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101. Sleep on it: insights into sleep-dependent memory consolidation with functional neuroimaging

Author: BMBF workshop "Neurophysiology meets fMRI" (14-15 November 2006: Hamburg, Germany), Peigneux, Philippe, BMBF workshop "Neurophysiology meets fMRI" (14-15 November 2006: Hamburg, Germany), and Peigneux, Philippe
Abstract: info:eu-repo/semantics/nonPublished
Published: 2006

102. Ausbreitungspfade von Antarktischem Zwischenwasser im Westen des Äquatorialen Pazifischen Ozeans

Author: Forschungszentrum Jülich GmbH, Projektträger des BMBF und BMWi, Zenk, Walter, Siedler, Gerold, Ishida, A., Holfort, J., Kashino, Y., Kuroda, Y., Miyama, T., Müller, Thomas J., Forschungszentrum Jülich GmbH, Projektträger des BMBF und BMWi, Zenk, Walter, Siedler, Gerold, Ishida, A., Holfort, J., Kashino, Y., Kuroda, Y., Miyama, T., and Müller, Thomas J.
Published: 2005

103. Integrale Erfassung der Intensität der meridionalen Umwälzzirkulation im tropischen Nordatlantik

Author: PTJ Projektträger des BMBF und BMWi, Forschungszentrum Jülich GmbH, Kanzow, Torsten, Send, Uwe, Zenk, Walter, Rhein, M., PTJ Projektträger des BMBF und BMWi, Forschungszentrum Jülich GmbH, Kanzow, Torsten, Send, Uwe, Zenk, Walter, and Rhein, M.
Published: 2005

104. Mid-Atlantic Expedition 2003/2004 : Forschungsschiff Meteor, Reise Nr. M60 ; 11. November 2003 15. April 2004

Author: DFG, BMBF, Christiansen, Bernd, Morgan, Jason Phipps, Kuhn, Thomas, Send, Uwe, Wallace, Douglas, Institut für Meereskunde Universität Hamburg, Leitstelle METEOR, DFG, BMBF, Christiansen, Bernd, Morgan, Jason Phipps, Kuhn, Thomas, Send, Uwe, Wallace, Douglas, and Institut für Meereskunde Universität Hamburg, Leitstelle METEOR
Abstract: Die Meteor-Reise 60 besteht aus 5 Fahrtabschnitten im subtropischen Wirbel des Nordatlantiks von den Azoren bzw. Madeira bis zum tropischen Westatlantik. Fahrtabschnitt 1 konzentriert sich auf die Ökologie und Biogeochemie von sogenannten Seamounts im östlichen Atlantik im Rahmen eines EU-Projektes; Fahrtabschnitt 2 umfasst, in Zusammenarbeit mit französischen Kollegen, detailierte seismische und geophysikalische Untersuchungen eines aktiven Segments des Mittelatlantischen Rückens; Fahrtabschnitt 3 ist eine multidisziplinäre (geologisch, biologisch und chemisch) Untersuchung über die Auswirkungen der hydrothermalen Zirkulation am Mittelatlantischen Rücken im Rahmen eines DFG-Schwerpunkt-programms; Fahrtabschnitt 4 ist einer physikalisch-ozeanographische Studie der langfristigen Variation der thermohalien Zirkulation in westlichen Becken des Atlantiks im Kontext des BMBF-CLIVAR programms gewidmet; und Fahrtabschnitt 5 schließlich, ist eine multidisziplinäre (chemisch/biologisch) Untersuchung über die CO2-Aufnahme und die biologische Pumpe in der Wassersäule des nordatlantischen Subtropenwirbels (DFG-Sonderforschungsbereich 460). Der erste Fahrtabschnitt der Reise M 60 dient der physikalischen, biogeochemischen und biologischen Probengewinnung im Rahmen des EU- Projektes OASIS (OceAnic Seamounts: an Integrated Study). OASIS ist ein interdisziplinäres Projekt mit 9 Partnern aus 5 europäischen Ländern und untersucht die funktionale Charakteristik von Seamount-Ökosystemen. Basierend auf 2 Fallstudien werden die Prozesse, die Seamount-Ökosysteme charakterisieren, und ihre Einflüsse auf den umgebenden Ozean beschrieben. Die wissenschaftlichen Ergebnisse, zusammengeführt in einem konzeptionellen Ökosystemmodell, werden Ausgangsbasis für die Entwicklung von generellen und ortspezifischen Managementplänen sein. Das primäre Ziel von OASIS, eine holistische Erfassung von Seamount-Ökosystemen, wird durch die Integration folgender Sachgebiete erreicht: a) Identifikation und Bes, The Meteor 60 expedition is comprised of 5 legs covering the sub-tropical gyre of the North Atlantic from the Azores and Madeira to the tropical western Atlantic. Leg 1 focuses on the ecology and biogeochemistry of seamounts in the eastern Atlantic in the context of an EU program; Leg 2 comprises a detailed seismic and geophysical investigation of a propagating ridge segment at the Mid-Atlantic Ridge in cooperation with French scientists; Leg 3 is a multidisciplinary (geological, biological and chemical) investigation of the effects of hydrothermal circulation at the Mid-Atlantic ridge in support of a DFG Special Priority Program; Leg 4 is a physical oceanographic study of long-term variation of the thermohaline circulation in the western basin of the Atlantic in the context of the BMBF-CLIVAR program; and Leg 5 is a multidisciplinary (chemical/biological) investigation of CO2 uptake and the biological pump in the water column of the North Atlantic sub-tropical gyre (DFG Special Research Area 460). The first leg of cruise M 60 aims at physical, biogeochemical and biological sampling in the framework of the EU project OASIS (OceAnic Seamounts: an Integrated Study). OASIS is an interdisciplinary project and comprises 9 partners from 5 European countries. The project studies the functional characteristics of seamount ecosystems. Based on two case studies, OASIS will yield an advanced mechanistic understanding of the processes characterizing seamount ecosystems, and their influence on the surrounding ocean. The scientific knowledge gained, condensed in a conceptual ecosystem model, will be applied to outline a model management plan as well as site-specific management plans for the seamounts investigated The primary goal of OASIS, to provide a holistic, integrated assessment of seamount ecology, will be achieved by addressing the following main objectives: a) To identify and describe the physical forcing mechanisms effecting seamount systems. b) To assess the origin, qua
Published: 2004

105. BMI or BIA: Is Body Mass Index or Body Fat Mass a Better Predictor of Cardiovascular Risk in Overweight or Obese Children and Adolescents?

Author: Bohn, Barbara, Müller, Manfred James, Simic-Schleicher, Gunter, Kiess, Wieland, Siegfried, Wolfgang, Oelert, Monika, Tuschy, Sabine, Berghem, Stefan, Holl, Reinhard W., and for the APV Initiative and the German BMBF Competence Network Obesity
Published: 2015
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106. Zur rechten Zeit am rechten Ort. Vom Anlieferproblem zum theoretischen Konzept der Stadtlogistik.

Author: BMBF, Deutschland [sponsor], Deecke, Helmut, FLÄMIG, Heike, Hesse, Markus, BMBF, Deutschland [sponsor], Deecke, Helmut, FLÄMIG, Heike, and Hesse, Markus
Abstract: Der Beitrag setzt sich mit den systembedingten Eigenschaften derjenigen Transporte auseinander, die bei der Güterversorgung städtischer Räume entstehen. Insbesondere wird ein kritischer Blick auf jene planerischen, verkehrsorganisatorischen sowie kommunikativen Aktivitäten geworfen, die unter dem Begriff der "Stadtlogistik" bereits Mitte der 1990er Jahre in ganz Europa eine große Beachtung fanden. Aufgrund der systembedingten Eigenschaften von Logistik und Gütertransport haben sich diese Aktivitäten seinerzeit jedoch als weitgehend wirkungslos erwiesen. Nachdem im Kontext der Verbreitung des Internets und des elektronischen Handels Liefer- und Zustellverkehre ein vermeintlich explodierendes Wachstum erfahren haben (eine These, die noch ihrer empirischen Überprüfung harrt), werden Ansätze der Stadt- oder City-Logistik wieder populär. In diesem Licht ist es womöglich eine Reflexion wert, was Stadtlogistik auszeichnen müsste, um effektive Steuerungswirkungen zu haben. Mit Blick auf diese Frage hat der Beitrag u.E. auch 20 Jahre nach der Erstpublikation des Bandes "Stadtökologische Forschung" nichts an Relevanz und Aktualität eingebüßt.
Published: 1999

107. Lower frequency of insulin pump treatment in children and adolescents of Turkish background with type 1 diabetes: analysis of 21,497 patients in Germany.

Author: Icks A, Razum O, Rosenbauer J, Bächle C, Hungele A, Mönkemöller K, Müller-Godeffroy E, Heidtmann B, Kapellen T, Scheuing N, Holl For The Dpv Initiative And The German Federal Ministry For Education And Research Bmbf Competence Network Diabetes Mellitus RW, Icks, Andrea, Razum, Oliver, Rosenbauer, Joachim, Bächle, Christina, Hungele, Andreas, Mönkemöller, Kirsten, Müller-Godeffroy, Esther, Heidtmann, Bettina, and Kapellen, Thomas
Published: 2012
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108. Improved metabolic control in children and adolescents with type 1 diabetes: a trend analysis using prospective multicenter data from Germany and Austria.

Author: Rosenbauer J, Dost A, Karges B, Hungele A, Stahl A, Bächle C, Gerstl EM, Kastendieck C, Hofer SE, Holl RW, DPV Initiative and the German BMBF Competence Network Diabetes Mellitus, Rosenbauer, Joachim, Dost, Axel, Karges, Beate, Hungele, Andreas, Stahl, Anna, Bächle, Christina, Gerstl, Eva Maria, Kastendieck, Christian, and Hofer, Sabine E
Abstract: Objective: To investigate the temporal trend of metabolic control and potential predictors in German and Austrian children and adolescents with type 1 diabetes.Research Design and Methods: This study is based on a large, multicenter database for prospective longitudinal documentation of diabetes care in Germany and Austria. Data from 30,708 patients documented in 305 diabetes centers between 1995 and 2009 were analyzed. Generalized linear mixed regression models were used to adjust trend analysis for relevant confounders.Results: Unadjusted mean HbA(1c) decreased from 8.7 ± 1.8% in 1995 to 8.1 ± 1.5% in 2009. In multiple regression analysis, treatment year, age, sex, diabetes duration, migration background, BMI-SDS, and daily insulin dose were significant predictors of metabolic control (P < 0.001). After multiple adjustment, mean HbA(1c) decreased significantly by 0.038% per year (95% CI 0.032-0.043%), average odds ratio (OR) per year for HbA(1c) >7.5% (>9.0%) was 0.969 (95% CI 0.961-0.977) (0.948, 95% CI 0.941-0.956). Intensified insulin regimen was associated with lower frequency of poor metabolic control (HbA(1c) >9%; P = 0.005) but not with average HbA(1c) (P = 0.797). Rate of severe hypoglycemia and hypoglycemic coma decreased significantly (relative risk [RR] per year 0.948, 95% CI 0.918-0.979; RR 0.917, 95% CI 0.885-0.950) over the study period. Diabetic ketoacidosis rate showed no significant variation over time.Conclusions: This study showed a significant improvement in metabolic control in children and adolescents with type 1 diabetes during the past decade and a simultaneous decrease in hypoglycemic events. The improvement was not completely explained by changes in the mode of insulin treatment. Other factors such as improved patient education may have accounted for the observed trend. [ABSTRACT FROM AUTHOR]
Published: 2012
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109. Polyendocrinopathy in children, adolescents, and young adults with type 1 diabetes: a multicenter analysis of 28,671 patients from the German/Austrian DPV-Wiss database.

Author: Warncke K, Fröhlich-Reiterer EE, Thon A, Hofer SE, Wiemann D, Holl RW, DPV Initiative of the German Working Group for Pediatric Diabetology, Warncke, Katharina, Fröhlich-Reiterer, Elke E, Thon, Angelika, Hofer, Sabine E, Wiemann, Dagobert, Holl, Reinhard W, and German BMBF Competence Network for Diabetes Mellitus
Abstract: Objective: To investigate diabetes-specific autoantibodies and additional autoimmune phenomena in a large cohort of young patients with type 1 diabetes.Research Design and Methods: Data from 28,671 patients <30 years with type 1 diabetes from 242 specialized centers in Germany and Austria were analyzed.Results: At least one beta-cell antibody was present in 81.6% of patients. beta-cell-Ab-negative patients were significantly younger at diabetes onset (P < 0.0001). A total of 19.6% had positive thyroid antibodies with female predominance (62%, P < 0.0001). Antibodies to tissue transglutaminase were present in 10.7%, with a significantly longer duration of diabetes (P < 0.0001). Parietal cell antibodies were found in 283 patients, associated with older age (P < 0.001), and adrenal antibodies were present in 94 patients. In 575 patients, at least three different autoimmune phenomena were present.Conclusions: Thyroid autoimmunity and antibodies suggestive for celiac disease are the most prevalent additional immune phenomena in type 1 diabetes. Parietal/adrenal antibodies are rare. [ABSTRACT FROM AUTHOR]
Published: 2010
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110. Long-acting insulin analogs and the risk of diabetic ketoacidosis in children and adolescents with type 1 diabetes: a prospective study of 10,682 patients from 271 institutions.

Author: Karges B, Kapellen T, Neu A, Hofer SE, Rohrer T, Rosenbauer J, Wolf J, Holl RW, Diabetes Prospective Documentation DPV Initiative, Karges, Beate, Kapellen, Thomas, Neu, Andreas, Hofer, Sabine E, Rohrer, Tilman, Rosenbauer, Joachim, Wolf, Johannes, Holl, Reinhard W, and German Federal Ministry for Education and Research BMBF Competence Network of Diabetes Mellitus
Abstract: OBJECTIVE To investigate if long-acting insulin analogs decrease the risk of diabetic ketoacidosis (DKA) in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Of 48,110 type 1 diabetic patients prospectively studied between 2001 and 2008, the incidence of DKA requiring hospitalization was analyzed in 10,682 individuals aged /=2 years. RESULTS The overall rate of DKA was 5.1 (SE +/- 0.2)/100 patient-years. Patients using insulin glargine or detemir (n = 5,317) had a higher DKA incidence than individuals using NPH insulin (n = 5,365, 6.6 +/- 0.4 vs. 3.6 +/- 0.3, P < 0.001). The risk for DKA remained significantly different after adjustment for age at diabetes onset, diabetes duration, A1C, insulin dose, sex, and migration background (P = 0.015, odds ratio 1.357 [1.062-1.734]). CONCLUSIONS Despite their long-acting pharmacokinetics, the use of insulin glargine or detemir is not associated with a lower incidence of DKA compared with NPH insulin. [ABSTRACT FROM AUTHOR]
Published: 2010
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111. Forschungsplattform Nordsee

Author: RF, BMBF and RF, BMBF
Published: 1975

112. Capacity of countries to reduce biological invasions

Author: Guillaume Latombe, Hanno Seebens, Bernd Lenzner, Franck Courchamp, Stefan Dullinger, Marina Golivets, Ingolf Kühn, Brian Leung, Núria Roura-Pascual, Emma Cebrian, Wayne Dawson, Christophe Diagne, Jonathan M. Jeschke, Cristian Pérez-Granados, Dietmar Moser, Anna Turbelin, Piero Visconti, Franz Essl, University of Vienna [Vienna], University of Edinburgh, Senckenberg Biodiversity and Climate Research Centre (SBiK-F), Goethe-Universität Frankfurt am Main-Senckenberg – Leibniz Institution for Biodiversity and Earth System Research - Senckenberg Gesellschaft für Naturforschung, Leibniz Association-Leibniz Association, Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Martin-Luther-University Halle-Wittenberg, Department of Geobotany and Botanical Garden, Martin-Luther-Universität Halle Wittenberg (MLU), McGill University = Université McGill [Montréal, Canada], Universitat de Girona [Girona], Universitat de Girona (UdG), Departament de Ciencies Ambientals, Centre d'Estudis Avançats de Blanes (CEAB), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institute of Aquatic Ecology, Durham University, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD [France-Sud])-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)-Université de Montpellier (UM), Freie Universität Berlin, Leibniz Institute of Freshwater Ecology and Inland Fisheries (IGB), Berlin-Brandenburg Institute of Advanced Biodiversity Research (BBIB), Universidad de Alicante, International Institute for Applied Systems Analysis [Laxenburg] (IIASA), This research was funded through the 2017-2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND programme, and with the funding organisations FWF (project no I 4011-B32–GL, BeL, SD, DM, FE), MCIN/AEI/https://doi.org/10.13039/501100011033 (PCI2018-092966–NRP, CPG, EC), BMBF (16LC1807C–MG, IK, 16LC1807A–HS, 16LC1807B–JMJ) and ANR (NR-18-EBI4-0004–FC, CB, CD, AT)., Universidad de Alicante. Departamento de Ecología, Ecología y Conservación de Poblaciones y Comunidades Animales (ECPCA), Department of Botany and Biodiversity Research, Institute of Biology/Geobotany and Botanical Garden, German Centre for Integrative Biodiversity Research (iDiv), Institute of Biology, Freie Universität Berlin, Berlin, Germany, Departamento de Ecología, Universidad de Alicante, Alicante, Spain, This research was funded through the 2017-2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND programme, and with the funding organisations FWF (project no I 4011-B32-GL, BeL, SD, DM, FE), MCIN/AEI/https://doi.org/10.13039/501100011033 (PCI2018-092966NRP, CPG, EC), BMBF (16LC1807C-MG, IK, 16LC1807A-HS, 16LC1807B-JMJ) and ANR (ANR-18-EBI4-0004-FC, CB, CD, AT).Document Information, and ANR-18-EBI4-0004,AlienScenarios,Developing and applying scenarios of biological invasions for the 21st century(2018)
Subjects: Governance, Global and Planetary Change, Established alien species, Health (social science), Sociology and Political Science, Ecology, [SDV]Life Sciences [q-bio], Geography, Planning and Development, 500 Naturwissenschaften und Mathematik::570 Biowissenschaften, Biologie::570 Biowissenschaften, Biologie, Management, Monitoring, Policy and Law, Lifestyle, Environmental performance, Scenarios, [SDE]Environmental Sciences, Trade, Innovation, Nature and Landscape Conservation
Abstract: Este artículo contiene 19 páginas, 4 figuras, 2 tablas., The extent and impacts of biological invasions on biodiversity are largely shaped by an array of socio-economic and environmental factors, which exhibit high variation among countries. Yet, a global analysis of how these factors vary across countries is currently lacking. Here, we investigate how five broad, country-specific socio-economic and environmental indices (Governance, Trade, Environmental Performance, Lifestyle and Education, Innovation) explain country-level (1) established alien species (EAS) richness of eight taxonomic groups, and (2) proactive or reactive capacity to prevent and manage biological invasions and their impacts. These indices underpin many aspects of the invasion process, including the introduction, establishment, spread and management of alien species. They are also general enough to enable a global comparison across countries, and are therefore essential for defining future scenarios for biological invasions. Models including Trade, Governance, Lifestyle and Education, or a combination of these, best explained EAS richness across taxonomic groups and national proactive or reactive capacity. Historical (1996 or averaged over 1996–2015) levels of Governance and Trade better explained both EAS richness and the capacity of countries to manage invasions than more recent (2015) levels, revealing a historical legacy with important implications for the future of biological invasions. Using Governance and Trade to define a two-dimensional socio-economic space in which the position of a country captures its capacity to address issues of biological invasions, we identified four main clusters of countries in 2015. Most countries had an increase in Trade over the past 25 years, but trajectories were more geographically heterogeneous for Governance. Declines in levels of Governance are concerning as they may be responsible for larger levels of invasions in the future. By identifying the factors influencing EAS richness and the regions most susceptible to changes in these factors, our results provide novel insights to integrate biological invasions into scenarios of biodiversity change to better inform decision-making for policy and the management of biological invasions., This research was funded through the 2017-2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND programme, and with the funding organisations FWF (project no I 4011-B32–GL, BeL, SD, DM, FE), MCIN/AEI/https:// doi. org/ 10. 13039/ 50110 00110 33 (PCI2018-092966– NRP, CPG, EC), BMBF (16LC1807C–MG, IK; 16LC1807A–HS; 16LC1807B–JMJ) and ANR (NR-18-EBI4-0004–FC, CB, CD, AT).
Published: 2022
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113. Simulation of winter wheat response to variable sowing dates and densities in a high-yielding environment

Author: Dueri, Sibylle, Brown, Hamish, Asseng, Senthold, Ewert, Frank, Webber, Heidi, George, Mike, Craigie, Rob, Guarin, Jose Rafael, Pequeno, Diego N.L., Stella, Tommaso, Ahmed, Mukhtar, Alderman, Phillip D., Basso, Bruno, Berger, Andres G., Mujica, Gennady Bracho, Cammarano, Davide, Chen, Yi, Dumont, Benjamin, Rezaei, Ehsan Eyshi, Fereres, Elias, Ferrise, Roberto, Gaiser, Thomas, Gao, Yujing, Garcia-Vila, Margarita, Gayler, Sebastian, Hochman, Zvi, Hoogenboom, Gerrit, Kersebaum, Kurt C., Nendel, Claas, Olesen, Jørgen E., Padovan, Gloria, Palosuo, Taru, Priesack, Eckart, Pullens, Johannes W.M., Rodríguez, Alfredo, Rötter, Reimund P., Ramos, Margarita Ruiz, Semenov, Mikhail A., Senapati, Nimai, Siebert, Stefan, Srivastava, Amit Kumar, Stöckle, Claudio, Supit, Iwan, Tao, Fulu, Thorburn, Peter, Wang, Enli, Weber, Tobias Karl David, Xiao, Liujun, Zhao, Chuang, Zhao, Jin, Zhao, Zhigan, Zhu, Yan, Martre, Pierre, Rebetzke, Greg, Écophysiologie des Plantes sous Stress environnementaux (LEPSE), 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), The New Zealand Institute for Plant & Food Research Limited [Auckland] (Plant & Food Research), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Leibniz-Zentrum für Agrarlandschaftsforschung = Leibniz Centre for Agricultural Landscape Research (ZALF), Institut für Nutzpflanzenwissenschaften und Ressourcenschutz (INRES), Rheinische Friedrich-Wilhelms-Universität Bonn, Brandenburg University of Technology [Cottbus – Senftenberg] (BTU), Foundation for Arable Research (FAR), University of Florida [Gainesville] (UF), Earth Institute at Columbia University, Columbia University [New York], International Maize and Wheat Improvement Center (CIMMYT), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), Swedish University of Agricultural Sciences (SLU), Pir Mehr Ali Shah Arid Agriculture University = PMAS-Arid Agriculture University Rawalpindi (AAUR), Oklahoma State University [Stillwater] (OSU), Michigan State University [East Lansing], Michigan State University System, Instituto Nacional de Investigación Agropecuaria (INIA), Georg-August-University = Georg-August-Universität Göttingen, Aarhus University [Aarhus], Institute of geographical sciences and natural resources research [CAS] (IGSNRR), Chinese Academy of Sciences [Beijing] (CAS), Gembloux Agro-Bio Tech [Gembloux], Université de Liège, Instituto de Agricultura Sostenible - Institute for Sustainable Agriculture (IAS CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universidad de Córdoba = University of Córdoba [Córdoba], Department of Agriculture, Food, Environment and Forestry (DAGRI), Università degli Studi di Firenze = University of Florence (UniFI), Institute of Crop Science and Resource Conservation [Bonn] (INRES), University of Hohenheim, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Global Change Research Centre (CzechGlobe), University of Potsdam = Universität Potsdam, Natural Resources Institute Finland (LUKE), Helmholtz Zentrum München = German Research Center for Environmental Health, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Institute of Biochemical Plant Pathology (BIOP), Centro de Estudios e Investigación para la Gestión de Riesgos Agrarios y Medioambientales (CEIGRAM), Universidad Politécnica de Madrid (UPM), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Centre for Biodiversity and Sustainable Land-use [University of Göttingen] (CBL), Rothamsted Research, Biotechnology and Biological Sciences Research Council (BBSRC), Washington State University (WSU), Wageningen University and Research [Wageningen] (WUR), Zhejiang University, Nanjing Agricultural University (NAU), China Agricultural University (CAU), Agricultural Model Intercomparison and Improvement Project (AgMIP) Wheat Phase 4 and was supported by the French National Research Institute for Agriculture, Food (INRAE) and the International Maize and Wheat Improvement Center (CIMMYT) through the International Wheat Yield Partnership (IWYP, grant IWYP115)., metaprogram Agriculture and forestry in the face of climate change: adaptation and mitigation (CLIMAE) of INRAE, grant-aided support from the Biotechnology and Biological Sciences Research Council (BBSRC) through Designing Future Wheat [BB/P016855/1] and Achieving Sustainable Agricultural Systems [NE/N018125/1] jointly funded with NERC, DivCSA project funded by the Academy of Finland (decision no. 316215)., National Natural Science Foundation of China (No. 31761143006), financial support from BARISTA project (031B0811A) through ERA-NET SusCrop under EU-FACCE JPI, German Federal Ministry of Education and Research (BMBF) through the BonaRes project ’’I4S’’ (031B0513I), German Federal Ministry of Education and Research (BMBF) through the BonaRes Project 'Soil3' (FKZ 031B0026A), Ministry of Education, Youth and Sports of Czech Republic through SustES—Adaption strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/000797), Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2070 – 390732324', German Research Foundation (DFG, Grant Agreement SFB 1253/1 2017), European Project: 618105,EC:FP7:KBBE,FP7-ERANET-2013-RTD,FACCE ERA NET PLUS(2013), Institut National de la Recherche Agronomique (France), International Maize and Wheat Improvement Center, International Wheat Yield Partnership, National Natural Science Foundation of China, European Commission, Federal Ministry of Education and Research (Germany), Ministry of Education, Youth and Sports (Czech Republic), German Research Foundation, Biotechnology and Biological Sciences Research Council (UK), Natural Environment Research Council (UK), and Academy of Finland
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Physiology, Climate Change, sowing date, Plant Science, CHINA, Multi-model Ensemble, New Zealand, Sowing Date, Sowing Density, Tiller Mortality, Tillering, Wheat, Yield Potential, tillering, wheat, USE EFFICIENCY, sowing density, Life Science, Biomass, ADAPTATION, PLANT-DENSITY, Triticum, METAANALYSIS, Multi-model ensemble, WIMEK, CLIMATE-CHANGE, tiller mortality, PRODUCTIVITY, Temperature, CROP MODELS, yield potential, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, ROTATION, GROWTH, Water Systems and Global Change, Seasons
Abstract: Crop multi-model ensembles (MME) have proven to be effective in increasing the accuracy of simulations in modelling experiments. However, the ability of MME to capture crop responses to changes in sowing dates and densities has not yet been investigated. These management interventions are some of the main levers for adapting cropping systems to climate change. Here, we explore the performance of a MME of 29 wheat crop models to predict the effect of changing sowing dates and rates on yield and yield components, on two sites located in a high-yielding environment in New Zealand. The experiment was conducted for 6 years and provided 50 combinations of sowing date, sowing density and growing season. We show that the MME simulates seasonal growth of wheat well under standard sowing conditions, but fails under early sowing and high sowing rates. The comparison between observed and simulated in-season fraction of intercepted photosynthetically active radiation (FIPAR) for early sown wheat shows that the MME does not capture the decrease of crop above ground biomass during winter months due to senescence. Models need to better account for tiller competition for light, nutrients, and water during vegetative growth, and early tiller senescence and tiller mortality, which are exacerbated by early sowing, high sowing densities, and warmer winter temperatures., This study was a part of the Agricultural Model Intercomparison and Improvement Project (AgMIP) Wheat Phase 4 and was supported by the French National Research Institute for Agriculture, Food (INRAE) and the International Maize and Wheat Improvement Center (CIMMYT) through the International Wheat Yield Partnership (IWYP, grant IWYP115). SD and PM acknowledge support from the metaprogram Agriculture and forestry in the face of climate change: adaptation and mitigation (CLIMAE) of INRAE. YC and FT acknowledge support from the National Natural Science Foundation of China (No. 31761143006). RPR and GBM acknowledge financial support from BARISTA project (031B0811A) through ERA-NET SusCrop under EU-FACCE JPI. KCK was funded by the German Federal Ministry of Education and Research (BMBF) through the BonaRes project ’’I4S’’ (031B0513I). AS and TG acknowledge funding by the German Federal Ministry of Education and Research (BMBF) through the BonaRes Project “Soil3” (FKZ 031B0026A). KCK and JEO were supported by the Ministry of Education, Youth and Sports of Czech Republic through SustES—Adaption strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/000797). FE acknowledges support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2070 – 390732324”. TKDW was funded by the German Research Foundation (DFG, Grant Agreement SFB 1253/1 2017). MAS and NS at Rothamsted Research received grant-aided support from the Biotechnology and Biological Sciences Research Council (BBSRC) through Designing Future Wheat [BB/P016855/1] and Achieving Sustainable Agricultural Systems [NE/N018125/1] jointly funded with NERC. TP and FT are supported by the DivCSA project funded by the Academy of Finland (decision no. 316215).
Published: 2022
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114. Ketoacidosis at diabetes onset is still frequent in children and adolescents: a multicenter analysis of 14,664 patients from 106 institutions.

