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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Implementation of human system integration workshop at NASA for human spaceflight 70

Implementation of human system integration workshop at NASA ...

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70th International Astronautical Congress, IAC 2019

作者： Silva-Martinez, Jackelynne Schoenstein, Nicole Swarmer, Tiffany M. Russi-Vigoya, Natalia Salazar, George Silva, Herbert Baturoni-Cortez, Alicia Love, John Wong, Doug Walker, Rachel Operations Division Flight Operations Directorate NASA Johnson Space Center 2101 NASA Parkway HoustonTX77058 United States Human Systems Engineering and Integration Division Human Health and Performance Directorate MEI Technologies 18050 Saturn Ln HoustonTX77058 United States Crew Systems Operations Flight Operations Directorate KBR 2400 E NASA Parkway HoustonTX77058 United States Human Systems Engineering and Integration Division Human Health and Performance Directorate KBR 2400 E NASA Parkway HoustonTX77058 United States Avionics Systems Division Engineering Directorate NASA Johnson Space Center 2101 NASA Parkway HoustonTX77058 United States Structural Engineering Division Engineering Directorate NASA Johnson Space Center 2101 NASA Pa rkway HoustonTX77058 United States Office of STEM Engagement External Relations Office NASA Johnson Space Center 2101 NASA Parkway HoustonTX77058 United States Research Integration Office International Space Station Program NASA Johnson Space Center 2101 NASA Parkway HoustonTX77058 United States International Space Station Division Safety and Mission Assurance Directorate NASA Johnson Space Center 2101 NASA Parkway HoustonTX77058 United States Pathways Internship Program NASA Johnson Space Center 2101 NASA Parkway HoustonTX77058 United States

The human is a key element in the complex system of systems underlying space exploration missions. As a critical system, its operating bands and requirements need to be characterized and integrated with other systems. Optimal integration of the human system with hardware and software elements has an impact on multiple aspects of mission execution, including human health and performance, risk mitigation, effective design and functionality, enhanced safety, and reduced lifecycle costs. The field of human systems Integration (HSI) represents an interdisciplinary and comprehensive cross-cutting approach encompassing technical and management processes for integrating human as a system consideration and objective within and across all other system components and multiple domains. In addition to human activities, HSI covers training, operations and support dimensions. Moreover, HSI is an essential enabler to systems engineering practice, emphasizing human system aspects toward optimizing fully integrated system of systems performance while systematically infusing the needs of all users during the earliest stages of development. Consistent with the National Space Exploration Campaign, NASA is developing the Gateway, a lunar orbiting platform that will serve as astronaut habitat, support transit to deep space, validate new technologies and systems, and function as a science laboratory and communications hub, among other uses. It is an essential element of a phase that will extend human exploration into deep space through evolvable infrastructure and advanced technology, supporting assembly and logistics of other exploration architecture elements. In an effort to explore the current status and forward plan of HSI implementation in the mission (system of systems) lifecycle, the HSI Employee Resource Group conducted an HSI workshop using the Gateway program as a case study. It revealed how different organizations at the Johnson Space Center incorporate HSI in their processes in

关键词： NASA

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The 2022 report of the Lancet Countdown on health and climate change: health at the mercy of fossil fuels (vol 400, pg 1619, 2022)

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LANCET 2022年第10365期400卷 1766-1766页

作者： Romanello, M. Di Napoli, C. Drummond, P. Institute for Global Health University College London London UK School of Agriculture Policy and Development University of Reading Reading UK Institute for Sustainable Resources University College London London UK Department of Global Health Centre for Health and the Global Environment University of Washington Seattle WA USA UCL Energy Institute University College London London UK Department of Health Sciences University of York York UK Department of Meteorology University of Reading Reading UK Institute for Risk and Disaster Reduction University College London London UK School of Earth and Environment University of Leeds Leeds UK Centre on Climate Change and Planetary Health London School of Hygiene & Tropical Medicine London UK School of Population Health University of Melbourne Melbourne VIC Australia Department of Earth System Science Tsinghua University Beijing China Mercator Research Institute on Global Commons and Climate Change Berlin Germany Department of Environment Climate Change and Health World Health Organization Geneva Switzerland Institute of Environmental Sciences University of Geneva Geneva Switzerland Cardiovascular Epidemiology Unit Department of Public Health & Primary Care University of Cambridge Cambridge UK School of Government University of Birmingham Birmingham UK Economic Analysis of Climate Impacts and Policy Division Centro Euro-Mediterraneo sui Cambiamenti Climatici Venice Italy Institute for Environmental Design and Engineering University College London London UK Natural Resources Institute University of Greenwich London UK Department of Environmental Health Sciences and Yale Center on Climate Change and Health Yale University New Haven CT USA Department of Civil and Environmental Engineering Northeastern University Boston MA USA Department of Fish and Wildlife Conservation Virginia Polytechnic Institute and State University Blacksburg VA USA Department of Geography University College London London UK NU

