,Life Style - Abstract
International audience; Objectives Clinical practice guidelines (CPGs) for the treatment of bipolar disorder (BD) provide guidance to health care professionals and patients about the management of core aspects of BD. This study evaluated the overall quality of CPGs and examined the quantity, specificity, clarity and utility of recommendations about four key contemporary themes: sleep, circadian rhythms, activity and energy, and healthy lifestyles. Methods English language editions of CPGs for the treatment of BD were identified by a systematic search of the literature from 2007 onwards (i.e. 15 years). Blind independent ratings were combined to give consensus scores for the quality of each CPGs (using the 14-item International Center for Allied Health Evidence guideline checklist). Composite ratings of the quantity, specificity, clarity and utility of recommendations about the key themes were undertaken using a 0-3 scale. Results Twenty-five CPGs were eligible for review. Overall quality was high (median checklist score=10), but only 11 (44%) CPGs included even basic information about circadian rhythm disturbances. Combined scores for composite ratings about sleep and circadian rhythms were significantly correlated with overall quality of the CPG (sleep, r = 0.43; circadian rhythms, r = 0.42) but not with year of publication. Limitations No reliable scale exists for generating composite ratings of the four themes we examined. Conclusions Circadian rhythms and chronobiology represent neglected domains in CPGs. Incorporating this important theme into future editions of CPGs would aid health care professionals to identify, prevent, or intervene with these problems and improve outcomes for a significant proportion of individuals with BD.
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- 2022
42. Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1/2 Trial
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Ashish Dugar, Eugenio Mercuri, Xiaodong Wang, Volker Straub, Baoguang Han, Daniela Leone, Navid Khan, Dan Wang, Erica Koenig, Laurent Servais, Andreea Mihaela Seferian, Michela Guglieri, Mariacristina Scoto, Francesco Muntoni, University of Oxford, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Liège, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, University College of London [London] (UCL), Great Ormond Street Hospital for Children [London] (GOSH), Sarepta Therapeutics, University of Oxford [Oxford], I-Motion Institut [CHU Trousseau], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università cattolica del Sacro Cuore [Roma] (Unicatt), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], and Gestionnaire, Hal Sorbonne Université
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Duchenne muscular dystrophy ,medicine.medical_specialty ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Population ,Oligonucleotides ,Walk Test ,golodirsen ,Biochemistry ,Dystrophin ,03 medical and health sciences ,FEV1/FVC ratio ,0302 clinical medicine ,Internal medicine ,Multicenter trial ,Drug Discovery ,Genetics ,medicine ,Clinical endpoint ,Humans ,education ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,business.industry ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Exons ,medicine.disease ,Original Papers ,Exon skipping ,3. Good health ,Clinical trial ,Muscular Dystrophy, Duchenne ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Ambulatory ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Molecular Medicine ,business ,030217 neurology & neurosurgery ,exon skipping - Abstract
The aim of this Phase 1/2, 2-part, multicenter trial was to report clinical safety and efficacy of long-term golodirsen treatment among ambulatory patients with exon 53 skip-amenable Duchenne muscular dystrophy (DMD). Part 1 was a 12-week, randomized, double-blind, placebo-controlled, dose-titration study followed by 9-week safety review. Part 2 was a 168-week, open-label evaluation of golodirsen 30 mg/kg. Part 1 primary endpoint was safety. Part 2 primary endpoints were dystrophin protein expression and 6-minute walk test (6MWT); secondary endpoints were percent predicted forced vital capacity (FVC%p) and safety. Post hoc ambulation analyses used mutation-matched external natural history controls. All patients from Part 1 (golodirsen, n = 8; placebo, n = 4) plus 13 additional patients entered Part 2; 23 completed the study. Adverse events were generally mild, nonserious, and unrelated to golodirsen, with no safety-related discontinuations or deaths. Golodirsen increased dystrophin protein (16.0-fold; P
- Published
- 2022
43. Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype
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Ramada R. Khasawneh, Simon D. Bamforth, Helen M. Phillips, Timothy J. Mohun, Jürgen E. Schneider, Stéphane Zaffran, Heiko Peters, Ralf Kist, Rachel Queen, Rafiqul Hussain, Jonathan Coxhead, Newcastle University [Newcastle], Yarmouk University (YU), University of Leeds, The Francis Crick Institute [London], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Malbec, Odile