Author: Neu A, Hofer SE, Karges B, Oeverink R, Rosenbauer J, Holl RW, DPV Initiative and the German BMBF Competency Network for Diabetes Mellitus, Neu, Andreas, Hofer, Sabine E, Karges, Beate, Oeverink, Rudolf, Rosenbauer, Joachim, and Holl, Reinhard W
Abstract: Objective: We aimed at analyzing the frequency, clinical characteristics, and trends associated with the occurrence of diabetic ketoacidosis (DKA) at the onset of type 1 diabetes on the basis of long-term follow-up data.Research Design and Methods: A total of 106 pediatric diabetes centers in Germany and Austria participated in this study. Data from 14,664 patients with type 1 diabetes collected between 1995 and 2007 were suitable for evaluation. DKA was defined and classified according to the International Society for Pediatric and Adolescent Diabetes consensus guidelines.Results: DKA was observed in 21.1% of patients. The frequency of DKA, including the severe form, remained unchanged throughout the 13-year observation period. The frequency of DKA was particularly striking among children <5 years of age (26.5%).Conclusions: Ketoacidosis occurring at diabetes onset continues to be a difficult problem. Our data show no significant change in the frequency and magnitude of DKA over the last 13 years. [ABSTRACT FROM AUTHOR]
Published: 2009
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115. Introduction pathways of economically costly invasive alien species

Author: Anna J. Turbelin, Christophe Diagne, Emma J. Hudgins, Desika Moodley, Melina Kourantidou, Ana Novoa, Philip J. Haubrock, Camille Bernery, Rodolphe E. Gozlan, Robert A. Francis, Franck Courchamp, Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD [France-Sud])-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)-Université de Montpellier (UM), Department of Biology, Carleton University (Carleton University), Carleton University, Institute of Botany of the Czech Academy of Sciences (IB / CAS), Czech Academy of Sciences [Prague] (CAS), University of Southern Denmark (SDU), Hellenic Centre for Marine Research (HCMR), Institute of Marine Biological Resources and Inland Waters, Senckenberg Research Institute and Natural History Museum [Frankfurt], Senckenberg – Leibniz Institution for Biodiversity and Earth System Research - Senckenberg Gesellschaft für Naturforschung, Leibniz Association-Leibniz Association, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses [University of South Bohemia] (CENAKVA), Faculty of Fisheries and Protection of Waters [University of South Bohemia], University of South Bohemia -University of South Bohemia, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), King‘s College London, The authors acknowledge the French National Research Agency (ANR-14-CE02-0021) and the BNP-Paribas Foundation Climate Initiative for funding the InvaCost project that allowed the construction of the InvaCost database. The present work was conducted following a workshop funded by the AXA Research Fund Chair of Invasion Biology and is part of the AlienScenario project funded by BiodivERsA and Belmont-Forum call 2018 on biodiversity scenarios. AJT contract comes from the AXA Research Fund Chair of Invasion Biology of University Paris Saclay. CD is funded by the BiodivERsA-Belmont Forum Project 'Alien Scenarios' (BMBF/PT DLR 01LC1807C). AN and DM acknowledge funding from EXPRO Grant No. 19-28807X (Czech Science Foundation) and long-term research development project RVO 67985939 (The Czech Academy of Sciences)., ANR-14-CE02-0021,InvaCosts,Insectes envahissants et leurs couts pour la biodiversité, l'économie et la santé humaine(2014), University of South Bohemia, and The authors acknowledge the French National Research Agency (ANR-14-CE02-0021) and the BNP-Paribas Foundation Climate Initiative for funding the InvaCost project that allowed the construction of the InvaCost database. The present work was conducted following a workshop funded by the AXA Research Fund Chair of Invasion Biology and is part of the AlienScenario project funded by BiodivERsA and Belmont-Forum call 2018 on biodiversity scenarios. AJT contract comes from the AXA Research Fund Chair of Invasion Biology of University Paris Saclay. CD is funded by the BiodivERsA-Belmont Forum Project 'Alien Scenarios' (BMBF/PT DLR 01LC1807C). AN and DM acknowledge funding from EXPRO Grant No. 19-28807X (Czech Science Foundation) and long-term research development project RVO 67985939 (The Czech Academy of Sciences). We also thank John Wilson and the two anonymous reviewers for their stimulating and helpful comments.
Subjects: InvaCost, Monetary impact, Non-native insects, Policy, Ecology, [SDE]Environmental Sciences, Exotic mammals, Invasive alien species, Introduction pathways, Ecology, Evolution, Behavior and Systematics, Management, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy
Abstract: Introduction pathways play a pivotal role in the success of Invasive Alien Species (IAS)—the subset of alien species that have a negative environmental and/or socio-economic impact. Pathways refer to the fundamental processes that leads to the introduction of a species from one geographical location to another—marking the beginning of all alien species invasions. Increased knowledge of pathways is essential to help reduce the number of introductions and impacts of IAS and ultimately improve their management. Here we use the InvaCost database, a comprehensive repository on the global monetary impacts of IAS, combined with pathway data classified using the Convention on Biological Diversity (CBD) hierarchical classification and compiled from CABI Invasive Species Compendium, the Global Invasive Species Database (GISD) and the published literature to address five key points. Data were available for 478 individual IAS. For these, we found that both the total and annual average cost per species introduced through the ‘Stowaway’ (US$144.9bn; US$89.4m) and ‘Contaminant’ pathways (US$99.3bn; US$158.0m) were higher than species introduced primarily through the ‘Escape’ (US$87.4bn; US$25.4m) and ‘Release’ pathways (US$64.2bn; US$16.4m). Second, the recorded costs (both total and average) of species introduced unintentionally was higher than that from species introduced intentionally. Third, insects and mammals, respectively, accounted for the greatest proportion of the total cost of species introduced unintentionally and intentionally respectively, at least of the available records; ‘Stowaway’ had the highest recorded costs in Asia, Central America, North America and Diverse/Unspecified regions. Fourthly, the total cost of a species in a given location is not related to the year of first record of introduction, but time gaps might blur the true pattern. Finally, the total and average cost of IAS were not related to their number of introduction pathways. Although our findings are directly limited by the available data, they provide important material which can contribute to pathway priority measures, notably by complementing studies on pathways associated with ecologically harmful IAS. They also highlight the crucial need to fill the remaining data gaps—something that will be critical in prioritising limited management budgets to combat the current acceleration of species invasions.
Published: 2022
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116. Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort

Author: Mathilde His, Vivian Viallon, Laure Dossus, Julie A. Schmidt, Ruth C. Travis, Marc J. Gunter, Kim Overvad, Cecilie Kyrø, Anne Tjønneland, Lucie Lécuyer, Joseph A. Rothwell, Gianluca Severi, Theron Johnson, Verena Katzke, Matthias B. Schulze, Giovanna Masala, Sabina Sieri, Salvatore Panico, Rosario Tumino, Alessandra Macciotta, Jolanda M. A. Boer, Evelyn M. Monninkhof, Karina Standahl Olsen, Therese H. Nøst, Torkjel M. Sandanger, Antonio Agudo, Maria-Jose Sánchez, Pilar Amiano, Sandra M. Colorado-Yohar, Eva Ardanaz, Linda Vidman, Anna Winkvist, Alicia K. Heath, Elisabete Weiderpass, Inge Huybrechts, Sabina Rinaldi, International Agency for Cancer Research (IACR), University of Oxford, Aarhus University [Aarhus], Danish Cancer Society Research Center [Copenhagen, Denmark] (DCSRC), University of Copenhagen = Københavns Universitet (UCPH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli Studi di Firenze = University of Florence (UniFI), Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke [Nuthetal, Germany] (GIHNP-R), University of Potsdam = Universität Potsdam, Istituto per lo Studio, la Prevenzione e la rete Oncologica [Florence, Italy] (ISPRO), IRCCS Istituto Nazionale dei Tumori [Milano], University of Naples Federico II = Università degli studi di Napoli Federico II, Provincial Health Authority (ASP 7) [Ragusa, Italy], Università degli studi di Torino = University of Turin (UNITO), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University Medical Center [Utrecht], The Arctic University of Norway [Tromsø, Norway] (UiT), Catalan Institute of Oncology [Barcelone, Espagne], L’Hospitalet de Llobregat [Barcelona, Spain], Escuela Andaluza de Salud Pública [Granada, Spain] (EASP), Universidad de Granada = University of Granada (UGR), CIBER de Epidemiología y Salud Pública (CIBERESP), Public Health Division of Gipuzkoa, Basque Government, CIBER en Salud Pública, CIBERSP, Biodonostia Health Research Institute [Donostia-San Sebastian, Spain] (IIS Biodonostia), Murcia Regional Health Council [Murcia], Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Navarra Public Health Institute, Umeå University, Imperial College London, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Cancer Research UK, CRUK, World Cancer Research Fund, WCRF, University of Cambridge, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2015-166, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk (DOI 10.22025/2019.10.105.00004), C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143, MR/N003284/1, MC-UU_12015/1 and MC_UU_00006/1 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). The funders were not involved in designing the study, collecting, analyzing, or interpreting the data, or writing or submitting the manuscript for publication., The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., This work was funded by the French National Cancer Institute (grant number 2015-166). Mathilde His’ work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC., The authors would like to thank Mr Bertrand Hemon for his support in preparing the databases, Ms Audrey Gicquiau and Dr David Achaintre for the analyses of samples in several of the original studies, and all EPIC participants. The EPIC-Norfolk team thank all the participants who have been part of the project and the many members of the study teams at the University of Cambridge who have enabled this research. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., and HAL UVSQ, Équipe
Subjects: cross-sectional, lifestyle, Estils de vida, BIOMARKERS, Lifestyles, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, DIET, SERUM, Càncer de mama, Cohort Studies, Medicine, General & Internal, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Cross-sectional, General & Internal Medicine, Metabolites, Humans, Metabolomics, Prospective Studies, VALIDITY, Life Style, 11 Medical and Health Sciences, metabolites, RISK, Cancer och onkologi, Science & Technology, anthropometry, Anthropometry, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, PROFILES, Lifestyle, AMINO-ACID, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, PHYSICAL-ACTIVITY, Cross-Sectional Studies, Metabolòmica, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cancer and Oncology, TARGETED METABOLOMICS, Medicine, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Life Sciences & Biomedicine, Research Article
Abstract: This work was funded by the French National Cancer Institute (grant number 2015-166). Mathilde His' work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk (DOI 10.22025/2019.10.105.00004); C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143, MR/N003284/1, MC-UU_12015/1 and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (UK). The funders were not involved in designing the study; collecting, analyzing, or interpreting the data; or writing or submitting the manuscript for publication., Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2). Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786). Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34: 2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed. Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated., Institut National du Cancer (INCA) France 2015-166, International Agency for Research on Cancer - Fondation ARC, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/N003284/1 MC-UU_12015/1 MC_UU_00006/1 MR/M012190/1
Published: 2021
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117. Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study

Author: Cole-Hunter, Thomas, Zhang, Jiawei, So, Rina, Samoli, Evangelia, Liu, Shuo, Chen, Jie, Strak, Maciej, Wolf, Kathrin, Weinmayr, Gudrun, Rodopolou, Sophia, Remfry, Elizabeth, de Hoogh, Kees, Bellander, Tom, Brandt, Jørgen, Concin, Hans, Zitt, Emanuel, Fecht, Daniela, Forastiere, Francesco, Gulliver, John, Hoffmann, Barbara, Hvidtfeldt, Ulla A, Jöckel, Karl-Heinz, Mortensen, Laust H, Ketzel, Matthias, Yacamán Méndez, Diego, Leander, Karin, Ljungman, Petter, Faure, Elodie, Lee, Pei-Chen, Elbaz, Alexis, Magnusson, Patrik K E, Nagel, Gabriele, Pershagen, Göran, Peters, Annette, Rizzuto, Debora, Vermeulen, Roel C H, Schramm, Sara, Stafoggia, Massimo, Katsouyanni, Klea, Brunekreef, Bert, Hoek, Gerard, Lim, Youn-Hee, Andersen, Zorana J, IRAS OH Epidemiology Chemical Agents, University of Copenhagen = Københavns Universitet (UCPH), National and Kapodistrian University of Athens (NKUA), Utrecht University [Utrecht], Helmholtz Zentrum München = German Research Center for Environmental Health, Universität Ulm - Ulm University [Ulm, Allemagne], Queen Mary University of London (QMUL), University of Basel (Unibas), Karolinska Institutet [Stockholm], Aarhus University [Aarhus], Medizinische Universität Wien = Medical University of Vienna, Imperial College London, University of Leicester, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Danish Cancer Society Research Center [Copenhagen, Denmark] (DCSRC), University of Duisburg-Essen, University of Surrey (UNIS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), National Cheng Kung University (NCKU), Ludwig-Maximilians-Universität München (LMU), Lazio Regional Health Service [Rome], NNF17OC0027812, U.S. Environmental Protection Agency, EPA: R-82811201, Health Effects Institute, HEI: 4954-RFA14-3/16-5-3, Bundesministerium für Bildung und Forschung, BMBF, Karolinska Institutet, KI, Vetenskapsrådet, VR: 2017-00641, Rijksinstituut voor Volksgezondheid en Milieu, RIVM, Novo Nordisk Fonden, NNF, Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München, This study was supported by the Health Effects Institute (HEI) (#4954-RFA14-3/16-5-3) and the Novo Nordisk Foundation Challenge Programme [NNF17OC0027812]. The HEI is an organization jointly funded by the United States Environmental Protection Agency (EPA) (Assistance Award No. R-82811201) and certain motor vehicle and engine manufacturers. The contents of this article do not necessarily reflect the views of HEI, or its sponsors, nor do they necessarily reflect the views and policies of the EPA or motor vehicle and engine manufacturers. While HEI has reviewed and approved the study design, it was not involved in data collection and analysis, decision to publish, or preparation of the manuscript. We give thanks to all participants in the pooled cohort studies and the respective study teams of the ELAPSE project for their hard work and effort. Accordingly, we especially thank Marjan Tewis for conducting data management tasks when creating the pooled cohort database. In addition, we specifically thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution to the ELAPSE project. SALT and TwinGene are sub-studies of The Swedish Twin Registry (STR), which is managed by Karolinska Institutet and receives additional funding through the Swedish Research Council (No. 2017-00641). The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. The Novo Nordisk Foundation, the Swedish Research Council, the German Federal Ministry of Education and Research, and the State of Bavaria were not involved in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., HAL UVSQ, Équipe, and IRAS OH Epidemiology Chemical Agents
Subjects: Parkinson’s Disease, [SDV] Life Sciences [q-bio], Parkinson's Disease, Environmental Science(all), [SDV]Life Sciences [q-bio], Long-term exposure, Medizin, Air pollution, Adults, Low-level exposure, Pooled-cohort study, General Environmental Science
Abstract: Background: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. Objective: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. Methods: Within the project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. Results: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01–1.55), NO2 (1.13; 0.95–1.34 per 10 µg/m3), and BC (1.12; 0.94–1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58–0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95–1.62) or BC (1.28; 0.96–1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. Conclusion: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.
Published: 2023
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118. A RESPONSE TO COMMUNITY QUESTIONS ON THE MARINE20 RADIOCARBON AGE CALIBRATION CURVE: MARINE RESERVOIR AGES AND THE CALIBRATION OF 14C SAMPLES FROM THE OCEANS

Author: T J Heaton, E Bard, C Bronk Ramsey, M Butzin, C Hatté, K A Hughen, P Köhler, P J Reimer, Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Collège de France - Chaire Evolution du climat et de l'océan, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche, ANR, Bundesministerium für Bildung und Forschung, BMBF: 01LP1505B, 01LP1919A, P. Köhler and M. Butzin are supported by the German Federal Ministry of Education and Research (BMBF), as Research for Sustainability initiative (FONA), ANR-10-EQPX-0024,ASTER-CEREGE,PLATEFORME DE GEOCHIMIE ISOTOPIQUE ASTER/CEREGE(2010), and ANR-21-CE01-0023,MARCARA,Variabilité de l'âge radiocarbone du réservoir marin et ses implications en paléocéanographie, paléoclimatologie et géochronologie(2021)
Subjects: Archeology, Marine20, Archaeology, marine calibration, radiocarbon, General Earth and Planetary Sciences, Earth and Planetary Sciences(all), calibration, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, dating
Abstract: Radiocarbon (14C) concentrations in the oceans are different from those in the atmosphere. Understanding these ocean-atmospheric 14C differences is important both to estimate the calendar ages of samples which obtained their 14C in the marine environment, and to investigate the carbon cycle. The Marine20 radiocarbon age calibration curve is created to address these dual aims by providing a global-scale surface ocean record of radiocarbon from 55,000–0 cal yr BP that accounts for the smoothed response of the ocean to variations in atmospheric 14C production rates and factors out the effect of known changes in global-scale palaeoclimatic variables. The curve also serves as a baseline to study regional oceanic 14C variation. Marine20 offers substantial improvements over the previous Marine13 curve. In response to community questions, we provide a short intuitive guide, intended for the lay-reader, on the construction and use of the Marine20 calibration curve. We describe the choices behind the making of Marine20, as well as the similarities and differences compared with the earlier Marine calibration curves. We also describe how to use the Marine20 curve for calibration and how to estimate ΔR—the localized variation in the oceanic 14C levels due to regional factors which are not incorporated in the global-scale Marine20 curve. To aid understanding, illustrative worked examples are provided.
Published: 2023
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119. Analysing economic costs of invasive alien species with the INVACOST R package

Author: Boris Leroy, Andrew M. Kramer, Anne‐Charlotte Vaissière, Melina Kourantidou, Franck Courchamp, Christophe Diagne, Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), University of South Florida [Tampa] (USF), Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Southern Denmark (SDU), Hellenic Centre for Marine Research (HCMR), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD [France-Sud])-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)-Université de Montpellier (UM), B.L., A.-C.V. and F.C. were funded by their salaries as French public servants. The post-doctoral contract of C.D. was funded by the BiodivERsA-Belmont Forum Project ‘Alien Scenarios’ (BMBF/PT DLR 01LC1807C)., Institute of Marine Biological Resources and Inland Waters, We thank Anna Turbelin and Phillip J. Haubrock for their assistance in proofreading and beta-testing the invacost r package. B.L., A.-C.V. and F.C. were funded by their salaries as French public servants. The post-doctoral contract of C.D. was funded by the BiodivERsA-Belmont Forum Project ‘Alien Scenarios’ (BMBF/PT DLR 01LC1807C)., and Université Paris-Saclay
Subjects: 0106 biological sciences, drivers of change in biodiversity, Process (engineering), Computer science, Big data, biological invasions, 010603 evolutionary biology, 01 natural sciences, Invasive species, economic costs, Resource (project management), Economic cost, economic impacts, Alien species, Ecology, Evolution, Behavior and Systematics, invasive alien species, business.industry, Ecological Modeling, 010604 marine biology & hydrobiology, Scale (chemistry), 15. Life on land, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Data science, [SDE.ES]Environmental Sciences/Environmental and Society, [SDE]Environmental Sciences, JEL: Q - Agricultural and Natural Resource Economics • Environmental and Ecological Economics/Q.Q5 - Environmental Economics/Q.Q5.Q51 - Valuation of Environmental Effects, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, ecosystem services
Abstract: The peer review history for this article is available at https://publons.com/publon/10.1111/2041-210X.13929. All data are freely available in the invacost r package, downloadable from the Comprehensive R Archive Network https://cran.r-project.org/package=invacost, and the R package code is open-source and available on github at https://github.com/Farewe/invacost. The version of the package used in this manuscript (v1.1-4) is stored on Zenodo (Leroy et al., 2022, 10.5281/zenodo.6653232).; International audience; 1. The reported costs of invasive alien species from the global database InvaCost are heterogeneous and cover different spatio-temporal scales. A standard procedure for aggregating invasive species cost estimates is necessary to ensure the repeatability and comparativeness of studies.2. We introduce here the invacost r package, an open-source software designed to query and analyse the InvaCost database. We illustrate this package and its framework with cost data associated with invasive alien invertebrates.3. First, the invacost package provides updates of this dynamic database directly in the analytical environment R. Second, it helps understand the heterogeneous nature of monetary cost data for invasive species, processes to harmonize the data and the inherent biases associated with such data. Third, it readily provides complementary methods to investigate the costs of invasive species at different scales, all the while accounting for econometric statistical issues.4. This tool will be useful for scientists working on invasive alien species, by (a) facilitating access to and use of this multidisciplinary data resource and (b) providing a standard procedure which will facilitate reproducibility and comparability among studies, one of the major critics of this topic until now. It should facilitate further interdisciplinary works including economists and invasion ecology researchers.
Published: 2022
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120. Les coûts économiques des invasions biologiques en Afrique : une menace croissante mais négligée ?

Author: Franck Courchamp, Justice Tambo, Gauthier Dobigny, Elena Angulo, Ana Novoa, Cheikh Abdou Khadre Mbacké Dia, Christophe Diagne, Desika Moodley, Tasnime Adamjy, Boris Leroy, Ahmed Taheri, Anna J. Turbelin, Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Invasion Ecology, Institute of Botany, Czech Academy of Sciences [Prague] (CAS), Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), Ecole Polytechnique d'Abomey Calavi (EPAC), University of Abomey Calavi (UAC), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Département de Biologie Animale, Université Chouaib Doukkali (UCD), Centre for Agricultural Bioscience International (CABI Europe Switzerland), The authors acknowledge the French National Research Agency (ANR-14-CE02-0021) and the BNP-Paribas Foundation Climate Initiative for funding the InvaCosts project which allowed the construction of the InvaCosts database. This work was initiated following a workshop funded by the AXA Research Fund Chair of Invasion Biology and is part of the AlienScenario project funded by BiodivERsA and Belmont-Forum call 2018 on biodiversity scenarios. AN and DM were supported by the Czech Science Foundation (project no. 19–13142S, and EXPRO no. 19–28807X) and the Czech Academy of Sciences (long-term research development project RVO 67985939). EA contract comes from the AXA Research Fund Chair of Invasion Biology of University Paris Saclay. JT was supported by CABI with core financial support from its member countries and lead agencies (see: https://www.cabi.org/what-we-do/how-we-work/cabi-donors-and-partners). CD was funded by the BiodivERsA-Belmont Forum Project 'Alien Scenarios' (BMBF/PT DLR 01LC1807C)., ANR-14-CE02-0021,InvaCosts,Insectes envahissants et leurs couts pour la biodiversité, l'économie et la santé humaine(2014), Institute of Botany of the Czech Academy of Sciences (IB / CAS), Centre for Agriculture and Biosciences International UK (CABI UK), The authors acknowledge the French National Research Agency (ANR-14-CE02-0021) and the BNP-Paribas Foundation Climate Initiative for funding the Invacost project which allowed the construction of the InvaCost database. This work was initiated following a workshop funded by the AXA Research Fund Chair of Invasion Biology and is part of the AlienScenario project funded by BiodivERsA and Belmont-Forum call 2018 on biodiversity scenarios. AN and DM were supported by the Czech Science Foundation (project no. 19–13142S, and EXPRO no. 19–28807X) and the Czech Academy of Sciences (long-term research development project RVO 67985939). EA contract comes from the AXA Research Fund Chair of Invasion Biology of University Paris Saclay. JT was supported by CABI with core financial support from its member countries and lead agencies (see: https://www.cabi.org/what-we-do/how-we-work/cabi-donors-and-partners/). CD was funded by the BiodivERsA-Belmont Forum Project 'Alien Scenarios' (BMBF/PT DLR 01LC1807C)., Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, 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), and Université d’Abomey-Calavi = University of Abomey Calavi (UAC)
Subjects: 0106 biological sciences, ሥነ-ሕይወታዊ ወረራዎች, Natural resource economics, ግብርና, ruuri ndundat yi, [SDV]Life Sciences [q-bio], biological invasions, Plant Science, 010501 environmental sciences, ኢኮኖሚያዊ ወጪዎች, 01 natural sciences, Afrika, economic costs, InvaCosts, Afrique, yàqu-yàyu, agricultura, Economic cost, coûts économiques, gestion, labarali, Economic impact analysis, Biology (General), bestuur, Alien species, ukubhekana, agriculture, 2. Zero hunger, landbou, አፍሪካ, Ecology, gestión, Ecological Modeling, ቁጥጥር፡፡, costes económicos, njeexital ci koom-koom, Geography, [SDE]Environmental Sciences, ኢንቫኮስት, Ɲanamaya finkuraw cyarili, damage, management, InvaCost, QH301-705.5, Farafina, Developing country, Aquatic Science, 010603 evolutionary biology, invasions biologiques, daños, mbay, kɔlɔlɔ, skade, pertes et dommages, umonakalo, Natural ecosystem, indringer spesies, Ecology, Evolution, Behavior and Systematics, izindleko zezomnotho, 0105 earth and related environmental sciences, África, musaka, 15. Life on land, ጉዳት, Afrig, sɛnɛ, invasiones biológicas, 13. Climate action, ezolimo, izimila nezilwanyana zokufika, Insect Science, Africa, saytu gi, Animal Science and Zoology, ekonomiese koste
Abstract: International audience; Biological invasions can dramatically impact natural ecosystems and human societies. However, although knowledge of the economic impacts of biological invasions provides crucial insights for efficient management and policy, reliable syntheses are still lacking. This is particularly true for low income countries where economic resources are insufficient to control the effects of invasions. In this study, we relied on the recently developed "InvaCost" database – the most comprehensive repository on the monetised impacts of invasive alien species worldwide – to produce the first synthesis of economic costs of biological invasions on the African continent. We found that the reported costs of invasions ranged between US$ 18.2 billion and US$ 78.9 billion between 1970 and 2020. This represents a massive, yet highly underestimated economic burden for African countries. More alarmingly, these costs are exponentially increasing over time, without any signs of abatement in the near future. The reported costs were mostly driven by damage caused by invaders rather than expenses incurred for management. This trend was highly skewed towards a few regions (i.e. Southern and Eastern Africa) and activity sectors (i.e. agriculture) and incurred by a small number of invasive taxa (i.e. mainly three insect pests: Chilo partellus , Tuta absoluta , Spodoptera frugiperda ). We also highlight crucial, large gaps in current knowledge on the economic costs of invasions that still need to be bridged with more widespread research effort and management actions across the continent. Finally, our study provides support for developing and implementing preventive measures as well as integrated post-invasion management actions at both national and regional levels. Considering the complex societal and economic realities in African countries, the currently neglected problem of biological invasions should become a priority for sustainable development.; Les invasions biologiques peuvent avoir un impact considérable sur les écosystèmes naturels et les sociétés humaines. Cependant, bien que les connaissances sur les impacts économiques des invasions biologiques fournissent des informations cruciales en termes de gestion, des synthèses récentes et fiables font encore défaut. Cela est particulièrement vrai pour les pays à faible revenu où les ressources économiques sont insuffisantes pour contrôler les effets des invasions. Dans cette étude, nous nous sommes appuyés sur la base de données "InvaCost" développée récemment - le référentiel le plus complet sur les impacts monétaires des espèces exotiques envahissantes dans le monde - pour produire la première synthèse des coûts économiques des invasions biologiques sur le continent africain. Nous avons constaté que les coûts déclarés des invasions varient entre 18,2 milliards de dollars américains (USD) et 78,9 milliards USD entre 1970 et 2020. Cela représente une charge économique énorme, mais encore très sous-estimée, pour les pays africains. Plus alarmant encore, ces coûts augmentent de façon exponentielle au fil du temps, sans aucun signe de réduction pour les années à venir. Les coûts reportés étaient principalement (i) dus aux dommages causés par les envahisseurs plutôt qu’aux dépenses engagées pour lutter contre leurs invasions, (ii) fortement biaisés vers quelques régions (Afrique australe et orientale) et secteurs d’activité (agriculture) et (iii) associés à un nombre restreint de taxons envahissants (essentiellement trois insectes ravageurs: Chilo partellus, Tuta absoluta, Spodoptera frugiperda). Notre étude met également en lumière de cruciales lacunes dans les connaissances actuelles sur les coûts économiques des invasions qui doivent encore être comblées par des efforts de recherche et des actions de gestion plus importants et étendus à travers le continent. Enfin, notre travail souligne la nécessité de l’élaboration et la mise en œuvre de mesures préventives pour empêcher l’introduction des espèces envahissantes, ainsi que l’intégration des actions de gestion aux niveaux national et régional. Compte tenu des réalités sociétales et économiques complexes des pays africains, le problème actuellement négligé des invasions biologiques devrait être une priorité pour le développement durable.
Published: 2021
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121. Vineyard Management and Its Impacts on Soil Biodiversity, Functions, and Ecosystem Services

