Author: "Nuffield Department of Clinical Medicine" - Searchworks@Jio Institute Digital Library Search Results

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2,905 results on '"Nuffield Department of Clinical Medicine"'

1. Frequent MAGE mutations in human melanoma

Author: LICR NY - Memorial Sloan-Kettering Cancer Center, J. Craig Venter Institute, Rockville, Maryland, USA - J. Craig Venter Institute, Rockville, Maryland, USA, LICR Lausanne - LICR Lausanne, LICR Melbourne - Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, Victoria, Australie, LICR Ltd, Oxford Branch, Headington, Oxford, UK - Nuffield Department of Clinical Medicine, University of Oxford, LICR NY & Ludwig Center for Cancer Immunotherapy, New York, USA - Memorial Sloan-Kettering Cancer Center & Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA - Department of Medicine and Ludwig Center for Cancer Immunotherapy, Oregon Health & Science University, Portland, Oregon, USA - Division of Gynecologic Oncology and the Knight Cancer Institute, Roswell Park Cancer Institute, Buffalo, New York, USA - Department of Gynecological Oncology and Center for Immunotherapy, LICR NY - LICR NY, UCL - Autre, Caballero, Otavia L., Zhao, Qi, Rimoldi, Donata, Stevenson, Brian J., Svobodova, Suzanne, Devalle, Sylvie, Röhrig, Ute F., Pagotto, Anna, Michielin, Olivier, Speiser, Daniel, Wolchok, Jedd D., Liu, Cailian, Pejovic, Tanja, Odunsi, Kunle, Brasseur, Francis, Van den Eynde, Benoît, Old, Lloyd J., Lu, Xin, Cebon, Jonathan, Strausberg, Robert L., Simpson, Andrew J., LICR NY - Memorial Sloan-Kettering Cancer Center, J. Craig Venter Institute, Rockville, Maryland, USA - J. Craig Venter Institute, Rockville, Maryland, USA, LICR Lausanne - LICR Lausanne, LICR Melbourne - Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, Victoria, Australie, LICR Ltd, Oxford Branch, Headington, Oxford, UK - Nuffield Department of Clinical Medicine, University of Oxford, LICR NY & Ludwig Center for Cancer Immunotherapy, New York, USA - Memorial Sloan-Kettering Cancer Center & Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA - Department of Medicine and Ludwig Center for Cancer Immunotherapy, Oregon Health & Science University, Portland, Oregon, USA - Division of Gynecologic Oncology and the Knight Cancer Institute, Roswell Park Cancer Institute, Buffalo, New York, USA - Department of Gynecological Oncology and Center for Immunotherapy, LICR NY - LICR NY, UCL - Autre, Caballero, Otavia L., Zhao, Qi, Rimoldi, Donata, Stevenson, Brian J., Svobodova, Suzanne, Devalle, Sylvie, Röhrig, Ute F., Pagotto, Anna, Michielin, Olivier, Speiser, Daniel, Wolchok, Jedd D., Liu, Cailian, Pejovic, Tanja, Odunsi, Kunle, Brasseur, Francis, Van den Eynde, Benoît, Old, Lloyd J., Lu, Xin, Cebon, Jonathan, Strausberg, Robert L., and Simpson, Andrew J.
Abstract: BACKGROUND: Cancer/testis (CT) genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes). Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1. SIGNIFICANCE: These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma.
Published: 2010

2. Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE (HPS2-THRIVE)

Author: Merck Sharp & Dohme LLC and Jane Armitage, Professor of Clinical trials and Epidemiology, Clinical trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Clinical Medicine, University of Oxford
Published: 2014

3. Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

Author: Abdel Hamid, Muzamil Mahdi, Abdelraheem, Mohamed Hassan, Acheampong, Desmond Omane, Ahouidi, Ambroise, Ali, Mozam, Almagro-Garcia, Jacob, Amambua-Ngwa, Alfred, Amaratunga, Chanaki, Amenga-Etego, Lucas, Andagalu, Ben, Anderson, Tim, Andrianaranjaka, Voahangy, Aniebo, Ifeyinwa, Aninagyei, Enoch, Ansah, Felix, Ansah, Patrick, Apinjoh, Tobias, Arnaldo, Paulo, Ashley, Elizabeth, Auburn, Sarah, Awandare, Gordon, Ba, Hampate, Baraka, Vito, Barry, Alyssa, Bejon, Philip, Bertin, Gwladys, Boni, Maciej, Borrmann, Steffen, Bousema, Teun, Bouyou-Akotet, Marielle, Branch, Oralee, Bull, Peter, Cheah, Huch, Chindavongsa, Keobouphaphone, Chookajorn, Thanat, Chotivanich, Kesinee, Claessens, Antoine, Conway, David, Corredor, Vladimir, Courtier, Erin, Craig, Alister, d'Alessandro, Umberto, Dama, Souleymane, Day, Nicholas, Denis, Brigitte, Dhorda, Mehul, Diakite, Mahamadou, Djimde, Abdoulaye, Dolecek, Christiane, Dondorp, Arjen, Doumbia, Seydou, Drakeley, Chris, Drury, Eleanor, Duffy, Patrick, Echeverry, Diego, Egwang, Thomas, Enosse, Sonia Maria Mauricio, Erko, Berhanu, Fairhurst, Rick, Faiz, Abdul, Fanello, Caterina, Fleharty, Mark, Forbes, Matthew, Fukuda, Mark, Gamboa, Dionicia, Ghansah, Anita, Golassa, Lemu, Goncalves, Sonia, Harrison, G, Healy, Sara Anne, Hendry, Jason, Hernandez-Koutoucheva, Anastasia, Hien, Tran Tinh, Hill, Catherine, Hombhanje, Francis, Hott, Amanda, Htut, Ye, Hussein, Mazza, Imwong, Mallika, Ishengoma, Deus, Jackson, Scott, Jacob, Chris, Jeans, Julia, Johnson, Kimberly, Kamaliddin, Claire, Kamau, Edwin, Keatley, Jon, Kochakarn, Theerarat, Konate, Drissa, Konaté, Abibatou, Kone, Aminatou, Kwiatkowski, Dominic, Kyaw, Myat, Kyle, Dennis, Lawniczak, Mara, Lee, Samuel, Lemnge, Martha, Lim, Pharath, Lon, Chanthap, Loua, Kovana, Mandara, Celine, Marfurt, Jutta, Marsh, Kevin, Maude, Richard James, Mayxay, Mayfong, Maïga-Ascofaré, Oumou, Miotto, Olivo, Mita, Toshihiro, Mobegi, Victor, Mohamed, Abdelrahim Osman, Mokuolu, Olugbenga, Montgomery, Jaqui, Morang'A, Collins Misita, Mueller, Ivo, Murie, Kathryn, Newton, Paul, Ngo Duc, Thang, Nguyen, Thuy, Nguyen, Thuy-Nhien, Nguyen Thi Kim, Tuyen, Nguyen Van, Hong, Noedl, Harald, Nosten, François, Noviyanti, Rintis, Ntui, Vincent Ntui-Njock, Nzila, Alexis, Ochola-Oyier, Lynette Isabella, Ocholla, Harold, Oduro, Abraham, Omedo, Irene, Onyamboko, Marie, Ouedraogo, Jean-Bosco, Oyebola, Kolapo, Oyibo, Wellington Aghoghovwia, Pearson, Richard, Peshu, Norbert, Phyo, Aung, Plowe, Christopher, Price, Ric, Pukrittayakamee, Sasithon, Quang, Huynh Hong, Randrianarivelojosia, Milijaona, Rayner, Julian, Ringwald, Pascal, Rosanas-Urgell, Anna, Rovira-Vallbona, Eduard, Ruano-Rubio, Valentin, Ruiz, Lastenia, Saunders, David, Shayo, Alex, Siba, Peter, Simpson, Victoria, Sissoko, Mahamadou, Smith, Christen, Su, Xin-Zhuan, Sutherland, Colin, Takala-Harrison, Shannon, Talman, Arthur, Tavul, Livingstone, Thanh, Ngo Viet, Thathy, Vandana, Thu, Aung Myint, Toure, Mahamoudou, Tshefu, Antoinette, Verra, Federica, Vinetz, Joseph, Wellems, Thomas, Wendler, Jason, White, Nicholas, Whitton, Georgia, Yavo, William, van der Pluijm, Rob, MalariaGEN, University of Khartoum, University of Cape Coast [Ghana], Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), The Wellcome Trust Sanger Institute [Cambridge], London School of Hygiene and Tropical Medicine [Fajara, Gambia], London School of Hygiene and Tropical Medicine (LSHTM), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), West African Centre for Cell Biology of Infectious Pathogens [Legon, Ghana] (WACCBIP), University of Ghana, Navrongo Health Research Centre [Navrongo, Ghana] (NHRC), Kenya Medical Research Institute (KEMRI), Texas Biomedical Research Institute [San Antonio, TX], Université d'Antananarivo, University of Buéa, Instituto Nacional de Saude [Maputo, Mozambique] (INS), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Menzies School of Health Research [Australia], Charles Darwin University [Australia], Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Institut de Recherche pour le Développement (IRD), Laboratory of Pathogen and Host Immunity [Montpellier] (LPHI), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)
Subjects: data resource, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], plasmodium falciparum, genomics, malaria, Medicine (miscellaneous), genomic epidemiology, General Biochemistry, Genetics and Molecular Biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 291985.pdf (Publisher’s version ) (Open Access) We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.
Published: 2023