With advancements in the science of detection and attribution studies, the influence of climate change over many events has now been quantified. Because of the rapidly increasing temperatures, vulnerable populations (adults older than 65 years, and children younger than one year of age) were exposed to 3·7 billion more heatwave days in 2021 than annually in 1986–2005 (indicator 1.1.2), and heat-related deaths increased by 68% between 2000–04 and 2017–21 (indicator 1.1.5), a death toll that was significantly exacerbated by the confluence of the COVID-19 pandemic. Despite the local cooling and overall health benefits of urban greenspaces, only 277 (27%) of 1038 global urban centres were at least moderately green in 2021 (indicator 2.2.3), and the number of households with air conditioning increased by 66% from 2000 to 2020, a maladaptive response that worsens the energy crisis and further increases urban heat, air pollution, and greenhouse gas emissions. [...]millions of people do not have access to the energy needed to keep their homes at healthy temperatures, preserve food and medication, and meet the seventh Sustainable Development Goal (to ensure access to affordable, reliable, sustainable, and modern energy for all). Aggravating this situation even further, governments continue to incentivise fossil fuel production and consumption: 69 (80%) of 86 countries reviewed had net-negative carbon prices (ie, provided a net subsidy to fossil fuels) for a net total of US$400 billion

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The 2021 report of the Lancet Countdown on health and climate change: code red for a healthy future

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The Lancet 2021年第10311期398卷 1619-1662页

作者： Romanello, Marina McGushin, Alice Di Napoli, Claudia Drummond, Paul Hughes, Nick Jamart, Louis Kennard, Harry Lampard, Pete Solano Rodriguez, Baltazar Arnell, Nigel Ayeb-Karlsson, Sonja Belesova, Kristine Cai, Wenjia Campbell-Lendrum, Diarmid Capstick, Stuart Chambers, Jonathan Chu, Lingzhi Ciampi, Luisa Dalin, Carole Dasandi, Niheer Dasgupta, Shouro Davies, Michael Dominguez-Salas, Paula Dubrow, Robert Ebi, Kristie L Eckelman, Matthew Ekins, Paul Escobar, Luis E Georgeson, Lucien Grace, Delia Graham, Hilary Gunther, Samuel H Hartinger, Stella He, Kehan Heaviside, Clare Hess, Jeremy Hsu, Shih-Che Jankin, Slava Jimenez, Marcia P Kelman, Ilan Kiesewetter, Gregor Kinney, Patrick L Kjellstrom, Tord Kniveton, Dominic Lee, Jason K W Lemke, Bruno Liu, Yang Liu, Zhao Lott, Melissa Lowe, Rachel Martinez-Urtaza, Jaime Maslin, Mark McAllister, Lucy McMichael, Celia Mi, Zhifu Milner, James Minor, Kelton Mohajeri, Nahid Moradi-Lakeh, Maziar Morrissey, Karyn Munzert, Simon Murray, Kris A Neville, Tara Nilsson, Maria Obradovich, Nick Sewe, Maquins Odhiambo Oreszczyn, Tadj Otto, Matthias Owfi, Fereidoon Pearman, Olivia Pencheon, David Rabbaniha, Mahnaz Robinson, Elizabeth Rocklöv, Joacim Salas, Renee N Semenza, Jan C Sherman, Jodi Shi, Liuhua Springmann, Marco Tabatabaei, Meisam Taylor, Jonathon Trinanes, Joaquin Shumake-Guillemot, Joy Vu, Bryan Wagner, Fabian Wilkinson, Paul Winning, Matthew Yglesias, Marisol Zhang, Shihui Gong, Peng Montgomery, Hugh Costello, Anthony Hamilton, Ian Institute for Global Health University College London London UK United Kingdom Institute for Sustainable Resources University College London London UK United Kingdom UCL Energy Institute University College London London UK United Kingdom Institute for Environmental Design and Engineering University College London London UK United Kingdom Department of Geography University College London London UK United Kingdom The Bartlett School of Sustainable Construction University College London London UK United Kingdom Centre for Human Health and Performance University College London London UK United Kingdom School of Agriculture Policy and Development University of Reading Reading United Kingdom Department of Meteorology University of Reading Reading United Kingdom The Walker Institute University of Reading Reading United Kingdom Department of Health Sciences University of York York United Kingdom Institute for Environment and Human Security United Nations University Bonn Germany Centre on Climate Change and Planetary Health London School of Hygiene & Tropical Medicine London UK United Kingdom Centre for Mathematical Modelling of Infectious Diseases London School of Hygiene & Tropical Medicine London UK United Kingdom Department of Public Health Environments and Society London School of Hygiene & Tropical Medicine London UK United Kingdom Department of Earth System Science Tsinghua University Beijing China Department of Environment Climate Change and Health World Health Organization Geneva Switzerland Institute for Environmental Sciences World Health Organization Geneva Switzerland Centre for Climate Change and Social Transformations School of Psychology Cardiff University Cardiff United Kingdom Yale Center on Climate Change and Health Yale University New Haven CT United States School of Government University of Birmingham Birmingham United Kingdom Economic analysis of Climate Impacts and Policy Centro Euro-Mediterraneo sui Cambiamenti Climatic

