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

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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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)

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NATURE GENETICS 2018年第5期50卷 765-766页

作者： Turcot, Valerie Lu, Yingchang Highland, Heather M. Schurmann, Claudia Justice, Anne E. Fine, Rebecca S. Bradfield, Jonathan P. Esko, Tonu Giri, Ayush Graff, Mariaelisa Guo, Xiuqing Hendricks, Audrey E. Karaderi, Tugce Lempradl, Adelheid Locke, Adam E. Mahajan, Anubha Marouli, Eirini Sivapalaratnam, Suthesh Young, Kristin L. Alfred, Tamuno Feitosa, Mary F. Masca, Nicholas G. D. Manning, Alisa K. Medina-Gomez, Carolina Mudgal, Poorva Ng, Maggie C. Y. Reiner, Alex P. Vedantam, Sailaja Willems, Sara M. Winkler, Thomas W. Abecasis, Goncalo Aben, Katja K. Alam, Dewan S. Alharthi, Sameer E. Allison, Matthew Amouyel, Philippe Asselbergs, Folkert W. Auer, Paul L. Balkau, Beverley Bang, Lia E. Barroso, Ines Bastarache, Lisa Benn, Marianne Bergmann, Sven Bielak, Lawrence F. Bluher, Matthias Boehnke, Michael Boeing, Heiner Boerwinkle, Eric Boger, Carsten A. Bork-Jensen, Jette Bots, Michiel L. Bottinger, Erwin P. Bowden, Donald W. Brandslund, Ivan Breen, Gerome Brilliant, Murray H. Broer, Linda Brumat, Marco Burt, Amber A. Butterworth, Adam S. Campbell, Peter T. Cappellani, Stefania Carey, David J. Catamo, Eulalia Caulfield, Mark J. Chambers, John C. Chasman, Daniel I. Chen, Yii-Der I. Chowdhury, Rajiv Christensen, Cramer Chu, Audrey Y. Cocca, Massimiliano Collins, Francis S. Cook, James P. Corley, Janie Galbany, Jordi Corominas Cox, Amanda J. Crosslin, David S. Cuellar-Partida, Gabriel D'Eustacchio, Angela Danesh, John Davies, Gail Bakker, Paul I. W. Groot, Mark C. H. Mutsert, Renee Deary, Ian J. Dedoussis, George Demerath, Ellen W. Heijer, Martin Hollander, Anneke I. Ruijter, Hester M. Dennis, Joe G. Denny, Josh C. Angelantonio, Emanuele Drenos, Fotios Du, Mengmeng Dube, Marie-Pierre Dunning, Alison M. Easton, Douglas F. Edwards, Todd L. Ellinghaus, David Ellinor, Patrick T. Elliott, Paul Evangelou, Evangelos Farmaki, Aliki-Eleni Farooqi, I. Sadaf Faul, Jessica D. Fauser, Sascha Feng, Shuang Ferrannini, Ele Ferrieres, Jean Florez, Jose C. Ford, Ian Fornage, Myriam Franco, Oscar H. Franke, Andre Franks, Paul W. Friedrich, Ne Montreal Heart Institute Université de Montréal Montreal Quebec Canada Division of Epidemiology Department of Medicine Vanderbilt-Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University School of Medicine Nashville TN USA Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai New York NY USA Genetics of Obesity and Related Metabolic Traits Program Icahn School of Medicine at Mount Sinai New York NY USA Department of Epidemiology University of North Carolina Chapel Hill NC USA Human Genetics Center University of Texas School of Public Health University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences University of Texas Health Science Center at Houston Houston TX USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Genetics Harvard Medical School Boston MA USA Division of Endocrinology and Center for Basic and Translational Obesity Research Boston Children’s Hospital Boston MA USA Center for Applied Genomics Division of Human Genetics Children’s Hospital of Philadelphia Philadelphia PA USA Quantinuum Research LLC San Diego CA USA Estonian Genome Center University of Tartu Tartu Estonia Division of Epidemiology Department of Medicine Institute for Medicine and Public Health Vanderbilt Genetics Institute Vanderbilt University Nashville TN USA Institute for Translational Genomics and Population Sciences LABioMed at Harbor-UCLA Medical Center Torrance CA USA Wellcome Trust Sanger Institute Hinxton UK Department of Mathematical and Statistical Sciences University of Colorado Denver CO USA Wellcome Trust Centre for Human Genetics University of Oxford Oxford UK Department of Biological Sciences Faculty of Arts and Sciences Eastern Mediterranean University Famagusta Cyprus Max Planck Institute of Immunobiology and Epigenetics Freiburg Germany Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (***35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

关键词： Genome-wide association studies Obesity

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Genomic basis for RNA alterations in cancer (vol 578, pg 129, 2020)

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NATURE 2023年第7948期614卷 E37-E37页