Author: Brice Giffard, Silvia Winter, Silvia Guidoni, Annegret Nicolai, Maurizio Castaldini, Daniel Cluzeau, Patrice Coll, Jérôme Cortet, Edith Le Cadre, Giada d’Errico, Astrid Forneck, Elena Gagnarli, Michaela Griesser, Muriel Guernion, Alessandra Lagomarsino, Silvia Landi, Yves Le Bissonnais, Elena Mania, Stefano Mocali, Cristina Preda, Simone Priori, Annette Reineke, Adrien Rusch, Hans-Josef Schroers, Sauro Simoni, Magdalena Steiner, Elena Temneanu, Sven Bacher, Edoardo A. C. Costantini, Johann Zaller, Ilona Leyer, Santé et agroécologie du vignoble (UMR SAVE), 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), Universität für Bodenkultur Wien = University of Natural Resources and Life [Vienne, Autriche] (BOKU), Università degli studi di Torino = University of Turin (UNITO), Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Centro di Ricerca Agricoltura e Ambiente [CREA] (CREA-AA), Consiglio per la Ricerca in Agricoltura e l’analisi dell’economia agraria = Council for Agricultural Research and Economics (CREA), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-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)-Université de Montpellier (UM), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, 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 Naples Federico II = Università degli studi di Napoli Federico II, Istituto per la Protezione Sostenibile delle Piante [Torino, Italia] (IPSP), Consiglio Nazionale delle Ricerche (CNR), Research Centre for Plant Protection and Certification, Laboratoire d'étude des Interactions Sol - Agrosystème - Hydrosystème (UMR LISAH), Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Ovidius University of Constanta, Hochschule Geisenheim University, Institut des Sciences de la Vigne et du Vin [Villenave d'Ornon] (ISVV), Université de Bordeaux (UB), Agricultural Institute of Slovenia, University of Fribourg, University of Agricultural Sciences and Veterinary Medicine Cluj Napoca, The review formed part of the PromESSinG and VineDivers projects, funded by the 2013–2014 BiodivERsA/FACCE JPI joint call for research proposals with the national funders Bundesministerium für Bildung und Forschung (BMBF, Germany), Agence Nationale de la Recherche (ANR, France), Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI, Romania), Ministerio des economía y competitividad (MINECO, Spain), FWF-Der Wissenschaftsfonds (Austria) and the Swiss National Science Foundation (SNSF, Switzerland Grant No: 40FA40_158390). The contract of BG was supported in 2017 by the European Union Seventh Framework Program via a grant from the PromESSinG project. Contributions to this review were also supported by the research project ReSolVe funded by transnational funding bodies, being partners of the FP7 ERA-net project, CORE Organic Plus, and the cofound from the European Commission, and by the research project SECBIVIT which was funded through the 2017–2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND program, and with the funding organizations: AEI/Spain, BMBF/Germany, ANR/France, NWO/Netherlands, UEFISCDI/Romania, FWF/Austria (Grant No: I 4025-B32) and the NSF/United States (Grant No: 1850943). Researches on soil biodiversity conducted in the SAVE unit (BG and ARu) were supported by the Conseil Interprofessionel des Vins de Bordeaux CIVB during the Phytae project (2018–2020) and the Endless project (2021–2024)., Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), CNR Istituto per la Protezione Sostenibile delle Piante [Torino, Italia] (IPSP), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Université de Fribourg = University of Fribourg (UNIFR), and University of Agricultural Sciences and Veterinary Medicine Cluj Napoca = Universitatea de Științe Agricole și Medicină Veterinară Cluj-Napoca
Subjects: microarthropods, Ecology, microarthropods, earthworms, gastropods, nematodes, plants, predatory arthropods, microflora, pest control, plants, [SDV]Life Sciences [q-bio], gastropods, nematodes, earthworms, microflora, predatory arthropods, Ecology, Evolution, Behavior and Systematics, pest control
Abstract: International audience; Healthy soils form the basis of sustainable viticulture, where soil characteristics have a direct impact on wine quantity and quality. Soil not only provides water and nutrients to vines, but is also a living medium containing micro- and macroorganisms that perform many ecological functions and provide ecosystem services. These organisms are involved in many processes, from decomposing organic matter to providing minerals to vine roots. They also control diseases, pests, and weeds, in addition to improving the soil structure in terms of its capacity to retain water and nutrients. Related to decomposition processes, the carbon content of vineyard soils influences fertility, erosion and biogeochemical cycles, with significant implications for the global climate. However, common agricultural practices represent strong threats to biodiversity and associated ecosystem services provided by vineyard soils. As consumers increasingly consider environmental aspects in their purchase decisions, winegrowers have to adapt their vineyard management strategies, raising the demand for sustainable pest- and weed-control methods. This article presents a comprehensive review of the impacts of vineyard practices on the soil ecosystem, biodiversity, and biodiversity-based ecosystem services, and provides future prospects for sustainable viticulture.
Published: 2022
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122. Economic costs of invasive alien ants worldwide

Author: Elena Angulo, Benjamin D. Hoffmann, Liliana Ballesteros-Mejia, Ahmed Taheri, Paride Balzani, Alok Bang, David Renault, Marion Cordonnier, Céline Bellard, Christophe Diagne, Danish A. Ahmed, Yuya Watari, Franck Courchamp, Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Université Chouaib Doukkali (UCD), Università degli Studi di Firenze = University of Florence (UniFI), Faculty of Fisheries and Protection of Waters [University of South Bohemia], University of South Bohemia, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses [University of South Bohemia] (CENAKVA), University of South Bohemia -University of South Bohemia, Society for Ecology Evolution and Development, Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Gulf University for Science and Technology (GUST), Forestry and Forest Products Research Institute (FFPRI), Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was funded through the 2017–2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND program. The French National Research Agency (ANR-14-CE02-0021) and the BNP-Paribas Foundation Climate Initiative funded the InvaCost project that allowed the construction of the InvaCost database. The work was conducted following a workshop funded by the AXA Research Fund Chair of Invasion Biology and is part of the AlienScenario project funded by BiodivERsA and Belmont-Forum call 2018 on biodiversity scenarios, which also funded CD contract (BMBF/PT DLR 01LC1807C). Funds for EA and LBM came from the AXA Research Fund Chair of Invasion Biology of University Paris Saclay. DA was funded by the Kuwait Foundation for the Advancement of Sciences (KFAS) (Grant number: PR1914SM-01) and the Gulf University for Science and Technology (GUST) internal seed fund (Grant Number: 253536). DR thanks InEE-CNRS who supports the national network ‘Biological Invasions’ (Groupement de Recherche InvaBio, 2014–2022). CB was also funded by her salary as a french public agent., ANR-14-CE02-0021,InvaCosts,Insectes envahissants et leurs couts pour la biodiversité, l'économie et la santé humaine(2014), Estación Biológica de Doñana (EBD), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut Ecologie et Environnement (INEE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD [France-Sud])-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)-Université de Montpellier (UM), BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND program, French National Research Agency [ANR-14-CE02-0021], BNP-Paribas Foundation Climate Initiative - AXA Research Fund Chair of Invasion Biology [BMBF/PT DLR 01LC1807C], AXA Research Fund Chair of Invasion Biology of University Paris Saclay - Kuwait Foundation for the Advancement of Sciences (KFAS) [PR1914SM-01], Gulf University for Science and Technology (GUST) [253536], InEE-CNRS [2014-2022], Spanish National Research Council (CSIC), and Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)
Subjects: InvaCost, Wasmannia, Ecology, Anoplolepis, Monetary impacts, JEL: Q - Agricultural and Natural Resource Economics • Environmental and Ecological Economics/Q.Q5 - Environmental Economics/Q.Q5.Q51 - Valuation of Environmental Effects, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Linepithema, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Formicidae, JEL: Q - Agricultural and Natural Resource Economics • Environmental and Ecological Economics/Q.Q5 - Environmental Economics/Q.Q5.Q57 - Ecological Economics: Ecosystem Services • Biodiversity Conservation • Bioeconomics • Industrial Ecology, [SDE.ES]Environmental Sciences/Environmental and Society, Ecology, Evolution, Behavior and Systematics
Abstract: International audience; Invasive ants are amongst the most destructive and widespread invaders across the globe; they can strongly alter invaded ecosystems and are responsible for the loss of native ant species. Several studies have reported that invasive ants can also lead to substantial economic costs. In this study, we search, describe and analyse 1342 reported costs of invasive ants compiled in the InvaCost database. Economic costs, reported since 1930 for 12 ant species in 27 countries, totalled US dollars 51.93 billion, from which US dollars 10.95 billion were incurred, and US$ 40.98 billion were potential costs (i.e., expected or predicted costs). More than 80% of total costs were associated with only two species, Solenopsis invicta and Wasmannia auropunctata ; and two countries, the USA and Australia. Overall, damage costs amounted to 92% of the total cost, mainly impacting the agriculture, public and social welfare sectors. Management costs were primarily post-invasion management (US dollars 1.79 billion), with much lower amounts dedicated to prevention (US dollars 235.63 million). Besides the taxonomic bias, cost information was lacking for an average of 78% of the invaded countries. Moreover, even in countries where costs were reported, such information was available for only 56% of the invaded locations. Our synthesis suggests that the global costs of invasive ants are massive but largely biased towards developed economies, with a huge proportion of underreported costs, and thus most likely grossly underestimated. We advocate for more and improved cost reporting of invasive ants through better collaborations between managers, practitioners and researchers, a crucial basis for adequately informing future budgets and improving proactive management actions of invasive ants.; El coste económico mundial de las hormigas invasoras Las hormigas invasoras están entre las especies más destructivas y más ampliamente extendidas en todo el mundo. Pueden alterar fuertemente los ecosistemas y son responsables de la pérdida de numerosas especies de hormigas nativas en los ecosistemas invadidos. Muchos estudios han mostrado que las hormigas invasoras pueden producir costes económicos importantes. En este estudio, recopilamos, describimos y analizamos 1342 entradas de costes económicos de hormigas invasoras usando la base de datos InvaCost. Los costes económicos fueron reportados desde 1930, para 12 hormigas invasoras, en 27 países, alcanzando un total de 51.93 mil millones de dólares americanos de los cuales 10.95 mil millones fueron observados (costes reales) mientras que 40.98 mil millones de dólares americanos fueron costes potenciales (es decir, costes esperados, no observados). Más del 80% de los costes totales fueron causados por dos especies: Solenopsis invicta y Wasmannia auropunctata ; y en dos países: Estados Unidos y Australia. Los costes debidos a daños alcanzaron el 92% del total, afectando principalmente a los sectores agrícola y de bienestar social. Los costes de gestión se invirtieron en su mayoría en la gestión de post-invasión (1.79 mil millones de dólares), con montos mucho menores de inversión en prevención (235.63 millones de dólares). A nivel geográfico, falta información de reportes de costes económicos para aproximadamente un 78% de los países invadidos. Además, incluso en los países donde existían costes reportados, dicha información sólo estaba disponible para el 56% de los lugares invadidos. Nuestra síntesis sugiere que los costes globales de las hormigas invasoras son enormes pero en gran medida sesgados hacia las economías desarrolladas, con una gran proporción de costes sin reportar y por lo tanto gravemente subestimados. Exhortamos entonces, a un mayor y mejor reporte de los costes económicos de las hormigas invasoras a través de una mayor colaboración entre gestores, profesionales e investigadores; lo cual es la base crucial para informar adecuadamente presupuestos futuros y mejorar las actuaciones hacia una gestión proactiva de las hormigas invasoras.
Published: 2022
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123. Association of epilepsy and type 1 diabetes mellitus in children and adolescents: is there an increased risk for diabetic ketoacidosis?

Author: Schober E, Otto KP, Dost A, Jorch N, Holl R, and German/Austrian DPV Initiative and the BMBF Competence Network Diabetes
Published: 2012

124. Massive economic costs of biological invasions despite widespread knowledge gaps: a dual setback for India

Author: Alok Bang, Ross N. Cuthbert, Phillip J. Haubrock, Romina D. Fernandez, Desika Moodley, Christophe Diagne, Anna J. Turbelin, David Renault, Tatenda Dalu, Franck Courchamp, Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Faculty of Fisheries and Protection of Waters [University of South Bohemia], University of South Bohemia, Senckenberg Research Institute and Natural History Museum [Frankfurt], Senckenberg – Leibniz Institution for Biodiversity and Earth System Research - Senckenberg Gesellschaft für Naturforschung, Leibniz Association-Leibniz Association, Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Universidad Nacional de Tucumán (UNT), Institute of Botany of the Czech Academy of Sciences (IB / CAS), Czech Academy of Sciences [Prague] (CAS), Université Paris-Saclay, Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), University of Mpumalanga (UMP), French National Research Agency French National Research Agency (ANR) [ANR-14-CE02-0021], BNP-Paribas Foundation Climate Initiative through the InvaCost Project, University Paris Saclay, CNRS Centre National de la Recherche Scientifique (CNRS) European Commission, AXA Research Fund Chair of Invasion Biology of University Paris Saclay, 2017-2018 Belmont Forum under the BiodivScen ERA-Net COFUND Programme [BMBF/PT DLR 01LC1807C], BiodivERsA Joint Call for Research proposals under the BiodivScen ERA-Net COFUND Programme with Project \'Alien Scenarios\' [BMBF/PT DLR 01LC1807C], Czech Science FoundationGrant Agency of the Czech Republic [18-18495S, 19-28807X], Czech Academy of Sciences Czech Academy of Sciences [RVO 67985939], Alexander von Humboldt Foundation Alexander von Humboldt Foundation, French National Network 'Biological Invasions' (GdR InvaBio), ANR-14-CE02-0021,InvaCosts,Insectes envahissants et leurs couts pour la biodiversité, l'économie et la santé humaine(2014), Queen's University [Belfast] (QUB), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut Ecologie et Environnement (INEE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2), and Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)
Subjects: InvaCost, Ecology, Non-native species, Nonnative species, SDG 8 - Decent Work and Economic Growth, Socioeconomic measures, South Asia, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, [SDE.ES]Environmental Sciences/Environmental and Society, Economic impact, JEL: Q - Agricultural and Natural Resource Economics • Environmental and Ecological Economics/Q.Q5 - Environmental Economics/Q.Q5.Q51 - Valuation of Environmental Effects, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Ecology, Evolution, Behavior and Systematics
Abstract: Biological invasions are one of the top drivers of the ongoing biodiversity crisis. An underestimated consequence of invasions is the enormity of their economic impacts. Knowledge gaps regarding economic costs produced by invasive alien species (IAS) are pervasive, particularly for emerging economies such as India—the fastest growing economy worldwide. To investigate, highlight and bridge this gap, we synthesised data on the economic costs of IAS in India. Specifically, we examine how IAS costs are distributed spatially, environmentally, sectorally, taxonomically, temporally, and across introduction pathways; and discuss how Indian IAS costs vary with socioeconomic indicators. We found that IAS have cost the Indian economy between at least US$ 127.3 billion to 182.6 billion (Indian Rupees ₹ 8.3 trillion to 11.9 trillion) over 1960–2020, and these costs have increased with time. Despite these massive recorded costs, most were not assigned to specific regions, environments, sectors, cost types and causal IAS, and these knowledge gaps are more pronounced in India than in the rest of the world. When costs were specifically assigned, maximum costs were incurred in West, South and North India, by invasive alien insects in semi-aquatic ecosystems; they were incurred mainly by the public and social welfare sector, and were associated with damages and losses rather than management expenses. Our findings indicate that the reported economic costs grossly underestimate the actual costs, especially considering the expected costs given India’s population size, gross domestic product and high numbers of IAS without reported costs. This cost analysis improves our knowledge of the negative economic impacts of biological invasions in India and the burden they can represent for its development. We hope this study motivates policymakers to address socio-ecological issues in India and launch a national biological invasion research programme, especially since economic growth will be accompanied by greater impacts of global change.
Published: 2022
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125. Genome-wide association analyses identify novel Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Author: Barc, Julien, Tadros, Rafik, Glinge, Charlotte, Chiang, David Y., Jouni, Mariam, Simonet, Floriane, Jurgens, Sean J., Baudic, Manon, Nicastro, Michele, Potet, Franck, Offerhaus, Joost A., Walsh, Roddy, Choi, Seung Hoan, Verkerk, Arie O., Mizusawa, Yuka, Anys, Soraya, Minois, Damien, Arnaud, Marine, Duchateau, Josselin, Wijeyeratne, Yanushi D., Muir, Alison, Papadakis, Michael, Castelletti, Silvia, Torchio, Margherita, Ortuño, Cristina Gil, Lacunza, Javier, Giachino, Daniela F., Cerrato, Natascia, Martins, Raphaël P., Campuzano, Oscar, Van Dooren, Sonia, Thollet, Aurélie, Kyndt, Florence, Mazzanti, Andrea, Clémenty, Nicolas, Bisson, Arnaud, Corveleyn, Anniek, Stallmeyer, Birgit, Dittmann, Sven, Saenen, Johan, Noël, Antoine, Honarbakhsh, Shohreh, Rudic, Boris, Marzak, Halim, Rowe, Matthew K., Federspiel, Claire, Le Page, Sophie, Placide, Leslie, Milhem, Antoine, Barajas-Martinez, Hector, Beckmann, Britt-Maria, Krapels, Ingrid P., Steinfurt, Johannes, Winkel, Bo Gregers, Jabbari, Reza, Shoemaker, Moore B., Boukens, Bas J., Škorić-Milosavljević, Doris, Bikker, Hennie, Manevy, Federico, Lichtner, Peter, Ribasés, Marta, Meitinger, Thomas, Müller-Nurasyid, Martina, Strauch, Konstantin, Peters, Annette, Schulz, Holger, Schwettmann, Lars, Leidl, Reiner, Heier, Margit, Veldink, Jan H., van den Berg, Leonard H., Van Damme, Philip, Cusi, Daniele, Lanzani, Chiara, Rigade, Sidwell, Charpentier, Eric, Baron, Estelle, Bonnaud, Stéphanie, Lecointe, Simon, Donnart, Audrey, Le Marec, Hervé, Chatel, Stéphanie, Karakachoff, Matilde, Bézieau, Stéphane, London, Barry, Tfelt-Hansen, Jacob, Roden, Dan, Odening, Katja E., Cerrone, Marina, Chinitz, Larry A., Volders, Paul G., van de Berg, Maarten P., Laurent, Gabriel, Faivre, Laurence, Antzelevitch, Charles, Kääb, Stefan, Arnaout, Alain Al, Dupuis, Jean-Marc, Pasquie, Jean-Luc, Billon, Olivier, Roberts, Jason D., Jesel, Laurence, Borggrefe, Martin, Lambiase, Pier D., Mansourati, Jacques, Loeys, Bart, Leenhardt, Antoine, Guicheney, Pascale, Maury, Philippe, Schulze-Bahr, Eric, Robyns, Tomas, Breckpot, Jeroen, Babuty, Dominique, Priori, Silvia G., Napolitano, Carlo, Defaye, Pascal, Anselme, Frédéric, Darmon, Jean Philippe, Wiart, François, de Asmundis, Carlo, Brugada, Pedro, Brugada, Ramon, Arbelo, Elena, Brugada, Josep, Mabo, Philippe, Behar, Nathalie, Giustetto, Carla, Molina, Maria Sabater, Gimeno, Juan R., Hasdemir, Can, Schwartz, Peter J., Crotti, Lia, McKeown, Pascal P., Sharma, Sanjay, Behr, Elijah R., Haissaguerre, Michel, Sacher, Frédéric, Rooryck, Caroline, Tan, Hanno L., Remme, Carol A., Postema, Pieter G., Delmar, Mario, Ellinor, Patrick T., Lubitz, Steven A., Gourraud, Jean-Baptiste, Tanck, Michael W., George, Alfred L., MacRae, Calum A., Burridge, Paul W., Dina, Christian, Probst, Vincent, Wilde, Arthur A., Schott, Jean-Jacques, Redon, Richard, Bezzina, Connie R., KORA-Study Group, Nantes Referral Ctr Inherited Card, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé - François Bonamy, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), 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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Amsterdam UMC - Amsterdam University Medical Center, The MINE study (J.H.V.) has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 772376—EScORIAL). The collaboration project is cofunded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public–private partnerships. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113, 085475 and 090355. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum München—German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. J. Barc is supported by the research program Etoiles montantes des Pays de la Loire REGIOCARD RPH081-U1087-REG-PDL, ANR JCJC LEARN (R21006NN, RPV21014NNA) and by the H2020-MSCA-IF-2014 Program of the European Commission (RISTRAD-661617). R.T. is supported by the Canadian Heart Rhythm Society’s George Mines Award, the European Society of Cardiology research award, and the Philippa and Marvin Carsley Cardiology Chair. D.Y.C. is supported by Fondation Leducq and National Institutes of Health (NIH) NHGRI T32 (no. 1T32HG010464-01). M. Baudic was supported by IRP—VERACITIES—New Mechanisms for VEntricular ARrhythmia And CardIomeTabolic DIseasES, an I-SITE NExT health and engineering initiative (Ecole Centrale and Nantes University) and by the IRP—GAINES—Genetic Architecture IN cardiovascular disEaSes funded by INSERM and CNRS. R.W. is supported by an Amsterdam Cardiovascular Sciences fellowship. S.C. is supported by the NHLBI BioData Catalyst Fellows Program. C.A.R. is supported by Fondation Leducq, the Dutch Heart Foundation (CVON PREDICT2) and the Innovational Research Incentives Scheme Vidi grant from the Netherlands Organisation for Health Research and Development (ZonMw, 91714371). Y.D.W. is supported by the Robert Lancaster Memorial Fund. M.P. is supported by Cardiac Risk in the Young. S.V.D. is supported by Wetenschappelijk Fonds Willy Gepts VUB-UZ Brussel, project ‘Unravelling the molecular genetic pathways of Brugada Syndrome by cardiomics research’, VUB IRP project ‘IMAGica: an Integrative personalized Medical Approach for Genetic diseases, Inherited Cardia Arrhythmias as a model’ and Innoviris BRIDGE 2017, project ‘IGenCare: Integrated Personalised Medical Genomics Care Solution for Patients with Rare Genetic Diseases’. S.H. is supported by the Barts BRC. B.R. is supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research). B.G.W. is supported by the Danish Heart Foundation. M.B.S. is supported by K23HL127704. Project MinE Belgium was supported by a grant from IWT (no. 140935), the ALS Liga België, the National Lottery of Belgium and the KU Leuven Opening the Future Fund. D.C. and C.L. are supported by HYPERGENES (HEALTH-F4-2007). D.R. is supported by R01 HL149826, P50 GM115305. P.J.S. acknowledges the support of Leducq Foundation for Cardiovascular Research grant 18CVD05. P.V.D. is supported by the Netherlands CardioVascular Research Initiative (CVON PREDICT2). C.A. is supported by NIH HL47678 and HL138103, W.W. Smith Charitable Trust and Wistar Morris Fund. M.B. is Supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research). P.D.L. is supported by UCL/UCLH Biomedicine NIHR and Barts BRC. B.L. is supported by GOA—Antigone 33933. J.B. is supported by a Senior Clinical Fellowship of the Flemish Science Foundation (FWO). E.B. is supported by the British Heart Foundation including BHF Clinical Research Training Fellowship (FS/11/71/28918: Future diagnostic role and new genetic loci in SADS), Cardiac Risk in the Young and Robert Lancaster Memorial fund sponsored by McColl’s Ltd. Retail Group. H.L.T. is supported by the European Union’s Horizon 2020 research and innovation program under acronym ESCAPE-NET, registered under grant agreement no. 733381, and the Dutch Heart Foundation (CVON RESCUED and PREDICT2 projects). M.D. is supported by NIH-RO1 HL134328. P.T.E. was supported by the Fondation Leducq (14CVD01), the NIH (1RO1HL092577, R01HL128914, K24HL105780), the American Heart Association (18SFRN34110082) and by a research grant from Bayer AG to the Broad Institute. S.A.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. J.-B.G. received a grant from the Fédération Française de Cardiologie (PREVENT project). A.L.G. is supported by the Fondation Leducq. C.A.M.R. is supported by the Leducq Foundation and Burroughs Wellecome Fund. A.A.W. is supported by the Dutch Heart Foundation (CVON PREDICT2 project). J.-J.S. is supported by the Fondation pour la Recherche Médicale (DEQ20140329545). R.R. and P.G. are supported by the National Agency for Research (ANR-GENSUD-14-CE10-0001). C.R.B. is supported by the Dutch Heart Foundation (CVON PREDICT2 project), the Netherlands Organization for Scientific Research (VICI fellowship, 016.150.610) and Fondation Leducq (17CVD02)., Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Cardiology, Graduate School, Medical Biology, ACS - Amsterdam Cardiovascular Sciences, ACS - Heart failure & arrhythmias, Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, APH - Methodology, Epidemiology and Data Science, MUMC+: DA KG Polikliniek (9), RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H04 Arrhythmogenesis and cardiogenetics, and Cardiovascular Centre (CVC)
Subjects: EXPRESSION, [SDV]Life Sciences [q-bio], DIAGNOSIS, GUIDELINES, ANNOTATION, Article, NAV1.5 Voltage-Gated Sodium Channel, Young Adult, MANAGEMENT, Genetics, GWAS, Humans, Genetic Predisposition to Disease, 610 Medicine & health, SCN5A, Alleles, Brugada Syndrome, Allele, [SDV.GEN]Life Sciences [q-bio]/Genetics, HERITABILITY, Microtubule-Associated Protein, Brugada Syndrome, GWAS, SNPs, COMMON VARIANTS, Mutation, Disease Susceptibility, Human medicine, ENRICHMENT, Microtubule-Associated Proteins, SNPs, Human, GENERATION, Genome-Wide Association Study
Abstract: Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na(V)1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na(V)1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings. Genome-wide association analyses identify new susceptibility loci for Brugada syndrome. Functional studies implicate microtubule-related trafficking effects on sodium channel expression as an underlying molecular mechanism., European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [772376-EScORIAL]; Health~Holland; Top Sector Life Sciences Health; Wellcome Trust [076113, 085475, 090355]; Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research; State of Bavaria; Munich Center of Health Sciences (MC Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ; research program Etoiles montantes des Pays de la Loire [REGIOCARD RPH081-U1087-REG-PDL]; ANR JCJC LEARN [R21006NN, RPV21014NNA]; H2020-MSCA-IF-2014 Program of the European Commission [RISTRAD-661617]; Canadian Heart Rhythm Society's George Mines Award; European Society of Cardiology research award; Philippa and Marvin Carsley Cardiology Chair; Fondation Leducq; National Institutes of Health (NIH) NHGRI T32 [1T32HG010464-01]; IRP-VERACITIES-New Mechanisms for VEntricular ARrhythmia And CardIomeTabolic DIseasES an I-SITE NExT health and engineering initiative (Ecole Centrale); IRP-VERACITIES-New Mechanisms for VEntricular ARrhythmia And CardIomeTabolic DIseasES an I-SITE NExT health and engineering initiative (Nantes University); IRP-GAINES-Genetic Architecture IN cardiovascular disEaSes - INSERM; CNRS; Amsterdam Cardiovascular Sciences fellowship; NHLBI BioData Catalyst Fellows Program; Dutch Heart Foundation [CVON PREDICT2]; Innovational Research Incentives Scheme Vidi grant from the Netherlands Organisation for Health Research and Development (ZonMw) [91714371]; Robert Lancaster Memorial Fund; Cardiac Risk in the Young; Wetenschappelijk Fonds Willy Gepts VUB-UZ Brussel; VUB IRP project `IMAGica: an Integrative personalized Medical Approach for Genetic diseases, Inherited Cardia Arrhythmias as a model' and Innoviris BRIDGE 2017; project `IGenCare: Integrated Personalised Medical Genomics Care Solution for Patients with Rare Genetic Diseases'; Barts BRC; DZHK (German Centre for Cardiovascular Research); BMBF (German Ministry of Education and Research); Danish Heart Foundation; IWT [140935]; ALS Liga Belgie; National Lottery of Belgium; KU Leuven Opening the Future Fund; HYPERGENES [HEALTH-F4-2007]; Leducq Foundation for Cardiovascular Research grant [18CVD05]; Netherlands CardioVascular Research Initiative [CVON PREDICT2]; NIH [HL47678, HL138103, 1RO1HL092577, R01HL128914, K24HL105780]; W.W. Smith Charitable Trust; Wistar Morris Fund; GOA-Antigone [33933]; Senior Clinical Fellowship of the Flemish Science Foundation (FWO); British Heart Foundation; BHF Clinical Research Training Fellowship [FS/11/71/28918]; Cardiac Risk in the Young and Robert Lancaster Memorial fund - McColl's Ltd. Retail Group; European Union's Horizon 2020 research and innovation program under acronym ESCAPE-NET [733381]; Dutch Heart Foundation; Fondation Leducq [14CVD01, 17CVD02]; American Heart Association [18SFRN34110082, 18SFRN34250007]; Bayer AG; NIH grant [1R01HL139731]; Federation Francaise de Cardiologie (PREVENT project); Leducq Foundation; Burroughs Wellecome Fund; Fondation pour la Recherche Medicale [DEQ20140329545]; National Agency for Research [ANR-GENSUD-14-CE10-0001]; Netherlands Organization for Scientific Research (VICI fellowship) [016.150.610]; [K23HL127704]; [R01 HL149826]; [P50 GM115305]; [NIH-RO1 HL134328], We are greatly indebted to the patients included in the study. We thank V. Cotard, C. Goutsmedt, M.-F. Le Cunff and N. Bourgeais for assistance in patient recruitment and L. Beekman for his technical support. We thank the biological resource centre for biobanking (CHU Nantes, Nantes Universite, Centre de ressources biologiques (BB0033-00040), F-44000 Nantes, France) for applying the following guidelines68. We are most grateful to the Genomics and Bioinformatics Core Facility of Nantes (GenoBiRD, Biogenouest, IFB) for its technical support. This research has been conducted using the UK Biobank resource; we are grateful to UK Biobank participants. The MINE study (J.H.V.) has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 772376-EScORIAL). The collaboration project is cofunded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk.Funding for the project was provided by the Wellcome Trust under award 076113, 085475 and 090355. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum Munchen-German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ. J. Barc is supported by the research program Etoiles montantes des Pays de la Loire REGIOCARD RPH081-U1087-REG-PDL, ANR JCJC LEARN (R21006NN, RPV21014NNA) and by the H2020-MSCA-IF-2014 Program of the European Commission (RISTRAD-661617). R.T. is supported by the Canadian Heart Rhythm Society's George Mines Award, the European Society of Cardiology research award, and the Philippa and Marvin Carsley Cardiology Chair. D.Y.C. is supported by Fondation Leducq and National Institutes of Health (NIH) NHGRI T32 (no. 1T32HG010464-01). M. Baudic was supported by IRP-VERACITIES-New Mechanisms for VEntricular ARrhythmia And CardIomeTabolic DIseasES, an I-SITE NExT health and engineering initiative (Ecole Centrale and Nantes University) and by the IRP-GAINES-Genetic Architecture IN cardiovascular disEaSes funded by INSERM and CNRS. R.W. is supported by an Amsterdam Cardiovascular Sciences fellowship. S.C. is supported by the NHLBI BioData Catalyst Fellows Program. C.A.R. is supported by Fondation Leducq, the Dutch Heart Foundation (CVON PREDICT2) and the Innovational Research Incentives Scheme Vidi grant from the Netherlands Organisation for Health Research and Development (ZonMw; 91714371). Y.D.W. is supported by the Robert Lancaster Memorial Fund. M.P. is supported by Cardiac Risk in the Young. S.V.D. is supported by Wetenschappelijk Fonds Willy Gepts VUB-UZ Brussel, project `Unravelling the molecular genetic pathways of Brugada Syndrome by cardiomics research', VUB IRP project `IMAGica: an Integrative personalized Medical Approach for Genetic diseases, Inherited Cardia Arrhythmias as a model' and Innoviris BRIDGE 2017, project `IGenCare: Integrated Personalised Medical Genomics Care Solution for Patients with Rare Genetic Diseases'. S.H. is supported by the Barts BRC. B.R.; is supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research). B.G.W. is supported by the Danish Heart Foundation. M.B.S. is supported by K23HL127704. Project MinE Belgium was supported by a grant from IWT (no. 140935), the ALS Liga Belgie, the National Lottery of Belgium and the KU Leuven Opening the Future Fund. D.C. and C.L. are supported by HYPERGENES (HEALTH-F4-2007). D.R. is supported by R01 HL149826, P50 GM115305. P.J.S. acknowledges the support of Leducq Foundation for Cardiovascular Research grant 18CVD05. P.V.D. is supported by the Netherlands CardioVascular Research Initiative (CVON PREDICT2). C.A. is supported by NIH HL47678 and HL138103, W.W. Smith Charitable Trust and Wistar Morris Fund. M.B. is Supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research). P.D.L. is supported by UCL/UCLH Biomedicine NIHR and Barts BRC. B.L. is supported by GOA-Antigone 33933. J.B. is supported by a Senior Clinical Fellowship of the Flemish Science Foundation (FWO). E.B. is supported by the British Heart Foundation including BHF Clinical Research Training Fellowship (FS/11/71/28918: Future diagnostic role and new genetic loci in SADS), Cardiac Risk in the Young and Robert Lancaster Memorial fund sponsored by McColl's Ltd. Retail Group. H.L.T. is supported by the European Union's Horizon 2020 research and innovation program under acronym ESCAPE-NET, registered under grant agreement no. 733381, and the Dutch Heart Foundation (CVON RESCUED and PREDICT2 projects). M.D. is supported by NIH-RO1 HL134328. P.T.E. was supported by the Fondation Leducq (14CVD01), the NIH (1RO1HL092577, R01HL128914, K24HL105780), the American Heart Association (18SFRN34110082) and by a research grant from Bayer AG to the Broad Institute. S.A.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. J.-B.G. received a grant from the Federation Francaise de Cardiologie (PREVENT project). A.L.G. is supported by the Fondation Leducq. C.A.M.R. is supported by the Leducq Foundation and Burroughs Wellecome Fund. A.A.W. is supported by the Dutch Heart Foundation (CVON PREDICT2 project). J.-J.S. is supported by the Fondation pour la Recherche Medicale (DEQ20140329545). R.R. and P.G. are supported by the National Agency for Research (ANR-GENSUD-14-CE10-0001). C.R.B. is supported by the Dutch Heart Foundation (CVON PREDICT2 project), the Netherlands Organization for Scientific Research (VICI fellowship, 016.150.610) and Fondation Leducq (17CVD02).
Published: 2022
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126. Long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in a large pooled European cohort:ELAPSE study