4. Convergent trends and spatiotemporal patterns of arboviruses in Mexico and Central America

Author: Bernardo Gutierrez, Darlan da Silva Candido, Sumali Bajaj, Abril Paulina Rodriguez Maldonado, Fabiola Garces Ayala, María de la Luz Torre Rodriguez, Adnan Araiza Rodriguez, Claudia Wong Arámbula, Ernesto Ramírez González, Irma López Martínez, José Alberto Díaz-Quiñónez, Mauricio Vázquez Pichardo, Sarah C. Hill, Julien Thézé, Nuno R. Faria, Oliver G. Pybus, Lorena Preciado-Llanes, Arturo Reyes-Sandoval, Moritz U.G. Kraemer, Marina Escalera-Zamudio, University of Oxford, Universidad San Francisco de Quito (USFQ), Faculdade de Medicina da Universidade de São Paulo [São Paulo, Brésil], Instituto de Diagnóstico y Referencia Epidemiológicos, Secretaría de Salud, Mexico city, Universidad Autónoma del Estado de Hidalgo (UAEH), Royal Veterinary College [London], University of London [London], Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MRC Centre for Global Infectious Disease Analysis, Imperial College London, The Abdul Latif Jameel Institute for Disease and Emergency Analytics, Nuffield Department of Clinical Medicine [Oxford], Instituto Politecnico Nacional [Mexico] (IPN), and European Project: EU H2020 - MOOD
Subjects: [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: BackgroundArboviruses cause both seasonal epidemics (e.g. dengue viruses, DENV) and emerging outbreaks (e.g. chikungunya and Zika viruses, CHIKV and ZIKV) with a significant impact on global health. These viruses share mosquito vector species, often infecting the same host population within overlapping geographic regions. Thus, comparative analyses of their evolutionary and epidemiological dynamics across spatial and temporal scales could reveal convergent transmission trends.Methodology/Principal FindingsFocusing on Mexico as a case study, we generated CHIKV, DENV-1 and DENV-2 genomes from an epidemiological surveillance-derived historical sample collection, and analysed them together with longitudinally-collected genome and epidemiological data from the Americas. Arboviruses endemically circulating within the country were found to be introduced multiple times from lineages predominantly sampled from the Caribbean and Central America. For CHIKV, at least thirteen introductions were inferred over a year, with six of these leading to persistent transmission chains. For both DENV-1 and DENV-2, at least seven introductions were inferred over a decade.Conclusions/SignificanceOur results suggest that CHIKV, DENV-1 and DENV-2 in Mexico share similar evolutionary and epidemiological trajectories. The southwest region of the country was determined to be the most likely location for viral introductions from abroad, with a subsequent spread into the Pacific coast towards the north of Mexico. The virus diffusion patterns observed across the country are likely driven by multiple factors, including mobility linked to human migration from Central towards North America. Considering Mexico‘s economic role and geographic positioning displaying a high human mobility across borders, our results prompt the need to better understand the role of anthropogenic factors in the transmission dynamics of arboviruses, particularly linked to land-based human migration.AUTHOR SUMMARYMexico is endemic to several mosquito-borne viruses relevant to global health, and ranks within the top five countries in the Americas that report the highest case numbers. Our study provides a general overview of arbovirus introduction, spread and establishment patterns in North and Central America, and should be of interest to both local health and global authorities. Moreover, it sets to explore the paradigm of convergence at different scales in independent virus populations, represented by comparable epidemiological and evolutionary trends in arboviruses sharing ecological niches. Our results represent important advances in the study of mosquito-borne viruses listed as a threat to global health, specifically applied to key countries within the developing world
Published: 2023

5. Preservation of Lymphopoietic Potential and Virus Suppressive Capacity by CD8+ T Cells in HIV-2-Infected Controllers

Author: Pierre Versmisse, Bénédicte Charmeteau-de Muylder, Victor Appay, Amel Besseghir, Olivier Lambotte, Glenn Wong, Rémi Cheynier, Mathieu Angin, Françoise Brun-Vézinet, Laura Papagno, Sarah Rowland-Jones, Charles Bayard, Sophie Matheron, Asier Sáez-Cirión, Rodolphe Thiébaut, Delphine Sauce, Faroudy Boufassa, Gianfranco Pancino, Annie David, HIV, Inflammation et persistance, Institut Pasteur [Paris], Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], This work was supported by the Agence Nationale de Recherches sur le SIDA (ANRS), ANRS CO5 IMMUNOVIR-2 Study Group., HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), University of Oxford, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), DARMIGNY, Sandrine, Nuffield Department of Clinical Medicine, University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital], Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Statistiques pour la médecine translationnelle ( SISTM ), Bordeaux population health ( BPH ), Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux ( UB ) -Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Hôpital Bichat - Claude Bernard
Subjects: Adult, Male, 0301 basic medicine, T cell, [SDV]Life Sciences [q-bio], Immunology, HIV Infections, CD8-Positive T-Lymphocytes, Biology, Virus, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, 030212 general & internal medicine, Progenitor cell, Aged, [ SDV ] Life Sciences [q-bio], Lymphopoiesis, virus diseases, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, Viral replication, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-2, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, CD8
Abstract: Compared with HIV-1, HIV-2 infection is characterized by a larger proportion of slow or nonprogressors. A better understanding of HIV-2 pathogenesis should open new therapeutic avenues to establish control of HIV-1 replication in infected patients. In this study, we studied the production of CD8+ T cells and their capacity for viral control in HIV-2 controllers from the French ANRS CO5 HIV-2 cohort. HIV-2 controllers display a robust capacity to support long-term renewal of the CD8+ T cell compartment by preserving immune resources, including hematopoietic progenitors and thymic activity, which could contribute to the long-term maintenance of the CD8+ T cell response and the avoidance of premature immune aging. Our data support the presence of HIV-2 Gag–specific CD8+ T cells that display an early memory differentiation phenotype and robust effector potential in HIV-2 controllers. Accordingly, to our knowledge, we show for the first time that HIV-2 controllers possess CD8+ T cells that show an unusually strong capacity to suppress HIV-2 infection in autologous CD4+ T cells ex vivo, an ability that likely depends on the preservation of host immune resources. This effective and durable antiviral response probably participates in a virtuous circle, during which controlled viral replication permits the preservation of potent immune functions, thus preventing HIV-2 disease progression.
Published: 2016

6. Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells

Author: Morozumi, Yuichi, Boussouar, Fayçal, Tan, Minjia, Chaikuad, Apirat, Jamshidikia, Mahya, Colak, Gozde, He, Huang, Nie, Litong, Petosa, Carlo, De Dieuleveult, Maud, Curtet, Sandrine, Vitte, Anne-Laure, Rabatel, Clothilde, Debernardi, Alexandra, François-Loïc, Cosset, Verhoeyen, Els, Emadali, Anouk, Schweifer, Norbert, Gianni, Davide, Gut, Marta, Guardiola, Philippe, Rousseaux, Sophie, Gérard, Matthieu, Knapp, Stefan, Zhao, Yingming, Khochbin, Saadi, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Structural Genomics Consortium, University of Oxford, Nuffield Department of Clinical Medicine [Oxford], Ben May Department of Cancer Research, The University of Chicago Medicine, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe 'Contrôle Métabolique des Morts Cellulaires' (INSERM U1065 - C3M), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Boehringer Ingelheim RCV, Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Oxford [Oxford], Target Discovery Institute (TDI), Nuffield Department of Clinical Medicine, Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Centre International de Recherche en Infectiologie ( CIRI ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-École normale supérieure - Lyon ( ENS Lyon ), Centre for Genomic Regulation [Barcelona] ( CRG ), Universitat Pompeu Fabra [Barcelona]-Centro Nacional de Analisis Genomico [Barcelona] ( CNAG ), Inserm u892, Centre de Recherches en Cancérologie, Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adenosine Triphosphatases, Male, Proteomics, histone turnover, Chromatin Immunoprecipitation, germ cells, Genome, Pax3, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], FACT, epidrug, Acetylation, Cell Differentiation, Article, Chromatin, Nucleosomes, DNA-Binding Proteins, histone chaperone, ATPases Associated with Diverse Cellular Activities, Humans, cancer drug target, Embryonic Stem Cells, Cell Proliferation, Protein Binding
Abstract: International audience; Although the conserved AAA ATPase and bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics, and RNA-seq experiments in embryonic stem cells where Atad2 is normally highly expressed, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication, and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells Atad2 becomes critical in sustaining specific gene expression programmes, controlling proliferation and differentiation. Altogether, this work defines Atad2 as a facilitator of general chromatin-templated activities such as transcription.
Published: 2016

7. High-throughput analysis of antimalarial susceptibility data by the WorldWide Antimalarial Resistance Network (WWARN) in vitro analysis and reporting tool

Author: Jacob D. Johnson, Véronique Sinou, Sabina Dahlström, Claribel Murillo, Harald Noedl, Jacques Le Bras, François Nosten, Jennifer A. Flegg, Carol Hopkins Sibley, Bruno Pradines, Neils B. Quashie, Charles J. Woodrow, Pharath Lim, Lise Musset, Philippe J Guerin, Sam L. Nsobya, Kanlaya Sriprawat, Hervé Le Nagard, Richard Cooksey, Didier Menard, Rick M. Fairhurst, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University [Bangkok], WorldWide Antimalarial Resistance Network In Vitro Module (WWARN), Hôpital Bichat-Claude Bernard, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), International Center for Medical Research and Training (CIDEIM), International Center for Medical Research and Training, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Institut Pasteur de la Guyane, Laboratoire de Parasitologie [Cayenne, Guyane française], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Epidemiology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Center for Parasitology, Entomology and Malaria Control, National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Department of Medicine, Makerere University [Kampala, Ouganda] (MAK), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Institute of Specific Prophylaxis and Tropical Medicine, Medizinische Universität Wien = Medical University of Vienna, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence du Paludisme, U.S. Army Medical Research Unit, Kenya, Walter Reed Project, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), WWARN is supported by a Bill and Melinda Gates Foundation grant. This work was supported in part by the Intramural Research Program of NIAID, NIH, WorldWide Antimalarial Resistance Network, Nuffield Department of Clinical Medicine ( WWARN ), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, WorldWide Antimalarial Resistance Network In Vitro Module ( WWARN ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), International Center for Medical Research and Training ( CIDEIM ), Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Shoklo Malaria Research Unit, Réseau International des Instituts Pasteur ( RIIP ), Makerere University ( MAK ), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques ( IP-TPT ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Service de Santé des Armées-Université de Montpellier ( UM ), Medical University of Vienna, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Department of Genome Sciences [Seattle] ( GS ), Mère et enfant face aux infections tropicales ( MERIT - UMR_D 216 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ), University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Shoklo Malaria Research Unit [Mae Sot, Thailand] (Faculty of Tropical Medicine), Mahidol University [Bangkok]-Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Wellcome Trust, Makerere University (MAK), and Mère et enfant face aux infections tropicales (MERIT - UMR_D 216)
Subjects: Drug, Artemisinins, Combination therapy, media_common.quotation_subject, 030231 tropical medicine, Plasmodium falciparum, Drug Resistance, Amodiaquine, Drug resistance, Pharmacology, 03 medical and health sciences, Antimalarials, 0302 clinical medicine, Parasitic Sensitivity Tests, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, High-Throughput Screening Assays, medicine, Pharmacology (medical), Artemisinin, Malaria, Falciparum, media_common, Automation, Laboratory, 0303 health sciences, Analytical Procedures, Internet, biology, Quinine, 030306 microbiology, Chloroquine, biology.organism_classification, 3. Good health, Mefloquine, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Drug Therapy, Combination, medicine.drug
Abstract: Assessment of in vitro susceptibility is a fundamental component of antimalarial surveillance studies, but wide variations in the measurement of parasite growth and the calculation of inhibitory constants make comparisons of data from different laboratories difficult. Here we describe a Web-based, high-throughput in vitro analysis and reporting tool (IVART) generating inhibitory constants for large data sets. Fourteen primary data sets examining laboratory-determined susceptibility to artemisinin derivatives and artemisinin combination therapy partner drugs were collated from 11 laboratories. Drug concentrations associated with half-maximal inhibition of growth (IC 50 s) were determined by a modified sigmoid E max model-fitting algorithm, allowing standardized analysis of 7,350 concentration-inhibition assays involving 1,592 isolates. Examination of concentration-inhibition data revealed evidence of apparent paradoxical growth at high concentrations of nonartemisinin drugs, supporting amendment of the method for calculating the maximal drug effect in each assay. Criteria for defining more-reliable IC 50 s based on estimated confidence intervals and growth ratios improved correlation coefficients for the drug pairs mefloquine-quinine and chloroquine-desethylamodiaquine in 9 of 11 and 8 of 8 data sets, respectively. Further analysis showed that maximal drug inhibition was higher for artemisinins than for other drugs, particularly in ELISA (enzyme-linked immunosorbent assay)-based assays, a finding consistent with the earlier onset of action of these drugs in the parasite life cycle. This is the first high-throughput analytical approach to apply consistent constraints and reliability criteria to large, diverse antimalarial susceptibility data sets. The data also illustrate the distinct biological properties of artemisinins and underline the need to apply more sensitive approaches to assessing in vitro susceptibility to these drugs.
Published: 2013