作者： Calabrese, Claudia Davidson, Natalie R. Demircioglu, Deniz Fonseca, Nuno A. He, Yao Lehmann, Kjong-Van Liu, Fenglin Shiraishi, Yuichi Soulette, Cameron M. Urban, Lara Greger, Liliana Li, Siliang Liu, Dongbing Perry, Marc D. Xiang, Qian Zhang, Fan Zhang, Junjun Bailey, Peter Erkek, Serap Hoadley, Katherine A. Hou, Yong Huska, Matthew R. Kilpinen, Helena Korbel, Jan O. Marin, Maximillian G. Markowski, Julia Nandi, Tannistha Pan-Hammarstrom, Qiang Pedamallu, Chandra Sekhar Siebert, Reiner Stark, Stefan G. Su, Hong Tan, Patrick Waszak, Sebastian M. Yung, Christina Zhu, Shida Awadalla, Philip Creighton, Chad J. Meyerson, Matthew Ouellette, B. F. Francis Wu, Kui Yang, Huanming Brazma, Alvis Brooks, Angela N. Goke, Jonathan Ratsch, Gunnar Schwarz, Roland F. Stegle, Oliver Zhang, Zemin European Molecular Biology Laboratory European Bioinformatics Institute Hinxton UK European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany CIBIO/InBIO - Research Center in Biodiversity and Genetic Resources Universidade do Porto Vairão Portugal Berlin Institute for Medical Systems Biology Max Delbruck Center for Molecular Medicine Berlin Germany German Cancer Consortium (DKTK) partner site Berlin Germany German Cancer Research Center (DKFZ) Heidelberg Germany Berlin Institute for Medical Systems Biology Max Delbrück Center for Molecular Medicine Berlin Germany German Cancer Consortium (DKTK) Partner site Berlin Berlin Germany European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Division of Computational Genomics and Systems Genetics German Cancer Research Center (DKFZ) Heidelberg Germany ETH Zurich Zurich Switzerland Memorial Sloan Kettering Cancer Center New York NY USA Weill Cornell Medical College New York NY USA SIB Swiss Institute of Bioinformatics Lausanne Switzerland University Hospital Zurich Zurich Switzerland Computational Biology Center Memorial Sloan Kettering Cancer Center New York NY USA Department of Biology ETH Zurich Zürich Switzerland Department of Computer Science ETH Zurich Zurich Switzerland Korea University Seoul South Korea Computational and Systems Biology Program Memorial Sloan Kettering Cancer Center 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 New York NY USA National University of Singapore Singapore Singapore Genome Institute of Singapore Singapore Singapore Computational and Systems Biology Genome Institute of Singap

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Abstracts Of Shellfish Technical Papers Presented at the joint meeting of the Northeast Aquaculture Conference and Exposition Milford Aquaculture Seminar and the International Conference on Shellfish Restoration Groton, Connecticut December 12–15, 2012

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Journal of Shellfish Research 2013年第2期32卷 571-612页

作者： Walter Blogoslawski Christopher Davis Dorothy Leonard Lisa Milke Steven Allen Peter Bergstrom A.C. Carpenter Mark Luckenbach Kennedy Paynter Angela Sowers Eric Weissberger James Wesson Stephanie Westby Steven Allen Stephanie Westby Claire O'Neil Angela Sowers Eric Weisberrger Oliver Bender Peter Boyce Gabriel Betty Mark Borrelli Anamarija Frankic Curtis Felix Jennifer Wilson Peter Boyce Oliver Bender Suzanne Bricker Tessa Getchis Cary Chadwick Julie Rose Cori Rose Kelsey Brockett Jessica Peterman David Bushek Daphne Munroe Eric Powell Lisa Calvo Barney Hollinger William Riggin William Shadel Jenny Paterno Ryan Carnegie David Bushek Carole Cyr Lisandre G. Solomon Francoise Bourque Tyler Carrier Stephen Eddy Sarah Redmond James Cervino Rand Weeks Jason Shorr Carmen Lin Dajana Gjoza Thomas J. Goreau Erik Chapman Derrick Chelikowsky Diane Kapareiko Dorothy Jefferess Gary Wikfors Carmela Cuomo Joseph Choromanski Sheila Stiles Dorothy Jeffress Haley Ladeau Loren Coen Boze Hancock Lesley Baggett Sean Powers Rob Brumbaugh Summer Morlock Bryan DeAngelis Anne Cohen Daniel McCorkle Gail Schwietermann Kathryn Rose Dave Conley SaiGiridhar Dasika April Croxton Soren Dahl Debra Barnes Bassem Allam Jonathan Davis Brian Allen Betsy Peabody Jonathan Davis Julie Davis William Walton Donatella Del Piero Michael Devin Molly Flanagan Paul Rawson Chauncey Devin Dana Morse Mark S. Dixon Genevieve Bernatchez Kelsey Boeff Eve Galimany Yaqin Li Aynur Lok Shannon L. Meseck Marguerite Petit Sean Dixon Sam Lee Dennis O'Connor Kelly Drake Shelley Edmundson Elizabeth Fairchild Melissa Evans Allison Fitzgerald Chester Zarnoch William Wallace Amy Fitzpatrick Gef Flimlin Sandra Macfarlane Gef Flimlin Thomas Foca David Bushek Timothy Visel Walter Blogoslawski Deborah A. Bouchard Joseph Buttner John Ewart Ann Faulds George E. Flimlin Doris Hicks Craig Hollingsworth Andrew Lazur Dale Leavitt Dennis McIntosh Dana L. Morse Tom Rippen Gregg Rivara Roxanna Smolowitz Dan Terlizzi Don Webster Michael Chambers Diane C. Murphy Robert Pomeroy Josh Reitsma Mic U.S. Department of Commerce National Oceanic and Atmospheric Administration National Marine Fisheries Service Northeast Fisheries Science Center Milford Laboratory 212 Rogers Avenue Milford CT 06460 Maine Aquaculture Innovation Center 5717 Corbett Hall Room 436 Orono ME 04469 Ocean Equities LLC 776 Rolling View Drive Annapolis MD 21409. Oyster Recovery Partnership 1805A Virginia St Annapolis MD 21401 NOAA Chesapeake Bay Office 410 Severn Ave Suite 207-A Annapolis MD 21403 Potomac River Fisheries Commission 222 Taylor St Colonial Beach VA 22443 Virginia Institute of Marine Science Eastern Shore Laboratory PO Box 350 Wachapreague VA 23480 1213 HJ Patterson Hall University of Maryland College Park MD 20742 U. S. Army Corps of Engineers Baltimore District P.O. Box 1715 Baltimore MD 21203 Maryland Department of Natural Resources 580 Taylor Ave Annapolis MD 21401 Virginia Marine Resources Commission 2600 Washington Ave Newport News VA 23607 NOAA Restoration Center 410 Severn Ave Annapolis MD 21403. Oyster Recovery Partnership 1805A Virginia St Annpolis MD 21401 National Oceanographic and Atmospheric Administration 410 Severn Ave Suite 107-A Annapolis MD 21403 USA Army Corps of Engineers 10 South Howard St Baltimore MD 21201 Maryland Department of Natural Resources 580 Taylor Ave Tawes State Office Building Annapolis MD 21401. Maria Mitchell Association 4 Vestal St Nantucket MA 02554 Maria Mitchell Association 65 Meadowview Drive Nantucket MA 02554. University of Rhode Island 620 Main St. Hopkinton RI 02832. Provincetown Center for Coastal Studies 5 Holway Avenue Provincetown MA 02657 University of Massachusetts Boston 100 Morrissey Blvd Boston Massachusetts Boston MA Town of Wellfleet 300 Main Street Wellfleet Massachusetts MA 02667. Maria Mitchell Association 65 Meadowview Dr Nantucket MA 02554. NOAA National Center for Coastal Ocean Science 1305 East West Highway Room 8110 Silver Spring MD 20910 Connecticut Sea Grant University o