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Model organisms ,Aortic arch ,Pathology ,medicine.medical_specialty ,QH301-705.5 ,[SDV]Life Sciences [q-bio] ,Cardiovascular development ,Pharyngeal endoderm ,Haploinsufficiency ,Biology ,Cardiovascular System ,Imaging ,03 medical and health sciences ,Mice ,Neural crest ,0302 clinical medicine ,medicine.artery ,medicine ,Animals ,Biology (General) ,030304 developmental biology ,MSX1 Transcription Factor ,Mice, Knockout ,0303 health sciences ,Research ,Hyoid bone ,Embryogenesis ,Interrupted aortic arch ,medicine.disease ,Pax9 ,[SDV] Life Sciences [q-bio] ,stomatognathic diseases ,medicine.anatomical_structure ,Branchial Region ,Phenotype ,PAX9 Transcription Factor ,Neural crest cell migration ,030217 neurology & neurosurgery ,Msx1 ,Developmental Biology ,Artery - Abstract
Background Successful embryogenesis relies on the coordinated interaction between genes and tissues. The transcription factors Pax9 and Msx1 genetically interact during mouse craniofacial morphogenesis, and mice deficient for either gene display abnormal tooth and palate development. Pax9 is expressed specifically in the pharyngeal endoderm at mid-embryogenesis, and mice deficient for Pax9 on a C57Bl/6 genetic background also have cardiovascular defects affecting the outflow tract and aortic arch arteries giving double-outlet right ventricle, absent common carotid arteries and interruption of the aortic arch. Results In this study we have investigated both the effect of a different genetic background and Msx1 haploinsufficiency on the presentation of the Pax9-deficient cardiovascular phenotype. Compared to mice on a C57Bl/6 background, congenic CD1-Pax9–/– mice displayed a significantly reduced incidence of outflow tract defects but aortic arch defects were unchanged. Pax9–/– mice with Msx1 haploinsufficiency, however, have a reduced incidence of interrupted aortic arch, but more cases with cervical origins of the right subclavian artery and aortic arch, than seen in Pax9–/– mice. This alteration in arch artery defects was accompanied by a rescue in third pharyngeal arch neural crest cell migration and smooth muscle cell coverage of the third pharyngeal arch arteries. Although this change in phenotype could theoretically be compatible with post-natal survival, using tissue-specific inactivation of Pax9 to maintain correct palate development whilst inducing the cardiovascular defects was unable to prevent postnatal death in the mutant mice. Hyoid bone and thyroid cartilage formation were abnormal in Pax9–/– mice. Conclusions Msx1 haploinsufficiency mitigates the arch artery defects in Pax9–/– mice, potentially by maintaining the survival of the 3rd arch artery through unimpaired migration of neural crest cells to the third pharyngeal arches. With the neural crest cell derived hyoid bone and thyroid cartilage also being defective in Pax9–/– mice, we speculate that the pharyngeal endoderm is a key signalling centre that impacts on neural crest cell behaviour highlighting the ability of cells in different tissues to act synergistically or antagonistically during embryo development.
- Published
- 2021
44. Using density of antecedent events and trajectory path analysis to investigate family-correlated patterns of onset of bipolar I disorder: a comparison of cohorts from Europe and USA
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Frank Bellivier, Bruno Etain, Joséphine Loftus, Florence Vorspan, Jan Scott, Newcastle University [Newcastle], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Département Médico-Universitaire Neurosciences [Sorbonne Université] (DMU Neurosciences), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Princesse Grace [Monaco], and Etain, Bruno
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Proband ,Neurophysiology and neuropsychology ,Antecedents ,Bipolar I disorder ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Family history ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Comorbidities ,Trajectories ,medicine ,Biological Psychiatry ,business.industry ,Research ,QP351-495 ,Hazard ratio ,Correction ,Mental illness ,medicine.disease ,Log-rank test ,Antecedent (grammar) ,Psychiatry and Mental health ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Cohort ,business ,Cohorts ,Demography ,RC321-571 - Abstract
Background Major contributors to the global burden of bipolar disorders (BD) are the early age at onset (AAO) and the co-occurrence of non-mood disorders before and after the onset of BD. Using data from two independent cohorts from Europe and the USA, we investigated whether the trajectories of BD-I onset and patterns of psychiatric comorbidities differed in (a) individuals with or without a family history (FH) of BD, or (b) probands and parents who both had BD-I. Methods First, we estimated cumulative probabilities and AAO of comorbid mental disorders in familial and non-familial cases of BD-I (Europe, n = 573), and sex-matched proband-parent pairs of BD-I cases (USA, n = 194). Then we used time to onset analyses to compare overall AAO of BD-I and AAO according to onset polarity. Next, we examined associations between AAO and polarity of onset of BD-I