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Stochastic optimization of GeantV code by use of genetic algorithms

Journal of Physics: Conference Series 2017年第4期898卷

作者： G. Amadio J. Apostolakis M. Bandieramonte S.P. Behera R. Brun P. Canal F. Carminati G. Cosmo L. Duhem D. Elvira G. Folger A. Gheata M. Gheata I. Goulas F. Hariri S.Y. Jun D. Konstantinov H. Kumawat V. Ivantchenko G. Lima T. Nikitina M. Novak W. Pokorski A. Ribon R. Seghal O. Shadura S. Vallecorsa S. Wenzel Parallel Computing Center at Sao Paulo State University (UNESP) Sao Paulo Brazil CERN Route de Meyrin Meyrin Switzerland Bhabha Atomic Research Centre (BARC) Mumbai India Fermilab MS234 P.O. Box 500 Batavia IL 60510 USA Intel Corporation Santa Clara CA 95052 USA Institute of Space Sciences Bucharest-Magurele Romania

GeantV is a complex system based on the interaction of different modules needed for detector simulation, which include transport of particles in fields, physics models simulating their interactions with matter and a geometrical modeler library for describing the detector and locating the particles and computing the path length to the current volume boundary. The GeantV project is recasting the classical simulation approach to get maximum benefit from SIMD/MIMD computational architectures and highly massive parallel systems. This involves finding the appropriate balance between several aspects influencing computational performance (floating-point performance, usage of off-chip memory bandwidth, specification of cache hierarchy, etc.) and handling a large number of program parameters that have to be optimized to achieve the best simulation throughput. This optimization task can be treated as a black-box optimization problem, which requires searching the optimum set of parameters using only point-wise function evaluations. The goal of this study is to provide a mechanism for optimizing complex systems (high energy physics particle transport simulations) with the help of genetic algorithms and evolution strategies as tuning procedures for massive parallel simulations. One of the described approaches is based on introducing a specific multivariate analysis operator that could be used in case of resource expensive or time consuming evaluations of fitness functions, in order to speed-up the convergence of the black-box optimization problem.

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Performance of GeantV EM Physics Models

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Journal of Physics: Conference Series 2017年第7期898卷

作者： G Amadio A Ananya J Apostolakis A Aurora M Bandieramonte A Bhattacharyya C Bianchini R Brun P Canal F Carminati G Cosmo L Duhem D Elvira G Folger A Gheata M Gheata I Goulas R Iope S Y Jun G Lima A Mohanty T Nikitina M Novak W Pokorski A Ribon R Seghal O Shadura S Vallecorsa S Wenzel Y Zhang Parallel Computing Center at São Paulo State University (UNESP) São Paulo Brazil CERN EP Department Geneva Switzerland Bhabha Atomic Research Centre (BARC) Mumbai India Mackenzie Presbyterian University São Paulo Brazil Fermilab† MS234 P.O. Box 500 Batavia IL 60510 USA Intel Corporation Santa Clara CA 95052 USA Institute of Space Sciences Bucharest-Magurele Romania

The recent progress in parallel hardware architectures with deeper vector pipelines or many-cores technologies brings opportunities for HEP experiments to take advantage of SIMD and SIMT computing models. Launched in 2013, the GeantV project studies performance gains in propagating multiple particles in parallel, improving instruction throughput and data locality in HEP event simulation on modern parallel hardware architecture. Due to the complexity of geometry description and physics algorithms of a typical HEP application, performance analysis is indispensable in identifying factors limiting parallel execution. In this report, we will present design considerations and preliminary computing performance of GeantV physics models on coprocessors (Intel Xeon Phi and NVidia GPUs) as well as on mainstream CPUs.