It was with great excitement that we planned the combined meetings of Northeast Aquaculture Conference and Exposition (NACE) and the International Conference on Shellfish Restoration (ICSR) with the 33rd Milford Aquaculture Seminar (MAS). Bringing these different but complementary audiences together resulted in a meeting that combined many different aspects of fisheries restoration and aquaculture under one *** hundred attendees including government representatives, research scientists, industry, and academia at both the university and vocational high school levels attended this event. The meeting commenced on Wednesday December 12th 2012, with over eighty people attending seven field trips to area aquaculture farms and research facilities. The formal program began on Thursday, December 13th with a plenary session including invited speakers Eric Schwabb, Acting Assistant Secretary for Conservation and Management at NOAA; Sebastian Belle, Executive Director of the Maine Aquaculture Association and Boze Hancock from the Nature Conservancy, who discussed the role of aquaculture in fisheries restoration. John Bullard, the Northeast Regional Administrator of NOAA Fisheries Service, addressed the group during the luncheon the following day. The technical papers and workshops presented were divided into 35 sessions over three days of the meeting and included topics such as the history of aquaculture, aquaculture hatchery innovations, siting and planning issues, risk management, aquaculture business management, ocean acidification, climate change, as well as aquaculture disease issues and potential remedies. Having persons present who have experienced problems and successes, along with those in manufacturing and government responsible for addressing concerns and sharing best practices, was invaluable. Discussions among this cross-section of persons who represent different aspects of aquaculture were as important as the well-presented and interesting formal papers

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Long-term study of the intermittent extreme behaviour of 1ES 2344+514 38

Long-term study of the intermittent extreme behaviour of 1ES...

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38th International Cosmic Ray Conference, ICRC 2023