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The repertoire of mutational signatures in human cancer (vol 578, pg 94, 2020)

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NATURE 2023年第7948期614卷 E41-E41页

作者： Alexandrov, Ludmil B. Kim, Jaegil Haradhvala, Nicholas J. Huang, Mi Ni Ng, Alvin Wei Tian Wu, Yang Boot, Arnoud Covington, Kyle R. Gordenin, Dmitry A. Bergstrom, Erik N. Islam, S. M. Ashiqul Lopez-Bigas, Nuria Klimczak, Leszek J. McPherson, John R. Morganella, Sandro Sabarinathan, Radhakrishnan Wheeler, David A. Mustonen, Ville Getz, Gad Rozen, Steven G. Stratton, Michael R. Department of Cellular and Molecular Medicine Department of Bioengineering Moores Cancer Center University of California San Diego CA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Cellular and Molecular Medicine and Department of Bioengineering University of California San Diego La Jolla CA USA UC San Diego Moores Cancer Center San Diego CA USA University of California San Diego San Diego CA USA Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Massachusetts General Hospital Boston MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Laboratory for Medical Science Mathematics RIKEN Center for Integrative Medical Sciences Yokohama Japan Computational Biology Program Ontario Institute for Cancer Research Toronto ON Canada Programme in Cancer & Stem Cell Biology Duke-NUS Medical School Singapore Singapore Centre for Computational Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Centre for Computational Biology Duke-NUS Medical School Singapore Singapore SingHealth Duke-NUS Institute of Precision Medicine National Heart Centre Singapore Singapore Singapore Cancer Science Institute of Singapore National University of Singapore Singapore Singapore Institute of Molecular and Cell Biology Singapore Singapore Laboratory of Cancer Epigenome Division of Medical Science National Cancer Centre Singapore Singapore Singapore Duke-NUS Medical School Singapore Singapore Human Genome Sequencing Center Baylor College of Medicine Houston TX USA Dan L. Duncan Cancer Center Baylor College of Medicine Houston TX USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA Genome Integrity and Structural Biology Laboratory National Ins

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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

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Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

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The evolutionary history of 2,658 cancers (vol 578, pg 122, 2020)

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NATURE 2023年第7948期614卷 E42-E42页

作者： Gerstung, Moritz Jolly, Clemency Leshchiner, Ignaty Dentro, Stefan C. Gonzalez, Santiago Rosebrock, Daniel Mitchell, Thomas J. Rubanova, Yulia Anur, Pavana Yu, Kaixian Tarabichi, Maxime Deshwar, Amit Wintersinger, Jeff Kleinheinz, Kortine Vazquez-Garcia, Ignacio Haase, Kerstin Jerman, Lara Sengupta, Subhajit Macintyre, Geoff Malikic, Salem Donmez, Nilgun Livitz, Dimitri G. Cmero, Marek Demeulemeester, Jonas Schumacher, Steven Fan, Yu Yao, Xiaotong Lee, Juhee Schlesner, Matthias Boutros, Paul C. Bowtell, David D. Zhu, Hongtu Getz, Gad Imielinski, Marcin Beroukhim, Rameen Sahinalp, S. Cenk Ji, Yuan Peifer, Martin Markowetz, Florian Mustonen, Ville Yuan, Ke Wang, Wenyi Morris, Quaid D. Spellman, Paul T. Wedge, David C. Van Loo, Peter European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Wellcome Sanger Institute Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany University of Ljubljana Ljubljana Slovenia The Francis Crick Institute London UK Big Data Institute University of Oxford Oxford UK Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Big Data Institute Li Ka Shing Centre University of Oxford Oxford UK University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Department of Applied Mathematics and Theoretical Physics Centre for Mathematical Sciences University of Cambridge Cambridge UK Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA Department of Statistics Columbia University New York NY USA Department of Haematology University of Cambridge Cambridge UK University of Leuven Leuven Belgium Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Charlestown MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Dana-Farber Cancer Institute Boston MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Oxford NIHR Biomedical Research Centre Oxford UK Oxford NIHR Biomedical Research Centre University of Oxford Oxford UK University of Toronto Toronto Ontario Canada Vector Institute Toronto Ontario Canada Vector Institute Toronto ON Canada Department of Computer Science University of Toronto Toronto ON Canada Ontario Institute for Cancer Research Toronto Ontario Canada University of California Los Angeles