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Foundational Competencies and Responsibilities of a Research Software Engineer

arXiv

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arXiv 2023年

作者： Goth, Florian Alves, Renato Braun, Matthias Castro, Leyla Jael Chourdakis, Gerasimos Christ, Simon Cohen, Jeremy Druskat, Stephan Erxleben, Fredo Grad, Jean-Noël Hagdorn, Magnus Hodges, Toby Juckeland, Guido Kempf, Dominic Lamprecht, Anna-Lena Linxweiler, Jan Löffler, Frank Martone, Michele Schwarzmeier, Moritz Seibold, Heidi Thiele, Jan Philipp Waldow, Harald von Wittke, Samantha Institute for Theoretical Physics and Astrophysics University of Würzburg Germany European Molecular Biology Laboratory Heidelberg Germany Cluster of Excellence IntCDC University of Stuttgart Germany ZB MED Information Centre for Life Sciences Cologne Germany School of Computation Information and Technology Technical University of Munich Garching Germany Institute for Parallel and Distributed Systems University of Stuttgart Stuttgart Germany Leibniz University Hannover Department of Cell Biology and Biophysics Computational Biology Germany Imperial College London London United Kingdom Institute for Software Technology Berlin Germany Humboldt-Universität zu Berlin Department of Computer Science Berlin Germany Helmholtz-Zentrum Dresden-Rossendorf Germany Institute for Computational Physics University of Stuttgart Germany Geschäftsbereich IT Charité Universitätsmedizin Berlin Germany The Carpentries United States Heidelberg University Scientific Software Center Germany Institute of Computer Science University of Potsdam Germany Technische Universität Braunschweig Germany Michael Stifel Center Jena Friedrich Schiller University Jena Germany Leibniz Supercomputing Centre Garching Germany Mathematical Modeling and Analysis TU Darmstadt Germany IGDORE Munich Germany Weierstrass Institute Berlin Germany Leibniz University Hannover Institute of Applied Mathematics Scientific Computing Hannover Germany Johann Heinrich von Thünen Institute Centre for Information Management Germany

The term Research Software Engineer, or RSE, emerged a little over 10 years ago as a way to represent individuals working in the research community but focusing on software development. The term has been widely adopted and there are a number of high-level definitions of what an RSE is. However, the roles of RSEs vary depending on the institutional context they work in. At one end of the spectrum, RSE roles may look similar to a traditional research role. At the other extreme, they resemble that of a software engineer in industry. Most RSE roles inhabit the space between these two extremes. Therefore, providing a straightforward, comprehensive definition of what an RSE does and what experience, skills and competencies are required to become one is challenging. In this community paper we define the broad notion of what an RSE is, explore the different types of work they undertake, and define a list of foundational competencies as well as values that outline the general profile of an RSE. Further research and training can build upon this foundation of skills and focus on various aspects in greater detail. We expect that graduates and practitioners will have a larger and more diverse set of skills than outlined here. On this basis, we elaborate on the progression of these skills along different dimensions. We look at specific types of RSE roles, propose recommendations for organisations, and give examples of future specialisations. An appendix details how existing curricula fit into this framework. © 2023, CC BY.

关键词： Computer aided software engineering

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CP2K: An electronic structure and molecular dynamics software package quickstep: Efficient and accurate electronic structure calculations