8. The anaemia of Plasmodium vivax malaria

Author: Pierre Buffet, Jeanne Rini Poespoprodjo, Nicholas M. Anstey, Nicholas M. Douglas, Ric N. Price, Nicholas J. White, Tsin W. Yeo, Global Health Division, Menzies School of Health Research, Centre for Tropical Medicine ( CCVTM ), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology-Nuffield Department of Clinical Medicine, Division of Medicine, Royal Darwin Hospital, Department de parasitologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Immunologie Moléculaire des Parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Immunité et Infection, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR113-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Mimika District Health Authority, Mimika District Hospital, Papuan Health, Timika-Community Development Foundation, Mahidol Oxford Tropical Medicine Research Unit, University of Oxford [Oxford]-Mahidol University [Bangkok], NMD received funding from the Rhodes Trust. NMA and TWY are supported by National Health and Medical Research Council Practitioner Fellowships., Nuffield Department of Clinical Medicine [Oxford], University of Oxford, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Papuan Health and Community Development Foundation [Timika, Papua Indonesia], University of Oxford-Mahidol University [Bangkok], University of Oxford [Oxford], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), and BMC, Ed.
Subjects: Pediatrics, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Blood transfusion, Epidemiology, lcsh:RC955-962, Anemia, medicine.medical_treatment, 030231 tropical medicine, Plasmodium vivax, Population, Anaemia, Review, Pathogenesis, lcsh:Infectious and parasitic diseases, Antimalarials, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Malaria, Vivax, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, education, education.field_of_study, biology, Transmission (medicine), Plasmodium falciparum, medicine.disease, biology.organism_classification, Malaria, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitology
Abstract: Plasmodium vivax threatens nearly half the world’s population and is a significant impediment to achievement of the millennium development goals. It is an important, but incompletely understood, cause of anaemia. This review synthesizes current evidence on the epidemiology, pathogenesis, treatment and consequences of vivax-associated anaemia. Young children are at high risk of clinically significant and potentially severe vivax-associated anaemia, particularly in countries where transmission is intense and relapses are frequent. Despite reaching lower densities than Plasmodium falciparum, Plasmodium vivax causes similar absolute reduction in red blood cell mass because it results in proportionately greater removal of uninfected red blood cells. Severe vivax anaemia is associated with substantial indirect mortality and morbidity through impaired resilience to co-morbidities, obstetric complications and requirement for blood transfusion. Anaemia can be averted by early and effective anti-malarial treatment.
Published: 2012

9. Surveillance to achieve malaria elimination in eastern Myanmar: a 7-year observational study

Author: Rae, JD, Nosten, S, Kajeechiwa, L, Wiladphaingern, J, Parker, DM, Landier, J, Thu, AM, Dah, H, Be, A, Cho, WC, Paw, KN, Paw, ES, Shee, PB, Poe, C, Nu, C, Nyaw, B, Simpson, JA, Devine, A, Maude, RJ, Moo, KL, Min, MC, Thwin, MM, Tun, SW, Nosten, FH, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, University of California [Irvine] (UC Irvine), University of California (UC), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), University of Melbourne, Charles Darwin University [Australia], The Open University [Milton Keynes] (OU), Harvard T.H. Chan School of Public Health, and Nuffield Department of Medicine [Oxford, UK] (Big Data Institute)
Subjects: MESH: Humans, [SDV]Life Sciences [q-bio], MESH: Malaria, COVID-19, MESH: Retrospective Studies, Myanmar, MESH: Myanmar, MESH: Antimalarials, Microbiology, Malaria, Vector-Borne Diseases, Antimalarials, Infectious Diseases, Rare Diseases, Good Health and Well Being, Medical Microbiology, Tropical Medicine, Public Health and Health Services, MESH: COVID-19, Humans, Parasitology, Infection, Retrospective Studies
Abstract: Background The collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance. Methods This retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021. To investigate changes in data completeness, malaria post performance, malaria case numbers, and the demographic details of malaria cases, summary statistics were used to compare data collected over space and time. Results In the first 3 years of the METF programme, improvements in data transmission routes resulted in a 18.9% reduction in late reporting, allowing for near real-time analysis of data collected at the malaria posts. In 2020, travel restrictions were in place across Karen State in response to COVID-19, and from February 2021 the military coup in Myanmar resulted in widescale population displacement. However, over that period there has been no decline in malaria post attendance, and the majority of consultations continue to occur within 48 h of fever onset. Case investigations found that 43.8% of cases travelled away from their resident village in the 3 weeks prior to diagnosis and 36.3% reported never using a bed net whilst sleeping in their resident village, which increased to 72.2% when sleeping away from their resident village. Malaria post assessments performed in 82.3% of the METF malaria posts found malaria posts generally performed to a high standard. Conclusions Surveillance data collected by the METF programme demonstrate that despite significant changes in the context in which the programme operates, malaria posts have remained accessible and continue to provide early diagnosis and treatment contributing to an 89.3% decrease in Plasmodium falciparum incidence between 2014 and 2021.
Published: 2022

10. Epitope specificity and relative clonal abundance do not affect CD8 differentiation patterns during lymphocytic choriomeningitis virus infection

Author: James P. Di Santo, Hélène Decaluwe, Benedita Rocha, Ivana Munitic, Agnes Le Bon, César Evaristo, Sara Lemos, Myriam F. Wlodarczyk, Liisa K. Selin, Yves Rivière, Andrew Worth, Persephone Borrow, Differenciation Thymique et Physiologie des Lymphocytes T (U591), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cytokines et Développement Lymphoïde, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Immunopathologie Virale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Nuffield Department of Clinical Medicine, Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Lymphocytic Choriomeningitis, Immunology, Receptors, Antigen, T-Cell, Epitopes, T-Lymphocyte, Immunodominance, CD8-Positive T-Lymphocytes, Lymphocytic Choriomeningitis, Biology, Lymphocytic choriomeningitis, Microbiology, Epitope, MESH: Epitopes, T-Lymphocyte, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Virology, Virus latency, medicine, CD8 T cells, clonal abundance, T cell differentiation, lymphocytic choriomeningitis virus infection, Animals, Lymphocytic choriomeningitis virus, MESH: Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Mice, 030304 developmental biology, 0303 health sciences, T-cell receptor, MESH: Virus Latency, MESH: Receptors, Antigen, T-Cell, medicine.disease, MESH: CD8-Positive T-Lymphocytes, MESH: Gene Expression Regulation, Virus Latency, Gene Expression Regulation, Insect Science, MESH: Immunologic Memory, Pathogenesis and Immunity, MESH: Lymphocytic choriomeningitis virus, Immunologic Memory, CD8, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030215 immunology
Abstract: To evaluate the impact of immunodominance on CD8 T-cell properties, we compared the functional properties of dominant and subdominant populations in the response to lymphocytic choriomeningitis virus (LCMV). To improve functional discrimination, in addition to the usual tests of phenotype and function, we used a sensitive technique that allows the screening of all CD8 effector genes simultaneously in single cells. Surprisingly, these methods failed to reveal a major impact of clonal dominance in CD8 properties throughout the response. Aiming to increase clonal dominance, we examined high-frequency transferred P14 T-cell receptor transgenic (TCR Tg) cells. Under these conditions LCMV is cleared faster, and accordingly we found an accelerated response. However, when Tg and endogenous cells were studied in the same mice, where they should be subjected to the same antigen load, they showed overlapping properties, and the presence of P14 cells did not modify endogenous responses to other LCMV epitopes or a perturbed immunodominance hierarchy in the memory phase. Using allotype-labeled Tg cells, we found that during acute infection up to 80% downregulated their TCR and were undetectable by tetramer binding, and that tetramer-negative and tetramer-positive cells had very different features. Since Tg cells are not available to evaluate immune responses in humans and, in many cases, are not available from the mouse, the tetramer-based evaluation of early immune responses in most situations of high viremia may be incomplete and biased.
Published: 2009