作者： Arbet-Engels, A. Mondal, H.A. Fukami, S. D’Ammando, F. Dorner, D. Chatterjee, R. Majumdar, P. Manganaro, M. Hovatta, T. Das, S. Raiteri, C.M. Villata, M. Perri, M. Verrechia, F. Leto, C. Filippenko, A. Zheng, W. Abe, H. Abe, S. Abhir, J. Acciari, V.A. Agudo, I. Aniello, T. Ansoldi, S. Antonelli, L.A. Arbet Engels, A. Arcaro, C. Artero, M. Asano, K. Baack, D. Babić, A. Baquero, A. Barres de Almeida, U. Barrio, J.A. Batković, I. Baxter, J. Becerra González, J. Bednarek, W. Bernardini, E. Bernardos, M. Bernete, J. Berti, A. Besenrieder, J. Bigongiari, C. Biland, A. Blanch, O. Bonnoli, G. Bošnjak, Ž. Burelli, I. Busetto, G. Campoy-Ordaz, A. Carosi, A. Carosi, R. Carretero-Castrillo, M. Castro-Tirado, A.J. Ceribella, G. Chai, Y. Chatterjee, R. Chilingarian, A. Cifuentes, A. Cikota, S. Colombo, E. Contreras, J.L. Cortina, J. Covino, S. D’Ammando, F. D’Amico, G. D’Elia, V. Da Vela, P. Dazzi, F. De Angelis, A. De Lotto, B. Del Popolo, A. Delfino, M. Delgado, J. Delgado Mendez, C. Depaoli, D. Di Pierro, F. Di Venere, L. Dominis Prester, D. Donini, A. Doro, M. Elsaesser, D. Emery, G. Escudero, J. Fariña, L. Fattorini, A. Foffano, L. Font, L. Fröse, S. Fukazawa, Y. García López, R.J. Garczarczyk, M. Gasparyan, S. Gaug, M. Giesbrecht Paiva, J.G. Giglietto, N. Giordano, F. Gliwny, P. Godinović, N. Grau, R. Green, D. Green, J.G. Hadasch, D. Hahn, A. Hassan, T. Heckmann, L. Herrera, J. Hrupec, D. Hütten, M. Imazawa, R. Inada, T. Iotov, R. Ishio, K. Jiménez Martínez, I. Jormanainen, J. Kerszberg, D. Kluge, G.W. Kobayashi, Y. Kouch, P.M. Kubo, H. Kushida, J. Láinez Lezáun, M. Lamastra, A. Lelas, D. Leone, F. Lindfors, E. Linhoff, L. Lombardi, S. Longo, F. López-Coto, R. López-Moya, M. López-Oramas, A. Loporchio, S. Lorini, A. Lyard, E. Machado de Oliveira Fraga, B. Majumdar, P. Makariev, M. Maneva, G. Mang, N. Manganaro, M. Mangano, S. Mannheim, K. Mariotti, M. Martínez, M. Martínez-Chicharro, M. Mas-Aguilar, A. Mazin, D. Menchiari, S. Saha Inst. of Nuclear Physics A CI of Homi Bhabha National Inst. West Bengal Kolkata700064 India INAF - Istituto di Radioastronomia Via Gobetti 101 BolognaI-40129 Italy School of Astrophysics Presidency University 86/1 College Street Kolkata700073 India University of Rijeka Faculty of Physics Rijeka51000 Croatia - ASI via del Politecnico s.n.c. RomaI-00133 Italy INAF Osservatorio Astrofisico di Torino Pino TorineseI-10025 Italy University of Turku TurkuFI-20014 Finland Aalto University Metsähovi Radio Observatory Metsähovintie 114 Kylmälä02540 Finland Italian Space Agency ASI via del Politecnico snc Roma00133 Italy INAF - Osservatorio Astronomico di Roma via di Frascati 33 MonteporzioI-00040 Italy Department of Astronomy University of California BerkeleyCA94720-3411 United States Miller Institute for Basic Research in Science University of California BerkeleyCA94720 United States The University of Tokyo Chiba Kashiwa277-8582 Japan ETH Zürich ZürichCH-8093 Switzerland Instituto de Astrofísica de Canarias Dpto. de Astrofísica Universidad de La Laguna Tenerife La LagunaE-38200 Spain Instituto de Astrofísica de Andalucía-CSIC Glorieta de la Astronomía s/n Granada18008 Spain RomeI-00136 Italy Università di Udine INFN Trieste UdineI-33100 Italy Max-Planck-Institut für Physik MünchenD-80805 Germany Università di Padova INFN PadovaI-35131 Italy Bellaterra BarcelonaE-08193 Spain Technische Universität Dortmund DortmundD-44221 Germany Zagreb10000 Croatia IPARCOS Institute EMFTEL Department Universidad Complutense de Madrid MadridE-28040 Spain URCA RJ Rio de Janeiro22290-180 Brazil University of Lodz Faculty of Physics and Applied Informatics Department of Astrophysics Lodz90-236 Poland Centro de Investigaciones Energéticas Medioambientales y Tecnológicas MadridE-28040 Spain Departament de Física CERES-IEEC Universitat Autònoma de Barcelona BellaterraE-08193 Spain Università di Pisa INFN Pisa Pisa

Extreme high-frequency-peaked BL Lac objects (EHBLs) are the most energetic persistent sources in the Universe. They are characterized by a spectral energy distribution (SED) featuring a synchrotron peak energy above 1 keV. 1ES 2344+514 is a blazar known to behave as an EHBL intermittently. Until now, its EHBL nature was only reported during flares, but a coherent picture is missing as unbiased monitoring campaigns are lacking. This work presents the longest observing campaign from radio to very-high-energy (VHE) frequencies performed so far on 1ES2344+514. Using observations during 2019-2021, we carry out a systematic investigation of the intermittent EHBL phases. Together with MAGIC, the dataset also includes X-ray observations from NuSTAR, XMM-Newton, and AstroSAT, providing an unprecedented determination of the two SED components. For the first time we report a clear EHBL behaviour during a low flux activity in 1ES 2344+514. It implies a significant hardening of the electron distribution inside the jet independent of flux. We also detect a bright X-ray state characterized by an unusually soft spectra, thus violating the harder-when-brighter relation typically found in blazars. The SED study further reveals an excess in the ultraviolet data with respect to the extrapolation of the X-ray spectrum, suggesting at least two regions contributing to the synchrotron flux. Finally we investigate a gamma-ray flare not accompanied by an X-ray counterpart. This peculiar outburst is interpreted using a time-dependent model involving two emitting components. © Copyright owned by the author(s) under the terms of the Creative Commons.

关键词： Synchrotrons

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Hazardous explosive eruptions of a recharging multi-cyclic island arc caldera

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Nature Geoscience 2024年 323-331页