arXiv

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arXiv 2020年

作者： Kühne, Thomas D. Iannuzzi, Marcella Ben, Mauro Del Rybkin, Vladimir V. Seewald, Patrick Stein, Frederick Laino, Teodoro Khaliullin, Rustam Z. Schütt, Ole Schiffmann, Florian Golze, Dorothea Wilhelm, Jan Chulkov, Sergey Bani-Hashemian, Mohammad Hossein Weber, Valéry Borštnik, Urban Taillefumier, Mathieu Jakobovits, Alice Shoshana Lazzaro, Alfio Pabst, Hans Müller, Tiziano Schade, Robert Guidon, Manuel Andermatt, Samuel Holmberg, Nico Schenter, Gregory K. Hehn, Anna Bussy, Augustin Belleflamme, Fabian Tabacchi, Gloria Glöß, Andreas Lass, Michael Bethune, Iain Mundy, Christopher J. Plessl, Christian Watkins, Matt VandeVondele, Joost Krack, Matthias Hutter, Jürg Dynamics of Condensed Matter and Center for Sustainable Systems Design Chair of Theoretical Chemistry Paderborn University Warburger Str. 100 PaderbornD-33098 Germany Department of Chemistry University of Zurich Winterthurerstrasse 190 ZürichCH-8057 Switzerland Computational Research Division Lawrence Berkeley National Laboratory BerkeleyCA94720 United States IBM Research - Zurich Säumerstrasse 4 RüschlikonCH-8803 Switzerland Department of Chemistry McGill University CH-801 Sherbrooke St. West MontrealQCH3A 0B8 Canada Department of Materials ETH Zürich ZürichCH-8092 Switzerland Centre of Policy Studies Victoria University Melbourne Australia Department of Applied Physics Aalto University Otakaari 1 EspooFI-02150 Finland Institute of Theoretical Physics University of Regensburg Universitätsstraße 31 RegensburgD-93053 Germany School of Mathematics and Physics University of Lincoln Brayford Pool Lincoln United Kingdom Integrated Systems Laboratory ETH Zürich ZürichCH-8092 Switzerland Scientific IT Services ETH Zürich Zürich Switzerland ETH Zürich HPE Switzerland GmbH Basel Switzerland Intel Extreme Computing Software and Systems Zürich Switzerland Department of Computer Science and Paderborn Center for Parallel Computing Paderborn University Warburger Str. 100 PaderbornD-33098 Germany Department of Chemistry and Materials Science Aalto University P.O. Box 16100 Aalto00076 Finland Physical Science Division Pacific Northwest National Laboratory P. O. Box 999 RichlandWA99352 United States Department of Science and High Technology University of Insubria INSTM via Valleggio 9 ComoI-22100 Italy BASF SE Carl-Bosch-Straße 38 Ludwigshafen am RheinD-67056 Germany Hartree Centre Science and Technology Facilities Council United Kingdom Laboratory for Scientific Computing and Modelling Paul Scherrer Institute Villigen PSICH-5232 Switzerland

CP2K is an open source electronic structure and molecular dynamics software package to perform atomistic simulations of solid-state, liquid, molecular and biological systems. It is especially aimed at massively-parallel and linear-scaling electronic structure methods and state-of-the-art ab-initio molecular dynamics simulations. Excellent performance for electronic structure calculations is achieved using novel algorithms implemented for modern high-performance computing systems. This review revisits the main capabilities of CP2K to perform efficient and accurate electronic structure simulations. The emphasis is put on density functional theory and multiple post-Hartree-Fock methods using the Gaussian and plane wave approach and its augmented all-electron extension. Copyright © 2020, The Authors. All rights reserved.

关键词： Electronic structure

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Cograph editing: Merging modules is equivalent to editing P4s

arXiv

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arXiv 2017年

作者： Fritz, Adrian Hellmuth, Marc Wieseke, Nicolas Stadler, Peter F. Computational Biology of Infection Research Helmholtz Centre for Infection Research Inhoffenstraße 7 BraunschweigD-38124 Germany University of Greifswald Dpt. of Mathematics and Computer Science Walther- Rathenau-Strasse 47 GreifswaldD-17487 Germany Saarland University Center for Bioinformatics Building e 2.1 P.O. Box 151150 SaarbrückenD-66041 Germany Parallel Computing and Complex Systems Group Department of Computer Science University of Leipzig Augustusplatz 10 LeipzigD-04109 Germany Bioinformatics Group Department of Computer Science Interdisciplinary Center of Bioinformatics University of Leipzig Härtelstraße 16-18 LeipzigD-04107 Germany Max-Planck-Institute for Mathematics in the Sciences Inselstraße 22 LeipzigD-04103 Germany Inst. F. Theoretical Chemistry University of Vienna Währingerstraße 17 WienA-1090 Austria Santa Fe Institute 1399 Hyde Park Rd. Santa FeNM87501 United States

The modular decomposition of a graph G = (V;E) does not contain prime modules if and only if G is a cograph, that is, if no quadruple of vertices induces a simple connected path P4. The cograph editing problem consists in inserting into and deleting from G a set F of edges so that H = (V,EΔF) is a cograph and |F| is minimum. This NP-hard combinatorial optimization problem has recently found applications, e.g., in the context of phylogenetics. Efficient heuristics are hence of practical importance. The simple characterization of cographs in terms of their modular decomposition suggests that instead of editing G one could operate directly on the modular decomposition. We show here that editing the induced P4s is equivalent to resolving prime modules by means of a suitable defined merge operation on the submodules. Moreover, we characterize so-called module-preserving edit sets and demonstrate that optimal pairwise sequences of module-preserving edit sets exist for every non-cograph. This eventually leads to an exact algorithm for the cograph editing problem. In addition, we provide two heuristics with time complexity O(|V|3), resp., O(|V|2). Copyright © 2017, The Authors. All rights reserved.