11. Predicting COVID-19 incidence in French hospitals using human contact network analytics

Author: Christian Selinger, Marc Choisy, Samuel Alizon, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Institut de Recherche pour le Développement (IRD), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-20-COVI-0098,PHYEPI,Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales(2020), Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford [Oxford], and Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU)
Subjects: Microbiology (medical), medicine.medical_specialty, Time series, Human mobility, Coronavirus disease 2019 (COVID-19), Computer science, Contact network, Infectious and parasitic diseases, RC109-216, 01 natural sciences, Proxy (climate), Article, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemic spread, Statistics, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, Cluster analysis, Epidemics, Infectious disease, business.industry, SARS-CoV-2, Public health, Incidence (epidemiology), Incidence, 010102 general mathematics, COVID-19, General Medicine, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Hospitals, 3. Good health, Infectious Diseases, Geography, Analytics, Mobile phone, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Networks, business
Abstract: Coronavirus disease (COVID-19) was detected in Wuhan, China in 2019 and spread worldwide within few weeks. The COVID-19 epidemic started to gain traction in France in March 2020. Sub-national hospital admissions and deaths were then recorded daily and served as the main policy indicators. Concurrently, mobile phone positioning data have been curated to determine the frequency of users being colocalized within a given distance. Contrarily to individual tracking data, these can provide a proxy of human contact networks between subnational administrative units. Motivated by numerous studies correlating human mobility data and disease incidence, we developed predictive time series models of hospital incidence between July 2020 and April 2021. Adding human contact network analytics such as clustering coefficients, contact network strength, null links or curvature as regressors, we found that predictions can be improved substantially (more than 50%) both at the national and sub-national for up to two weeks. Our sub-national analysis also revealed the importance of spatial structure, as incidence in colocalized administrative units improved predictions. This original application of network analytics from co-localisation data to epidemic spread opens new perspectives for epidemics forecasting and public health.HighlightsWe use novel human contact network analytics based on colocation data of mobile app users to follow the dynamics of disease incidence and interventions of COVID-19 in France.Time series predictions of hospital incidence are greatly improved by adding these analytics as regressors.Sub-national analysis highlights both spatial correlations of incidence and network analytics to obtain high-precision predictions.
Published: 2021

12. Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis

Author: David L. Saunders, Ari W. Satyagraha, Sunil Parikh, Daniel A. Pfeffer, Benedikt Ley, Yongshu He, François Nosten, Asrat Hailu Mekuria, Marcus V. G. Lacerda, Kamala Ley-Thriemer, Ayodhia Pitaloka Pasaribu, Wasif A. Khan, Duangdao Palasuwan, Liwang Cui, Germana Bancone, Sampa Pal, Rosalind E. Howes, Jeanne Rini Poespoprodjo, Mohammad Shafiul Alam, Saorin Kim, Michael E. von Fricken, Chanthap Lon, Muzamil Mahdi Abdel Hamid, Gonzalo J. Domingo, Michelle E. Roh, Nwe Nwe Oo, Patrick Adu, Fe Espino, David J. Price, Lorenz von Seidlein, Ochaka Julie Egesie, Yap Boum, Nimol Khim, Arantxa Roca-Feltrer, Marcelo A M Brito, Pimlak Charoenkwan, Gisela Henriques, Archie C. A. Clements, Inge Sutanto, Michele D. Spring, Pooja Bansil, Zeshuai Deng, Wuelton Marcelo Monteiro, Ric N. Price, Thomas A. Weppelmann, Didier Menard, Menzies School of Health Research [Australia], Charles Darwin University, Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford], University of Cape Coast [Ghana], International Center for Diarrheal Disease Research [Mohakhali, Bangladesh], PATH [Seattle], Mbarara University of Science and Technology [Mbarara] (MUST), Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], Epicentre [Paris] [Médecins Sans Frontières], Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), Chiang Mai University (CMU), Curtin University [Perth], Planning and Transport Research Centre (PATREC), Pennsylvania State University (Penn State), Penn State System, Kunming University of Science and Technology (KMUST), University of Jos [Nigeria], Research Institute for Tropical Medicine [Muntinlupa City, Philippines], George Mason University [Fairfax], University of Khartoum, London School of Hygiene and Tropical Medicine (LSHTM), Laboratoire d'épidémiologie moléculaire, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Armed Forces Research Institute of Medical Sciences [Bangkok] (AFRIMS), Addis Ababa University (AAU), Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris], Mahidol Oxford Tropical Medicine Research Unit, University of Oxford [Oxford]-Mahidol University [Bangkok], Department of Medical Research (Lower Myanmar) [Yangon], Chulalongkorn University [Bangkok], Yale School of Public Health (YSPH), Universitas Sumatera Utara, Yayasan Pengembangan Kesehatan dan Masyarakat Papua (YPKMP), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, Malaria Consortium [Phnom Penh, Cambodge], University of California [San Francisco] (UCSF), University of California, Uniformed Services University of the Health Sciences (USUHS), University of Indonesia (UI), Florida International University [Miami] (FIU), Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Eijkman Institute for Molecular Biology [Jakarta], Nuffield Department of Clinical Medicine [Oxford], This work was funded by the Wellcome Trust (200909 awarded to RNP) and the Bill & Melinda Gates Foundation (OPP1164105). GB and FN are part of the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme funded by the Wellcome Trust. This work was supported by the Australian Centre for Research Excellence on Malaria Elimination (ACREME), funded by the National Health and Medical Research Council of Australia (APP 1134989)., Charles Darwin University [Australia], University of Oxford, Institut Pasteur [Paris] (IP), University of Oxford-Mahidol University [Bangkok], University of California [San Francisco] (UC San Francisco), University of California (UC), and University of Oxford-Mahidol University [Bangkok]-Wellcome Trust
Subjects: Male, Plasmodium, Glucose-6-phosphate dehydrogenase activity, Primaquine, 030204 cardiovascular system & hematology, Gastroenterology, 0302 clinical medicine, Spectrum Analysis Techniques, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Spectrophotometry, Medicine and Health Sciences, 030212 general & internal medicine, Child, Glucose-6-Phosphate Dehydrogenase Deficiency, Aged, 80 and over, education.field_of_study, medicine.diagnostic_test, Chemistry, Drugs, Anemia, Repeatability, Hematology, General Medicine, Middle Aged, Haemolysis, 3. Good health, Meta-analysis, Child, Preschool, Engineering and Technology, Medicine, Female, medicine.drug, Research Article, Quality Control, Adult, medicine.medical_specialty, Adolescent, Coefficient of variation, Population, Glucosephosphate Dehydrogenase, Research and Analysis Methods, 03 medical and health sciences, Antimalarials, Young Adult, Internal medicine, Parasite Groups, Industrial Engineering, Parasitic Diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Aged, Pharmacology, Chromatography, business.industry, Hemolytic Anemia, Infant, Newborn, Biology and Life Sciences, Infant, Correction, medicine.disease, Tropical Diseases, Malaria, Glucosephosphate Dehydrogenase Deficiency, Parasitology, business, Apicomplexa, Glucose-6-phosphate dehydrogenase deficiency
Abstract: Background The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. Methods and findings Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3–14.0) for the Trinity assay and 8.3 U/g Hb (6.8–15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%–94%) to 100% (95% CI: 96%–100%) and specificity from 96% (95% CI: 89%–99%) to 100% (100%–100%). However, when considering intermediate deficiency (, Daniel Pfeffer and coauthors report on the assessment of glucose-6-phosphate dehydrogenase activity, which is required for safe use of some malaria treatments., Author summary Why was this study done? Complete cure of vivax malaria, the most geographically widespread malaria species, requires the use of 8-aminoquinoline drugs to clear dormant liver stages of the parasite (‘radical cure’); however, these drugs can cause severe haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Ultraviolet (UV) spectrophotometry is used as the reference test to measure G6PD activity, for validating new point-of-care diagnostics, and to determine population-specific definitions of G6PD deficiency. Currently, there is no universal threshold to define G6PD deficiency, and each laboratory must invest time and resources to derive site- and laboratory-specific definitions of G6PD deficiency. What did the researchers do and find? We pooled measurements of G6PD activity from studies conducted across different countries and laboratories worldwide. We assessed the comparability of spectrophotometry results between these laboratories to see whether a universal definition and diagnostic cutoff for G6PD deficiency could be determined. There was substantial variation in the performance and absolute measurements of spectrophotometry conducted in different laboratories, hindering the definition of a universal cutoff for G6PD deficiency. What do these findings mean? These findings highlight the importance of quality-control measures to minimise the influence of laboratory procedures on observed measurements. The data suggest that while a robust universal, assay-specific G6PD activity cutoff value can be established for diagnosis of severe G6PD deficiency (
Published: 2020