作者： Jonas Preine Christian Hübscher Jens Karstens Steffen Kutterolf Katharina Pank Gareth Crutchley Tim Druitt Abigail Metcalfe Paraskevi Nomikou Dimitrios Papanikolaou Michael Manga Ralf Gertisser Sarah Beethe Carole Berthod Iona McIntosh Thomas Ronge Zenon Mateo Masako Tominaga Acacia Clark Susan DeBari Raymond Johnston Ally Peccia Christopher Jones Günther Kletetschka Alexis Bernard Hehe Chen Shun Chiyonobu Tatiana Fernandez-Perez Kumar Batuk Joshi Olga Koukousioura Molly McCanta Antony Morris Paraskevi Polymenakou Adam Woodhouse Yuzuru Yamamoto Kuo-Lung Wang Hao-Yang Lee Xiaohui Li Institute of Geophysics University of Hamburg Hamburg Germany GEOMAR Helmholtz Centre for Ocean Research Kiel Kiel Germany University Clermont-Auvergne CNRS IRD OPGC Laboratoire Magmas et Volcans Clermont-Ferrand France Department of Geology and Geoenvironment National and Kapodistrian University of Athens Athens Greece Department of Earth and Planetary Science University of California Berkeley CA USA School of Geography Geology and the Environment Keele University Keele UK College of Earth Ocean and Atmospheric Sciences Oregon State University Corvallis OR USA Institut De Physique Du Globe De Paris Centre National de la Recherche Scientifique (CNRS) Paris France Japan Agency for Marine-Earth Science and Technology Yokosuka Japan International Ocean Discovery Program Texas A&M University College Station TX USA Department of Geology and Geophysics Woods Hole Oceanographic Institution Woods Hole MA USA School of Natural Sciences/CODES University of Tasmania Hobart Tasmania Australia Geology Department Western Washington University Bellingham WA USA School of Geosciences University of South Florida Tampa FL USA Lamont-Doherty Earth Observatory Columbia University Palisades NY USA Department of Earth and Planetary Sciences University of California Riverside CA USA Geophysical Institute University of Alaska Fairbanks Fairbanks AK USA Charles University Faculty of Science Prague Czech Republic Laboratoire des Fluides Complexes et leurs Réservoirs Université de Pau et des Pays de l’Adour Pau France School of Ocean Sciences China University of Geosciences Beijing China Faculty of International Resource Sciences Akita University Akita Japan Department of Geology Kent State University Kent OH USA Solid Earth Research Group National Centre for Earth Science Studies Thiruvananthapuram India School of Geology Aristotle University of Thessaloniki Thessaloniki Greece University of Cologne Institute of Geology and Mineralogy Cologne Germany

Caldera-forming eruptions of silicic volcanic systems are among the most devastating events on Earth. By contrast, post-collapse volcanic activity initiating new caldera cycles is generally considered less hazardous. Formed after Santorini’s latest caldera-forming eruption of ~1600bce, the Kameni Volcano in the southern Aegean Sea enables the eruptive evolution of a recharging multi-cyclic caldera to be reconstructed. Kameni’s eruptive record has been documented by onshore products and historical descriptions of mainly effusive eruptions dating back to 197bce. Here we combine high-resolution seismic reflection data with cored lithologies from International Ocean Discovery program Expedition 398 at four sites to determine the submarine architecture and volcanic history of intra-caldera deposits from Kameni. Our shore-crossing analysis reveals the deposits of a submarine explosive eruption that produced up to 3.1 km3of pumice and ash, which we relate to a historical eruption in 726ce. The estimated volcanic explosivity index of magnitude 5 exceeds previously considered worst-case eruptive scenarios for Santorini. Our finding that the Santorini caldera is capable of producing large explosive eruptions at an early stage in the caldera cycle implies an elevated hazard potential for the eastern Mediterranean region, and potentially for other recharging silicic calderas.

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Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations

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Human molecular genetics 2017年第2期26卷 454-465页

作者： Wei Jie Seow Keitaro Matsuo Chao Agnes Hsiung Kouya Shiraishi Minsun Song Hee Nam Kim Maria Pik Wong Yun-Chul Hong H Dean Hosgood Zhaoming Wang I-Shou Chang Jiu-Cun Wang Nilanjan Chatterjee Margaret Tucker Hu Wei Tetsuya Mitsudomi Wei Zheng Jin Hee Kim Baosen Zhou Neil E Caporaso Demetrius Albanes Min-Ho Shin Lap Ping Chung She-Juan An Ping Wang Hong Zheng Yasushi Yatabe Xu-Chao Zhang Young Tae Kim Xiao-Ou Shu Young-Chul Kim Bryan A Bassig Jiang Chang James Chung Man Ho Bu-Tian Ji Michiaki Kubo Yataro Daigo Hidemi Ito Yukihide Momozawa Kyota Ashikawa Yoichiro Kamatani Takayuki Honda Hiromi Sakamoto Hideo Kunitoh Koji Tsuta Shun-Ichi Watanabe Hiroshi Nokihara Yohei Miyagi Haruhiko Nakayama Shingo Matsumoto Masahiro Tsuboi Koichi Goto Zhihua Yin Jianxin Shi Atsushi Takahashi Akiteru Goto Yoshihiro Minamiya Kimihiro Shimizu Kazumi Tanaka Tangchun Wu Fusheng Wei Jason Y Y Wong Fumihiko Matsuda Jian Su Yeul Hong Kim In-Jae Oh Fengju Song Victor Ho Fun Lee Wu-Chou Su Yuh-Min Chen Gee-Chen Chang Kuan-Yu Chen Ming-Shyan Huang Pan-Chyr Yang Hsien-Chih Lin Yong-Bing Xiang Adeline Seow Jae Yong Park Sun-Seog Kweon Chien-Jen Chen Haixin Li Yu-Tang Gao Chen Wu Biyun Qian Daru Lu Jianjun Liu Hyo-Sung Jeon Chin-Fu Hsiao Jae Sook Sung Ying-Huang Tsai Yoo Jin Jung Huan Guo Zhibin Hu Wen-Chang Wang Charles C Chung Charles Lawrence Laurie Burdett Meredith Yeager Kevin B Jacobs Amy Hutchinson Sonja I Berndt Xingzhou He Wei Wu Junwen Wang Yuqing Li Jin Eun Choi Kyong Hwa Park Sook Whan Sung Li Liu Chang Hyun Kang Lingmin Hu Chung-Hsing Chen Tsung-Ying Yang Jun Xu Peng Guan Wen Tan Chih-Liang Wang Alan Dart Loon Sihoe Ying Chen Yi Young Choi Jen-Yu Hung Jun Suk Kim Ho-Il Yoon Qiuyin Cai Chien-Chung Lin In Kyu Park Ping Xu Jing Dong Christopher Kim Qincheng He Reury-Perng Perng Chih-Yi Chen Roel Vermeulen Junjie Wu Wei-Yen Lim Kun-Chieh Chen John K C Chan Minjie Chu Yao-Jen Li Jihua Li Hongyan Chen Chong-Jen Yu Li Jin Yen-Li Lo Ying-Hsiang Chen Joseph F Fraumeni Jie Liu Taiki Yamaji Yang Yang Belynda Hicks Kathleen Wyatt Shengchao A Li Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA. Saw Swee Hock School of Public Health National University of Singapore and National University Health System Singapore. Division of Molecular Medicine Aichi Cancer Center Research Institute Nagoya Japan. Institute of Population Health Sciences National Health Research Institutes Zhunan Taiwan. Division of Genome Biology National Cancer Center Research Institute Tokyo Japan. Department of Statistics Sookmyung Women's University Seoul Republic of Korea. Department of Preventive Medicine Chonnam National University Medical School Gwangju Republic of Korea. Department of Pathology The University of Hong Kong Queen Mary Hospital Hong Kong. Department of Preventive Medicine Seoul National University College of Medicine Seoul Republic of Korea. Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx NY USA. Department of Computational Biology St. Jude Children's Research Hospital Memphis TN 38105 USA. National Institute of Cancer Research National Health Research Institutes Zhunan Taiwan. Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences Fudan University Shanghai People's Republic of China. State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University Shanghai People's Republic of China. Division of Thoracic Surgery Kinki University School of Medicine Sayama Japan. Division of Epidemiology Department of Medicine Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center Nashville TN USA. Department of Integrative Bioscience & Biotechnology Sejong University Seoul Republic of Korea. Department of Epidemiology School of Public Health China Medical University Shenyang People's Republic of China. Guangdong Lung Cancer Institute Medical Research Center and Cancer Center of Guangdong General Hospital Guangdong Academy of Medical Sciences Guangzhou People's Republic