关键词： Graph theory

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Design choices for productive, secure, data-intensive research at scale in the cloud

arXiv

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arXiv 2019年

作者： Arenas, Diego Atkins, Jon Austin, Claire Beavan, David Egea, Alvaro Cabrejas Carlysle-Davies, Steven Carter, Ian Clarke, Rob Cunningham, James Doel, Tom Forrest, Oliver Gabasova, Evelina Geddes, James Hetherington, James Jersakova, Radka Kiraly, Franz Lawrence, Catherine Manser, Jules O'Reilly, Martin T. Robinson, James Sherwood-Taylor, Helen Tierney, Serena Vallejos, Catalina A. Vollmer, Sebastian Whitaker, Kirstie University of St Andrews KY16 9SX United Kingdom Alan Turing Institute 96 Euston Rd Kings Cross LondonNW1 2DB United Kingdom MRC Human Genetics Unit Institute of Genetics & Molecular Medicine University of Edinburgh Western General Hospital Crewe Road EdinburghEH4 2XU United Kingdom Department of Psychiatry University of Cambridge Herchel Smith Buidling for Brain & Mind Sciences Forvie Site Robinson Way CambridgeCB2 0SZ United Kingdom VWV LLP 24 King William Street LondonEC4R 9AT United Kingdom Division of Informatics Imaging and Data Sciences School of Health Sciences Faculty of Biology Medicine and Health University of Manchester Oxford Road ManchesterM13 9PL United Kingdom Warwick Mathematics Institute Department of Statistics University of Warwick CV4 7AL United Kingdom MathSys Centre for Doctoral Training Warwick Mathematics Institute University of Warwick CV4 7AL United Kingdom British Library 96 Euston Road LondonNW1 2DB United Kingdom Edinburgh Parallel Computing Centre University of Edinburgh Bayes Centre 47 Potterrow EdinburghEH8 9BT United Kingdom

We present a policy and process framework for secure environments for productive data science research projects at scale, by combining prevailing data security threat and risk profiles into five sensitivity tiers, and, at each tier, specifying recommended policies for data classification, data ingress, software ingress, data egress, user access, user device control, and analysis environments. By presenting design patterns for security choices for each tier, and using software defined infrastructure so that a different, independent, secure research environment can be instantiated for each project appropriate to its classification, we hope to maximise researcher productivity and minimise risk, allowing research organisations to operate with confidence. Copyright © 2019, The Authors. All rights reserved.

关键词： Risk assessment

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First experience of vectorizing electromagnetic physics models for detector simulation

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Journal of Physics: Conference Series 2015年第9期664卷

作者： G Amadio J Apostolakis M Bandieramonte C Bianchini G Bitzes R Brun P Canal F Carminati J de Fine Licht L Duhem D Elvira A Gheata S Y Jun G Lima M Novak M Presbyterian O Shadura R Seghal S Wenzel Parallel Computing Center at São Paulo State University (UNESP) São Paulo Brazil CERN PH Department CH-1211 Geneva Switzerland Instituto Nazionale di Astrofisica Osservatorio Astrofisico di Catania Catania Italy Mackenzie Presbyterian University São Paulo Brazil Fermilab MS234 P.O. Box 500 Batavia IL 60510 USA University of Copenhagen Copenhagen Denmark Intel Corporation Santa Clara CA USA Bhabha Atomic Research Centre (BARC) Mumbai India

The recent emergence of hardware architectures characterized by many-core or accelerated processors has opened new opportunities for concurrent programming models taking advantage of both SIMD and SIMT architectures. The GeantV vector prototype for detector simulations has been designed to exploit both the vector capability of mainstream CPUs and multi-threading capabilities of coprocessors including NVidia GPUs and Intel Xeon Phi. The characteristics of these architectures are very different in terms of the vectorization depth, parallelization needed to achieve optimal performance or memory access latency and speed. An additional challenge is to avoid the code duplication often inherent to supporting heterogeneous platforms. In this paper we present the first experience of vectorizing electromagnetic physics models developed for the GeantV project.