13. Binomial nomenclature for virus species: a consultation

Author: Siddell, Stuart G, Walker, Peter J, Lefkowitz, Elliot J, Mushegian, Arcady R, Dutilh, Bas E, Harrach, Balázs, Harrison, Robert L, Junglen, Sandra, Knowles, Nick J, Kropinski, Andrew M, Krupovic, Mart, Kuhn, Jens H, Nibert, Max L, Rubino, Luisa, Sabanadzovic, Sead, Simmonds, Peter, Varsani, Arvind, Zerbini, Francisco Murilo, Davison, Andrew J, Sub Bioinformatics, Theoretical Biology and Bioinformatics, School of Cellular and Molecular Medicine [Bristol] (CellModMed), University of Bristol [Bristol], School of Biological Sciences [Brisbane], University of Queensland [Brisbane], University of Alabama at Birmingham [ Birmingham] (UAB), Division of Molecular and Cellular Biosciences [Alexandria, USA] (MCB), National Science Foundation [Arlington] (NSF), Theoretical Biology and Bioinformatics [Utrecht, The Netherlands], Utrecht University [Utrecht], Radboud University Medical Center [Nijmegen], Institute for Veterinary Medical Research [Budapest] (AOTI), Centre for Agricultural Research [Budapest] (ATK), Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Invasive Insect Biocontrol and Behavior Laboratory [Beltsville, USA], USDA Agricultural Research Service [Beltsville, Maryland], USDA-ARS : Agricultural Research Service-USDA-ARS : Agricultural Research Service, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), The Pirbright Institute, Biotechnology and Biological Sciences Research Council (BBSRC), University of Guelph, Virologie des archées - Archaeal Virology, Institut Pasteur [Paris] (IP), Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Blavatnik Institute [Boston], Harvard Medical School [Boston] (HMS), CNR Istituto per la Protezione Sostenibile delle Piante [Torino, Italia] (IPSP), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology [Mstate, USA] (BCH-EPP), Mississippi State University [Mississippi], Nuffield Department of Clinical Medicine [Oxford], University of Oxford, School of Life Sciences [Tempe, USA], Arizona State University [Tempe] (ASU), Departamento de Fitopatologia [Viçosa, Brazil] (BIOAGRO), Universidade Federal de Viçosa = Federal University of Viçosa (UFV), MRC - University of Glasgow Centre for Virus Research, A.D. is supported by Medical Research Council programme Grant MC_UU_12014/3. B.E.D. is supported by the Netherlands Organization for Scientific Research (NWO) Vidi Grant 864.14.004. B.H. is supported by National Research, Development and Innovation Office–NKFIH, NN128309. N.J.K. is funded by the Department for Environment, Food and Rural Affairs (Defra), UK (Grant no. SE2944), work at the Pirbright Institute is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/E/I/00007035, BB/E/I/00007036 and BBS/E/I/00007037). J.H.K is supported through Battelle Memorial Institute’s prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract no. HHSN272200700016I. S.S. acknowledges partial financial support from Mississippi Agricultural and Forestry Experiment Station (MAFES), Mississippi State University., The authors acknowledge the contribution of ICTV Life Member, Dr. Mike Adams, to previous discussions on the need for a standard binomial nomenclature for virus species., Institute for Animal Health, the Pirbright Institute, Institut Pasteur [Paris], Istituto per la Protezione Sostenibile delle Piante [Torino, Italia] (IPSP), Consiglio Nazionale delle Ricerche (CNR), University of Oxford [Oxford], Universidade Federal de Vicosa (UFV), Sub Bioinformatics, and Theoretical Biology and Bioinformatics
Subjects: Library science, Biology, MESH: Terminology as Topic, Binomial species names, Executive committee, International committee on taxonomy of viruses (ICTV), 03 medical and health sciences, Virology Division News, Terminology as Topic, Virology, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Nomenclature, Virus classification, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Binomial nomenclature, Virus taxonomy, Species nomenclature, General Medicine, Classification, MESH: Viruses/classification, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Taxonomy (biology), MESH: Classification/methods
Abstract: Erratum in : Correction to: Binomial nomenclature for virus species: a consultation. [Arch Virol. 2020]; International audience; The Executive Committee of the International Committee on Taxonomy of Viruses (ICTV) recognizes the need for a standardized nomenclature for virus species. This article sets out the case for establishing a binomial nomenclature and presents the advantages and disadvantages of different naming formats. The Executive Committee understands that adopting a binomial system would have major practical consequences, and invites comments from the virology community before making any decisions to change the existing nomenclature. The Executive Committee will take account of these comments in deciding whether to approve a standardized binomial system at its next meeting in October 2020. Note that this system would relate only to the formal names of virus species and not to the names of viruses.
Published: 2020

14. Correction to: Combination of ELISA screening and seroneutralisation tests to expedite Zika virus seroprevalence studies