Author: Zorana J. Andersen, Jiawei Zhang, Jeanette T. Jørgensen, Evangelia Samoli, Shuo Liu, Jie Chen, Maciej Strak, Kathrin Wolf, Gudrun Weinmayr, Sophia Rodopolou, Elizabeth Remfry, Kees de Hoogh, Tom Bellander, Jørgen Brandt, Hans Concin, Emanuel Zitt, Daniela Fecht, Francesco Forastiere, John Gulliver, Barbara Hoffmann, Ulla A. Hvidtfeldt, W.M. Monique Verschuren, Karl-Heinz Jöckel, Rina So, Tom Cole-Hunter, Amar J. Mehta, Laust H. Mortensen, Matthias Ketzel, Anton Lager, Karin Leander, Petter Ljungman, Gianluca Severi, Marie-Christine Boutron-Ruault, Patrik K.E. Magnusson, Gabriele Nagel, Göran Pershagen, Annette Peters, Debora Rizzuto, Yvonne T. van der Schouw, Sara Schramm, Massimo Stafoggia, Klea Katsouyanni, Bert Brunekreef, Gerard Hoek, Youn-Hee Lim, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, NNF17OC0027812, U.S. Environmental Protection Agency, EPA: R-82811201, Health Effects Institute, HEI: 4954-RFA14-3/16-5-3, Bundesministerium für Bildung und Forschung, BMBF, Karolinska Institutet, KI, Vetenskapsrådet, VR: 2017-00641, China Scholarship Council, CSC: 201806010406, Novo Nordisk Fonden, NNF, Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München, Supported by the Health Effects Institute (No. 4954-RFA14-3/16-5-3), the Novo Nordisk Foundation Challenge Programme (No. NNF17OC0027812), and scholarship from the China Scholarship Council (No. 201806010406). SALT and TwinGene are sub-studies of The Swedish Twin Registry (STR), which is managed by Karolinska Institutet and receives additional funding through the Swedish Research Council (No. 2017-00641). The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. The China Scholarship Council, China, the Novo Nordisk Foundation, Denmark, the Swedish Research Council, Sweden, the German Federal Ministry of Education and Research, and the State of Bavaria were not involved in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., The research described in this article was conducted under contract to the Health Effects Institute (HEI), an organization jointly funded by the United States Environmental Protection Agency (EPA) (Assistance Award No. R-82811201) and certain motor vehicle and engine manufacturers. The contents of this article do not necessarily reflect the views of HEI, or its sponsors, nor do they necessarily reflect the views and policies of the EPA or motor vehicle and engine manufacturers. HEI has reviewed and approved the study design. HEI was not involved in data collection and analysis, decision to publish, or preparation of the manuscript. The authors would also like to thank all participants in the pooled cohort studies and the respective study teams of the ELAPSE project for their hard work and effort. We thank Marjan Tewis for the data management tasks in creating the pooled cohort database., and HAL UVSQ, Équipe
Subjects: Air Pollution, Dementia, Long-term Exposure, Mortality, Psychiatric Disorders, Suicide, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Long-term exposure, Air pollution, Medizin, Psychiatric disorders, Air pollution Dementia Long-term exposure Mortality Psychiatric disorders Suicide, General Environmental Science
Abstract: Ambient air pollution is an established risk factor for premature mortality from chronic cardiovascular, respiratory and metabolic diseases, while evidence on neurodegenerative diseases and psychiatric disorders remains limited. We examined the association between long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in seven European cohorts. Within the multicenter project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven European cohorts from six countries. Based on the residential addresses, annual mean levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), ozone (O3), and 8 PM2.5 components were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and mortality from dementia, psychiatric disorders, and suicide. Of 271,720 participants, 900 died from dementia, 241 from psychiatric disorders, and 164 from suicide, during a mean follow-up of 19.7 years. In fully adjusted models, we observed positive associations of NO2 (hazard ratio [HR] = 1.38; 95 % confidence interval [CI]: 1.13, 1.70 per 10 µg/m3), PM2.5 (HR = 1.29; 95 % CI: 0.98, 1.71 per 5 µg/m3), and BC (HR = 1.37; 95 % CI: 1.11, 1.69 per 0.5 × 10−5/m) with psychiatric disorders mortality, as well as with suicide (NO2: HR = 1.13 [95 % CI: 0.92, 1.38]; PM2.5: HR = 1.19 [95 % CI: 0.76, 1.87]; BC: HR = 1.08 [95 % CI: 0.87, 1.35]), and no association with dementia mortality. We did not detect any positive associations of O3 and 8 PM2.5 components with any of the three mortality outcomes. Long-term exposure to NO2, PM2.5, and BC may lead to premature mortality from psychiatric disorders and suicide.
Published: 2022
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127. Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA interdisciplinary expert consensus

Author: Buske, C., Dreyling, M., Alvarez-Larran, A., Apperley, J., Arcaini, L., Besson, C., Bullinger, L., Corradini, P., Giovanni Della Porta, M., Dimopoulos, M., D'Sa, S., Eich, H. T., Foa, R., Ghia, P., da Silva, M. G., Gribben, J., Hajek, R., Harrison, C., Heuser, M., Kiesewetter, B., Kiladjian, J. J., Kroger, N., Moreau, P., Passweg, J. R., Peyvandi, F., Rea, D., Ribera, J. -M., Robak, T., San-Miguel, J. F., Santini, V., Sanz, G., Sonneveld, P., von Lilienfeld-Toal, M., Wendtner, C., Pentheroudakis, G., Passamonti, F., Hematology, Buske, C., Dreyling, M., Alvarez-Larran, A., Apperley, J., Arcaini, L., Besson, C., Bullinger, L., Corradini, P., Giovanni Della Porta, M., Dimopoulos, M., D'Sa, S., Eich, H. T., Foa, R., Ghia, P., da Silva, M. G., Gribben, J., Hajek, R., Harrison, C., Heuser, M., Kiesewetter, B., Kiladjian, J. J., Kroger, N., Moreau, P., Passweg, J. R., Peyvandi, F., Rea, D., Ribera, J. -M., Robak, T., San-Miguel, J. F., Santini, V., Sanz, G., Sonneveld, P., von Lilienfeld-Toal, M., Wendtner, C., Pentheroudakis, G., Passamonti, F., Universitätsklinikum Ulm - University Hospital of Ulm, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Imperial College London, Hammersmith Hospital NHS Imperial College Healthcare, Fondazione IRCCS Policlinico San Matteo [Pavia], Università degli Studi di Pavia = University of Pavia (UNIPV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), Charité Campus Virchow-Klinikum (CVK), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Freie Universität Berlin, Humboldt University Of Berlin, Medical Oncology Unit, Dept of Medical Oncology and Hematology [Fondazione IRCCS Istituto Nazionale Tumori, Milan], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Università degli Studi di Milano = University of Milan (UNIMI), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), National and Kapodistrian University of Athens (NKUA), University College London Hospitals (UCLH), NHS Foundation Trust [London], The Royal Marsden, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), IRCCS Ospedale San Raffaele [Milan, Italy], Queen Mary University of London (QMUL), Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava, Medizinische Universität Wien = Medical University of Vienna, Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospital Basel [Basel], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Physiopatology and Transplantation, University of Milan (DEPT), Josep Carreras Leukaemia Research Institute (IJC), Universitat Autònoma de Barcelona (UAB), Medical University of Łódź (MUL), Clínica Universidad de Navarra [Pamplona], Azienda Ospedaliero-Universitaria Careggi [Firenze] (AOUC), Università degli Studi di Firenze = University of Florence (UniFI), Jena University Hospital [Jena], Ludwig Maximilian University [Munich] (LMU), Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Boehringer Ingelheim, BI, Amgen, Bristol-Myers Squibb, BMS, Pfizer, Astellas Pharma US, APUS, AstraZeneca, Bayer, Novartis, Roche, Sanofi, Gilead Sciences, Celgene, AbbVie, Meso Scale Diagnostics, MSD, Takeda Pharmaceutical Company, TPC, Janssen Pharmaceuticals, Merck KGaA, Jazz Pharmaceuticals, Deutsche Forschungsgemeinschaft, DFG, Bundesministerium für Bildung und Forschung, BMBF, Daiichi-Sankyo, José Carreras Leukämie-Stiftung, Deutsche Krebshilfe, Ipsen, The panel would like to acknowledge the work of Klizia Marinoni and Delanie Young, from the Scientific and Medical Division at ESMO, for the project coordination and editorial assistance. None declared. CB reports honoraria from Roche/Genentech, Janssen, BeiGene, Novartis, Pfizer, Incyte, AbbVie, Gilead Sciences, Celltrion, MorphoSys, Regeneron, he reports consulting or advisory role: Gilead Sciences, Janssen, Roche, Pfizer, BeiGene, Celltrion, AbbVie, Incyte, Regeneron, MorphoSys, Novartis, he reports speaker's engagement: Roche, Janssen, BeiGene, Celltrion, AbbVie, Pfizer, Gilead Sciences, he reports research funding: Roche/Genentech, Janssen, Celltrion, Merck Sharp & Dohme (MSD), Pfizer, Amgen. MD reports honoraria as Advisory Board Member of AstraZeneca, Bayer, BeiGene, Celgene, Genmab, Gilead, Incyte, Janssen, Lilly, MorphoSys, Novartis, Roche, he reports honoraria for speaker's engagement from Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Novartis, Roche, he reports institutional research grants from AbbVie, Bayer, Gilead, Celgene, Janssen, Roche. AA-L has declared no conflicts of interest. JA reports personal financial interests as advisory board and invited speaker from Incyte, advisory board from Mallinckrodt, advisory board and invited speaker from Novartis, advisory board and invited speaker from Pfizer, she reports non-financial interests as principal investigator from Incyte, principal investigator from Novartis. LA received advisory honoraria from Roche, Celgene, Janssen-Cilag, Verastem, Eusa Pharma, Incyte, ADC Therapeutics and Gilead, research support from Gilead, and travel expenses from Roche, Celgene, Janssen-Cilag, and Eusa Pharma, speakers bureau from Novartis. CB has declared no conflicts of interest. LB reports Advisory Committee activities for AbbVie, Amgen, Astellas, Bristol Myers Squibb (BMS), Celgene, Daiichi Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Sanofi, Seattle Genetics and has research support from Bayer and Jazz Pharmaceuticals. PC has declared no conflicts of interest. MGDP has declared no conflicts of interest. MD reports personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, personal fees from BeiGene, personal fees from BMS, outside the submitted work. SD reports personal financial interests as advisory board, invited speaker, fellow funding, and coordinating PI from BeiGene, writing engagement from Karger, advisory board and coordinating PI from Sanofi, funding, and other from Janssen, she reports non-financial interests as advisory role at British Society for Haematology Lymphoma Special Interest Group, advisory role at Lymphoma Action, member of board of directors at WMUK Charity. HTE has declared no conflicts of interest. RF reports honoraria for advisory boards and/or speaker bureau from Janssen, Gilead, AbbVie, Amgen, Novartis, Roche, Incyte, Pfizer, all outside the submitted work. PG reports grants and personal fees from AbbVie, grants and personal fees from Acerta/AstraZeneca, personal fees from BeiGene, personal fees from Celgene/Juno/BMS, grants and personal fees from Janssen, personal fees from Lilly/Loxo, personal fees from MEI, personal fees from Roche, personal fees from Sanofi, personal fees from ArQule/MSD, outside the submitted work, MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work. JG reports personal fees from AbbVie, grants and personal fees from AstraZeneca, grants and personal fees from BMS/Celgene, grants and personal fees from Janssen, personal fees from Kite/Gilead, personal fees from MorphoSys, personal fees from Novartis, personal fees from TG Therapeutics, outside the submitted work. RH has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda, has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda, has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda. CH reports grants and personal fees from Novartis, grants and personal fees from BMS, personal fees from Sierra Oncology, personal fees from CTI pharmaceuticals, personal fees from Jannsen, personal fees from Geron, grants and personal fees from AOP Orphan Pharma, personal fees from Galecto, grants, personal fees and other from Constellation, outside the submitted work. MH reports personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from AbbVie, personal fees from Daiichi Sankyo, personal fees from Bayer Pharma AG, personal fees from Jazz Pharmaceuticals, personal fees from BMS, personal fees from Tolremo, outside the submitted work. BK has received honoraria for lectures from Ipsen, Novartis and MSD (all outside of the submitted work). J-JK reports consulting fees and honoraria from Novartis, consulting fees from AbbVie, honoraria from AOP Orphan Pharma, participation on a monitoring board or advisory board from BMS/Celgene, participation on a monitoring board or advisory board from Incyte. NK reports grants and honoraria from Neovii, honoraria from Sanofi, grants and honoraria from Jazz, grants and honoraria from Celgene, grants and honoraria from Riemser, honoraria from Gilead/Kite, honorarium from AOP Oprhan Pharma, grants and honorarium from Novartis, honorarium from Amgen. PM reports personal fees from Celgene, Amgen, Janssen, AbbVie, Sanofi, outside the submitted work. JP has declared no conflicts of interest. FP has declared no conflicts of interest. DR received honoraria from Incyte, Novartis Pharma, Pfizer, clinical trial steering committee membership: Novartis, membership on advisory boards: Incyte, Novartis Pharma, Pfizer. J-MR reports grants and honoraria from Novartis, Amgen, Pfizer, Takeda, Incyte, and Servier. TR has declared no conflicts of interest. JF-M reports consulting and advisory boards honoraria (received by CUN ) from AbbVie, Amgen, BMS, Celgene, Janssen, GlaxoSmithKline, Karyopharm, MSD, Novartis, Takeda, Sanofi, SecuraBio, Regeneron, Roche, outside the submitted work. VS has declared no conflicts of interest. GFS reports personal fees and other from AbbVie, other from Amgen, other from Astellas, other from Boehringer-Ingelheim, grants, personal fees and other from Celgene, other from Helsinn Healthcare, grants, personal fees, and other from Janssen-Cilag, grants and other from Novartis, other from Onconova, grants, personal fees and other from Roche, and other from Takeda, outside the submitted work. PS reports honoraria from Amgen, Celgene, Janssen, Karyopharm, SkylineDx, Takeda, and research support from Celgene, Janssen, Amgen, Takeda, BMS, SkylineDx, Karyopharm, all outside the submitted work. MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca, is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leuk?mie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG). CW has declared no conflicts of interest. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. FP reports grants from Novartis, Celgene, BMS, Abbvie, Karyopharma, Janssen., MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work., MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca, is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leukämie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG)., and HAL UVSQ, Équipe
Subjects: Cancer Research, Consensus, consensus manuscript, COVID-19, hematological malignancies, COVID-19, consensus manuscript, hematological malignancies, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19 Testing, Humans, Pandemics, Hematologic Neoplasms, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, SDG 3 - Good Health and Well-being, Original Research
Abstract: The panel would like to acknowledge the work of Klizia Marinoni and Delanie Young, from the Scientific and Medical Division at ESMO, for the project coordination and editorial assistance. None declared. CB reports honoraria from Roche/Genentech, Janssen, BeiGene, Novartis, Pfizer, Incyte, AbbVie, Gilead Sciences, Celltrion, MorphoSys, Regeneron; he reports consulting or advisory role: Gilead Sciences, Janssen, Roche, Pfizer, BeiGene, Celltrion, AbbVie, Incyte, Regeneron, MorphoSys, Novartis; he reports speaker's engagement: Roche, Janssen, BeiGene, Celltrion, AbbVie, Pfizer, Gilead Sciences; he reports research funding: Roche/Genentech, Janssen, Celltrion, Merck Sharp & Dohme (MSD), Pfizer, Amgen. MD reports honoraria as Advisory Board Member of AstraZeneca, Bayer, BeiGene, Celgene, Genmab, Gilead, Incyte, Janssen, Lilly, MorphoSys, Novartis, Roche; he reports honoraria for speaker's engagement from Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Novartis, Roche; he reports institutional research grants from AbbVie, Bayer, Gilead, Celgene, Janssen, Roche. AA-L has declared no conflicts of interest. JA reports personal financial interests as advisory board and invited speaker from Incyte, advisory board from Mallinckrodt, advisory board and invited speaker from Novartis, advisory board and invited speaker from Pfizer; she reports non-financial interests as principal investigator from Incyte, principal investigator from Novartis. LA received advisory honoraria from Roche, Celgene, Janssen-Cilag, Verastem, Eusa Pharma, Incyte, ADC Therapeutics and Gilead; research support from Gilead, and travel expenses from Roche, Celgene, Janssen-Cilag, and Eusa Pharma; speakers bureau from Novartis. CB has declared no conflicts of interest. LB reports Advisory Committee activities for AbbVie, Amgen, Astellas, Bristol Myers Squibb (BMS), Celgene, Daiichi Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Sanofi, Seattle Genetics and has research support from Bayer and Jazz Pharmaceuticals. PC has declared no conflicts of interest. MGDP has declared no conflicts of interest. MD reports personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, personal fees from BeiGene, personal fees from BMS, outside the submitted work. SD reports personal financial interests as advisory board, invited speaker, fellow funding, and coordinating PI from BeiGene, writing engagement from Karger, advisory board and coordinating PI from Sanofi, funding, and other from Janssen; she reports non-financial interests as advisory role at British Society for Haematology Lymphoma Special Interest Group, advisory role at Lymphoma Action, member of board of directors at WMUK Charity. HTE has declared no conflicts of interest. RF reports honoraria for advisory boards and/or speaker bureau from Janssen, Gilead, AbbVie, Amgen, Novartis, Roche, Incyte, Pfizer, all outside the submitted work. PG reports grants and personal fees from AbbVie, grants and personal fees from Acerta/AstraZeneca, personal fees from BeiGene, personal fees from Celgene/Juno/BMS, grants and personal fees from Janssen, personal fees from Lilly/Loxo, personal fees from MEI, personal fees from Roche, personal fees from Sanofi, personal fees from ArQule/MSD, outside the submitted work;, MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work. JG reports personal fees from AbbVie, grants and personal fees from AstraZeneca, grants and personal fees from BMS/Celgene, grants and personal fees from Janssen, personal fees from Kite/Gilead, personal fees from MorphoSys, personal fees from Novartis, personal fees from TG Therapeutics, outside the submitted work. RH has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda. CH reports grants and personal fees from Novartis, grants and personal fees from BMS, personal fees from Sierra Oncology, personal fees from CTI pharmaceuticals, personal fees from Jannsen, personal fees from Geron, grants and personal fees from AOP Orphan Pharma, personal fees from Galecto, grants, personal fees and other from Constellation, outside the submitted work. MH reports personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from AbbVie, personal fees from Daiichi Sankyo, personal fees from Bayer Pharma AG, personal fees from Jazz Pharmaceuticals, personal fees from BMS, personal fees from Tolremo, outside the submitted work. BK has received honoraria for lectures from Ipsen, Novartis and MSD (all outside of the submitted work). J-JK reports consulting fees and honoraria from Novartis, consulting fees from AbbVie, honoraria from AOP Orphan Pharma, participation on a monitoring board or advisory board from BMS/Celgene, participation on a monitoring board or advisory board from Incyte. NK reports grants and honoraria from Neovii, honoraria from Sanofi, grants and honoraria from Jazz, grants and honoraria from Celgene, grants and honoraria from Riemser, honoraria from Gilead/Kite, honorarium from AOP Oprhan Pharma, grants and honorarium from Novartis, honorarium from Amgen. PM reports personal fees from Celgene, Amgen, Janssen, AbbVie, Sanofi, outside the submitted work. JP has declared no conflicts of interest. FP has declared no conflicts of interest. DR received honoraria from Incyte, Novartis Pharma, Pfizer; clinical trial steering committee membership: Novartis; membership on advisory boards: Incyte, Novartis Pharma, Pfizer. J-MR reports grants and honoraria from Novartis, Amgen, Pfizer, Takeda, Incyte, and Servier. TR has declared no conflicts of interest. JF-M reports consulting and advisory boards honoraria (received by CUN) from AbbVie, Amgen, BMS, Celgene, Janssen, GlaxoSmithKline, Karyopharm, MSD, Novartis, Takeda, Sanofi, SecuraBio, Regeneron, Roche, outside the submitted work. VS has declared no conflicts of interest. GFS reports personal fees and other from AbbVie, other from Amgen, other from Astellas, other from Boehringer-Ingelheim, grants, personal fees and other from Celgene, other from Helsinn Healthcare, grants, personal fees, and other from Janssen-Cilag, grants and other from Novartis, other from Onconova, grants, personal fees and other from Roche, and other from Takeda, outside the submitted work. PS reports honoraria from Amgen, Celgene, Janssen, Karyopharm, SkylineDx, Takeda, and research support from Celgene, Janssen, Amgen, Takeda, BMS, SkylineDx, Karyopharm, all outside the submitted work. MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca; is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leukämie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG). CW has declared no conflicts of interest. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. FP reports grants from Novartis, Celgene, BMS, Abbvie, Karyopharma, Janssen. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. Background: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. Methods: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. Results and conclusion: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.
Published: 2022
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128. Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations

Author: Katharina Nimptsch, Krasimira Aleksandrova, Veronika Fedirko, Mazda Jenab, Marc J. Gunter, Peter D. Siersema, Kana Wu, Verena Katzke, Rudolf Kaaks, Salvatore Panico, Domenico Palli, Anne M May, Sabina Sieri, Bas Bueno-de-Mesquita, Karina Standahl, Maria-Jose Sánchez, Aurora Perez-Cornago, Anja Olsen, Anne Tjønneland, Catalina Bonet Bonet, Christina C. Dahm, María-Dolores Chirlaque, Valentina Fiano, Rosario Tumino, Aurelio Barricarte Gurrea, Marie-Christine Boutron-Ruault, Florence Menegaux, Gianluca Severi, Bethany van Guelpen, Young-Ae Lee, Tobias Pischon, HAL UVSQ, Équipe, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Harvard T.H. Chan School of Public Health, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, University of Bremen, The University of Texas M.D. Anderson Cancer Center [Houston], Emory University [Atlanta, GA], Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Radboud University Medical Center [Nijmegen], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, World Health Organization, WHO, Cancer Prevention and Research Institute of Texas, CPRIT: RR200056, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Consejería de Salud y Familias, Junta de Andalucía, NIHR Imperial Biomedical Research Centre, BRC, We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Jose-Ramon Quiros-Garcia and EPI-San Sebastian, PI Amiano Pilar. Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization., The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/M012190/1 to EPIC-Oxford) (United Kingdom). The EPIC-Norfolk study (DOI https://doi.org/10.22025/2019.10.105.00004 ) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research., The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., and We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Jose-Ramon Quiros-Garcia and EPI-San Sebastian, PI Amiano Pilar. Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056).
Subjects: Cancer Research, Cancer och onkologi, Public Health, Global Health, Social Medicine and Epidemiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Polymorphism, Single Nucleotide, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], C-Reactive Protein, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiovascular and Metabolic Diseases, Risk Factors, Cancer and Oncology, Genetics, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genetic Predisposition to Disease, Prospective Studies, Colorectal Neoplasms
Abstract: Background The role of elevated pre-diagnostic C-reactive protein (CRP) concentrations on mortality in individuals with colorectal cancer (CRC) remains unclear. Methods We investigated the association between pre-diagnostic high-sensitivity CRP concentrations and CRP genetic variation associated with circulating CRP and CRC-specific and all-cause mortality based on data from 1,235 individuals with CRC within the European Prospective Investigation into Cancer and Nutrition cohort using multivariable-adjusted Cox proportional hazards regression. Results During a median follow-up of 9.3 years, 455 CRC-specific deaths were recorded, out of 590 deaths from all causes. Pre-diagnostic CRP concentrations were not associated with CRC-specific (hazard ratio, HR highest versus lowest quintile 0.92, 95% confidence interval, CI 0.66, 1.28) or all-cause mortality (HR 0.91, 95% CI 0.68, 1.21). Genetic predisposition to higher CRP (weighted score based on alleles of four CRP SNPs associated with higher circulating CRP) was not significantly associated with CRC-specific mortality (HR per CRP-score unit 0.95, 95% CI 0.86, 1.05) or all-cause mortality (HR 0.98, 95% CI 0.90, 1.07). Among four investigated CRP genetic variants, only SNP rs1205 was significantly associated with CRC-specific (comparing the CT and CC genotypes with TT genotype, HR 0.54, 95% CI 0.35, 0.83 and HR 0.58, 95% CI 0.38, 0.88, respectively) and all-cause mortality (HR 0.58, 95% CI 0.40, 0.85 and 0.64, 95% CI 0.44, 0.92, respectively). Conclusions The results of this prospective cohort study do not support a role of pre-diagnostic CRP concentrations on mortality in individuals with CRC. The observed associations with rs1205 deserve further scientific attention.
Published: 2022
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129. Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition