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Considering discrepancy when calibrating a mechanistic electrophysiology model

arXiv

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arXiv 2020年

作者： Lei, Chon Lok Ghosh, Sanmitra Whittaker, Dominic G. Aboelkassem, Yasser Beattie, Kylie A. Cantwell, Chris D. Delhaas, Tammo Houston, Charles Novaes, Gustavo Montes Panfilov, Alexander V. Pathmanathan, Pras Riabiz, Marina Weber dos Santos, Rodrigo Worden, Keith Mirams, Gary R. Wilkinson, Richard D. Computational Biology & Health Informatics Dept. of Computer Science University of Oxford United Kingdom MRC Biostatistics Unit University of Cambridge United Kingdom Centre for Mathematical Medicine & Biology School of Mathematical Sciences University of Nottingham United Kingdom Department of Bioengineering University of California San Diego United States Systems Modeling and Translational Biology GlaxoSmithKline R&D Stevenage United Kingdom ElectroCardioMaths Programme Centre for Cardiac Engineering Imperial College London United Kingdom CARIM School for Cardiovascular Diseases Maastricht University Netherlands Graduate Program in Computational Modeling Universidade Federal de Juiz de Fora Brazil Department of Physics and Astronomy Ghent University Belgium Laboratory of Computational Biology and Medicine Ural Federal University Ekaterinburg Russia U.S. Food and Drug Administration Center for Devices and Radiological Health Office of Science and Engineering Laboratories United States Department of Biomedical Engineering King’s College London Alan Turing Institute United Kingdom Dynamics Research Group Department of Mechanical Engineering University of Sheffield United Kingdom School of Mathematics and Statistics University of Sheffield United Kingdom

Uncertainty quantification (UQ) is a vital step in using mathematical models and simulations to take decisions. The field of cardiac simulation has begun to explore and adopt UQ methods to characterise uncertainty in model inputs and how that propagates through to outputs or predictions. In this perspective piece we draw attention to an important and under-addressed source of uncertainty in our predictions — that of uncertainty in the model structure or the equations themselves. The difference between imperfect models and reality is termed model discrepancy, and we are often uncertain as to the size and consequences of this discrepancy. Here we provide two examples of the consequences of discrepancy when calibrating models at the ion channel and action potential scales. Furthermore, we attempt to account for this discrepancy when calibrating and validating an ion channel model using different methods, based on modelling the discrepancy using Gaussian processes (GPs) and autoregressive-moving-average (ARMA) models, then highlight the advantages and shortcomings of each approach. Finally, suggestions and lines of enquiry for future work are provided. Copyright © 2020, The Authors. All rights reserved.

关键词： Uncertainty analysis

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The overlapping burden of the three leading causes of disability and death in sub-Saharan African children

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Nature Communications 2022年第1期13卷 1-14页