Author: Boris Pastorino, Bouba Gake, Paola Mariela Saba Villarroel, Pierre Gallian, Elif Nurtop, Jan Felix Drexler, Yelin Roca, Stéphane Priet, Xavier de Lamballerie, Christophe N. Peyrefitte, Audrey Dubot-Pérès, Gilda Grard, Laetitia Ninove, Unité des Virus Emergents (UVE), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Virology, University of Bonn Medical Centre, Centro Nacional de Enfermedades Tropicales [Santa Cruz de la Sierra, Bolivia] (CENETROP), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Centre National de Référence des Arbovirus [Marseille], Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)-Unité d'Arbovirologie [Marseille], Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées-Service de Santé des Armées-Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées-Service de Santé des Armées, Emerging Pathogens Laboratory, Fondation Mérieux, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Oxford
Subjects: 0303 health sciences, biology, viruses, [SDV]Life Sciences [q-bio], Short Report, biology.organism_classification, Virology, 3. Good health, Zika virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, 030220 oncology & carcinogenesis, Seroprevalence, lcsh:RC109-216, Virus neutralization test, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology, Seroepidemiology
Abstract: Here we propose a strategy allowing implementing efficient and practicable large-scale seroepidemiological studies for Zika Virus (ZIKV). It combines screening by a commercial NS1 protein-based Zika IgG ELISA, and confirmation by a cytopathic effect-based virus neutralization test (CPE-based VNT). In post-epidemic samples from Martinique Island blood donors (a population with a dengue seroprevalence above 90%), this strategy allowed reaching specificity and sensitivity values over 98%. The CPE-based VNT consists of recording CPE directly under the optical microscope, which is easy to identify with ZIKV strain H/PF/2013 at day 5 pi. Overall, considered that CPE-based VNT is cost effective and widely automatable, the NS1 protein-based Zika IgG ELISA+CPE-based VNT combination strategy represents a convenient tool to expedite ZIKV seroprevalence studies. Electronic supplementary material The online version of this article (10.1186/s12985-018-1105-5) contains supplementary material, which is available to authorized users.
Published: 2019

15. Meta-transcriptomic identification of hepatitis B virus in cerebrospinal fluid in patients with central nervous system disease

Author: Viengmon Davong, Mayfong Mayxay, Xavier de Lamballerie, Sayaphet Rattanavong, Kristian Alfsnes, Audrey Dubot-Pérès, Vegard Eldholm, Paul N. Newton, Edward C. Holmes, John H.-O. Pettersson, Géraldine Piorkowski, Manivanh Vongsouvath, Department of Medical Biochemistry and Microbiology [Uppsala, Sweden], Uppsala University, Public Health Agency of Sweden, The University of Sydney, Norwegian Institute of Public Health [Oslo] (NIPH), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Institute of Research and Education Development [Vientiane, Lao People’s Democratic Republic], University of Health Sciences [Vientiane, Laos] (UHS), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], JHOP is funded by the Swedish research council FORMAS (grant no: 2015–710). ECH is funded by an ARC Australian Laureate Fellowship (FL170100022). JHOP, VE, XDL are members of the ZIKAlliance Programme of the European Union. This study was supported by the ZIKAlliance project under European Union Horizon 2020 programme (Grant Agreement no: 734548), the European Union's Horizon 2020 research and innovation programme EVAg under grant agreement N°653316, and Aix-Marseille University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The work in Laos was funded by the Wellcome Trust of UK, which also supports Paul Newton, and the Institute of Research for Development (IRD)., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 734548,ZIKAlliance(2016), University of Oxford, BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, and A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID
Subjects: 0301 basic medicine, Microbiology (medical), Male, Infectious Medicine, Hepatitis B virus, Genotype, 030106 microbiology, Infektionsmedicin, Genome, Viral, medicine.disease_cause, Real-Time Polymerase Chain Reaction, Virus, Article, Central nervous system disease, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cerebrospinal fluid, Central Nervous System Infections, Streptococcus pneumoniae, medicine, Humans, 030212 general & internal medicine, Meta-transcriptomics, Phylogeny, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business.industry, Gene Expression Profiling, RNA sequencing, General Medicine, medicine.disease, Hepatitis B, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Treatment Outcome, Immunology, DNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Etiology, Encephalitis, business
Abstract: Determining the etiological basis of central nervous system (CNS) infections is inherently challenging, primarily due to the multi-etiological nature. Using RNA sequencing, we aimed to identify microbes present in cerebrospinal fluid (CSF) of two patients suffering CNS infection, previously diagnosed with Cryptococcus sp. and Streptococcus pneumoniae infection, respectively. After meta-transcriptomic analysis, and confirmation with real-time PCR, hepatitis B virus (HBV) was detected in the CSF of two patients diagnosed with CNS syndrome. Phylogenetic analysis of the partial HBV genomes from these patients showed that they belonged to genotypes B and C and clustered with other viruses of Asian origin. In countries with high levels of HBV endemicity, the virus is likely to be found in patients diagnosed with CNS infections, although whether it contributes to symptoms and pathology, or is simply a coincidental infection, is unknown and merits further investigation. (C) 2019 The Authors. Published by Elsevier Inc.
Published: 2019

16. Crystallization and preliminary X-ray structural studies of a high-affinity CD8αα co-receptor to pMHC

Author: Gao, George [Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford OX3 9DU (United Kingdom)]
Published: 2005
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17. Rapid Diagnostic Tests as a Source of Dengue Virus RNA for Envelope Gene Amplification: A Proof of Concept

Author: Cassidy-Seyoum, S, Vongsouvath, M, Sengvilaipaseuth, O, Seephonelee, M, Bharucha, T, De Lamballerie, X, Newton, P, Dubot-Pérès, A, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, London School of Hygiene and Tropical Medicine (LSHTM), University College of London [London] (UCL), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nuffield Department of Clinical Medicine [Oxford], University of Oxford, This study was funded by the Wellcome Trust of Great Britain, the Institute of Research for Development, and AixMarseille University. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., BUISINE, Soline, and University of Oxford [Oxford]
Subjects: Immunoassay, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Gene Amplification, Articles, Sequence Analysis, DNA, Dengue Virus, Antibodies, Viral, Proof of Concept Study, Molecular Diagnostic Techniques, Viral Envelope Proteins, Laos, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, RNA, Viral
Abstract: International audience; Molecular epidemiological data are key for dengue outbreak characterization and preparedness. However, sparse Dengue virus (DENV) molecular information is available in Laos because of limited resources. In this proof-of-concept study, we evaluated whether DENV1 RNA extracted from rapid diagnostic tests (RDTs) could be amplified and sequenced. The protocol for envelope gene amplification from RNA purified from RDTs was first assessed using viral isolate dilutions then conducted using 14 dengue patient sera. Envelope gene amplification was successful from patient sera with high virus titer, as was sequencing but with lower efficiency. Hence, based on our results, RDTs can be a source of DENV1 RNA for subsequent envelope gene amplification and sequencing. This is a promising tool for collecting molecular epidemiology data from rural dengue-endemic areas. However, further investigations are needed to improve assay efficiency and to assess this tool's level of efficacy on a larger scale in the field.
Published: 2019

18. Nasal or throat sampling is adequate for the detection of the human respiratory syncytial virus in children with acute respiratory infections