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Assessing Trustworthy AI in Times of COVID-19: Deep Learning for Predicting a Multiregional Score Conveying the Degree of Lung Compromise in COVID-19 Patients

IEEE Transactions on Technology and Society

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IEEE Transactions on Technology and Society 2022年第4期3卷 272-289页

作者： Allahabadi, Himanshi Amann, Julia Balot, Isabelle Beretta, Andrea Binkley, Charles Bozenhard, Jonas Bruneault, Frederick Brusseau, James Candemir, Sema Cappellini, Luca Alessandro Chakraborty, Subrata Cherciu, Nicoleta Cociancig, Christina Coffee, Megan Ek, Irene Espinosa-Leal, Leonardo Farina, Davide Fieux-Castagnet, Genevieve Frauenfelder, Thomas Gallucci, Alessio Giuliani, Guya Golda, Adam Van Halem, Irmhild Hildt, Elisabeth Holm, Sune Kararigas, Georgios Krier, Sebastien A. Kuhne, Ulrich Lizzi, Francesca Madai, Vince I. Markus, Aniek F. Masis, Serg Mathez, Emilie Wiinblad Mureddu, Francesco Neri, Emanuele Osika, Walter Ozols, Matiss Panigutti, Cecilia Parent, Brendan Pratesi, Francesca Moreno-Sanchez, Pedro A. Sartor, Giovanni Savardi, Mattia Signoroni, Alberto Sormunen, Hanna-Maria Spezzatti, Andy Srivastava, Adarsh Stephansen, Annette F. Theng, Lau Bee Tithi, Jesmin Jahan Tuominen, Jarno Umbrello, Steven Vaccher, Filippo Vetter, Dennis Westerlund, Magnus Wurth, Renee Zicari, Roberto V. Ey Netherlands Enterprise Intelligence Department Amsterdam1083 HP Netherlands Eth Zurich Health Ethics and Policy Lab Department of Health Sciences and Technology Zürich8092 Switzerland Center for Diplomatic and Strategic Studies Postgraduate Studies in Diplomacy and International Relations Paris75015 France Pisa56124 Italy Hackensack Meridian Health Bioethics Center EdisonNJ08820 United States University of Oxford Faculty of Philosophy OxfordOX2 6GG United Kingdom Collège André- Laurendeau Philosophie Department MontrealQCH8N 2J4 Canada Université du Québec À Montréal École des Médias MontrealQCH2L 2C4 Canada Pace University Philosophy Department New YorkNY10038 United States The Ohio State University Wexner Medical Center Department of Radiology ColumbusOH43210 United States Humanitas Research Hospital Department of Radiology Milan20089 Italy Humanitas University Department of Biomedical Sciences Milan20089 Italy University of New England Faculty of Science Agriculture Business and Law ArmidaleNSW2351 Australia University of Technology Sydney Faculty of Engineering and Information Technology SydneyNSW2007 Australia Scuola Superiore Sant'Anna European Centre of Excellence on the Regulation of Robotics and Ai Pisa56127 Italy University of Bremen Group of Computer Architecture Bremen28359 Germany New York University Grossman School of Medicine Division of Infectious Diseases and Immunology Department of Medicine New YorkNY10016 United States Digital Institute Ai Research Section Stockholm16731 Sweden Arcada University of Applied Sciences Department of Business Management and Analytics Helsinki00550 Finland University of Brescia Radiological Sciences and Public Health Department of Medical and Surgical Specialties Brescia25121 Italy Sncf Reseau Sa Ethique Groupe La Plaine93418 France Institute of Diagnostic and Interventional Radiology University Hospital Zurich Zürich8091 Switzerland Eindhoven University of Tech