Author: Marie Breeur, Pietro Ferrari, Laure Dossus, Mazda Jenab, Mattias Johansson, Sabina Rinaldi, Ruth C. Travis, Mathilde His, Tim J. Key, Julie A. Schmidt, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Joseph A. Rothwell, Nasser Laouali, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Fabian Eichelmann, Domenico Palli, Sara Grioni, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Bas Bueno-de-Mesquita, Karina Standahl Olsen, Torkjel Manning Sandanger, Therese Haugdahl Nøst, J. Ramón Quirós, Catalina Bonet, Miguel Rodríguez Barranco, María-Dolores Chirlaque, Eva Ardanaz, Malte Sandsveden, Jonas Manjer, Linda Vidman, Matilda Rentoft, David Muller, Kostas Tsilidis, Alicia K. Heath, Hector Keun, Jerzy Adamski, Pekka Keski-Rahkonen, Augustin Scalbert, Marc J. Gunter, Vivian Viallon, Cancer Research UK, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC: 2014/1183, C8221/A19170, Seventh Framework Programme, FP7: 2014/1193, 313010, C19335/A21351, National Research Council, NRC, World Cancer Research Fund International, WCRF, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, European Commission, EC, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Generalitat de Catalunya, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2009-139, 2013/1002, 2014-1-RT-02-CIRC-1, 2015-166, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Consejería de Salud y Familias, Junta de Andalucía, NIHR Imperial Biomedical Research Centre, BRC, The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., This paper is dedicated to the memory our of colleague Dr. Bas Bueno-de-Mesquita. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). IDIBELL acknowledges support from the Generalitat de Catalunya through the CERCA Program. The breast cancer study was funded by the French National Cancer Institute (grant number 2015-166). The colorectal cancer studies were funded by World Cancer Research Fund (reference: 2013/1002, reference: 313010, reference: 2014/1193, INCa, grant numbers 2009-139 and 2014-1-RT-02-CIRC-1) and by internal funds of the IARC. For the participants in the prostate cancer study, sample retrieval and preparation, and assays of metabolites were supported by Cancer Research UK (C8221/A19170), and funding for grant 2014/1183 was obtained from the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme. Mathilde His’ work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC. The funders were not involved in designing the study, collecting, analysing, and interpreting results, or writing and submitting the manuscript for publication., and HAL UVSQ, Équipe
Subjects: Male, Carcinoma, Hepatocellular, Proline, Glutamine, Kidney, Risk Factors, General & Internal Medicine, Humans, Metabolomics, Histidine, Prospective Studies, Breast, Càncer, 11 Medical and Health Sciences, Colorectal, Cancer, Cancer och onkologi, Liver Neoplasms, Prostate, Lysophosphatidylcholines, General Medicine, Sphingomyelins, Metabolòmica, Liver, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Cancer and Oncology, Carcinoma, Hepatocellular/diagnosis, Phosphatidylcholines, Epic, Endometrial, Lasso, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, EPIC
Abstract: Background Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. Results Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. Conclusions These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
Published: 2022
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130. Urbanisation modulates the attractiveness of plant communities to pollinators by filtering for floral traits

Author: Valentin Cabon, Alice Kracht, Birgit Seitz, Ingo Kowarik, Moritz von der Lippe, Sascha Buchholz, Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Technical University of Berlin / Technische Universität Berlin (TU), Berlin-Brandenburg Institute of Advanced Biodiversity Research (BBIB), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), and German Federal Ministry of Education and Research BMBF Federal Ministry of Education and Research (BMBF) [01LC1501A-H]
Subjects: urban ecology, plant assemblage, flower traits, pollinator attraction, urbanisation gradient, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, pollinator-mediated selection, Ecology, Evolution, Behavior and Systematics
Abstract: International audience; Urbanisation is known to change biodiversity patterns and plant-animal interactions such as pollination - a key ecological process. Floral traits like colour, size or UV-patterns are essential attractors for many pollinators. It is largely unknown, though, how the distribution of such floral traits within plant communities changes along an urbanisation gradient. This study aims to understand to which extent floral traits known to attract pollinators are filtered by urban environments. We used dry grassland, spanning a broad urbanisation gradient in the Berlin metropolitan area, Germany, as a model ecosystem and identified the distribution of plant traits related to bee-perceived flower colours, UV reflection and flower size in 47 grassland patches. We analysed how these traits were related to abiotic and biotic factors at different spatial scales. The most influent predictor was an abiotic factor measured at the landscape scale: the proportion of impervious surface, found to be positively related to UV-reflectance strength and floral UV patterns, but negatively to floral size diversity. At the local scale, abiotic factors showed an intermediary number of relationships. Temperature was negatively associated with the bee-colour 'green + UV-green' and with flower size. The light environment was negatively related to the same bee-colour and to floral size diversity. Biotic factors related to local pollinator communities were less important: species richness was negatively related to flower size, while proportion of bees to floral sizes diversity. This study shows that floral traits known to attract pollinators are mostly filtered by abiotic factors related to urbanisation (share of impervious surface) or the urban heat island (local temperature). Biotic factors related to local pollinator communities were less important. These results increase our functional understanding of plant-animal interactions in cities by illustrating how urban environments modulate the attractiveness of plant communities to pollinators by filtering for floral plant traits.
Published: 2022
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131. The chaos in calibrating crop models:Lessons learned from a multi-model calibration exercise

Author: Eckart Priesack, Johannes Wilhelmus Maria Pullens, Heidi Horan, Anne Klosterhalfen, Elisabet Lewan, Marco Moriondo, Emmanuelle Gourdain, Roberto Ferrise, Tobias K. D. Weber, Camilla Dibari, Neil M.J. Crout, Daniel Wallach, Amir Souissi, Jing Wang, Eric Justes, Kurt Christian Kersebaum, Benjamin Dumont, Mohamed Jabloun, Niels Schütze, Qi Jing, G. Padovan, Bernardo Maestrini, Steven Hoek, Mingxia Huang, Sebastian Gayler, Giacomo Trombi, Gerrit Hoogenboom, Qunying Luo, Jørgen E. Olesen, Chuang Zhao, Evelyn Wallor, Per-Erik Jansson, Tommaso Stella, Peter J. Thorburn, Santosh Hiremath, Arne Poyda, Thomas Wöhling, Amit Kumar Srivastava, Thomas Gaiser, Sabine J. Seidel, Budong Qian, Vakhtang Shelia, Henrike Mielenz, Afshin Ghahramani, Allard de Wit, Senthold Asseng, Fety Andrianasolo, Bruno Basso, Liujun Xiao, Zvi Hochman, Taru Palosuo, Yan Zhu, Marie Launay, Cécile Garcia, Xenia Specka, Thilo Streck, Lutz Weihermüller, Hasti Nariman Zadeh, Samuel Buis, AGroécologie, Innovations, teRritoires (AGIR), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Natural Resources Institute Finland (LUKE), CSIRO Agriculture and Food (CSIRO), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), ARVALIS - Institut du végétal [Paris], ARVALIS - Institut du Végétal [Boigneville], University of Florida [Gainesville] (UF), Michigan State University [East Lansing], Michigan State University System, Environnement Méditerranéen et Modélisation des Agro-Hydrosystèmes (EMMAH), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Nottingham, UK (UON), Department of Agriculture, Food, Environment and Forestry (DAGRI), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Gembloux Agro-Bio Tech [Gembloux], Université de Liège, Institute of Crop Science and Resource Conservation [Bonn] (INRES), Rheinische Friedrich-Wilhelms-Universität Bonn, University of Hohenheim, University of Southern Queensland (USQ), Aalto University School of Science and Technology [Aalto, Finland], Wageningen University and Research [Wageningen] (WUR), China Agricultural University (CAU), Royal Institute of Technology [Stockholm] (KTH ), Agriculture and Agri-Food Canada, Saskatoon Research Centre, Agriculture and Agri-Food [Ottawa] (AAFC), Département Performances des systèmes de production et de transformation tropicaux (Cirad-PERSYST), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Leibniz-Zentrum für Agrarlandschaftsforschung = Leibniz Centre for Agricultural Landscape Research (ZALF), Global Change Research Institute (CAS), Institute of Bio- and Geosciences [Jülich] (IBG), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Agroclim (AGROCLIM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Swedish University of Agricultural Sciences (SLU), Hillridge Technology Pty Ltd, Julius Kühn-Institut - Federal Research Centre for Cultivated Plants (JKI), Institute of Bioeconomy (IBE), Consiglio Nazionale delle Ricerche (CNR), Aarhus University [Aarhus], Kiel University, Helmholtz-Zentrum München (HZM), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Université de Carthage - University of Carthage, Helmholtz-Gemeinschaft = Helmholtz Association, Lincoln Agritech Ltd, Nanjing Agricultural University, Collaborative Research Center 1253 CAMPOS (Project 7: Stochastic Modelling Framework), funded by the German Research Foundation (DFG, Grant Agreement SFB 1253/1 2017), Academy of Finland through projects AICropPro (316172) and DivCSA (316215), National Science Foundation for Distinguished Young Scholars (31725020), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), China Scholarship Council, Agriculture and Agri-Food Canada's Project 1387 under the Canadian Agricultural Partnership, DFG Research Unit FOR 1695 ‘Agricultural Landscapes under Global Climate Change – Processes and Feedbacks on a Regional Scale, U.S. Department of Agriculture National Institute of Food and Agriculture (award no. 2015-68007-23133) and USDA/NIFA HATCH grant N. MCL02368, National Key Research and Development Program of China (2016YFD0300105), Broadacre Agriculture Initiative, a research partnership between University of Southern Queensland and the Queensland Department of Agriculture and Fisheries, Academy of Finland through project AI-CropPro (315896), JPI FACCE MACSUR2 project, funded by the Italian Ministry for Agricultural, Food, and Forestry Policies (D.M. 24064/7303/15 of 6/Nov/2015), Natural Resources Institute Finland (Luke) through a strategic project BoostIA, BonaRes project 'Soil3' (BOMA 03037514) of the Federal Ministry of Education and Research (BMBF), Germany, Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2070 – 390732324 EXC (PhenoRob), Project BiomassWeb of the GlobeE programme (Grant number: FKZ031A258B) funded by the Federal Ministry of Education and Research (BMBF, Germany), INRA ACCAF meta-programme, German Federal Ministry of Education and Research (BMBF) in the framework of the funding measure 'Soil as a Sustainable Resource for the Bioeconomy – BonaRes', project 'BonaRes (Module B): BonaRes Centre for Soil Research, subproject B' (grant 031B0511B), and National Key Research and Development Program of China (2017YFD0300205)
Subjects: Earth Observation and Environmental Informatics, Environmental Engineering, 010504 meteorology & atmospheric sciences, Computer science, Process (engineering), Process-based models, Model parameters, Machine learning, computer.software_genre, 01 natural sciences, paramètre, Software, F01 - Culture des plantes, Component (UML), Aardobservatie en omgevingsinformatica, Calibration, Parameter estimation, Applied Ecology, 0105 earth and related environmental sciences, U10 - Informatique, mathématiques et statistiques, Modélisation des cultures, business.industry, Estimation theory, Ecological Modeling, Toegepaste Ecologie, Calibration recommendations, Experimental data, 04 agricultural and veterinary sciences, PE&RC, [STAT]Statistics [stat], CHAOS (operating system), Phenology, Calibration Recommendations, Process-based Models, Parameter Estimation, [SDE]Environmental Sciences, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Artificial intelligence, ddc:004, Phénologie, Modèle végétal, business, computer
Abstract: International audience; Calibration, the estimation of model parameters based on fitting the model to experimental data, is among the first steps in many applications of process-based models and has an important impact on simulated values. We propose a novel method of developing guidelines for calibration of process-based models, based on development of recommendations for calibration of the phenology component of crop models. The approach was based on a multi-model study, where all teams were provided with the same data and asked to return simulations for the same conditions. All teams were asked to document in detail their calibration approach, including choices with respect to criteria for best parameters, choice of parameters to estimate and software. Based on an analysis of the advantages and disadvantages of the various choices, we propose calibration recommendations that cover a comprehensive list of decisions and that are based on actual practices.
Published: 2021
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132. Pre-diagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma

Author: Heinz Freisling, Susana Merino, Aurelio Barricarte, Augustin Scalbert, Domenico Palli, Eleni Peppa, Hanna Nyström, Klas Sjöberg, Magdalena Stepien, Antonia Trichopoulou, Aurora Perez-Cornago, Marina Lopez-Nogueroles, Gianluca Severi, Carlotta Sacerdote, Dragos Ciocan, Tilman Kühn, Elisabete Weiderpass, Cosmin Sebastian Voican, Manuela M. Bergmann, Gabriel Perlemuter, Eugene Jansen, Rudolf Kaaks, Michael F. Leitzmann, Julie A. Schmidt, Catherine Dong, Anna Karakatsani, María José Sánchez, Rosario Tumino, Bodil Ohlsson, H. Bas Bueno-de-Mesquita, Marc J. Gunter, Raul Zamora Ros, Guri Skeie, José Mª Huerta, Heiner Boeing, Agustín Lahoz, Vittorio Krogh, Pilar Amiano, Francesca Mancini, Anne Tjønneland, Marie-Christine Boutron-Ruault, Salvatore Panico, Mazda Jenab, Sofia Christakoudi, Vivian Viallon, Renée T. Fortner, Mårten Werner, Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: 1000143, MR/M012190/1, Cancer Research UK, CRUK: 14136, C8221/A29017, World Cancer Research Fund, WCRF, University of Cambridge, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2009‐139, 2014‐1‐RT‐02‐CIRC‐1, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, This work was supported in part by the French National Cancer Institute (L'Institut National du Cancer, INCa, grant numbers 2009‐139 and 2014‐1‐RT‐02‐CIRC‐1, PI: M. Jenab) and by internal funds of the IARC. The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam‐Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C8221/A29017 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford) (United Kingdom). The funding sources had no influence on the design of the study, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication. Funding information, and We would like to acknowledge Dr Krasimira Aleksandrova for input on the present manuscript, along with the National Institute for Public Health and the Environment (Bilthoven, The Netherlands), the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands, Department of Public Health Aarhus University (Aarhus, Denmark), University of Cambridge (Cambridge, United Kingdom), for their contributions and ongoing support to the EPIC Study.
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, obesity, Carcinoma, Hepatocellular, medicine.drug_class, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Bile Acids and Salts, Cohort Studies, chemistry.chemical_compound, Internal medicine, medicine, Biomarkers, Tumor, Choline, Humans, Prospective cohort study, Carcinogen, Aged, Cancer prevention, Bile acid, cancer prevention, business.industry, Confounding, Liver Neoplasms, bile acid metabolism, biomarkers, hepatocellular carcinoma, Middle Aged, medicine.disease, Obesity, Oncology, chemistry, Hepatocellular carcinoma, Case-Control Studies, Female, business
Abstract: This is the peer reviewed version of the following article: Stepien et.al (2021). Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.33885. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.
Published: 2021
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133. Topology identifies emerging adaptive mutations in SARS-CoV-2

Author: Bleher, Michael, Hahn, Lukas, Patiño-Galindo, Juanángel, Carriere, Mathieu, Bauer, Ulrich, Rabadán, Raúl, Ott, Andreas, Heidelberg University, Department of biology [Columbia University], Columbia University [New York], Understanding the Shape of Data (DATASHAPE), 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)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria), Technical University of Munich (TUM), Karlsruhe Institute of Technology (KIT), The authors acknowledge scientists and laboratories for sharing SARS-CoV-2 genome sequencing datawith the research community via the GISAID database. A list of all contributions used in this workdetailing authors from the originating laboratories responsible for obtaining the specimens and the submitting laboratories where genetic sequence data were generated is available in Table S1. This work was supported by the BMBF-funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI) (031A532B, 031A533A, 031A533B, 031A534A, 031A535A, 031A537A,031A537B, 031A537C, 031A537D, 031A538A). The authors acknowledge the use of de.NBI cloud and the support by the High Performance and Cloud Computing Group at the Zentrum für Datenverar-beitung of the University of Tübingen and the Federal Ministry of Education and Research (BMBF)through grant no 031 A535A. They thank M. Hanussek for IT support and early access to VALET. The authors further acknowledge support from the Interdisciplinary Center for Scientific Computing at Heidelberg University and the development work of the Scientific Software Center of Heidelberg University carried out by D. Kempf and L. Keegan. This research was supported by the DFG Collaborative Research Center SFB/TRR 109 'Discretization in Geometry and Dynamics'. M.B.was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy EXC 2181/1 - 390900948 (the Heidelberg STRUCTURES ExcellenceCluster). L.H. thanks the Evangelisches Studienwerk Villigst for their support. A.O. acknowledgesfunding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 281869850(RTG 2229)., and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)
Subjects: [MATH.MATH-AT]Mathematics [math]/Algebraic Topology [math.AT], [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [INFO.INFO-CG]Computer Science [cs]/Computational Geometry [cs.CG]
Abstract: The COVID-19 pandemic has lead to a worldwide effort to characterize its evolution through the mapping of mutations in the genome of the coronavirus SARS-CoV-2. As the virus spreads and evolves it acquires new mutations that could have important public health consequences, including higher transmissibility, morbidity, mortality, and immune evasion, among others. Ideally, we would like to quickly identify new mutations that could confer adaptive advantages to the evolving virus by leveraging the large number of SARS-CoV-2 genomes. One way of identifying adaptive mutations is by looking at convergent mutations, mutations in the same genomic position that occur independently. The large number of currently available genomes, more than a million at this moment, however precludes the efficient use of phylogeny-based techniques. Here, we establish a fast and scalable Topological Data Analysis approach for the early warning and surveillance of emerging adaptive mutations of the coronavirus SARS-CoV-2 in the ongoing COVID-19 pandemic. Our method relies on a novel topological tool for the analysis of viral genome datasets based on persistent homology. It systematically identifies convergent events in viral evolution merely by their topological footprint and thus overcomes limitations of current phylogenetic inference techniques. This allows for an unbiased and rapid analysis of large viral datasets. We introduce a new topological measure for convergent evolution and apply it to the complete GISAID dataset as of February 2021, comprising 303,651 high-quality SARS-CoV-2 isolates taken from patients all over the world since the beginning of the pandemic. A complete list of mutations showing topological signals of convergence is compiled. We find that topologically salient mutations on the receptor-binding domain appear in several variants of concern and are linked with an increase in infectivity and immune escape. Moreover, for many adaptive mutations the topological signal precedes an increase in prevalence. We demonstrate the capability of our method to effectively identify emerging adaptive mutations at an early stage. By localizing topological signals in the dataset, we are able to extract geo-temporal information about the early occurrence of emerging adaptive mutations. The identification of these mutations can help to develop an alert system to monitor mutations of concern and guide experimentalists to focus the study of specific circulating variants.
Published: 2021

134. Podocytes maintain high basal levels of autophagy independent of mtor signaling

Author: Bjoern Hartleben, Wei Liang, Shuya Liu, Kosuke Yamahara, Ketan Patel, Kathrin Thedieck, Tillmann Bork, Olivia Lenoir, Philipp Lee, Christoph Schell, Tobias B. Huber, Zhejia Tian, Pierre-Louise Tharaux, Department of Medicine IV [Freiburg, Germany] (Faculty of Medicine), University of Freiburg [Freiburg], Division of Nephrology [Wuhan, China], Wuhan University [China]-Renmin Hospital [Wuhan, China], Department of Medicine [Otsu, Japan], Shiga University of Medical Science, Department of Medicine [Hamburg, Germany], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Molecular Biosciences Innsbruck [Innsbruck, Austria] (Institute of Biochemistry), University of Innsbruck, University Medical Center Groningen [Groningen] (UMCG), University of Oldenburg, Hannover Medical School [Hannover] (MHH), Freiburg Institute for Advanced Studies [Freiburg, Germany], Albert-Ludwigs-Universität Freiburg, School of Biological Sciences [Reading], University of Reading (UOR), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie [Hôpital Européen Georges Pompidou - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), This work was supported by the German Research Foundation [CRC1140, CRC1192], European Foundation for the Study of Diabetes (EFSD), German Research Foundation Heisenberg Program [HU1016/ 5-1], German Research Foundation Heisenberg Program [HU1016/8-2], EC | European Research Council (ERC), H2020-IMI2 BEAt-DKD [115974], BMBF-STOP-FSGS [01GM1518C], Excellence Initiative of the German Federal and State Governments BIOSS, FRIAS Freiburg Institute of Advanced Studies, Alexander von Humboldt Foundation, German Research Foundation [CRC992], National Natural Science Foundation of China (NSFC) [81470912], Berta Ottenstein Program, Else Kroener Fresenius Foundation NAKSYS, BMBF GlioPATH [01ZX1402B], BMBF MAPTor-NET [031A426B], German Research Foundation [TH 1358/3-1], MESI-STRAT [754688], Uehara Memorial Foundation, German TS Foundation, Stichting TSC Fonds (calls 2015 and 2017), PoLiMeR Innovative Training Network (Marie SklodowskaCurie grant agreement No. 812616, Rosalind-Franklin Fellowship of the Universitiy of Groningen., Tharaux, Pierre-Louis, Leopold Franzens Universität Innsbruck - University of Innsbruck, and Center for Liver, Digestive and Metabolic Diseases (CLDM)
Subjects: AMPK, 0301 basic medicine, podocyte, Research Paper - Basic Science, PROTEIN, glomerulus, Podocyte, ACTIVATION, LC3, PHOSPHORYLATION, ULK1, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, CELL-LINE, biology, Podocytes, TOR Serine-Threonine Kinases, MTOR, Raptor, Cell biology, medicine.anatomical_structure, signaling, Signal Transduction, Research Article, autophagy, kidney, Mice, Transgenic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mechanistic Target of Rapamycin Complex 1, DIABETIC-NEPHROPATHY, Nephrin, 03 medical and health sciences, medicine, Animals, Humans, Protein kinase A, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Mechanistic target of rapamycin, PI3K/AKT/mTOR pathway, Sirolimus, 030102 biochemistry & molecular biology, rapamycin, RPTOR, Autophagy, KIDNEY-DISEASE, Cell Biology, Tsc1, 030104 developmental biology, MAMMALIAN TARGET, biology.protein, Podocin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; While constant basal levels of macroautophagy/autophagy are a prerequisite to preserve long-lived podocytes at the filtration barrier, MTOR regulates at the same time podocyte size and compensatory hypertrophy. Since MTOR is known to generally suppress autophagy, the apparently independent regulation of these two key pathways of glomerular maintenance remained puzzling. We now report that long-term genetic manipulation of MTOR activity does in fact not influence high basal levels of autophagy in podocytes either in vitro or in vivo. Instead we present data showing that autophagy in podocytes is mainly controlled by AMP-activated protein kinase (AMPK) and ULK1 (unc-51 like kinase 1). Pharmacological inhibition of MTOR further shows that the uncoupling of MTOR activity and autophagy is time dependent. Together, our data reveal a novel and unexpected cell-specific mechanism, which permits concurrent MTOR activity as well as high basal autophagy rates in podocytes. Thus, these data indicate manipulation of the AMPK-ULK1 axis rather than inhibition of MTOR as a promising therapeutic intervention to enhance autophagy and preserve podocyte homeostasis in glomerular diseases.Abbreviations: AICAR: 5-aminoimidazole-4-carboxamide ribonucleotide; AMPK: AMP-activated protein kinase; ATG: autophagy related; BW: body weight; Cq: chloroquine; ER: endoplasmic reticulum; ESRD: end stage renal disease; FACS: fluorescence activated cell sorting; GFP: green fluorescent protein; i.p.: intra peritoneal; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NPHS1: nephrosis 1, nephrin; NPHS2: nephrosis 2, podocin; PLA: proximity-ligation assay; PRKAA: 5'-AMP-activated protein kinase catalytic subunit alpha; RPTOR/RAPTOR: regulatory associated protein of MTOR, complex 1; RFP: red fluorescent protein; TSC1: tuberous sclerosis 1; ULK1: unc-51 like kinase 1.
Published: 2019
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135. Autoimmunity plays a role in the onset of diabetes after 40 years of age

Author: Vittorio Krogh, Rudolf Kaaks, Yvonne T. van der Schouw, Gianluca Severi, Eva Ardanaz, Marc J. Gunter, Tilman Kühn, Nicholas J. Wareham, Timothy J. Key, Francesca Mancini, Carlotta Sacerdote, María José Sánchez, Heiner Boeing, Annemieke M.W. Spijkerman, Peter M. Nilsson, Guy Fagherazzi, Miren Dorronsoro, María Dolores Chirlaque, Kay-Tee Khaw, Olov Rolandsson, Stephen J. Sharp, Salvatore Panico, Domenico Palli, Nita G. Forouhi, Christiane S. Hampe, Claudia Langenberg, Kim Overvad, Rosario Tumino, Elio Riboli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), LSHM_CT_2006_037197 N∫ 6236 National Institutes of Health, NIH: DK26190 Compagnia di San Paolo Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Medical Research Council, MRC: MC_UU_12015/1, MC_UU_12015/5, MR/N003284/1 Cancer Research UK, CRUK World Cancer Research Fund, WCRF Bundesministerium für Bildung und Forschung, BMBF Västerbotten Läns Landsting Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agentschap NL: IGE05012 Vetenskapsrådet, VR Umeå Universitet Bundesministerium für Forschung und Technologie, BMFT Deutsche Krebshilfe Bundesministerium fÃ¼r Bildung und Frauen, BMBF Stichting Diabetes Onderzoek Nederland NIHR Imperial Biomedical Research Centre, BRC NIHR Cambridge Biomedical Research Centre: IS-BRC-1215-20014, O. Rolandsson: The Västerboten County Council, M. Dorronsoro: We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as to the team of trained nurses who participated in the recruitment, R. Kaaks: German Cancer Aid, German Ministry of Research (BMBF), K. T. Khaw: Medical Research Council UK, Cancer Research UK, T. Kühn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), S. Panico: Compagnia di San Paolo, A. M. W. Spijkerman: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Statistics Netherlands (the Netherlands), EPIC Ragusa acknowledges for their participation blood donors of AVIS-Ragusa (local blood donors association), Y. T. van der Schouw: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Dutch ZON (Zorg Onderzoek Nederland), WCRF, Statistics Netherland, E. Riboli: Imperial College Biomedical Research Centre., Open access funding provided by Umea University. Funding for the InterAct project was provided by the EU FP6 Programme (grant number LSHM_CT_2006_037197). The autoantibody measurement was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH) and the Medical Research Council (MC_UU_12015/1) (NJW). OR: the Västerbotten County Council, Umeå University, MDC: Health Research Fund (FIS) of the Spanish Ministry of Health, Murcia Regional Government (N∫ 6236), EA: the Health Research Fund (FIS) of the Spanish Ministry of Health and Navarre Regional Government, RK: German Cancer Aid, the German Ministry of Research (BMBF), TJK: Cancer Research UK, KTK: the Medical Research Council UK, Cancer Research UK, PMN: the Swedish Research Council, KO: the Danish Cancer Society, SP: Compagnia di San Paolo, AMWS: the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, AMWS: LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), YTvdS: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, LK Research Funds, Dutch Prevention Funds, NGF: MRC core support (MC_UU_12015/5), NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Acknowledgements, We thank all EPIC participants and staff for their contribution to this study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data and the laboratory team at the MRC Epidemiology Unit, Cambridge for managing the blood samples for the EPIC-InterAct project. We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as the team of trained nurses who participated in the recruitment. O. Rolandsson: The V?sterboten County Council, T. K?hn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), E. Riboli: Imperial College Biomedical Research Centre. Some of the data were presented as an abstract at the 54th EASD Annual Meeting in 2018., Rolandsson, Olov [0000-0002-1341-6828], and Apollo - University of Cambridge Repository
Subjects: Male, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Autoimmunity, Type 2 diabetes, medicine.disease_cause, LADA, Endocrinology, Autoantibody, 0302 clinical medicine, POPULATION, RISK, 0303 health sciences, Glutamate Decarboxylase, ANTIBODY POSITIVITY, GAD, Middle Aged, Phenotype, Genetic risk score, Pathophysiology, 3. Good health, Diabetes and Metabolism, Type 1 diabetes, Endokrinologi och diabetes, Female, Life Sciences & Biomedicine, Adult, 030209 endocrinology & metabolism, Endocrinology and Diabetes, Antibodies, Article, 1117 Public Health and Health Services, Endocrinology & Metabolism, 03 medical and health sciences, GLUTAMIC-ACID DECARBOXYLASE, Insulin resistance, Diabetes mellitus, Internal Medicine, medicine, Humans, TYPE-1, Aged, 030304 developmental biology, Science & Technology, business.industry, RECOGNITION, 1103 Clinical Sciences, ADULTS, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Incident diabetes, Case-Control Studies, Immunology, 1114 Paediatrics and Reproductive Medicine, AUTOANTIBODIES, indident diabetes, business
Abstract: Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
Published: 2019
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136. Consumption of ultra-processed foods associated with weight gain and obesity in adults: A multi-national cohort study