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.

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Stroke genetics informs drug discovery and risk prediction across ancestries (vol 611, pg 115, 2022)

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NATURE 2022年第7938期612卷 E7-E7页

作者： Mishra, Aniket Malik, Rainer Hachiya, Tsuyoshi Jurgenson, Tuuli Namba, Shinichi Posner, Daniel C. Kamanu, Frederick K. Koido, Masaru Le Grand, Quentin Shi, Mingyang He, Yunye Georgakis, Marios K. Caro, Ilana Krebs, Kristi Liaw, Yi-Ching Vaura, Felix C. Lin, Kuang Winsvold, Bendik Slagsvold Srinivasasainagendra, Vinodh Parodi, Livia Bae, Hee-Joon Chauhan, Ganesh Chong, Michael R. Tomppo, Liisa Akinyemi, Rufus Roshchupkin, Gennady V. Habib, Naomi Jee, Yon Ho Thomassen, Jesper Qvist Abedi, Vida Carcel-Marquez, Jara Nygaard, Marianne Leonard, Hampton L. Yang, Chaojie Yonova-Doing, Ekaterina Knol, Maria J. Lewis, Adam J. Judy, Renae L. Ago, Tetsuro Amouyel, Philippe Armstrong, Nicole D. Bakker, Mark K. Bartz, Traci M. Bennett, David A. Bis, Joshua C. Bordes, Constance Borte, Sigrid Cain, Anael Ridker, Paul M. Cho, Kelly Chen, Zhengming Cruchaga, Carlos Cole, John W. de Jager, Phil L. de Cid, Rafael Endres, Matthias Ferreira, Leslie E. Geerlings, Mirjam I. Gasca, Natalie C. Gudnason, Vilmundur Hata, Jun He, Jing Heath, Alicia K. Ho, Yuk-Lam Havulinna, Aki S. Hopewell, Jemma C. Hyacinth, I. Hyacinth Inouye, Michael Jacob, Mina A. Jeon, Christina E. Jern, Christina Kamouchi, Masahiro Keene, Keith L. Kitazono, Takanari Kittner, Steven J. Konuma, Takahiro Kumar, Amit Lacaze, Paul Launer, Lenore J. Lee, Keon-Joo Lepik, Kaido Li, Jiang Li, Liming Manichaikul, Ani Markus, Hugh S. Marston, Nicholas A. Meitinger, Thomas Mitchell, Braxton D. Montellano, Felipe A. Morisaki, Takayuki Mosley, Thomas H. Nalls, Mike A. Nordestgaard, Borge G. O'Donnell, Martin J. Okada, Yukinori Onland-Moret, N. Charlotte Ovbiagele, Bruce Peters, Annette Psaty, Bruce M. Rich, Stephen S. Rosand, Jonathan Sabatine, Marc S. Sacco, Ralph L. Saleheen, Danish Sandset, Else Charlotte Salomaa, Veikko Sargurupremraj, Muralidharan Sasaki, Makoto Satizabal, Claudia L. Schmidt, Carsten O. Shimizu, Atsushi Smith, Nicholas L. Sloane, Kelly L. Sutoh, Yoichi Sun, Yan V. Tanno, Kozo Tiedt, Steffen Tatlisumak, Turgut Torres-Aguila, Nuria P. Tiwari, Hemant K. Tregouet, Bordeaux Population Health Research Center University of Bordeaux Inserm UMR 1219 Bordeaux France Department of Public Health Bordeaux University Hospital Bordeaux France Department of Neurology Memory Clinic Bordeaux University Hospital Bordeaux France Department of Neurology Institute for Neurodegenerative Diseases CHU de Bordeaux Bordeaux France Institute for Stroke and Dementia Research (ISD) University Hospital LMU Munich Munich Germany Center for Genomic Medicine Massachusetts General Hospital Boston MA USA Program in Medical and Population Genetics Broad Institute of Harvard and the Massachusetts Institute of Technology Cambridge MA USA Munich Cluster for Systems Neurology Munich Germany German Center for Neurodegenerative Diseases (DZNE) Munich Germany Iwate Tohoku Medical Megabank Organization Iwate Medical University Iwate Japan Estonian Genome Centre Institute of Genomics University of Tartu Tartu Estonia Institute of Mathematics and Statistics University of Tartu Tartu Estonia Department of Computational Biology University of Lausanne Lausanne Switzerland Swiss Institute of Bioinformatics Lausanne Switzerland University Center for Primary Care and Public Health Lausanne Switzerland Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan Department of Genome Informatics Graduate School of Medicine The University of Tokyo Tokyo Japan Laboratory for Systems Genetics RIKEN Center for Integrative Medical Sciences Yokohama Japan Laboratory of Statistical Immunology Immunology Frontier Research Center (WPI-IFReC) Osaka University Suita Japan Integrated Frontier Research for Medical Science Division Institute for Open and Transdisciplinary Research Initiatives Osaka University Suita Japan Center for Infectious Disease Education and Research (CiDER) Osaka University Suita Japan Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) VA Boston Healthcare System Boston MA USA TIMI S