according to individual experiences of comorbidities. This included analysis of the density of antecedent events (defined as the number of antecedent comorbidities per year of exposure to mental illness per individual) and time trend analysis of trajectory paths plotted for the subgroups included in each cohort (using R2 goodness of fit analysis). Results Earlier AAO of BD-I was found in FH versus non-FH cases (log rank test = 7.63; p = 0.006) and in probands versus parents with BD-I (log rank test = 15.31; p = 0.001). In the European cohort, AAO of BD-I was significantly associated with factors such as: FH of BD (hazard ratio [HR]: 0.60), earlier AAO of first non-mood disorder (HR: 0.93) and greater number of comorbidities (HR: 0.74). In the USA cohort, probands with BD-I had an earlier AAO for depressive and manic episodes and AAO was also associated with e.g., number of comorbidities (HR: 0.65) and year of birth (HR: 2.44). Trajectory path analysis indicated significant differences in density of antecedents between subgroups within each cohort. However, the time trend R2 analysis was significantly different for the European cohort only. Conclusions Estimating density of antecedent events and comparing trajectory plots for different BD subgroups are informative adjuncts to established statistical approaches and may offer additional insights that enhance understanding of the evolution of BD-I.
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- 2021
45. Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood
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van Cruchten, Remco, van As, Daniël, Glennon, Jeffrey, van Engelen, Baziel, Okkersen, K, Jimenez-Moreno, C, Wenninger, S, Daidj, F, Cumming, S, Littleford, R, Monckton, D, Lochmüller, H, Catt, M, Faber, C, Hapca, A, Donnan, P, Gorman, G, Bassez, G, Schoser, B, Knoop, H, Treweek, S, Wansink, Derick, Impens, Francis, Gabriels, Ralf, Claeys, Tine, Ravel-Chapuis, Aymeric, Jasmin, Bernard, Mahon, Niamh, Nieuwenhuis, Sylvia, Martens, Lennart, Novak, Petr, Furling, Denis, Baak, Arie, Gourdon, Genevieve, Mackenzie, Alex, Martinat, Cecile, Neault, Nafisa, Roos, Andreas, Duchesne, Elise, Salz, Renee, Thompson, Rachel, Baghdoyan, Sandrine, Varghese, Anu, Blom, Paul, Spendiff, Sally, Manta, Alexander, Medical Psychology, APH - Mental Health, Radboud University Medical Center [Nijmegen], University College Dublin [Dublin] (UCD), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Newcastle University [Newcastle], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Universiteit Gent = Ghent University [Belgium] (UGENT), Centre de recherche en Myologie – U974 SU-INSERM, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
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Lifestyle intervention ,Myotonic dystrophy type 1 ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Therapeutic Response ,Gene Expression ,Peripheral blood ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Nerve Tissue Proteins ,General Medicine ,Biomarker ,HSP40 Heat-Shock Proteins ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,All institutes and research themes of the Radboud University Medical Center ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Humans ,Myotonic Dystrophy ,RNA, Messenger ,RNA-seq ,Carrier Proteins ,Trinucleotide Repeat Expansion ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] - Abstract
Background Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Through a process of reverse engineering, this study aims to identify druggable molecular biomarkers associated with the clinical improvement in the OPTIMISTIC cohort. Methods Based on full blood samples collected during OPTIMISTIC, we performed paired mRNA sequencing for 27 patients before and after the CBT intervention. Linear mixed effect models were used to identify biomarkers associated with the disease-causing CTG expansion and the mean clinical improvement across all clinical outcome measures. Results We identified 608 genes for which their expression was significantly associated with the CTG-repeat expansion, as well as 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes associated with both returned to more normal levels in patients who benefited the most from CBT. This main finding has been replicated based on an external dataset of mRNA data of DM1 patients and controls, singling these genes out as candidate biomarkers for therapy response. Among these candidate genes were DNAJB12, HDAC5, and TRIM8, each belonging to a protein family that is being studied in the context of neurological disorders or muscular dystrophies. Across the different gene sets, gene pathway enrichment analysis revealed disease-relevant impaired signaling in, among others, insulin-, metabolism-, and immune-related pathways. Furthermore, evidence for shared dysregulations with another neuromuscular disease, Duchenne muscular dystrophy, was found, suggesting a partial overlap in blood-based gene dysregulation. Conclusions DM1-relevant disease signatures can be identified on a molecular level in peripheral blood, opening new avenues for drug discovery and therapy efficacy assessments.