Author: Salvatore Panico, Vivian Viallon, José María Huerta, Heinz Freisling, Miguel Rodríguez-Barranco, Christopher Millett, Marc J. Gunter, Paolo Vineis, Christina C. Dahm, Giovanna Masala, Nasser Laouali, Elisabete Weiderpass, Verena Katzke, Charlotta Rylander, Lousie Brunkwall, Yvonne T. van der Schouw, Franziska Jannasch, Aurelio Barricarte, Fernanda Rauber, Carlos Augusto Monteiro, Jie Zhang, Jeroen W.G. Derksen, Paula Jakszyn, Geneviève Nicolas, Reynalda Cordova, Karl-Heinz Wagner, Renata Bertazzi Levy, Corinne Casagrande, Marie-Christine Boutron-Ruault, Francesca Mancini, Stina Ramne, Stina Bodén, Eszter P. Vamos, Guri Skeie, Anne Tjønneland, Jytte Halkjær, Aurora Perez-Cornago, Bernard Srour, Inge Huybrechts, Nathalie Kliemann, Sara Grioni, Matthias B. Schulze, Alicia K Heath, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Deutsches Krebsforschungszentrum, DKFZ, National Research Council, NRC, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C570/A16491, C8221/A19170, World Cancer Research Fund, WCRF, Institut National de la Santé et de la Recherche Médicale, Inserm, Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP: 2016/14302-7, Österreichischen Akademie der Wissenschaften, ÖAW, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Fondation de France: 00081166, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, School for Public Health Research, NIHR SPHR, The Public Health Policy Evaluation Unit is grateful for support from the NIHR School for Public Health Research . Swedish Cancer Society , Swedish Research Council and County Council of Västerbotten , Sweden., This work was partially financially supported by the Fondation de France (FDF, grant no. 00081166 , HF, RC)., Fernanda Rauber is a beneficiary of a postdoctoral fellowship from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) , grant numbers 2016/14302-7 ., The national cohorts are supported by the following funders: Ligue Contre le Cancer , Institut Gustave-Roussy , Mutuelle Générale de l'Education Nationale , Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid , German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health,Welfare and Sports (VWS) , Netherlands Cancer Registry (NKR) , LK Research Funds , Dutch Prevention Funds , Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS-ISCIII) , the Regional Governments of Andalucía , Asturias , Basque Country, Murcia , Navarra , and the Catalan Institute of Oncology (Barceloan), Spain), Cancer Research UK ( 14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK)., Reynalda Cordova is a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Nutritional Sciences, University of Vienna.This work was partially financially supported by the Fondation de France (FDF, grant no. 00081166, HF, RC).Fernanda Rauber is a beneficiary of a postdoctoral fellowship from the Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP), grant numbers 2016/14302-7.The national cohorts are supported by the following funders: Ligue Contre le Cancer, Institut Gustave-Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany), Dutch Ministry of Public Health,Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland),World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS-ISCIII), the Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barceloan), Spain), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).The Public Health Policy Evaluation Unit is grateful for support from the NIHR School for Public Health Research. Swedish Cancer Society, Swedish Research Council and County Council of V?sterbotten, Sweden.
Subjects: Male, NOVA, Food Handling, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], Overweight, Critical Care and Intensive Care Medicine, DISEASE, Body Mass Index, 0302 clinical medicine, Risk Factors, Weight management, Prevalence, PARTICIPANTS, Poisson Distribution, Prospective Studies, 030212 general & internal medicine, 2. Zero hunger, RISK, 0303 health sciences, Nutrition and Dietetics, Middle Aged, CANCER, AGES, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Multilevel Analysis, Female, medicine.symptom, Cohort study, Adult, DIET, 03 medical and health sciences, Ultra-processed foods, medicine, Humans, Adults, Obesity, VALIDITY, Weight gain, Aged, Nutrition & Dietetics, business.industry, medicine.disease, Diet, PRODUCTS, Relative risk, Linear Models, Fast Foods, 1111 Nutrition and Dietetics, business, Body mass index, Demography
Abstract: Background: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity. Methods: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI). Results: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0.12 kg/5 years, 95% CI 0.09 to 0.15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1.11, 1.19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1.09, 1.23) of becoming obese in participants who were overweight at baseline. Conclusions: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management. (c) 2021 Published by Elsevier Ltd.
Published: 2021
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137. Monocyte transcriptomes from patients with axial spondyloarthritis reveal dysregulated monocytopoiesis and a distinct inflammatory imprint

Author: Karow, Fabian, Smiljanovic, Biljana, Grün, J. R., Poddubnyy, Denis, Proft, Fabian, Talpin, Alice, Hue, Christophe, Boland, Anne, Deleuze, Jean François, Garchon, Henri Jean, Ergenç, Ilkay, De Craemer, Ann Sophie, Erben, Ulrike, Häupl, Thomas, Elewaut, Dirk, Breban, Maxime, Grützkau, Andreas, Syrbe, Uta, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bundesministerium für Bildung und Forschung, BMBF: 01EC1009A, Charité – Universitätsmedizin Berlin, Foundation for Research in Rheumatology, FOREUM, Funding: This work was supported by the FOREUM — Foundation for Research in Rheumatology. B.S. was supported by the German Federal Ministry of Education and Research (BMBF) with the network project ArthroMark (01EC1009A). Open Access funding enabled and organized by Projekt DEAL., Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Ambroise Paré [AP-HP], Universiteit Gent = Ghent University (UGENT), Deutsches Rheuma-ForschungsZentrum (DRFZ), and Deutsches Rheuma-ForschungsZentrum
Subjects: Gut translocation, SUBSETS, Gene Expression Profiling, Biology and Life Sciences, ANKYLOSING-SPONDYLITIS, Diseases of the musculoskeletal system, DISEASE-ACTIVITY, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Monocytes, Transcriptomes, LIPOPOLYSACCHARIDE-BINDING PROTEIN, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, RC925-935, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], CELLS, Spondyloarthritis, Spondylarthritis, Medicine and Health Sciences, CRITERIA, Cytokines, Humans, Transcriptome, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, GENE-EXPRESSION
Abstract: International audience; Background: In patients with axial spondyloarthritis (axSpA), monocytes show a pre-activated phenotype. Gut inflammation is a trigger of monocyte activation and may also affect their development in the bone marrow (BM). As gut inflammation is commonly observed in axSpA patients, we performed a detailed analysis of monocyte transcriptomes of axSpA patients in two cohorts and searched for signs of activation and developmental adaptations as putative imprints of gut inflammation. Methods: Transcriptomes of blood CD14+ monocytes of HLA-B27+ axSpA patients and healthy controls (HC) were generated by microarrays from cohort 1 and by RNA-sequencing from cohort 2. Differentially expressed genes from both analyses were subjected to gene set enrichment analysis (GSEA) and to co-expression analysis in reference transcriptomes from BM cells, blood cells and activated monocytes. As serological markers of translocation, 1,3 beta-glycan, intestinal fatty acid binding protein, and lipopolysaccharide binding protein (LBP) were determined by LAL and ELISA. Results: Transcriptome analysis identified axSpA-specific monocyte signatures showing an imprint of LPS/cytokine-activated monocytes, late granulopoietic BM cells, blood neutrophils, and G-CSF-mobilized blood cells, which suggests LPS/TNF activation and more prominent BM adaptation promoting a neutrophil-like phenotype. GSEA mapped axSpA upregulated genes to inflammatory responses and TNFα signaling and downregulated probe-sets to metabolic pathways. Among translocation markers, LBP levels were significantly increased in axSpA patients vs. HC (p < 0.001). Stratified analysis by disease activity and stage identified an “active disease signature” (BASDAI ≥ 4) with an imprint of LPS/cytokine-activated monocytes and CD16+ monocyte subsets. The “AS signature” (vs. non-radiographic axSpA) showed a reinforced neutrophil-like phenotype due to deprivation of dendritic cell transcripts. Conclusions: The neutrophil-like phenotype of axSpA monocytes points towards a biased monocytopoiesis from granulocyte-monocyte progenitors. This shift in monocytopoiesis and the LPS/cytokine imprint as well as the elevated LBP levels are indicators of systemic inflammation, which may result from bacterial translocation. The BM adaptation is most prominent in AS patients while disease activity appears to be linked to activation and trafficking of monocytes.
Published: 2021
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138. Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling

Author: Christian Trautwein, Maiju Myllys, Antje Mohs, Lena Susanna Candels, Till Strowig, Maximilian Hatting, Lijun Liao, Carolin V. Schneider, Tom H. Karlsen, A. Sloan Devlin, Sebastian Zühlke, Hanns-Ulrich Marschall, Konrad Kilic, Eric J. C. Gálvez, A Zaza, Annika Wahlström, Reham Hassan, Ahmed Ghallab, Johannes R. Hov, Jan G. Hengstler, Antonio Molinaro, Kai Markus Schneider, Marcus Henricsson, Dirk Drasdo, M. Frissen, C Elfers, Department of Medicine III, University hospital (UKA), University of Aachen (RWTH), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH)-University hospital (UKA), Oslo University Hospital [Oslo], Leibniz Research Centre for Working Environment and Human Factors [Dortmund] (IFADO), Technische Universität Dortmund [Dortmund] (TU), Sahlgrenska Academy at University of Gothenburg [Göteborg], SImulations en Médecine, BIOtechnologie et ToXicologie de systèmes multicellulaires (SIMBIOTX ), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Department of Biological Chemistry and Molecular Pharmacology [Harvard Medical School], Harvard Medical School [Boston] (HMS), Helmholtz Centre for Infection Research, Braunschweig, Germany, Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Helmholtz Centre for Infection Research (HZI), and This study was supported by the German Research Foundation (DFG) (grants CRC1382, TR285/10-2, GRK 2375 to C.T.), the Federal Ministry of Education and Research (ObiHep grant no. 01KU1214A to C.T.), the Liver-LiSyM grant (BMBF) to C.T. (031L0041), A.G. (FKZ 031L0052) and J.G.H. (031L0045), the HDHL-INTIMIC Di-Mi-Liv to C.T., K.M.S. and H.U.M., the BMBF Knowledge Platform on Food, Diet, Intestinal Microbiomics and Human Health to C.T. and K.M.S., the SFB 985 project C3 to C.T., the Interdisciplinary Centre for Clinical Research (START grant no. 691438) within the Faculty of Medicine at RWTH Aachen University, the Helmholtz Association (to T.S.), the Swedish Research Council to H.U.M., and the German National Academic Foundation (to C.E. and K.M.S.). C.V.S. is supported by a Walter-Benjamin Fellowship from the DFG (SCHN 1640/1-1). K.M.S. is supported by the DFG consortium (SCHN 1626/1-1).
Subjects: ATP Binding Cassette Transporter, Subfamily B, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Cholangitis, Sclerosing, Receptors, Cytoplasmic and Nuclear, Gut flora, Cholesterol 7 alpha-hydroxylase, digestive system, Primary sclerosing cholangitis, Bile Acids and Salts, 03 medical and health sciences, Mice, 0302 clinical medicine, Physiology (medical), Internal Medicine, Medicine, Animals, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Liver injury, 0303 health sciences, Cholestasis, biology, Bile acid, business.industry, Bile duct, digestive, oral, and skin physiology, Cell Biology, biology.organism_classification, medicine.disease, Prognosis, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Pathophysiology, 3. Good health, Anti-Bacterial Agents, Gastrointestinal Microbiome, medicine.anatomical_structure, Liver, Cancer research, 030211 gastroenterology & hepatology, Farnesoid X receptor, business, Signal Transduction
Abstract: International audience; Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes.
Published: 2021
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139. Projected land ice contributions to twenty-first-century sea level rise

Author: Luke D. Trusel, Brian Anderson, Youngmin Choi, Michiel R. van den Broeke, Courtney Shafer, Cheng Zhao, William H. Lipscomb, Erika Simon, Sébastien Le clec'h, Victoria Lee, Thomas Kleiner, Donald Slater, Tore Hattermann, Matthias Huss, James F. O’Neill, Sainan Sun, Philip Kraaijenbrink, Benjamin K. Galton-Fenzi, Ayako Abe-Ouchi, Richard I. Cullather, Christophe Dumas, Christopher J. Smith, Nicolas C. Jourdain, Eric Larour, Rupert Gladstone, Jonas Van Breedam, Xavier Fettweis, Christine M. McKenna, Fiona Turner, Nicole Schlegel, Patrick Alexander, Walter W. Immerzeel, Gunter R. Leguy, Torsten Albrecht, Nicholas R. Golledge, Fabien Maussion, Fiammetta Straneo, Valentina Radić, Antony J. Payne, Robin S. Smith, Andrew Bliss, Heiko Goelzer, Andrew Shepherd, Frank Pattyn, Lev Tarasov, Mathieu Morlighem, Christopher Chambers, Tamsin L. Edwards, Reinhard Calov, Koji Fujita, Harry Zekollari, Nicolas Champollion, Akiko Sakai, Sarah Shannon, Ralf Greve, Stephen Price, Isabel Nias, Ricarda Winkelmann, David R. Rounce, Tong Zhang, Jan Hendrik Malles, Ben Marzeion, Roderik S. W. van de Wal, Helene Seroussi, Christopher M. Little, Cécile Agosta, Martin Rückamp, Philippe Huybrechts, Regine Hock, Angelika Humbert, Xylar Asay-Davis, Denis Felikson, Aurélien Quiquet, Daniel F. Martin, Andy Aschwanden, Matthew J. Hoffman, Tyler Pelle, Ronja Reese, Jonathan M. Gregory, Thomas Zwinger, Alice Barthel, Sophie Nowicki, J. K. Cuzzone, Daniel P. Lowry, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Glaces et Continents, Climats et Isotopes Stables (GLACCIOS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Modélisation du climat (CLIM), Fonds De La Recherche Scientifique - FNRS, FNRS Horizon 2020: 820829 Australian Government: ASCI000002 Horizon 2020 Framework Programme, H2020: 869304 U.S. Department of Energy, USDOE O0100718F British Antarctic Survey, BAS Bundesministerium für Bildung und Forschung, BMBF: 01LP1504D, FKZ 01LP1502C Ministerie van Onderwijs, Cultuur en Wetenschap, OCW: 024.002.001 Natural Environment Research Council, NERC: NE/T007443/1 Deutsche Forschungsgemeinschaft, DFG: WI4556/2-1, 01LP1925D, WI4556/4-1 Norges Forskningsråd: 270061, 295046 American Research Center in Sofia, ARCS National Science Foundation, NSF: 1852977 National Center for Atmospheric Research, NCAR Horizon 2020 Framework Programme, H2020: NNX17AG65G, 820575 U.S. Department of Energy, USDOE Japan Society for the Promotion of Science, KAKEN: JP16H02224, JP17H06104, JP17H06323 Ministerie van Onderwijs, Cultuur en Wetenschap, OCW Office of Science, SC Suomen Akatemia: 286587, 322430 National Centre for Atmospheric Science, NCAS National Aeronautics and Space Administration, NASA Netherlands Earth System Science Centre, NESSC European Space Agency, ESA U.S. Department of Energy, USDOE Belgian Federal Science Policy Office, BELSPO: SR/00/336 National Science Foundation, NSF: PLR-1644277, PLR-1603799 Universiteit Utrecht, UU European Regional Development Fund, ERDF Bundesministerium für Bildung und Forschung, BMBF: WI4556/3-1 Ministry of Education, Culture, Sports, Science and Technology, Monbusho National Aeronautics and Space Administration, NASA Natural Environment Research Council, NERC Natural Environment Research Council, NERC Ministry for Business Innovation and Employment, MBIE: RTUV1705, ANTA1801 International Institute for Applied Systems Analysis, IIASA: NE/T009381/1 Biological and Environmental Research, BER: DE-AC02-05CH11231 Australian Research Council, ARC: SR140300001 European Commission, EC Office of Science, SC: DE-SC0020073 Ministry of Education, Culture, Sports, Science and Technology, Monbusho: JPMXD1420318865, JPMXD1300000000 Advanced Scientific Computing Research, ASCR, Acknowledgements We thank J. Rougier for providing advice and support throughout, and writing the original random effects model. We also thank B. Fox-Kemper, H. Hewitt, R. Kopp, S. Drijfhout and J. Rohmer for discussions, suggestions and support. We thank N. Barrand, W. Chang, V. Volodina and D. Williamson for their thorough and constructive comments, which greatly improved the manuscript. We thank the Climate and Cryosphere (CliC) Project, which provided support for ISMIP6 and GlacierMIP through sponsoring of workshops, hosting the websites and ISMIP6 wiki, and promotion. We acknowledge the World Climate Research Programme, which, through its Working Group on Coupled Modelling, coordinated and promoted CMIP5 and CMIP6. We thank the climate modelling groups for producing and making available their model output, the Earth System Grid Federation (ESGF) for archiving the CMIP data and providing access, the University at Buffalo for ISMIP6 data distribution and upload, and the multiple funding agencies who support CMIP5 and CMIP6 and ESGF. We thank the ISMIP6 steering committee, the ISMIP6 model selection group and the ISMIP6 dataset preparation group for their continuous engagement in defining ISMIP6. This is ISMIP6 contribution no. 13. This publication was supported by PROTECT, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 869304. This is PROTECT contribution number 12. T.L.E. was supported by PROTECT and the UK Natural Environment Research Council grant NE/T007443/1. F.T. was supported by PROTECT. J.F.O’N. was supported by the UK Natural Environment Research Council London Doctoral Training Partnership. R. Gladstone’s contribution was supported by Academy of Finland grants 286587 and 322430, and T. Zwinger’s by grant 322430. W.H.L. and G.R.L. were supported by the National Center for Atmospheric Research, which is a major facility sponsored by the National Science Foundation under Cooperative Agreement no. 1852977. Computing and data storage resources for CISM simulations, including the Cheyenne supercomputer (https://doi.org/10.5065/D6RX99HX), were provided by the Computational and Information Systems Laboratory (CISL) at NCAR. Support for X.A.-D., M.J.H., S.F.P. and T. Zhang was provided through the Scientific Discovery through Advanced Computing (SciDAC) programme funded by the US Department of Energy (DOE), Office of Science, Advanced Scientific Computing Research and Biological and Environmental Research programmes. N.R.G., D.P.L. and B.A. were supported by New Zealand Ministry for Business, Innovation and Employment contracts RTUV1705 (‘NZSeaRise’) and ANTA1801 (‘Antarctic Science Platform’). J.M.G. and R.S.S. were supported by the National Centre for Atmospheric Science, funded by the UK National Environment Research Council. R. Calov was funded by the PalMod project of the Bundesministerium für Bildung und Forschung (BMBF) with the grants FKZ 01LP1502C and 01LP1504D. D.F.M. and C.S. were supported by the Director, Office of Science, Offices of Advanced Scientific Computing Research (ASCR) and Biological and Environmental Research (BER), of the US Department of Energy under contract no. DE-AC02-05CH11231, as a part of the ProSPect SciDAC Partnership. BISICLES simulations used resources of the National Energy Research Scientific Computing Center (NERSC), a US Department of Energy Office of Science User Facility operated under contract no. DE-AC02-05CH11231. C.Z. and B.K.G.-F. were supported under the Australian Research Council’s Special Research Initiative for Antarctic Gateway Partnership (project ID SR140300001) and received grant funding from the Australian Government for the Australian Antarctic Program Partnership (project ID ASCI000002). Work was performed by E.L., N.-J.S. and H.S. at the California Institute of Technology’s Jet Propulsion Laboratory under a contract with the National Aeronautics and Space Administration, support was provided by grants from NASA’s Cryospheric Science, Sea Level Change Team, and Modeling, Analysis and Prediction (MAP) programmes. They acknowledge computational resources and support from the NASA Advanced Supercomputing Division. The CMIP5 and CMIP6 projection data were processed by C.M.M. with funding from the European Union’s CONSTRAIN project as part of the Horizon 2020 Research and Innovation Programme under grant agreement number 820829. A. Barthel was supported by the DOE Office of Science HiLAT-RASM project and Early Career Research programme. T.A. and R.W. are supported by the Deutsche Forschungsgemeinschaft (DFG) in the framework of the priority programme ‘Antarctic research with comparative investigations in Arctic ice areas’ by grants WI4556/2-1 and WI4556/4-1, and within the framework of the PalMod project (FKZ: 01LP1925D) supported by the German Federal Ministry of Education and Research (BMBF) as a Research for Sustainability initiative (FONA). R.R. is supported by the Deutsche Forschungsgemeinschaft (DFG) by grant WI4556/3-1 and through the TiPACCs project that receives funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement no. 820575. Development of PISM is supported by NASA grant NNX17AG65G and NSF grants PLR-1603799 and PLR-1644277. The authors gratefully acknowledge the European Regional Development Fund (ERDF), the German Federal Ministry of Education and Research and the Land Brandenburg for supporting this project by providing resources for the high-performance computer system at the Potsdam Institute for Climate Impact Research. Computer resources for this project have also been provided by the Gauss Centre for Supercomputing, Leibniz Supercomputing Centre (http://www.lrz.de, last access: 16 July 2020) under project IDs pr94ga and pn69ru. R. Greve and C.C. were supported by Japan Society for the Promotion of Science (JSPS) KAKENHI grant nos JP16H02224 and JP17H06323. R. Greve was supported by JSPS KAKENHI grant no. JP17H06104, by a Leadership Research Grant of Hokkaido University’s Institute of Low Temperature Science (ILTS), and by the Arctic Challenge for Sustainability (ArCS, ArCS II) project of the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) (programme grant nos JPMXD1300000000, JPMXD1420318865). F.P. and S. Sun were supported by the MIMO project within the STEREO III programme of the Belgian Science Policy Office, contract SR/00/336 and the Fonds de la Recherche Scientifique (FNRS) and the Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO) under the EOS project no. O0100718F. A. Shepherd was supported by the UK Natural Environment Research Council in partnership with the Centre for Polar Observation and Modelling and the British Antarctic Survey and by the European Space Agency Climate Change Initiative. D.F. was supported by an appointment to the NASA Postdoctoral Program at the NASA Goddard Space Flight Center, administered by Universities Space Research Association under contract with NASA. R.v.d.W. acknowledges the support of the Future Deltas programme of Utrecht University. C.J.S. was supported by a NERC/IIASA Collaborative Research Fellowship (NE/T009381/1). H.G. has received funding from the programme of the Netherlands Earth System Science Centre (NESSC), financially supported by the Dutch Ministry of Education, Culture and Science (OCW) under grant no. 024.002.001 and from the Research Council of Norway under projects INES (270061) and KeyClim (295046). F.S. acknowledges support from DOE Office of Science grant no. DE-SC0020073. High-performance computing and storage resources were provided by the Norwegian Infrastructure for Computational Science through projects NN9560K, NN9252K, NS9560K, NS9252K and NS5011K., University of St Andrews. School of Geography & Sustainable Development, University of St Andrews. Environmental Change Research Group, Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Sub Dynamics Meteorology, Hydrologie, Landscape functioning, Geocomputation and Hydrology, Proceskunde, Sub Algemeen Marine & Atmospheric Res, Earth System Sciences, Geography, Physical Geography, and Faculty of Sciences and Bioengineering Sciences
Subjects: 010504 meteorology & atmospheric sciences, General Science & Technology, [SDV]Life Sciences [q-bio], 01 natural sciences, 010104 statistics & probability, Taverne, G1, SDG 13 - Climate Action, 0101 mathematics, General, Coastal flood, Sea level, 0105 earth and related environmental sciences, geography, Multidisciplinary, geography.geographical_feature_category, Global warming, G Geography (General), DAS, Glacier, Glaciologie, Snow, Climate Action, Current (stream), Sea level rise, 13. Climate action, Climatology, Environmental science, Ice sheet, Sciences exactes et naturelles
Abstract: The land ice contribution to global mean sea level rise has not yet been predicted 1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models 2–8, but primarily used previous-generation scenarios 9 and climate models 10, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios 11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.
Published: 2021
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140. Causal effects of lifetime smoking on breast and colorectal cancer risk:Mendelian randomization study