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Insights from the first flaring activity of a high-synchrotron-peaked blazar with X-ray polarization and VHE gamma rays

arXiv

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arXiv 2024年

作者： Abe, K. Abe, S. Abhir, J. Abhishek, A. Acciari, V.A. Aguasca-Cabot, A. Agudo, I. Aniello, T. Ansoldi, S. Antonelli, L.A. Engels, A. Arbet Arcaro, C. Asano, K. Babić, A. de Almeida, U. Barres Barrio, J.A. Barrios-Jiménez, L. Batković, I. Baxter, J. González, J. Becerra Bednarek, W. Bernardini, E. Bernete, J. Berti, A. Besenrieder, J. Bigongiari, C. Biland, A. Blanch, O. Bonnoli, G. Bošnjak, Ž. Bronzini, E. Burelli, I. Campoy-Ordaz, A. Carosi, A. Carosi, R. Carretero-Castrillo, M. Castro-Tirado, A.J. Cerasole, D. Ceribella, G. Chai, Y. Chilingarian, A. Cifuentes, A. Colombo, E. Contreras, J.L. Cortina, J. Covino, S. D’Ammando, F. D’Amico, G. Da Vela, P. Dazzi, F. De Angelis, A. De Lotto, B. de Menezes, R. Delfino, M. Delgado, J. Mendez, C. Delgado Di Pierro, F. Di Tria, R. Di Venere, L. Dinesh, A. Prester, D. Dominis Donini, A. Dorner, D. Doro, M. Eisenberger, L. Elsaesser, D. Escudero, J. Fariña, L. Foffano, L. Font, L. Fröse, S. Fukazawa, Y. López, R.J. García Garczarczyk, M. Gasparyan, S. Gaug, M. Paiva, J.G. Giesbrecht Giglietto, N. Giordano, F. Gliwny, P. Godinović, N. Gradetzke, T. Grau, R. Green, D. Green, J.G. Günther, P. Hadasch, D. Hahn, A. Hassan, T. Heckmann, L. Llorente, J. Herrera Hrupec, D. Imazawa, R. Israyelyan, D. Itokawa, T. Martínez, I. Jiménez Quiles, J. Jiménez Jormanainen, J. Kankkunen, S. Kayanoki, T. Kerszberg, D. Khachatryan, M. Kluge, G.W. Kobayashi, Y. Konrad, J. Kouch, P.M. Kubo, H. Kushida, J. Láinez, M. Lamastra, A. Lindfors, E. Lombardi, S. Longo, F. López-Coto, R. López-Moya, M. López-Oramas, A. Loporchio, S. Lorini, A. Lyard, E. Majumdar, P. Makariev, M. Maneva, G. Manganaro, M. Mangano, S. Mannheim, K. Mariotti, M. Martínez, M. Maruševec, P. Mas-Aguilar, A. Mazin, D. Menchiari, S. Mender, S. Miceli, D. Miranda, J.M. Mirzoyan, R. González, M. Molero Molina, E. Mondal, H.A. Moralejo, A. Nakamori, T. Nanci, C. Neustroev, V. Nickel, L. Rosillo, M. Nievas Nigro, C. Nikolic, L. Nilsson, K. Nishijima, K. Ekoume, T. Njoh Japanese MAGIC Group Department of Physics Tokai University Kanagawa Hiratsuka259-1292 Japan The University of Tokyo Chiba Kashiwa277-8582 Japan ETH Zürich ZürichCH-8093 Switzerland Università di Siena INFN Pisa SienaI-53100 Italy Barcelona BellaterraE-08193 Spain Universitat de Barcelona ICCUB IEEC-UB BarcelonaE-08028 Spain Instituto de Astrofísica de Andalucía CSIC Glorieta de la Astronomía s/n Granada18008 Spain RomeI-00136 Italy Università di Udine INFN Trieste UdineI-33100 Italy Max-Planck-Institut für Physik GarchingD-85748 Germany Università di Padova INFN PadovaI-35131 Italy Zagreb10000 Croatia URCA RJ Rio de Janeiro22290-180 Brazil IPARCOS Institute EMFTEL Department Universidad Complutense de Madrid MadridE-28040 Spain Instituto de Astrofísica de Canarias Dpto. de Astrofísica Universidad de La Laguna Tenerife La LagunaE-38200 Spain University of Lodz Faculty of Physics and Applied Informatics Department of Astrophysics Lodz90-236 Poland Centro de Investigaciones Energéticas Medioambientales y Tecnológicas MadridE-28040 Spain Departament de Física CERES-IEEC Universitat Autònoma de Barcelona BellaterraE-08193 Spain Università di Pisa INFN Pisa PisaI-56126 Italy INFN MAGIC Group INFN Sezione di Bari Dipartimento Interateneo di Fisica dell’Università e del Politecnico di Bari BariI-70125 Italy Armenian MAGIC Group A. Alikhanyan National Science Laboratory Yerevan0036 Armenia Department for Physics and Technology University of Bergen Norway INFN MAGIC Group INFN Sezione di Torino Università degli Studi di Torino TorinoI-10125 Italy Croatian MAGIC Group University of Rijeka Faculty of Physics Rijeka51000 Croatia Universität Würzburg WürzburgD-97074 Germany Technische Universität Dortmund DortmundD-44221 Germany Japanese MAGIC Group Physics Program Graduate School of Advanced Science and Engineering Hiroshima University Hiroshima739-8526 Japan ZeuthenD-15738 Germany Armenian MAGIC Gr