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- 2022
46. Developing an Evidence and Theory Based Multimodal Integrative Intervention for the Management of Renal Cachexia: A Theory of Change
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Carolyn Blair, Adrian Slee, Andrew Davenport, Denis Fouque, William Johnston, Kamyar Kalantar-Zadeh, Peter Maxwell, Clare McKeaveney, Robert Mullan, Helen Noble, Sam Porter, David Seres, Joanne Shields, Ian Swaine, Miles Witham, Joanne Reid, CarMeN, laboratoire, Queen's University [Belfast] (QUB), University College of London [London] (UCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), University of California [Irvine] (UC Irvine), University of California (UC), Antrim Area Hospital - Northern Health and Social Care Trust [Antrim, Northern Ireland] (AAH-NHSCT), Bournemouth University [Poole] (BU), Columbia University Irving Medical Center (CUIMC), Belfast City Hospital, University of Greenwich, Newcastle University [Newcastle], and Newcastle Upon Tyne Hospitals NHS Foundation Trust
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theory of change ,[SDV.BA] Life Sciences [q-bio]/Animal biology ,Leadership and Management ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,Health Policy ,kidney disease ,Health Informatics ,have no competing interest ,cachexia ,Article ,complex intervention ,Health Information Management ,renal disease ,end-stage kidney disease ,multimodal intervention ,personal and public involvement - Abstract
In this study, we aimed to develop a theoretical framework for a multimodal, integrative, exercise, anti-inflammatory and dietary counselling (MMIEAD) intervention for patients with renal cachexia with reference to how this addresses the underlying causal pathways for renal cachexia, the outcomes anticipated, and how these will be evaluated. We used a Theory of Change (ToC) approach to guide six steps. Step 1 included inputs from a workshop to obtain key stakeholder views on the potential development of a multimodal intervention for renal cachexia. Step 2 included the findings of a mixed-methods study with Health Care Practitioners (HCPs) caring for individuals with End Stage Kidney Disease (ESKD) and cachexia. Step 3 included the results from our systematic literature review on multimodal interventions for cachexia management. In step 4, we used the body of our research team’s cachexia research and wider relevant research to gather evidence on the specific components of the multimodal intervention with reference to how this addresses the underlying causal pathways for renal cachexia. In steps 5 and 6 we developed and refined the ToC map in consultation with the core research team and key stakeholders which illustrates how the intervention components of MMIEAD interact to achieve the intended long-term outcomes and anticipated impact. The results of this study provide a theoretical framework for the forthcoming MMIEAD intervention for those with renal cachexia and in subsequent phases will be used to determine whether this intervention is effective. To the best of our knowledge no other multimodal intervention trials for cachexia management have reported a ToC. Therefore, this research may provide a useful framework and contribute to the ongoing development of interventions for cachexia management.
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- 2022
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47. Community perceptions on the factors in the social food environment that influence dietary behaviour in cities of Kenya and Ghana: A Photovoice study
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Milkah N Wanjohi, Rebecca Pradeilles, Gershim Asiki, Michelle Holdsworth, Elizabeth W Kimani-Murage, Stella K Muthuri, Ana Irache, Amos Laar, Francis Zotor, Akua Tandoh, Senam Klomegah, Fiona Graham, Hibbah Araba Osei-Kwasi, Mark A Green, Nathaniel Coleman, Kobby Mensah, Robert Akparibo, Richmond Aryeteey, Emily K Rousham, Nicolas Bricas, Marco Bohr, Paula Griffiths, African Population and Health Research Center, Inc (APHRC Campus), Loughborough University, Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), University of Warwick [Coventry], University of Ghana, University of Health and Allied Sciences [Ho] (UHAS), Newcastle University [Newcastle], University of Sheffield [Sheffield], University of Liverpool, Département Environnements et Sociétés (Cirad-ES), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Nottingham Trent University, University of the Witwatersrand [Johannesburg] (WITS), and This work was supported by two funders. The ‘Dietary transitions in Ghana’ project was funded by a grant from the Drivers of Food Choice Competitive Grants Programme [grant number OPP1110043], which is funded by the Bill & Melinda Gates Foundation Seattle, WA and the Foreign, Commonwealth & Development Office, and managed by the University of South Carolina Arnold School of Public Health, USA. The TACLED project was funded by a Global Challenges Research Fund (GCRF) Foundation Award led by the MRC [grant number MR/P025153/1], and supported by Arts and Humanities Research Council (AHRC),Biotechnology and Biological Sciences Research (BBSRC), Economic and Social Research Council (ESRC) and Natural Environment Research Council (NERC).