This article's main contributions are twofold: 1) to demonstrate how to apply the general European Union's High-Level Expert Group's (EU HLEG) guidelines for trustworthy AI in practice for the domain of healthcare and 2) to investigate the research question of what does 'trustworthy AI' mean at the time of the COVID-19 pandemic. To this end, we present the results of a post-hoc self-assessment to evaluate the trustworthiness of an AI system for predicting a multiregional score conveying the degree of lung compromise in COVID-19 patients, developed and verified by an interdisciplinary team with members from academia, public hospitals, and industry in time of pandemic. The AI system aims to help radiologists to estimate and communicate the severity of damage in a patient's lung from Chest X-rays. It has been experimentally deployed in the radiology department of the ASST Spedali Civili clinic in Brescia, Italy, since December 2020 during pandemic time. The methodology we have applied for our post-hoc assessment, called Z-Inspection®, uses sociotechnical scenarios to identify ethical, technical, and domain-specific issues in the use of the AI system in the context of the pandemic. © 2020 IEEE.

关键词： COVID-19

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parallel AND DISTRIBUTED TLM COMPUTATION WITH SIGNAL-PROCESSING FOR ELECTROMAGNETIC-FIELD MODELING

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INTERNATIONAL JOURNAL OF NUMERICAL MODELLING-ELECTRONIC NETWORKS DEVICES AND FIELDS 1995年第3-4期8卷 169-185页

作者： SO, PPM ESWARAPPA, C HOEFER, WJR NSERC/MPR Teltech Research Chair in RF Engineering Department of Electrical and Computer Engineering University of Victoria Victoria British Columbia V8W 3P6 Canada Poman So received his B.Sc. degree in computer science and physics from the University of Toronto Toronto Onatario Canada in 1985. He obtained his B.A. Sc. and M.A.Sc. degrees in electrical engineering (summa cum laude) from the University of Ottawa Ottawa Ontario Canada in 1987 and 1989 respectively. Mr So was a research engineer in the University of Ottawa from January 1989 to October 1991 his research interests included CAD techniques of microwave circuits and numerical methods for electromagnetic wave modelling. He specialized in the development of electromagnetic engineering CAD software and successfully implemented a number of electromagnetic wave simulators based on the two-dimensional and three-dimensional transmission-line matrix methods. From August 1990 to February 1991 he accompanied Professor W. J. R. Hoefer to Rome Italy and Sophia Antiopolas France. During that time he implemented a parallel version of the 3D-TLM simulator for the CM-2 Connection Machine using C-Star and X Windows Library. He is a research engineer and a Ph.D. student at the University of Victoria Victoria British Columbia Canada. He ported the 2D- and 3D-TLM simulators to DECmpp 1200 massively parallel computer using MPL C and C++. He also combined OSA90/hope a commercially available microwave CAD program with a 2D-TLM simulation module for geometry optimization using the Datapipe technique of OSA90/hope. Recently he has developed a distributed client-server computing technique for the TLM method this technique could accelerate the TLM simulation by more than an order of magnitude. Channabasappa Eswarappa received the M.Tech. degree in electrical engineering from the Indian Institute of Technology Kanpur India in 1983 and Ph. D. degree from the University of Ottawa Canada in 1990. He worked as an Assistant Executive Engineer and later as

This paper describes the implementation of transmission-line matrix (TLM) method algorithms on a massively parallel computer (DECmpp 12000), the technique of distributed computing in the UNIX environment, and the combination of TLM analysis with Prony's method as well as with autoregressive moving average (ARMA) digital signal processing for electromagnetic field modelling. By combining these advanced computation techniques, typical electromagnetic field modelling of microwave structures by TLM analysis can be accelerated by a few orders of magnitude.

关键词： Mathematical models

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Genomic investigations of unexplained acute hepatitis in children

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Nature 2023年第7961期617卷 564-573页