Context. Blazars exhibit strong variability across the entire electromagnetic spectrum, including periods of high-flux states commonly dubbed as flares. The physical mechanisms in blazar jets responsible for flares remain to date poorly understood. Aims. We aim to better understand the emission mechanisms during blazar flares using X-ray polarimetry and broadband observations from the archetypical TeV blazar Mrk 421, which can be studied with higher accuracy than other blazars that are dimmer and/or located farther away. Methods. We study a flaring activity from December 2023 that was characterized from radio to very-high-energy (VHE;E > 0.1 TeV) gamma rays with MAGIC, Fermi-LAT, Swift, XMM-Newton and several optical and radio telescopes. These observations included, for the first time for a gamma-ray flare of a blazar, simultaneous X-ray polarization measurements with IXPE, besides optical and radio polarimetry data. We quantify the variability and correlations among the multi-band flux and polarization measurements, and describe the varying broadband emission within a theoretical scenario constrained by the polarization data. Results. We find substantial variability in both X-rays and VHE gamma rays throughout the campaign, with the highest VHE flux above 0.2 TeV occurring during the IXPE observing window, and exceeding twice the flux of the Crab Nebula. However, the VHE and X-ray spectra are on average softer, and the correlation between these two bands weaker that those reported in previous flares of Mrk 421. IXPE reveals an X-ray polarization degree significantly higher than that at radio and optical frequencies, similar to previous results on Mrk 421 and other high-synchrotron-peaked blazars. Differently to past observations, the X-ray polarization angle varies by ∼100◦ on timescales of days, and the polarization degree changes by more than a factor 4. The highest X-ray polarization degree, analyzed in 12 hrs time intervals, reaches 26 ± 2%, around which an X-

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Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for the Global Burden of Disease Study 2017 (vol 395, pg 1779, 2020)

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LANCET 2020年第10239期395卷 1762-1762页

作者： Reiner, R. C., Jr. Hay, S., I Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Global Health School of Medicine University of Washington Seattle WA United States Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States College of Health and Medical Sciences Haramaya University Harar Ethiopia Department of Epidemiology and Biostatistics Haramaya University Harar Ethiopia Department of Medical Laboratory Sciences Haramaya University Harar Ethiopia School of Nursing and Midwifery Haramaya University Harar Ethiopia School of Pharmacy Haramaya University Harar Ethiopia School of Public Health Haramaya University Harar Ethiopia Haramaya University Harar Ethiopia Advanced Diagnostic and Interventional Radiology Research Center Tehran University of Medical Sciences Tehran Iran Cancer Biology Research Center Tehran University of Medical Sciences Tehran Iran Cancer Research Institute Tehran University of Medical Sciences Tehran Iran Department of Economics and Management Sciences for Health Tehran University of Medical Sciences Tehran Iran Department of Environmental Health Engineering Tehran University of Medical Sciences Tehran Iran Department of Epidemiology and Biostatistics Tehran University of Medical Sciences Tehran Iran Department of Health Management and Economics Tehran University of Medical Sciences Tehran Iran Department of Microbiology Tehran University of Medical Sciences Tehran Iran Department of Pharmacology Tehran University of Medical Sciences Tehran Iran Digestive Diseases Research Institute Tehran University of Medical Sciences Tehran Iran Endocrinology and Metabolism Research Center Tehran University of Medical Sciences Tehran Iran Hematology-Oncology and Stem Cell Transplantation Research Center Tehran University of Medical Sciences Tehran Iran Iran National Institute of Health Research Tehran University of Medical Sciences Tehran Iran Metabolomics and

Summary Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood *** We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor *** The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1-65·8), 17·4% (7·7-28·4), and 59·5% (34·2-86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy *** By co-analysing geospatial trends in d

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