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Food environment ,Nutrition and Dietetics ,Social factors ,Africa ,Photovoice ,Public Health, Environmental and Occupational Health ,Urban ,Medicine (miscellaneous) ,Dietary behaviour ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition - Abstract
Objective:To explore communities’ perspectives on the factors in the social food environment that influence dietary behaviours in African cities.Design:A qualitative study using participatory photography (Photovoice). Participants took and discussed photographs representing factors in the social food environment that influence their dietary behaviours. Follow-up in-depth interviews allowed participants to tell the ‘stories’ of their photographs. Thematic analysis was conducted, using data-driven and theory-driven (based on the socio-ecological model) approaches.Setting:Three low-income areas of Nairobi (n 48) in Kenya and Accra (n 62) and Ho (n 32) in Ghana.Participants:Adolescents and adults, male and female aged ≥13 years.Results:The ‘people’ who were most commonly reported as influencers of dietary behaviours within the social food environment included family members, friends, health workers and food vendors. They mainly influenced food purchase, preparation and consumption, through (1) considerations for family members’ food preferences, (2) considerations for family members’ health and nutrition needs, (3) social support by family and friends, (4) provision of nutritional advice and modelling food behaviour by parents and health professionals, (5) food vendors’ services and social qualities.Conclusions:The family presents an opportunity for promoting healthy dietary behaviours among family members. Peer groups could be harnessed to promote healthy dietary behaviours among adolescents and youth. Empowering food vendors to provide healthier and safer food options could enhance healthier food sourcing, purchasing and consumption in African low-income urban communities.
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- 2022
48. Guidelines for mouse and human DC generation
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Manfred B. Lutz, Shafaqat Ali, Cindy Audiger, Stella E. Autenrieth, Luciana Berod, Venetia Bigley, Laura Cyran, Marc Dalod, Jan Dörrie, Diana Dudziak, Georgina Flórez‐Grau, Lucila Giusiano, Gloria J. Godoy, Marion Heuer, Anne B. Krug, Christian H. K. Lehmann, Christian T. Mayer, Shalin H. Naik, Stefanie Scheu, Gerty Schreibelt, Elodie Segura, Kristin Seré, Tim Sparwasser, Jurjen Tel, Huaming Xu, Martin Zenke, University of Würzburg, Institute of Medical Microbiology and Hospital Hygiene (University of Düsseldorf), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Tübingen, University Medical Center of the Johannes Gutenberg-University Mainz, Newcastle University [Newcastle], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum Erlangen [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital Erlangen = Uniklinikum Erlangen, Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Ludwig Maximilian University [Munich] (LMU), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Eindhoven University of Technology [Eindhoven] (TU/e), University of Duisburg-Essen, and Dalod, Marc
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In vitro ,Immunology ,Generation ,Immunology and Allergy ,endritic cells ,[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Isolation - Abstract
European journal of immunology (2022). doi:10.1002/eji.202249816, Published by Wiley-VCH, Weinheim
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- 2022
49. NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice
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Konstantina Chachlaki, Andrea Messina, Virginia Delli, Valerie Leysen, Csilla Maurnyi, Chieko Huber, Gaëtan Ternier, Katalin Skrapits, Georgios Papadakis, Sonal Shruti, Maria Kapanidou, Xu Cheng, James Acierno, Jesse Rademaker, Sowmyalakshmi Rasika, Richard Quinton, Marek Niedziela, Dagmar L’Allemand, Duarte Pignatelli, Mirjam Dirlewander, Mariarosaria Lang-Muritano, Patrick Kempf, Sophie Catteau-Jonard, Nicolas J. Niederländer, Philippe Ciofi, Manuel Tena-Sempere, John Garthwaite, Laurent Storme, Paul Avan, Erik Hrabovszky, Alan Carleton, Federico Santoni, Paolo Giacobini, Nelly Pitteloud, Vincent Prevot, CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), FHU 1,000 Days for Health [Lille], Université de Lille, Université de Lausanne = University of Lausanne (UNIL), National and Kapodistrian University of Athens (NKUA), Lausanne University Hospital, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA), Université de Genève = University of Geneva (UNIGE), Oxford Brookes University, Newcastle University [Newcastle], Poznan University of Medical Sciences [Poland] (PUMS), University of Applied Sciences of Eastern Switzerland (FHO), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Geneva University Hospitals and Geneva University, University Children’s Hospital Zurich, Bern University Hospital [Berne] (Inselspital), University of Bern, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de Córdoba = University of Córdoba [Córdoba], Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Instituto de Salud Carlos III [Madrid] (ISC), University College of London [London] (UCL), Wolfson Institute for Biomedical Research (WIBR), Université de Clermont-Ferrand, ANR-17-CE16-0015,GRAND,Vieillissement et démence: un rôle hormonal?(2017), and Prevot, Vincent