作者： Reiner, Robert C. Welgan, Catherine A. Troeger, Christopher E. Baumann, Mathew M. Weiss, Daniel J. Deshpande, Aniruddha Blacker, Brigette F. Miller-Petrie, Molly K. Earl, Lucas Bhatt, Samir Abolhassani, Hassan Abosetugn, Akine Eshete Abu-Gharbieh, Eman Adekanmbi, Victor Adetokunboh, Olatunji O. Aghaali, Mohammad Aji, Budi Alahdab, Fares Al-Aly, Ziyad Alhassan, Robert Kaba Ali, Saqib Alizade, Hesam Aljunid, Syed Mohamed Almasi-Hashiani, Amir Al-Mekhlafi, Hesham M. Altirkawi, Khalid A. Alvis-Guzman, Nelson Amare, Azmeraw T. Amini, Saeed Amugsi, Dickson A. Ancuceanu, Robert Andrei, Catalina Liliana Ansari, Fereshteh Anvari, Davood Appiah, Seth Christopher Yaw Arabloo, Jalal Aremu, Olatunde Atout, Maha Moh’d Wahbi Ausloos, Marcel Ausloos, Floriane Ayanore, Martin Amogre Aynalem, Yared Asmare Azene, Zelalem Nigussie Badawi, Alaa Baig, Atif Amin Banach, Maciej Bedi, Neeraj Bhagavathula, Akshaya Srikanth Bhandari, Dinesh Bhardwaj, Nikha Bhardwaj, Pankaj Bhattacharyya, Krittika Bhutta, Zulfiqar A. Bijani, Ali Birhanu, Tesega Tesega Mengistu Bitew, Zebenay Workneh Boloor, Archith Brady, Oliver J. Butt, Zahid A. Car, Josip Carvalho, Felix Casey, Daniel C. Chattu, Vijay Kumar Chowdhury, Mohiuddin Ahsanul Kabir Chu, Dinh-Toi Coelho, Camila H. Cook, Aubrey J. Damiani, Giovanni Daoud, Farah Gela, Jiregna Darega Darwish, Amira Hamed Daryani, Ahmad Das, Jai K. Davis Weaver, Nicole Deribe, Kebede Desalew, Assefa Dharmaratne, Samath Dhamminda Dianatinasab, Mostafa Diaz, Daniel Djalalinia, Shirin Dorostkar, Fariba Dubljanin, Eleonora Duko, Bereket Dwyer-Lindgren, Laura Effiong, Andem El Sayed Zaki, Maysaa El Tantawi, Maha Enany, Shymaa Fattahi, Nazir Feigin, Valery L. Fernandes, Eduarda Ferrara, Pietro Fischer, Florian Foigt, Nataliya A. Folayan, Morenike Oluwatoyin Foroutan, Masoud Frostad, Joseph Jon Fukumoto, Takeshi Gaidhane, Abhay Motiramji Gebrekrstos, Hailemikael Gebrekidan G. K. Gebremeskel, Leake Gebreslassie, Assefa Ayalew Gething, Peter W. Gezae, Kebede Embaye Ghadiri, Keyghobad Ghashghaee, Ahmad Golechha, Mahaveer Gubar Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States Malaria Atlas Project University of Oxford Oxford United Kingdom Imperial College London London United Kingdom Department of Laboratory Medicine Karolinska University Hospital Huddinge Sweden Research Center for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Department of Public Health Debre Berhan University Debre Berhan Ethiopia Department of Clinical Sciences University of Sharjah Sharjah United Arab Emirates Population Health Sciences King’s College London London United Kingdom Centre of Excellence for Epidemiological Modelling and Analysis Stellenbosch University Stellenbosch South Africa Department of Global Health Stellenbosch University Cape Town South Africa Department of Epidemiology and Biostatistics Qom University of Medical Sciences Qom Iran Faculty of Medicine and Public Health Jenderal Soedirman University Purwokerto Indonesia Mayo Evidence-based Practice Center Mayo Clinic Foundation for Medical Education and Research Rochester MN United States John T. Milliken Department of Internal Medicine Washington University in St. Louis St. Louis MO United States Clinical Epidemiology Center Department of Veterans Affairs St Louis MO United States Institute of Health Research University of Health and Allied Sciences Ho Ghana Department of Information Systems College of Economics and Political Science Sultan Qaboos University Muscat Oman Infectious and Tropical Disease Research Center Hormozgan University of Medical Sciences Bandar Abbas Iran Department of Health Policy and Management Kuwait University Safat Kuwait International Centre for Casemix and Clinical Coding National University of Malaysia Bandar Tun Razak Malaysia Department of Epidemiology Arak University of Medical Sciences Arak Iran Medical Research Center

Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseases, while others had one or two dominant sources of unit-level burden, with no consistent pattern geographically across the entire subcontinent. Using a subnational counterfactual analysis, we show that nearly 300 million DALYs could have been averted since 2000 by raising all units to their national average. Our findings are directly relevant for decision-makers in determining which and targeting where the most appropriate interventions are for increasing child survival. © 2022, The Author(s).

关键词： Biogeography Epidemiology Infectious diseases Malaria

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