Author: Marc J. Gunter, Inger T. Gram, Elisabete Weiderpass, Hilary A. Tindle, Sun-Seog Kweon, Renée T. Fortner, Rudolf Kaaks, Sarah J Lewis, James Yarmolinsky, Stephen B. Gruber, Marije F. Bakker, Li Hsu, Yi Lin, Neil Murphy, Polly A. Newcomb, Konstantinos K. Tsilidis, Noralane M. Lindor, Rosario Tumino, Gianluca Severi, Hermann Brenner, Emmanouil Bouras, Jane C. Figueiredo, Niki Dimou, Richard M. Martin, Bethany Van Guelpen, María-José Sánchez-Pérez, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Cancerfonden Cancer Research Foundation in Northern Sweden Deutsche Krebshilfe Vetenskapsrådet, VR Australian Lions Childhood Cancer Research Foundation, ALCCRF Knut och Alice Wallenbergs Stiftelse State of Maryland Vetenskapsrådet, VR: VR 2017-00650 Centers for Disease Control and Prevention, CDC Institut National Du Cancer, INCa National Institutes of Health, NIH National Cancer Institute, NCI: P30 CA015704 Centre Hospitalier Universitaire de Nantes, CHU de Nantes Conseil Régional des Pays de la Loire Association Anne de Bretagne Genetique Centre Hospitalier Universitaire de Nantes, CHU de Nantes U.S. Public Health Service, USPHS: HHSN261201500005C U.S. Department of Health and Human Services, HHS National Institutes of Health, NIH National Cancer Institute, NCI National Institute on Aging, NIA: U01 AG18033 Institut National Du Cancer, INCa: P30 CA006973, U01 CA86308 American Institute for Cancer Research, AICR European Commission, EC National Institutes of Health, NIH: R01 CA189184, 2P30CA015704-40, R01 CA207371, U01 CA206110 Matthias Lackas-Stiftung Johns Hopkins University, JHU: HHSN268201200008I National Cancer Institute, NCI National Institutes of Health, NIH: R01 CA143247, R01 CA81488, U01 CA122839, U19 CA148107, U01 CA167551 National Institutes of Health, NIH National Institute of Environmental Health Sciences, NIEHS: T32 ES013678 National Cancer Institute, NCI U.S. Department of Health and Human Services, HHS: R01 CA197350, R01 CA81488, R01 CA201407, P01 CA196569, U19 CA148107, P30 CA014089 Österreichische Forschungsförderungsgesellschaft, FFG: 829675 Instituto de Salud Carlos III, ISCIII European Regional Development Fund, ERDF: PI14-613, PI09-1286 Xarxa de Bancs de Tumors de Catalunya, XBTC: PT13/0010/0013 Generalitat de Catalunya: 2017SGR723 Junta de Castilla y León: LE22A10-2 Agència de Gestió d'Ajuts Universitaris i de Recerca, AGAUR Ministerstvo Zdravotnictví Ceské Republiky, MZCR: AZV 17-30920A, AZV 15-27580A Grantová Agentura České Republiky, GA ČR: CZ GA CR: GAP304/10/1286, 1585 Deutsche Forschungsgemeinschaft, DFG: HO 5117/2-1, BR 1704/6-1, KL 2354/3-1, BR 1704/6-4, BR 1704/6-3, CH 117/1-1, HE 5998/2-1, RO 2270/8-1, BR1704/17-1 Bundesministerium für Bildung und Forschung, BMBF: 01ER0814, 01KH0404, 01ER0815, 01ER1505A, 01ER1505B U01 CA 84968-06 National Cancer Institute, NCI University of Maryland School of Public Health, SPH NIHR Imperial Biomedical Research Centre, BRC Imperial College London NIHR Imperial Biomedical Research Centre, BRC Centre International de Recherche sur le Cancer, CIRC Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A29017 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Vetenskapsrådet, VR Ligue Contre le Cancer Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Kræftens Bekæmpelse, DCS Associazione Italiana per la Ricerca sul Cancro, AIRC Instituto de Salud Carlos III, ISCIII Deutsches Krebsforschungszentrum, DKFZ Institut National de la Santé et de la Recherche Médicale, Inserm National Research Council, NRC Institut Gustave-Roussy Deutsches Krebsforschungszentrum, DKFZ Cancerfonden World Cancer Research Fund, WCRF Medical Research Council, MRC: MR/M012190/1 Generalitat de Catalunya: 2017SGR653, 2014SGR135, 2014SGR255, 2017SGR21 SAF2014-54453R, SAF07-64873, SAF 2010-19273 Xunta de Galicia: PGIDIT07PXIB9101209PR Instituto de Salud Carlos III, ISCIII European Regional Development Fund, ERDF: PS09/02368, PI14/00230, 17/00878, PI08/1276, PI17/00509, PI08/0024, PI11/00681, P111/00219, PI14/00173 Xarxa de Bancs de Tumors de Catalunya, XBTC: SLT002/ 16/00398 GCB13131592CAST European Cooperation in Science and Technology, COST: CA17118, BM1206 Deutsche Krebshilfe National Institutes of Health, NIH: K07 CA190673, P01 CA055075, K07CA190673, R35CA197735, U01 CA167552, UM1 CA167552, R01 CA042182, P01 CA087969, R01 CA151993, P50 CA127003, UM1 CA186107, R35 CA197735, R01 CA137178 HCRI15011-1 National Cancer Institute, NCI: R01CA136726 Damon Runyon Cancer Research Foundation, DRCRF: CI-8 Food Standards Agency, FSA Cancer Research UK, CRUK: C588/A19167 VicHealth Cancer Council Victoria National Health and Medical Research Council, NHMRC: 251553, 209057, 509348, 504711 National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: R01 CA81488 Florida Department of Health: 09BN-13 National Institutes of Health, NIH: R01 CA189184, P30 CA076292 National Institutes of Health, NIH: P30 DK034987, R01 CA66635 18226, 18223 Canadian Institutes of Health Research, CIHR: CRT 43821 National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: U01 CA74783 Cancerfonden Cancer Research Foundation, CRF Vetenskapsrådet, VR Australian Lions Childhood Cancer Research Foundation, ALCCRF Canadian Cancer Society National Institutes of Health, NIH: U01/ U24 CA074783, U01 CA167551 Pelotonia CA16058, CA67941 Canadian Institutes of Health Research, CIHR: 112746 Ontario Research Foundation, ORF: GL201-043 National Cancer Institute, NCI U.S. Department of Health and Human Services, HHS: U01 HG004446, GEI U01 HG 004438, Z01 CP 010200 Division of Cancer Epidemiology and Genetics, National Cancer Institute, DCEG Institut National Du Cancer, INCa National Institutes of Health, NIH Division of Cancer Prevention, National Cancer Institute, DCP, NCI National Institutes of Health, NIH: U24 CA074794, U01 CA074794, R01 CA076366, U01 CA167551 National Cancer Institute, NCI National Institutes of Health, NIH: UM1 CA182883, U10 CA37429 National Cancer Institute, NCI Institut National Du Cancer, INCa: R03 CA153323, P01 CA074184, K05 CA152715, R01 CA097325 National Institutes of Health, NIH: KL2 TR000421 National Center for Advancing Translational Sciences, NCATS Stockholms Läns Landsting Vetenskapsrådet, VR: K2015-55X-22674-01-4, K2008-55X-20157-03-3, K2006-72X-20157-01-2 Karolinska Institutet, KI National Institutes of Health, NIH: K05 CA154337 Swedish Cancer Foundation National Heart, Lung, and Blood Institute, NHLBI National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: HHSN268201100004C, HHSN268201100003C, HHSN268201100001C, HHSN271201100004C, HHSN268201100046C, HHSN268201100002C, R.M. Martin reports grants from Cancer Research UK during the conduct of the study. R.T. Fortner reports that grants from German Cancer Aid and from German Ministry of Education and Research supported the conduct of EPIC Heidelberg. S.B. Gruber reports other from Brogent International LLC outside the submitted work. B. van Guelpen reports grants from Swedish Research Council, Swedish Cancer Society, Knut and Alice Wallenberg Foundation, Lion’s Cancer Research Foundation at Umea° University, and Cancer Research Foundation in Northern Sweden during the conduct of the study. No disclosures were reported by the other authors., CLUE: We appreciate the continued efforts of the staff members at the Johns Hopkins George W. Comstock Center for Public Health Research and Prevention in the conduct of the CLUE II study. We thank the participants in CLUE. Cancer incidence data for CLUE were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Maryland Department of Health, 201 W. Preston Street, Room 400, Baltimore, MD 21201, http://phpa.dhmh.maryland.gov/cancer, 410-767-4055. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data., CPS-II: The authors thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program., NSHDS investigators thank the Biobank Research Unit at Umea° University, the V€asterbotten Intervention Programme, the Northern Sweden MONICA study and Region V€asterbotten for providing data and samples and acknowledge the contribution from Biobank Sweden, supported by the Swedish Research Council (VR 2017-00650)., Cancer incidence data have been provided by the District of Columbia Cancer Registry, Georgia Cancer Registry, Hawaii Cancer Registry, Minnesota Cancer Surveillance System, Missouri Cancer Registry, Nevada Central Cancer Registry, Pennsylvania Cancer Registry, Texas Cancer Registry, Virginia Cancer Registry, and Wisconsin Cancer Reporting System. All are supported in part by funds from the Center for Disease Control and Prevention, National Program for Central Registries, local states or by the National Cancer Institute, Surveillance, Epidemiology, and End Results program. The results reported here and the conclusions derived are the sole responsibility of the authors., Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088, R01 CA059045, R01CA201407). This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704., ASTERISK: a Hospital Clinical Research Program (PHRC-BRD09/C) from the University Hospital Center of Nantes (CHU de Nantes) and supported by the Regional Council of Pays de la Loire, the Groupement des EntreprisesFranc¸aises dans la Luttecontre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue RégionaleContre le Cancer (LRCC)., The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services., CLUE funding was from the National Cancer Institute (U01 CA86308, Early Detection Research Network, and P30 CA006973), National Institute on Aging (U01 AG18033), and the American Institute for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. COLO2&3: NIH (R01 CA60987).
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Epidemiology, medicine.drug_class, Colorectal cancer, Breast Neoplasms, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, Mendelian randomization, Genetic predisposition, Humans, Medicine, Risk factor, 11 Medical and Health Sciences, business.industry, Smoking, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Confidence interval, 3. Good health, Causality, 030104 developmental biology, Estrogen, 030220 oncology & carcinogenesis, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ICEP, Colorectal Neoplasms, business, Genome-Wide Association Study
Abstract: Background: Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer. Methods: Genome-Wide Association Study summary data were used to identify genetic variants associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/105,974 controls) and colorectal cancer (52,775 cases/45,940 controls). Results: In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-SD increment: 1.13; 95% confidence interval (CI): 1.00–1.26; P = 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor–positive and estrogen receptor–negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer (OR per 1-SD increment, 1.21; 95% CI, 1.04–1.40; P = 0.01), colon cancer (OR, 1.31; 95% CI, 1.11–1.55; P < 0.01), and rectal cancer (OR, 1.36; 95% CI, 1.07–1.73; P = 0.01). Ever having smoked regularly was not associated with risks of breast (OR, 1.01; 95% CI, 0.90–1.14; P = 0.85) or colorectal cancer (OR, 0.97; 95% CI, 0.86–1.10; P = 0.68). Conclusions: These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer. Impact: The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.
Published: 2021
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141. Time-resolved imaging of OErsted field induced magnetization dynamics in cylindrical magnetic nanowires

Author: Julien Bachmann, C. Thirion, Jörg Raabe, Jean-Christophe Toussaint, Olivier Fruchart, A. De Riz, M. Schöbitz, Simone Finizio, Jérôme Hurst, D. Gusakova, Micro et NanoMagnétisme (NEEL - MNM), Institut Néel (NEEL), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), SPINtronique et TEchnologie des Composants (SPINTEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), The Swiss Light Source (SLS) (SLS-PSI), Paul Scherrer Institute (PSI), Saint Petersburg University (SPBU), RENATECH, German Bundesministerium für Bildung und Forschung (BMBF) 05K16WED, German Bundesministerium für Bildung und Forschung (BMBF) 05K19WE2, ANR-10-LABX-0051,LANEF,Laboratory of Alliances on Nanosciences - Energy for the Future(2010), ANR-17-CE24-0017,MATEMAC-3D,Manipulation de textures magnétiques par courant – modélisation 3D par éléments finis(2017), ANR-18-CE92-0045,C3DS,Chimie pour une spintronique 3D(2018), and Micro et NanoMagnétisme (MNM)
Subjects: 010302 applied physics, Magnetization dynamics, Materials science, Condensed Matter - Mesoscale and Nanoscale Physics, Physics and Astronomy (miscellaneous), Spintronics, Condensed matter physics, Field (physics), Nanowire, 02 engineering and technology, Nanosecond, 021001 nanoscience & nanotechnology, 01 natural sciences, 3. Good health, Magnetization, Domain wall (magnetism), Spin wave, 0103 physical sciences, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], 0210 nano-technology
Abstract: Recent studies in three dimensional spintronics propose that the \OE rsted field plays a significant role in cylindrical nanowires. However, there is no direct report of its impact on magnetic textures. Here, we use time-resolved scanning transmission X-ray microscopy to image the dynamic response of magnetization in cylindrical Co$_{30}$Ni$_{70}$ nanowires subjected to nanosecond \OE rsted field pulses. We observe the tilting of longitudinally magnetized domains towards the azimuthal \OE rsted field direction and create a robust model to reproduce the differential magnetic contrasts and extract the angle of tilt. Further, we report the compression and expansion, or breathing, of a Bloch-point domain wall that occurs when weak pulses with opposite sign are applied. We expect that this work lays the foundation for and provides an incentive to further studying complex and fascinating magnetization dynamics in nanowires, especially the predicted ultra-fast domain wall motion and associated spin wave emissions., Comment: 6 pages, 3 figures in main text and supplementary materials
Published: 2021
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142. Multi-model evaluation of phenology prediction for wheat in Australia

Author: Elisabet Lewan, Xenia Specka, Arne Poyda, Bernardo Maestrini, Liujun Xiao, Amir Souissi, Sabine J. Seidel, Roberto Ferrise, G. Padovan, Steven Hoek, Tobias K. D. Weber, Thilo Streck, Mingxia Huang, Qunying Luo, Niels Schütze, Jørgen E. Olesen, Samuel Buis, Qi Jing, Budong Qian, Yan Zhu, Marie Launay, Allard de Wit, Thomas Wöhling, Sebastian Gayler, Fety Andrianasolo, Eckart Priesack, Bruno Basso, Senthold Asseng, Benjamin Dumont, Heidi Horan, Eric Justes, Thomas Gaiser, Mohamed Jabloun, Giacomo Trombi, Santosh Hiremath, Lutz Weihermüller, Daniel Wallach, Jing Wang, Zvi Hochman, Taru Palosuo, Amit Kumar Srivastava, Marco Moriondo, Vakhtang Shelia, Peter J. Thorburn, Gerrit Hoogenboom, Evelyn Wallor, Kurt Christian Kersebaum, Johannes Wilhelmus Maria Pullens, Neil M.J. Crout, Chuang Zhao, Per-Erik Jansson, Tommaso Stella, AGroécologie, Innovations, teRritoires (AGIR), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Natural Resources Institute Finland (LUKE), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), ARVALIS - Institut du Végétal [Boigneville], ARVALIS - Institut du végétal [Paris], University of Florida [Gainesville] (UF), Department of Agricultural and Biological Engineering [Gainesville] (UF|ABE), Institute of Food and Agricultural Sciences [Gainesville] (UF|IFAS), University of Florida [Gainesville] (UF)-University of Florida [Gainesville] (UF), Michigan State University [East Lansing], Michigan State University System, DEPARTMENT OF EARTH AND ENVIRONMENTAL SCIENCES MICHIGAN STATE UNIVERSITY USA, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Environnement Méditerranéen et Modélisation des Agro-Hydrosystèmes (EMMAH), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Nottingham, UK (UON), Université de Liège - Gembloux, Department Terra & AgroBioChem, Gembloux Agro‐Bio Tech, Université de Liège, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Agriculture, Food, Environment and Forestry (DAGRI), University of Bonn, Institute of Crop Science and Resource Conservation [Bonn] (INRES), Rheinische Friedrich-Wilhelms-Universität Bonn, University of Hohenheim, Institute of Soil Science and Land Evaluation, Soil Biology Section, Aalto University School of Science and Technology [Aalto, Finland], Wageningen University and Research [Wageningen] (WUR), CSIRO Agriculture and Food (CSIRO), Food Systems Institute [Gainesville] (UF|IFAS), China Agriculture University [Beijing], College of Resources and Environmental Sciences, China Agricultural University (CAU), Royal Institute of Technology [Stockholm] (KTH ), Agriculture and Agri-Food [Ottawa] (AAFC), Ottawa Research and Development Center, Fonctionnement et conduite des systèmes de culture tropicaux et méditerranéens (UMR SYSTEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-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 d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), Département Performances des systèmes de production et de transformation tropicaux (Cirad-PERSYST), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Leibniz-Zentrum für Agrarlandschaftsforschung = Leibniz Centre for Agricultural Landscape Research (ZALF), Global Change Research Institute (CAS), Agroclim (AGROCLIM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Swedish University of Agricultural Sciences (SLU), Hillridge Technology Pty Ltd, Institute of Bioeconomy (IBE), Consiglio Nazionale delle Ricerche (CNR), Aarhus University [Aarhus], Department of Agroecology, Aarhus University, Tjele, Denmark, Kiel University, Institute of Crop Science and Plant Breeding, Christian-Albrechts University of Kiel, Helmholtz-Zentrum München (HZM), German Res Ctr Environm Hlth, Partenaires INRAE, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Université de Carthage - University of Carthage, Institut National de la Recherche Agronomique de Tunisie (INRAT), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, Institute of Bio- and Geosciences [Jülich] (IBG), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Lincoln Agritech Ltd, Nanjing Agricultural University, National Engineering and Technology Center for Information Agriculture, Jiangsu Key Laboratory for Information Agriculture, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricutural University, This work was in part supported by the Collaborative Research Center 1253 CAMPOS (Project 7: Stochastic Modelling Framework), funded by the German Research Foundation (DFG, Grant Agreement SFB 1253/1 2017), the Academy of Finland through projects AI-CropPro (316172 and 315896) and DivCSA (316215) and Natural Resources Institute Finland (Luke) through a strategic project BoostIA, the BonaRes projects 'Soil3' (BOMA 03037514) and 'I4S' (031B0513I) of the Federal Ministry of Education and Research (BMBF), Germany, the German Research Foundation (DFG) under Germany's Excellence Strategy -EXC 2070 -390732324, the project BiomassWeb of the GlobeE programme (Grant number: FKZ031A258B) funded by the Federal Ministry of Education and Research (BMBF, Germany), the EU funded SustEs project (CZ.02.1.01/0.0/0.0/16_019/0000797), the INRAE ACCAF metaprogramme, the German Federal Ministry of Education and Research (BMBF) in the framework of the funding measure 'Soil as a Sustainable Resource for the Bioeconomy -BonaRes', project 'BonaRes (Module B): BonaRes Centre for Soil Research, subproject B' (grant 031B0511B), the National Key Research and Development Program of China (2017YFD0300205), the National Science Foundation for Distinguished Young Scholars (31725020), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the 111 project (B16026), and China Scholarship Council, the Agriculture and AgriFood Canada's Project 1387 under the Canadian Agricultural Partnership, the DFG Research Unit FOR 1695 `Agricultural Landscapes under Global Climate Change -Processes and Feedbacks on a Regional Scale, the U.S. Department of Agriculture (USDA), National Institute of Food and Agriculture (award no. 2015-68007-23133) and USDA/NIFA HATCH grant N. MCL02368, the National Key Research and Development Program of China (2016YFD0300105), The Broadacre Agriculture Initiative, a research partnership between University of Southern Queensland and the Queensland Department of Agriculture and Fisheries, the JPI FACCE MACSUR2 project, funded by the Italian Ministry for Agricultural, Food, and Forestry Policies (D.M. 24064/7303/15 of 26/Nov/2015). The field work was jointly funded by CSIRO and the Grains Research and Development Corporation (GRDC) under the 'Adding Value to GRDC's National Variety Trial Network' project (CSA00027). The order in which the donors are listed is arbitrary., INRAE, Luke Natural Resources Institute Finland, CSIRO, Arvalis Institut du Végétal, University of Florida, Michigan State University, University of Nottingham, University of Liege, University of Florence, Department of Computer Science, Wageningen University and Research Centre, China Agricultural University, KTH Royal Institute of Technology, Ottawa Research and Development Centre, Leibniz Centre for Agricultural Landscape Research, Swedish University of Agricultural Sciences, National Research Council of Italy, Aarhus University, Helmholtz Zentrum München - German Research Center for Environmental Health, Technische Universität Dresden, University of Carthage, Forschungszentrum Jülich, Aalto-yliopisto, and Aalto University
Subjects: 0106 biological sciences, Atmospheric Science, 010504 meteorology & atmospheric sciences, Calibration (statistics), Structure uncertainty, 01 natural sciences, F01 - Culture des plantes, Aardobservatie en omgevingsinformatica, Statistics, Range (statistics), ddc:550, Evaluation, Applied Ecology, Triticum, Mathematics, 2. Zero hunger, Global and Planetary Change, U10 - Informatique, mathématiques et statistiques, Phenology, Toegepaste Ecologie, Forestry, 04 agricultural and veterinary sciences, Australia, Parameter Uncertainty, Structure Uncertainty, Wheat, technique de prévision, PE&RC, [SDE]Environmental Sciences, Incertitude, Phénologie, Earth Observation and Environmental Informatics, F40 - Écologie végétale, Parameter uncertainty, Benchmark (surveying), Baseline (configuration management), Selection (genetic algorithm), 0105 earth and related environmental sciences, Modélisation des cultures, cultivar selection [EN], Global change, 15. Life on land, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Stage (hydrology), Agronomy and Crop Science, 010606 plant biology & botany
Abstract: Predicting wheat phenology is important for cultivar selection, for effective crop management and provides a baseline for evaluating the effects of global change. Evaluating how well crop phenology can be predicted is therefore of major interest. Twenty-eight wheat modeling groups participated in this evaluation. Model predictions depend not only on model structure but also on the parameter values. This study is thus an evaluation of modeling groups, which choose the structure and fix or estimate the parameters, rather than an evaluation just of model structures. Our target population was wheat fields in the major wheat growing regions of Australia under current climatic conditions and with current local management practices. The environments used for calibration and for evaluation were both sampled from this same target population. The calibration and evaluation environments had neither sites nor years in common, so this is a rigorous evaluation of the ability of modeling groups to predict phenology for new sites and weather conditions. Mean absolute error (MAE) for the evaluation environments, averaged over predictions of three phenological stages and over modeling groups, was 9 days, with a range from 6 to 20 days. Predictions using the multi-modeling group mean and median had prediction errors nearly as small as the best modeling group. For a given modeling group, MAE for the evaluation environments was significantly correlated with MAE for the calibration environments, which suggests that it would be of interest to test ensemble predictors that weight individual modeling groups based on performance for the calibration data. About two thirds of the modeling groups performed better than a simple but relevant benchmark, which predicts phenology by assuming a constant temperature sum for each development stage. The added complexity of crop models beyond just the effect of temperature was thus justified in most cases. Finally, there was substantial variability between modeling groups using the same model structure, which implies that model improvement could be achieved not only by improving model structure, but also by improving parameter values, and in particular by improving calibration techniques.
Published: 2021
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143. Inflammatory potential of the diet and risk of breast cancer in the European Investigation into Cancer and Nutrition (EPIC) study

Author: Verena Katzke, Anne M. May, Carlota Castro-Espin, Paula Jakszyn, Christina C. Dahm, Elisabete Weiderpass, Matthias B. Schulze, Guri Skeie, María José Sánchez, Catalina Bonet, Maria Dolores Chirlaque, Sanam Shah, Nasser Laouali, Dagfinn Aune, José Ramón Quirós, Sabina Sieri, Eva Ardanaz, Salvatore Panico, Gianluca Severi, Carlotta Sacerdote, Antonio Agudo, Stina Bodén, Melissa A. Merritt, Iger T Gram, Rosario Tumino, Krasimira Aleksandrova, Giovanna Masala, Elio Riboli, Renée Turzanski-Fortner, Pilar Amiano, Anne Tjønneland, Laure Dossus, Manon Cairat, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII: PI15/00639, European Social Fund, ESF, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Rijksinstituut voor Volksgezondheid en Milieu, RIVM, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, European Regional Development Fund, ERDF: FI19/00197, NIHR Imperial Biomedical Research Centre, BRC, This work was funded by Instituto de Salud Carlos III through the project PI15/00639 (Co-funded by European Regional Development Fund [ERDF], a way to build Europe). C. Castro-Espin was funded by Instituto de Salud Carlos III through the Grant FI19/00197 (Co-funded by European Social Fund. ESF investing in your future). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders of this study had no role in the decisions about the analysis or interpretation of the data, or preparation, review or approval of the manuscript., and We thank CERCA Programme/Generalitat de Catalunya for institutional support. We also thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study.
Subjects: Adult, medicine.medical_specialty, Epidemiology, Nutritional Status, Breast Neoplasms, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Inflammatory potential of the diet, Prospective study, Prospective cohort study, Life Style, Inflammation, 2. Zero hunger, business.industry, Proportional hazards model, Hazard ratio, Chronic inflammation, Middle Aged, medicine.disease, Obesity, Diet, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Cohort, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index
Abstract: International audience; The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01–1.07). Women in the highest quintile of the ISD (indicating a most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR = 1.12; 95% CI 1.04–1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR = 1.08; 95% CI 1.01–1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity, or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.
Published: 2021
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144. Large-scale features of Last Interglacial climate: Results from evaluating the lig127k simulations for the Coupled Model Intercomparison Project (CMIP6)-Paleoclimate Modeling Intercomparison Project (PMIP4)