作者： Morfopoulou, Sofia Buddle, Sarah Torres Montaguth, Oscar Enrique Atkinson, Laura Guerra-Assunção, José Afonso Moradi Marjaneh, Mahdi Zennezini Chiozzi, Riccardo Storey, Nathaniel Campos, Luis Hutchinson, J. Ciaran Counsell, John R. Pollara, Gabriele Roy, Sunando Venturini, Cristina Antinao Diaz, Juan F. Siam, Ala’a Tappouni, Luke J. Asgarian, Zeinab Ng, Joanne Hanlon, Killian S. Lennon, Alexander McArdle, Andrew Czap, Agata Rosenheim, Joshua Andrade, Catarina Anderson, Glenn Lee, Jack C. D. Williams, Rachel Williams, Charlotte A. Tutill, Helena Bayzid, Nadua Martin Bernal, Luz Marina Macpherson, Hannah Montgomery, Kylie-Ann Moore, Catherine Templeton, Kate Neill, Claire Holden, Matt Gunson, Rory Shepherd, Samantha J. Shah, Priyen Cooray, Samantha Voice, Marie Steele, Michael Fink, Colin Whittaker, Thomas E. Santilli, Giorgia Gissen, Paul Kaufer, Benedikt B. Reich, Jana Andreani, Julien Simmonds, Peter Alrabiah, Dimah K. Castellano, Sergi Chikowore, Primrose Odam, Miranda Rampling, Tommy Houlihan, Catherine Hoschler, Katja Talts, Tiina Celma, Cristina Gonzalez, Suam Gallagher, Eileen Simmons, Ruth Watson, Conall Mandal, Sema Zambon, Maria Chand, Meera Hatcher, James De, Surjo Baillie, Kenneth Semple, Malcolm Gracie Bellos, Evangelos Broderick, Claire Channon-Wells, Samuel De, Tisham D’Souza, Giselle Elorrieta, Leire Estramiana Estrada-Rivadeneyra, Diego Galassini, Rachel Habgood-Coote, Dominic Hamilton, Shea Jackson, Heather Kavanagh, James Marjaneh, Mahdi Moradi Menikou, Stephanie Nichols, Samuel Nijman, Ruud Patel, Harsita Pennisi, Ivana Powell, Oliver Reid, Ruth Vito, Ortensia Whittaker, Elizabeth Wilson, Clare Womersley, Rebecca Abdulla, Amina Darnell, Sarah Mustafa, Sobia Georgiou, Pantelis Manzano, Jesus-Rodriguez Moser, Nicolas Carter, Michael Tibby, Shane Cohen, Jonathan Davis, Francesca Kenny, Julia Wellman, Paul White, Marie Fish, Matthew Jennings, Aislinn Shankar-Hari Fidler, Katy Agranoff, Dan Richmond, Vivien Seal, Matthew Faust, Saul Owen, Dan Ensom, Ruth McKay, Sarah Mondo, Diana Shaji, Mariya Schra Infection Immunity and Inflammation Department Great Ormond Street Institute of Child Health University College London London United Kingdom Section for Paediatrics Department of Infectious Diseases Faculty of Medicine Imperial College London London United Kingdom Department of Microbiology Virology and Infection Control Great Ormond Street Hospital for Children NHS Foundation Trust London United Kingdom Section of Virology Department of Infectious Diseases Faculty of Medicine Imperial College London London United Kingdom University College London Mass Spectrometry Science Technology Platform Division of Biosciences University College London London United Kingdom Histopathology Department Great Ormond Street Hospital for Children NHS Foundation Trust London United Kingdom Research Department of Targeted Intervention Division of Surgery and Interventional Science University College London London United Kingdom Division of Infection and Immunity University College London London United Kingdom Gene Transfer Technology Group EGA-Institute for Women’s Health University College London London United Kingdom Genetics and Genomic Medicine Department Great Ormond Street Institute of Child Health University College London London United Kingdom Department of Neurodegenerative Disease Queen Square Institute of Neurology University College London London United Kingdom Wales Specialist Virology Centre Public Health Wales Microbiology Cardiff University Hospital of Wales Cardiff United Kingdom Department of Medical Microbiology Edinburgh Royal Infirmary Edinburgh United Kingdom Public Health Agency Northern Ireland Belfast United Kingdom School of Medicine University of St. Andrews St. Andrews United Kingdom Public Health Scotland Edinburgh United Kingdom West of Scotland Specialist Virology Centre Glasgow United Kingdom Micropathology Ltd University of Warwick Science Park Coventry United Kingdom Molecular and Cellular Immunology Great Ormond Street Institute of C

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 6... 详细信息

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK¹. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children. © 2023, The Author(s).

关键词： Clinical microbiology Paediatric research

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