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Hypogonadism ,General Medicine ,Nitric Oxide Synthase Type I ,Nitric Oxide ,Animals ,Cognition ,Gonadotropin-Releasing Hormone/genetics ,Gonadotropin-Releasing Hormone/metabolism ,Humans ,Hypogonadism/complications ,Hypogonadism/congenital ,Hypogonadism/genetics ,Mice ,Mutant Proteins ,Mutation/genetics ,Nitric Oxide Synthase Type I/genetics ,Nitrites ,Gonadotropin-Releasing Hormone ,Mutation ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,610 Medicine & health - Abstract
The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was performed on a cohort of 341 probands with congenital hypogonadotropic hypogonadism to identify ultrarare variants in NOS1 . The activity of the identified NOS1 mutant proteins was assessed by their ability to promote nitrite and cGMP production in vitro. In addition, physiological and pharmacological characterization was carried out in a Nos1 -deficient mouse model. We identified five heterozygous NOS1 loss-of-function mutations in six probands with congenital hypogonadotropic hypogonadism (2%), who displayed additional phenotypes including anosmia, hearing loss, and intellectual disability. NOS1 was found to be transiently expressed by GnRH neurons in the nose of both humans and mice, and Nos1 deficiency in mice resulted in dose-dependent defects in sexual maturation as well as in olfaction, hearing, and cognition. The pharmacological inhibition of NO production in postnatal mice revealed a critical time window during which Nos1 activity shaped minipuberty and sexual maturation. Inhaled NO treatment at minipuberty rescued both reproductive and behavioral phenotypes in Nos1 -deficient mice. In summary, lack of NOS1 activity led to GnRH deficiency associated with sensory and intellectual comorbidities in humans and mice. NO treatment during minipuberty reversed deficits in sexual maturation, olfaction, and cognition in Nos1 mutant mice, suggesting a potential therapy for humans with NO deficiency.
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- 2022
50. Effects of integrating grass‐clover leys with livestock into arable crop rotations on soil carbon stocks and particulate and mineral‐associated soil organic matter fractions in conventional and organic systems
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James Taylor, Caio Fernandes Zani, Julia Cooper, Elisa Lopez-Capel, Geoffrey D. Abbott, Newcastle University [Newcastle], Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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organomineral fractions ,Arable crop ,010504 meteorology & atmospheric sciences ,agricultural system ,Soil carbon stocks ,[SDU.STU]Sciences of the Universe [physics]/Earth Sciences ,Soil Science ,01 natural sciences ,Organic systems ,0105 earth and related environmental sciences ,2. Zero hunger ,Mineral ,business.industry ,Soil organic matter ,04 agricultural and veterinary sciences ,carbon storage ,15. Life on land ,Particulates ,Pollution ,livestock ,mixed farming ,Agronomy ,[SDE]Environmental Sciences ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Environmental science ,Livestock ,ley-arable rotation ,business ,Mixed farming ,Agronomy and Crop Science - Abstract
International audience; Organic systems, integrated crop-livestock systems (ICL) and leys are posited as strategies to increase soil carbon (C) stocks. However, previous studies have: i) only considered one driver of change; ii) evaluated soil C content instead of stocks; iii) been limited to the 0.20 m depth; iv) used short-term leys; and v) rarely assessed the distribution of C among soil organic matter (SOM) fractions, which relates to C stabilisation. The aim of this study was to investigate the impact of conventional vs. organic agricultural systems, grazing regimes (non-grazed vs. grazed) and different proportions of temporary grass-clover leys in crop rotations (ley time proportion-LTP) on soil C stocks and C distribution among SOM fractions down to 0.60 m soil depth. SOM fractions assessed were particulate organic matter (POM>53 μm), heavy fraction (HF>53 μm) and mineral-associated silt and clay fraction (SC
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- 2021
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