Author: Yarrow Axford, Ayako Abe-Ouchi, Maria-Vittoria Guarino, Qiong Zhang, Elizabeth B. Isaacs, Bette L. Otto-Bliesner, Robert A. Tomas, Jeremy S. Hoffman, Zhongshi Zhang, Anne de Vernal, Nicholas K. H. Yeung, Masa Kageyama, Weipeng Zheng, Katrin J. Meissner, Christian Stepanek, Jian Cao, Chris Brierley, Gerrit Lohmann, Anni Zhao, Laurie Menviel, David Salas y Mélia, Polina Morozova, Louise C. Sime, Eric W. Wolff, Ryouta O'ishi, Silvana Ramos Buarque, Emilie Capron, Allegra N. LeGrande, Charles Williams, Marie Sicard, Polychronis C Tzedakis, Pascale Braconnot, Evgeny Volodin, Chuncheng Guo, Esther C. Brady, Xaoxu Shi, Paolo Scussolini, Aline Govin, Kerim H. Nisancioglu, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Climat et Magnétisme (CLIMAG), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Modélisation du climat (CLIM), Modelling the Earth Response to Multiple Anthropogenic Interactions and Dynamics (MERMAID), National Science Foundation, NSF National Center for Atmospheric Research, NCAR: 1852977 Natural Environment Research Council, NERC: NE/S009736/1 Nederlandse Organisatie voor Wetenschappelijk Onderzoek, NWO: ALWOP.164 Sorbonne Université California Earthquake Authority, CEA Carlsbergfondet École Polytechnique Fédérale de Lausanne, EPFL Royal Society Centre National d’Etudes Spatiales, CNES 742224 European Research Council, ERC NE/P01903X/1, ANR-18-BELM-0001-06 312979 Centre National de la Recherche Scientifique, CNRS RSF Social Finance: 20-17-00190 Natural Environment Research Council, NERC: NE/P013279/1 Vetenskapsrådet, VR Bundesministerium für Bildung und Forschung, BMBF Vetenskapsrådet, VR: 2016-07213, 2013-06476, 2017-04232 Achievement Rewards for College Scientists Foundation, ARCS: JPMXD1300000000 JPMXD1420318865 Australian Research Council, ARC: FT180100606 2016YFC1401401 Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research, AWI Japan Society for the Promotion of Science, KAKEN: 17H06104 Ministry of Education, Culture, Sports, Science and Technology, Monbusho: 17H06323 Chinese Academy of Sciences, CAS: XDB42000000, XDA19060102 Japan Agency for Marine-Earth Science and Technology, JAMSTEC: 0148-2019-0009 National Natural Science Foundation of China, NSFC: 91958201and 41376002 National Science Foundation, NSF Chinese Academy of Sciences, CAS Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF Akademie der Naturwissenschaften, SCNAT National Science Foundation, NSF: 1852977 National Center for Atmospheric Research, NCAR, Acknowledgements. Bette L. Otto-Bliesner, Esther C. Brady and Robert Tomas acknowledge the CESM project, which is supported primarily by the National Science Foundation (NSF). This material is based upon work supported by the National Center for Atmospheric Research (NCAR), which is a major facility sponsored by the NSF under Cooperative Agreement No. 1852977. Computing and data storage resources, including the Cheyenne supercomputer (https://doi.org/10.5065/D6RX99HX), were provided by the Computational and Information Systems Laboratory (CISL) at NCAR. Chris M. Brierley acknowledges the financial support of the Natural Environment Research Council through grant NE/S009736/1. Anni Zhao and Chris M. Brierley would like to thank Rachel Eyles for her sterling work curating the local replica of the PMIP archive at UCL., Charles J. R. Williams acknowledges the financial support of the UK Natural Environment Research Council-funded SWEET project (Super-Warm Early Eocene Temperatures), research grant NE/P01903X/1, and the financial support of the Belmont-funded PACMEDY (PAlaeo-Constraints on Monsoon Evolution and Dynamics) project. Aline Govin acknowledges the support of the French national program LEFE/INSU (CircLIG project) and of the Belmont-funded ACCEDE project (ANR-18-BELM-0001-06). Eric Wolff has received funding from the European Research Council under the Horizon 2020 program research and innovation program (grant agreement no. 742224, WACSWAIN). Eric Wolff is also funded by a Royal Society Professorship. Paolo Scussolini acknowledges funding from the NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) under grant ALWOP.164. Emilie Capron acknowledges financial support from the ChronoCli-mate project, funded by the Carlsberg Foundation. Pascale Bra-connot and Masa Kageyama acknowledge the HPC resources of TGCC allocated to the IPSL CMIP6 project by GENCI (Grand Equipment National de Calcul Intensif) under the allocations 2016-A0030107732, 2017-R0040110492, and 2018-R0040110492 (project gencmip6). This work was undertaken in the framework of the LABEX L-IPSL and the IPSL Climate Graduate School, under the 'Investissements d’avenir' program with the reference ANR-11-IDEX-0004-17-EURE-0006. This study benefited from the ES-PRI (Ensemble de Services Pour la Recherche à l’IPSL) computing and data center (https://mesocentre.ipsl.fr, last access: 22 December 2020), which is supported by CNRS, Sorbonne Université, École Polytechnique, and CNES and through national and international projects, including the EU-FP7 Infrastructure project IS-ENES2 (grant no. 312979). Marie Sicard is funded by a scholarship from CEA and 'Convention des Services Climatiques' from IPSL., Laurie Menviel acknowledges support from the Australian Research Council FT180100606. The ACCESS-ESM 1.5 experiments were performed on Raijin at the NCI National Facility at the Australian National University, through awards under the National Computational Merit Allocation Scheme, the Intersect allocation scheme, and the UNSW HPC at NCI Scheme. Qiong Zhang acknowledges the support from the Swedish Research Council (Vetenskapsrådet, grant nos. 2013-06476 and 2017-04232). The EC-Earth simulations are performed on ECMWF’s computing and archive facilities and on resources provided by the Swedish National Infrastructure for Computing (SNIC) at the National Supercomputer Centre (NSC) partially funded by the Swedish Research Council through grant agreement no. 2016-07213. Weipeng Zheng acknowledges the financial support from National Key R&D Program for Developing Basic Sciences (grant no. 2016YFC1401401), the Strategic Priority Research Program of Chinese Academy of Sciences (grant nos. XDA19060102 and XDB42000000) and the National Natural Science Foundation of China (grant nos. 91958201and 41376002), and the technical support from the National Key Scientific and Technological Infrastructure project 'Earth System Science Numerical Simulator Facility' (EarthLab). Maria Vittoria Guarino and Louise Sime acknowledge the financial support of the NERC research grant NE/P013279/1. Silvana Ramos Buarque and David Salas y Mélia acknowledge Météo-France/DSI for providing computing and data storage resources. Xiaoxu Shi and Christian Stepanek acknowledge computing and data storage resources for the generation of the AWI-ESM-1/AWI-ESM-2 and MPI-ESM-1-2 simulations of Deutsches Klimarechenzentrum (DKRZ) granted by its Scientific Steering Committee (WLA) under project ID ba1066. The Max Planck Institute for Meteorology in Hamburg is acknowledged for development and provision of the MPI-ESM as well as the ECHAM6/JSBACH, which provides the atmosphere and land surface component of AWI-ESM. Gerrit Lohmann acknowledges funding via the Alfred Wegener Institute’s research program PACES2. Christian Stepanek acknowledges funding by the Helmholtz Climate Initiative REKLIM and the Alfred Wegener Institute’s research program PACES2. Xiaoxu Shi acknowledges financial support through the BMBF funded PACMEDY and PalMOD initiatives. Ayako Abe-Ouchi and Ryouta O’ishi acknowledge the financial support from Arctic Challenge for Sustainability (ArCS) Project (grant JPMXD1300000000), Arctic Challenge for Sustainability II (ArCS II) Project (grant no. JPMXD1420318865), JSPS KAKENHI grant 17H06104 and MEXT KAKENHI grant 17H06323, and the support from JAMSTEC for the use of the Earth Simulator supercomputer. Polina A. Morozova was supported by the state assignment project 0148-2019-0009. Evgeny Volodin was supported by RSF grant 20-17-00190., The authors acknowledge QUIGS (Quaternary Interglacials), a working group of Past Global Changes (PAGES), which in turn received support from the US National Science Foundation, Swiss National Science Foundation, Swiss Academy of Sciences, and the Chinese Academy of Sciences. We are grateful to the World Climate Research Programme (WCRP), which, through its Working Group on Coupled Modelling, coordinated and promoted CMIP6., Financial support. Funding of the publication has been supported by the National Center for Atmospheric Research (NCAR), which is a major facility sponsored by the National Science Foundation under cooperative agreement no. 1852977., Water and Climate Risk, Wolff, Eric [0000-0002-5914-8531], Apollo - University of Cambridge Repository, Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: IMPACTS, 010506 paleontology, 010504 meteorology & atmospheric sciences, Orbital forcing, sub-01, EXPERIMENTAL-DESIGN, Stratigraphy, lcsh:Environmental protection, 3705 Geology, POLAR AMPLIFICATION, MIDHOLOCENE, 01 natural sciences, lcsh:Environmental pollution, Paleoclimatology, Sea ice, lcsh:TD169-171.8, SDG 14 - Life Below Water, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, TEMPERATURE, AFRICAN MONSOON, lcsh:Environmental sciences, 0105 earth and related environmental sciences, lcsh:GE1-350, 13 Climate Action, Global and Planetary Change, geography, Coupled model intercomparison project, geography.geographical_feature_category, EARTH SYSTEM MODEL, CHRONOLOGY AICC2012, Northern Hemisphere, Paleontology, 37 Earth Sciences, 3709 Physical Geography and Environmental Geoscience, Arctic ice pack, ANTARCTIC ICE, 13. Climate action, Climatology, lcsh:TD172-193.5, 3701 Atmospheric Sciences, Climate sensitivity, Environmental science, Climate model, SENSITIVITY
Abstract: The modeling of paleoclimate, using physically based tools, is increasingly seen as a strong out-of-sample test of the models that are used for the projection of future climate changes. New to the Coupled Model Intercomparison Project (CMIP6) is the Tier 1 Last Interglacial experiment for 127 000 years ago (lig127k), designed to address the climate responses to stronger orbital forcing than the midHolocene experiment, using the same state-of-the-art models as for the future and following a common experimental protocol. Here we present a first analysis of a multi-model ensemble of 17 climate models, all of which have completed the CMIP6 DECK (Diagnostic, Evaluation and Characterization of Klima) experiments. The equilibrium climate sensitivity (ECS) of these models varies from 1.8 to 5.6 ∘C. The seasonal character of the insolation anomalies results in strong summer warming over the Northern Hemisphere continents in the lig127k ensemble as compared to the CMIP6 piControl and much-reduced minimum sea ice in the Arctic. The multi-model results indicate enhanced summer monsoonal precipitation in the Northern Hemisphere and reductions in the Southern Hemisphere. These responses are greater in the lig127k than the CMIP6 midHolocene simulations as expected from the larger insolation anomalies at 127 than 6 ka. New synthesis for surface temperature and precipitation, targeted for 127 ka, have been developed for comparison to the multi-model ensemble. The lig127k model ensemble and data reconstructions are in good agreement for summer temperature anomalies over Canada, Scandinavia, and the North Atlantic and for precipitation over the Northern Hemisphere continents. The model–data comparisons and mismatches point to further study of the sensitivity of the simulations to uncertainties in the boundary conditions and of the uncertainties and sparse coverage in current proxy reconstructions. The CMIP6–Paleoclimate Modeling Intercomparison Project (PMIP4) lig127k simulations, in combination with the proxy record, improve our confidence in future projections of monsoons, surface temperature, and Arctic sea ice, thus providing a key target for model evaluation and optimization.
Published: 2021
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145. Dietary intake and plasma phospholipid concentrations of saturated, monounsaturated and trans fatty acids and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Joseph A. Rothwell, Giovanna Masala, José María Huerta, Aurora Perez-Cornago, Elisabete Weiderpass, Anja Olsen, Magritt Brustad, Claudia Agnoli, Corinne Casagrande, Guri Skeie, Ulrika Ericson, Verena Katzke, Mazda Jenab, Christina C. Dahm, Anne Tjønneland, Geneviève Nicolas, Rudolf Kaaks, Inge Huybrechts, Veronika Fedirko, Carlotta Sacerdote, Neil Murphy, Maria Wennberg, Veronique Chajes, Jeroen W.G. Derksen, Matthias B. Schulze, Elom K. Aglago, Bas Bueno-de-Mesquita, Alicia K Heath, Pilar Amiano, Salvatore Panico, Paula Jakszyn, Rosario Tumino, Marc J. Gunter, Inger T. Gram, María José Sánchez, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 1000143, MR/M012190/1, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Cancer Research UK, CRUK: 14136, C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Rijksinstituut voor Volksgezondheid en Milieu, RIVM, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, World Cancer Research Fund, Grant/Award Number: WCRF 2013/1002 Funding information trans, The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Ms Beatrice Vozar, Mr Bertrand Hemon and Ms Carine Biessy for the analysis of plasma samples, and the preparation of the databases. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C8221/A29017 to EPIC‐Oxford), MedicalResearch Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford). (United Kingdom), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. The EPIC‐Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC‐PC_13048 and MC‐UU_12015/1). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. The authors would like to acknowledge the use of data and samples from EPIC centres in Cambridge, France, Asturias, and Navarro. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Our study was funded by a grant from the World Cancer Research Fund to Marc Gunter (Grant number: WCRF 2013/1002)., Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Health Research Fund (FIS)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology?ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), MedicalResearch Council (1000143 to EPIC-Norfolk, and MR/M012190/1 to EPIC-Oxford). (United Kingdom), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC-PC_13048 and MC-UU_12015/1). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. The authors would like to acknowledge the use of data and samples from EPIC centres in Cambridge, France, Asturias, and Navarro. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Our study was funded by a grant from the World Cancer Research Fund to Marc Gunter (Grant number: WCRF 2013/1002).
Subjects: Cancer Research, medicine.medical_specialty, Colorectal cancer, Myristic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, Gastroenterology, fatty acids, DISEASE, Palmitic acid, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, COLON, medicine, 2 SIDES, 2. Zero hunger, chemistry.chemical_classification, business.industry, Fatty acid, Odds ratio, ASSOCIATION, medicine.disease, Elaidic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Oncology, chemistry, 030220 oncology & carcinogenesis, biomarker, Stearic acid, business, dietary intake, LIPIDS
Abstract: International audience; Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up = 15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD = 0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD = 1.04, 95%CI:0.95-1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD = 1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.
Published: 2021
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146. Climate change reduces winter overland travel across the Pan-Arctic even under low-end global warming scenarios

Author: Wim Thiery, Melissa Head, Moritz Langer, Eleanor J. Burke, Sibyll Schaphoff, Julia Boike, Kirsten Thonicke, Anne Gädeke, Jinfeng Chang, Christopher P. O. Reyer, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Bundesministerium für Bildung und Forschung, BMBF: 01LS1711C, This research was supported by the German Federal Ministry of Education and Research (BMBF) and the European Research Area for Climate Services ERA4CS with project funding reference 518 number 01LS1711C (ISIPedia project). CPOR acknowledges funding from the Horizon 2020 project CASCADES (Grant Agreement 821010). ML was supported by a BMBF grant (project PermaR-isk, Grant No. 01LN1709A). WT acknowledges the Uniscientia Foundation and the ETH Zurich Foundation for their support to this research. EJB was funded by the European Commission’s Horizon 2020 Framework Programme, under Grant Agreement number 641816, the ‘Coordinated Research in Earth Systems and Climate: Experiments, Knowledge, Dissemination and Outreach (CRESCENDO)’ project (11/2015–10/2020) and the Met Office Had-ley Centre Climate Programme funded by BEIS and Defra., European Project: 641816,H2020,H2020-SC5-2014-two-stage,CRESCENDO(2015), Hydrology and Hydraulic Engineering, Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Earth and Climate
Subjects: Resource (biology), 333.7 Landflächen, Naturräume für Freizeit und Erholung, Naturreservate, Energie, 010504 meteorology & atmospheric sciences, Climate change, Permafrost, Environmental Sciences & Ecology, 010501 environmental sciences, 01 natural sciences, Permafrost degradation, ice roads, permafrost, climate change, land surface models, Arctic transport, winter roads, Arctic accessibility, ddc:333, Meteorology & Atmospheric Sciences, 0105 earth and related environmental sciences, General Environmental Science, Science & Technology, Winter roads, Renewable Energy, Sustainability and the Environment, Pan arctic, Global warming, Public Health, Environmental and Occupational Health, Livelihood, 13. Climate action, [SDU]Sciences of the Universe [physics], General Circulation Model, Physical Sciences, Environmental science, Physical geography, Life Sciences & Biomedicine, Environmental Sciences
Abstract: Amplified climate warming has led to permafrost degradation and a shortening of the winter season, both impacting cost-effective overland travel across the Arctic. Here we use, for the first time, four state-of-the-art Land Surface Models that explicitly consider ground freezing states, forced by a subset of bias-adjusted CMIP5 General Circulation Models to estimate the impact of different global warming scenarios (RCP2.6, 6.0, 8.5) on two modes of winter travel: overland travel days (OTDs) and ice road construction days (IRCDs). We show that OTDs decrease by on average −13% in the near future (2021–2050) and between −15% (RCP2.6) and −40% (RCP8.5) in the far future (2070–2099) compared to the reference period (1971–2000) when 173 d yr−1 are simulated across the Pan-Arctic. Regionally, we identified Eastern Siberia (Sakha (Yakutia), Khabarovsk Krai, Magadan Oblast) to be most resilient to climate change, while Alaska (USA), the Northwestern Russian regions (Yamalo, Arkhangelsk Oblast, Nenets, Komi, Khanty-Mansiy), Northern Europe and Chukotka are highly vulnerable. The change in OTDs is most pronounced during the shoulder season, particularly in autumn. The IRCDs reduce on average twice as much as the OTDs under all climate scenarios resulting in shorter operational duration. The results of the low-end global warming scenario (RCP2.6) emphasize that stringent climate mitigation policies have the potential to reduce the impact of climate change on winter mobility in the second half of the 21st century. Nevertheless, even under RCP2.6, our results suggest substantially reduced winter overland travel implying a severe threat to livelihoods of remote communities and increasing costs for resource exploration and transport across the Arctic. Met Office Hadley Centre Climate Programme Bundesministerium für Bildung und Forschunghttp://dx.doi.org/10.13039/501100002347 Horizon 2020 Framework Programmehttp://dx.doi.org/10.13039/100010661 Uniscientia Foundation
Published: 2021
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147. Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross-sectional and longitudinal data

Author: Daniel F. Schmidt, Rory P. Wilson, Melanie Waldenberger, Laura Baglietto, Harindra Jayasekara, Benjamin Lehne, Graham G. Giles, Pierre Antoine Dugué, Jaspal S. Kooner, Melissa C. Southey, Xiaochuan Wang, Annette Peters, Karl-Heinz Ladwig, Dallas R. English, John C Chambers, Jihoon E. Joo, Christian Gieger, Roger L. Milne, Chol-Hee Jung, Gianluca Severi, Enes Makalic, Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, Melbourne School of Population and Global Health [Melbourne], University of Melbourne, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, W2 1PG, Melbourne Bioinformatics [Australia], The University of MelbourneParkville, VIC, Australia., Department of Clinical and Experimental Medicine, University of Pisa, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), München, Technische Universität München, German Research Center for Cardiovascular Disease (DZHK), Partner site Munich Heart Alliance, Institute of Epidemiology and Medical Biometry, University of Ulm, Munich, Germany, Ealing Hospital, Imperial College Healthcare NHS Trust, Monash University [Clayton], Nanyang Technological University [Singapour], Imperial College Healthcare NHS Trust Oregon Department of Agriculture, ODA: 16/136/68 279143 Wellcome Trust, WT: 084723/Z/08/Z, 090532, RP‐PG‐0407‐10371, 098381 Cancer Council Victoria: 1026892, 1027505, 251553, 209057, 1050198, 1011618, 1074383, 504711, 1043616 Bundesministerium für Bildung und Forschung, BMBF VicHealth British Heart Foundation, BHF: SP/04/002 Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München National Institute for Health Research, NIHR National Health and Medical Research Council, NHMRC: 1088405 Horizon 2020 Framework Programme, H2020: 643774 ERAB: The European Foundation for Alcohol Research, ERAB: ERAB 2018 – EA1817 Medical Research Council, MRC: G0601966, G0700931 National Medical Research Council, NMRC: NMRC/STaR/0028/2017, and This work (MCCS) was supported by the Australian National Health and Medical Research Council (NHMRC) (Grant 1088405). MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC Grants 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases were ascertained through the Victorian Cancer Registry (VCR) and the Australian Cancer Database (Australian Institute of Health and Welfare). The nested case‐control methylation studies were supported by the NHMRC Grants 1011618, 1026892, 1027505, 1050198, 1043616, and 1074383. M.C.S. is an NHMRC Senior Research Fellow (1061177). The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research has been supported within the Munich Center of Health Sciences (MC‐Health), Ludwig‐Maximilians‐Universität, as part of LMUinnovativ. This work has received funding from the European Foundation for Alcohol Research (ERAB 2018 – EA1817). We thank all members of field staffs who were involved in the planning and conduct of the MONICA/KORA Augsburg studies. The LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966, G0700931), the Wellcome Trust (084723/Z/08/Z, 090532, and 098381), the NIHR (RP‐PG‐0407‐10371), the NIHR Official Development Assistance (ODA, award 16/136/68), the European Union FP7 (EpiMigrant, 279143), and H2020 programs (iHealth‐T2D, 643774). We acknowledge support of the MRC‐PHE Centre for Environment and Health and the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards. The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the Imperial College Healthcare NHS Trust, the NHS, the NIHR, or the Department of Health. We thank the participants and research staff who made the study possible. JC is supported by the Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research Investigator (STaR) Award (NMRC/STaR/0028/2017).
Subjects: Male, longitudinal data, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Physiology, Alcohol, Disease, Epigenesis, Genetic, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Prospective Studies, education.field_of_study, 0303 health sciences, DNA methylation, Confounding, Regression analysis, Methylation, Middle Aged, epigenome-wide association study, Substance abuse, Psychiatry and Mental health, 030220 oncology & carcinogenesis, Female, Alcohol consumption, Cohort study, Adult, Alcohol Drinking, Longitudinal data, alcohol consumption, Population, 03 medical and health sciences, Genetic, cross-sectional data, EWAS, HM450 assay, Aged, CpG Islands, Cross-Sectional Studies, Genome-Wide Association Study, Humans, DNA Methylation, Epigenetics, education, 030304 developmental biology, Pharmacology, business.industry, Alcohol Consumption, Cross-sectional Data, Dna Methylation, Epigenome-wide Association Study, Ewas, Hm450 Assay, Longitudinal Data, medicine.disease, 030227 psychiatry, chemistry, business, 030217 neurology & neurosurgery, Epigenesis
Abstract: Background:DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart.Methods:Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined using baseline peripheral blood samples from 5,606 adult Melbourne Collaborative Cohort Study (MCCS) participants. For a subset of 1,088 of them, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. Independent data from the LOLIPOP (N=4,042) and KORA (N=1,662) cohorts were used to replicate associations discovered in the MCCS.Results:Cross-sectional analyses identified 1,414 CpGs associated with alcohol intake at P-7, 1,243 of which had not been reported previously. Of these 1,243 novel associations, 1,078 were replicated (PConclusion:Our study indicates that, for middle-aged and older adults, alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with changes in alcohol consumption.
Published: 2021
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148. Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Amanda J. Cross, Kristin Benjaminsen Borch, Renée T. Fortner, Vittorio Simeon, Paul Brennan, Guri Skeie, Elio Riboli, Rosario Tumino, Elisabete Weiderpass, Gianluca Severi, Carlotta Sacerdote, Kim Overvad, Manuela M. Bergmann, Isabel Drake, Sara Grioni, Panagiota Pagoni, Giovanna Masala, Pietro Ferrari, Heinz Freisling, Matthias B. Schulze, Maria Dolores Chirlaque, Pilar Amiano, Mattias Johansson, Ioanna Tzoulaki, Konstantinos K. Tsilidis, Timothy J. Key, J. Ramón Quirós, Eva Ardanaz, Antonio Agudo, Neil Murphy, Marie-Christine Boutron-Ruault, Christel Häggström, Sofia Christakoudi, Rudolf Kaaks, Merete Ellingjord-Dale, Sophia Harlid, Charlotta Rylander, Tanja Stocks, Anne Tjønneland, Fanny Artaud, Laure Dossus, Jytte Halkjær, Miguel Rodríguez-Barranco, Aurora Perez-Cornago, David C. Muller, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC National Research Council, NRC Medical Research Council, MRC: MC_UU_00011/6, MR/M012190/1 Cancer Research UK, CRUK: C570/A16491, C8221/A19170 World Cancer Research Fund, WCRF European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Vetenskapsrådet, VR Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Rijksinstituut voor Volksgezondheid en Milieu, RIVM Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN NIHR Imperial Biomedical Research Centre, BRC Fondation Gustave Roussy, The authors thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC study. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Kr?ftens Bek?mpelse) (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid (Deutsche Krebshilfe), German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Federal Ministry of Education and Research (Bundesministerium f?r Bildung und Forschung, BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS-ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain), Swedish Cancer Society (Cancerfonden), Swedish Research Council (Vetenskapsr?det), County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (MR/M012190/1 to EPIC-Oxford) (United Kingdom). Panagiota Pagoni is funded by Medical Research Council (grant reference MC_UU_00011/6). Infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London (UK) was provided by the NIHR Imperial Biomedical Research Centre (BRC). The funders had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or the preparation, review and approval of the manuscript, or in the decision to submit the manuscript for publication., The authors thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC study. The coordination of EPIC is financially supported by the European Commission (DG‐SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Kræftens Bekæmpelse) (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid (Deutsche Krebshilfe), German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Health Research Fund (FIS‐ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain), Swedish Cancer Society (Cancerfonden), Swedish Research Council (Vetenskapsrådet), County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/M012190/1 to EPIC‐Oxford) (United Kingdom). Panagiota Pagoni is funded by Medical Research Council (grant reference MC_UU_00011/6). Infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London (UK) was provided by the NIHR Imperial Biomedical Research Centre (BRC). The funders had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or the preparation, review and approval of the manuscript, or in the decision to submit the manuscript for publication., Associazione Italiana per la Ricerca sul Cancro, Bundesministerium für Bildung und Forschung, Cancer Research UK, Grant/Award Numbers: C570/A16491, C8221/A19170, Cancerfonden, Catalan Institute of Oncology Barcelona, Centre International de Recherche sur le Cancer, County Council of Skåne Sweden, County Council of Västerbotten Sweden, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, Directorate‐General for Health and Consumers, Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), Health Research Fund (FIS‐ISCIII) Spain, Institut Gustave‐Roussy, Institut National de la Santé et de la Recherche Médicale, Kræftens Bekæmpelse, Ligue Contre le Cancer, LK Research Funds, Medical Research Council, Grant/Award Numbers: MC_UU_00011/6, MR/M012190/1, Mutuelle Générale de l'Education Nationale, National Research Council Italy, Netherlands Cancer Registry, Regional Government of Andalucía, Regional Government of Asturias, Regional Government of Basque Country, Regional Government of Murcia, Regional Government of Navarra, Statistics Netherlands, Vetenskapsrådet, World Cancer Research Fund (WCRF), Institut Gustave Roussy, International Agency for Research on Cancer, European Commission (DG‐SANCO) Funding information, Christakoudi, S., Pagoni, P., Ferrari, P., Cross, A. J., Tzoulaki, I., Muller, D. C., Weiderpass, E., Freisling, H., Murphy, N., Dossus, L., Turzanski Fortner, R., Agudo, A., Overvad, K., Perez-Cornago, A., Key, T. J., Brennan, P., Johansson, M., Tjonneland, A., Halkjaer, J., Boutron-Ruault, M. -C., Artaud, F., Severi, G., Kaaks, R., Schulze, M. B., Bergmann, M. M., Masala, G., Grioni, S., Simeon, V., Tumino, R., Sacerdote, C., Skeie, G., Rylander, C., Borch, K. B., Quiros, J. R., Rodriguez-Barranco, M., Chirlaque, M. -D., Ardanaz, E., Amiano, P., Drake, I., Stocks, T., Haggstrom, C., Harlid, S., Ellingjord-Dale, M., Riboli, E., Tsilidis, K. K., and Cancer Research UK
Subjects: Male, Cancer Research, middle adulthood, Overweight, Body Mass Index, Cohort Studies, 0302 clinical medicine, Weight loss, Risk Factors, Neoplasms, Prospective Studies, Correlation of Data, 2. Zero hunger, Ovarian Neoplasms, Obstetrics, Hazard ratio, PROLIFERATION, WOMEN, weight gain, Middle Aged, Kidney Neoplasms, 3. Good health, European Prospective Investigation into Cancer and Nutrition, BMI change, Europe, Oncology, 030220 oncology & carcinogenesis, ddc:540, Female, SQUAMOUS-CELL CARCINOMA, medicine.symptom, Life Sciences & Biomedicine, EXPRESSION, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, LEPTIN, FATNESS, medicine, Humans, cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Obesity, Risk factor, Proportional Hazards Models, Cancer och onkologi, Science & Technology, business.industry, Weight change, Endometrial Neoplasms, BODY-MASS INDEX, ESTROGEN-RECEPTORS, Pancreatic Neoplasms, Nutrition Assessment, Cancer and Oncology, Institut für Ernährungswissenschaft, GAIN, weight loss, business, Weight gain, Body mass index
Abstract: International audience; Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
Published: 2021
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149. Effects of temporary grassland introduction into annual crop rotations and nitrogen fertilisation on earthworm communities and forage production

Author: Daniel Cluzeau, François Gastal, Kevin Hoeffner, Guénola Pérès, Hoël Hotte, Xavier Charrier, AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Fourrages Environnement Ruminants Lusignan (FERLUS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), EU SoilMan project through the 2015-2016 BiodivERsA COFUND call for research proposals [01LC1620], Federal Ministry of Education and Research (BMBF) Federal Ministry of Education and Research (BMBF), French National Research Agency (ANR) French National Research Agency (ANR), Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) Swedish Research Council Formas, Spanish Ministry of Economy and Competitiveness (MINECO), Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI)Consiliul National al Cercetarii Stiintifice (CNCS) Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI), Estonian Research Council (ETAG), AnaEE France [ANR-11-INBS-0001], AllEnvi, CNRS-INSU Centre National de la Recherche Scientifique (CNRS), ANR-11-INBS-0001,ANAEE-FR,ANAEE-Services(2011), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), and Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Soil Science, Context (language use), Forage, 01 natural sciences, Grassland, Abundance (ecology), Ecological category, Grassland management, Mineral fertilisation, 2. Zero hunger, geography, Biomass (ecology), geography.geographical_feature_category, Ecology, biology, business.industry, Earthworm, 04 agricultural and veterinary sciences, 15. Life on land, Crop rotation, biology.organism_classification, Agricultural and Biological Sciences (miscellaneous), Soil biodiversity, Agronomy, Agriculture, Grassland duration, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, 010606 plant biology & botany
Abstract: International audience; Earthworms contribute to a wide range of ecosystem services in agriculture. Most studies focusing on impacts of annual crop management on earthworm communities are related to soil tillage, fertilisation or pesticides, while the effect of introducing temporary grassland into an annual crop rotation remains largely unknown. In this context, the aims of the present study were to evaluate effects of (i) introducing grassland into a crop rotation, (ii) grassland duration and (iii) grassland fertilisation on earthworm communities and grassland forage production in a long-term experimental station in western France. Three years of highly fertilised (230 kg ha(-1) yr(-1) of mineral nitrogen) grassland preceded by three years of annual crop rotation was compared to an annual crop rotation without grassland and to six years of grassland either lightly (30 kg ha(-1) yr(-1) of mineral nitrogen) or highly (230 kg ha(-1) yr(-1) of mineral nitrogen) fertilised. Grassland introduction into a crop rotation significantly increased earthworm abundance, biomass, and diversity, especially for anecic species, and improved the functional structure of the earthworm community. Grassland duration and fertilisation increased earthworm abundance and biomass, especially for anecics, without affecting endogeic species and earthworm diversity. Grassland duration did not increase forage production, but the increase in fertilisation did. Three years of highly fertilised grassland significantly increased earthworm abundance and biomass, improved the functional structure of the earthworm community and produced as much forage per year as six years of highly fertilised grassland. Overall, the introduction of grassland into annual crop rotations appears an effective way to rapidly increase earthworm community parameters and, given the important role of earthworms in soils, enhance soil functioning.
Published: 2021
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150. A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Author: Ingegerd Johansson, David S. Lopez, Alicia K Heath, Amanda J. Cross, Anne Tjønneland, J. Ramón Quirós, Melissa A. Merritt, Paula Jakszyn, Bas Bueno-de-Mesquita, Pilar Amiano, Anne Kirstine Eriksen, Manuela M. Bergmann, Marc J. Gunter, Bernard Srour, David C. Muller, Piet A. van den Brandt, Matthias B. Schulze, Salvatore Panico, Claudia Agnoli, Pietro Ferrari, Marco Lukic, José María Huerta, Christina C. Dahm, Therese Haugdahl Nøst, Areti Papadopoulou, Aurelio Barricarte Gurrea, Rosario Tumino, María José Sánchez, Fulvio Ricceri, Nadia Bastide, Paolo Vineis, Ulrika Ericson, Eva Ardanaz, Gianluca Severi, Guri Skeie, Aurora Perez-Cornago, Nikos Papadimitriou, Emmanouil Bouras, Elisabete Weiderpass, Ellio Riboli, Ioanna Tzoulaki, Heiner Boeing, Stina Bodén, Giovanna Masala, Jeroen W.G. Derksen, Jonna Berntsson, Verena Katzke, Elena Critselis, Konstantinos K. Tsilidis, University of Ioannina, Maastricht University [Maastricht], Imperial College London, Biomedical Research Foundation of the Academy of Athens (BRFAA), International Agency for Cancer Research (IACR), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Hawai'i [Honolulu] (UH), The University of Texas Health Science Center at Houston (UTHealth), University of Oxford [Oxford], University of Potsdam, The Arctic University of Norway (UiT), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Umeå University, Università degli studi di Torino = University of Turin (UNITO), Lund University [Lund], Instituto de Salud Carlos III [Madrid] (ISC), Aarhus University [Aarhus], IRCCS Istituto Nazionale dei Tumori [Milano], University of Copenhagen = Københavns Universitet (KU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Naples Federico II, La Salle [Ramon Llull University], Utrecht University [Utrecht], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, International Council of Ophthalmology, ICO, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF: WCRF 2014/1180, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme (WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (ICO) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford) and Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme ( WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre . The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research ( BMBF ) (Germany), Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)– Instituto de Salud Carlos III ( ISCIII ), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ( ICO ) (Spain), Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Epidemiologie, and RS: GROW - R1 - Prevention
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Riboflavin, colorectal cancer, Lower risk, Cohort Studies, Animal science, beta-Carotene, Risk Factors, Epidemiology, medicine, cohort study, Humans, Prospective Studies, Hepatology, Gastroenterology & Hepatology, business.industry, Hazard ratio, Gastroenterology, food and beverages, 1103 Clinical Sciences, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Diet, epidemiology, nutrition, business, Colorectal Neoplasms, Cohort study
Abstract: Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04–1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04–1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93–0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90–0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90–0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92–0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93–0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.
Published: 2020
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