Author: Nguyen, V, Russell, F, Dance, D, Vilivong, K, Phommachan, S, Syladeth, C, Lai, J, Lim, R, Morpeth, M, Mayxay, M, Newton, P, De Lamballerie, X, Dubot-Pérès, A, Unité des Virus Emergents (UVE), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Murdoch Children's Research Institute (MCRI), Department of Paediatrics [Melbourne], Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne-Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], London School of Hygiene and Tropical Medicine (LSHTM), Institute of Research and Education Development [Vientiane, Lao People’s Democratic Republic], University of Health Sciences [Vientiane, Laos] (UHS), Murdoch Children’s Research Institute, European Union’s Horizon 2020 research and innovation programme EVAg, Grant/Award Number: 653316, Aix‐Marseille University, Bill & Melinda Gates Foundation, Grant/Award Number: OPP1115490, Wellcome Trust of Great Britain, Grant/Award Number: 089275/H/09/Z0, Institute of Research for Development, European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford, BUISINE, Soline, and European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID
Subjects: Male, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, detection rate, nasal swab, Infant, Reproducibility of Results, throat swab, Respiratory Syncytial Virus Infections, Viral Load, Real-Time Polymerase Chain Reaction, nasopharyngeal swab, Laos, Child, Preschool, Respiratory Syncytial Virus, Human, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, Pharynx, Female, Nasal Cavity, human respiratory syncytial virus, Research Articles, Research Article
Abstract: International audience; Human respiratory syncytial virus (HRSV) is one of the most important causes of acute respiratory infections (ARI) in young children. HRSV diagnosis is based on the detection of the virus in respiratory specimens. Nasopharyngeal swabbing is considered the preferred method of sampling, although there is limited evidence of the superiority of nasopharyngeal swabs (NPS) over the less invasive nasal (NS) and throat (TS) swabs for virus detection by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). In the current study, we compared the three swabbing methods for the detection of HRSV by RT-qPCR in children hospitalized with ARI at Mahosot Hospital, Vientiane, Laos. In 2014, NS, NPS, and TS were collected from 288 children. All three samples were tested for HRSV by RT-qPCR; 141 patients were found positive for at least one sample. Almost perfect agreements (κ > 0.8) between the swabs, compared two by two, were observed. Detection rates for the three swabs (between 93% and 95%) were not significantly different, regardless of the clinical presentation. Our findings suggest that the uncomfortable and technically more demanding NPS method is not mandatory for HRSV detection by RT-qPCR.
Published: 2019

19. Management of Central Nervous System Infections, Vientiane, Laos, 2003–2011

Author: Phonelavanh Phoumin, Amphonesavanh Sengduangphachanh, Rattanaphone Phetsouvanh, Mary-Anne Burns, Scott B. Craig, Valy Keoluangkot, Audrey Dubot-Pérès, Olay Lattana, Khonesavanh Luangxay, Prasith Phimmasone, Koukeo Phommasone, Sue J. Lee, Manivanh Vongsouvath, Kongkham Sisout, David A. B. Dance, Amphaivanh Seubsanith, Catrin E. Moore, Mayfong Mayxay, Khamsai Detleuxay, Vilada Chansamouth, Viengmon Davong, Sabine Dittrich, Xavier de Lamballerie, S. M. Tulsiani, Stuart D. Blacksell, Inpanh Phouangsouvanh, Sayaphet Rattanavong, Phonepasith Panyanivong, Paul N. Newton, Anisone Chanthongthip, Bountoy Sibounheuang, Manivone Simmalavong, Joy Sirisouk, Davanh Sengdatka, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, University of Health Sciences, Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Mahosot Hospital, Queensland Health Forensic and Scientific Services, London School of Hygiene and Tropical Medicine (LSHTM), This work was supported by the Wellcome Trust of Great Britain, the Institute of Research for Development, AixMarseille University, and the European Union’s Horizon 2020 research and innovation program European Virus Archive global (grant agreement no. 653316)., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), Graduate School, AII - Infectious diseases, APH - Global Health, APH - Methodology, University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of Oxford, BUISINE, Soline, and European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID
Subjects: Infectious Encephalitis, Male, Orientia tsutsugamushi, Epidemiology, encephalitis, Antibiotics, Cryptococcus, lcsh:Medicine, antibiotics, 0302 clinical medicine, 030212 general & internal medicine, Prospective Studies, Rickettsia, Child, bacteria, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Leptospira, Cross Infection, biology, diabetes, Mortality rate, Health Policy, meningitis, 3. Good health, Infectious Diseases, Laos, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Ceftriaxone, Female, meningitis/encephalitis, Meningitis, Encephalitis, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, patient care management, Asia, Adolescent, medicine.drug_class, viral infections, 030231 tropical medicine, central nervous system infections, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Young Adult, Internal medicine, WHO meningitis, medicine, Humans, lcsh:RC109-216, viruses, antimicrobial medicines, business.industry, Research, lcsh:R, Infant, WHO encephalitis, Japanese encephalitis, medicine.disease, biology.organism_classification, mortality, Japanese encephalitis virus, bacterial infections, Lao, business
Abstract: International audience; During 2003-2011, we recruited 1,065 patients of all ages admitted to Mahosot Hospital (Vientiane, Laos) with suspected central nervous system (CNS) infection. Etiologies were laboratory confirmed for 42.3% of patients, who mostly had infections with emerging pathogens: viruses in 16.2% (mainly Japanese encephalitis virus [8.8%]); bacteria in 16.4% (including Orientia tsutsugamushi [2.9%], Leptospira spp. [2.3%], and Rickettsia spp. [2.3%]); and Cryptococcus spp. fungi in 6.6%. We observed no significant differences in distribution of clinical encephalitis and meningitis by bacterial or viral etiology. However, patients with bacterial CNS infection were more likely to have a history of diabetes than others. Death (26.3%) was associated with low Glasgow Coma Scale score, and the mortality rate was higher for patients with bacterial than viral infections. No clinical or laboratory variables could guide antibiotic selection. We conclude that high-dependency units and first-line treatment with ceftriaxone and doxycycline for suspected CNS infections could improve patient survival in Laos.
Published: 2019

20. Viral RNA Degradation Makes Urine a Challenging Specimen for Detection of Japanese Encephalitis Virus in Patients With Suspected CNS Infection

Author: Bharucha, Tehmina, Sengvilaipaseuth, Onanong, Seephonelee, Malee, Vongsouvath, Malavanh, Vongsouvath, Manivanh, Rattanavong, Sayaphet, Piorkowski, Géraldine, Lecuit, Marc, Gorman, Christopher, Pommier, Jean-David, Garson, Jeremy, Newton, Paul, De Lamballerie, Xavier, Dubot Pérès, Audrey, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, University College of London [London] (UCL), Unité des Virus Emergents (UVE), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], The research has been implemented in collaboration with the ComAcross project (www.onehealthsea.org/comacross) thanks to the financial support of the European Union (EuropeAid, INNOVATE contract 315-047). It was also supported by Total Foundation, Horizon 2020 research and the innovation program EVAg under grant agreement No. 653316, the Institute of Research for Development, Aix-Marseille University, and the Wellcome Trust of Great Britain., We are very grateful to the patients and to Asst. Prof. Bounthaphany Bounxouei, the Director of Mahosot Hospital, the late Dr. Rattanaphone Phetsouvanh, Director of the Microbiology Laboratory, Dr. Mayfong Mayxay, and the staff of the wards and Microbiology Laboratory of Mahosot Hospital. We also thank Ooyanong Phonemixay for technical help and support, Asst. Prof. Dr. Bounnak Saysanasongkham, Director of the Department of Health and Rehabilitation (DHR), Ministry of Health, and Prof. Bounkong Syhavong, Minister of Health, Lao P.D.R., for their very kind help and support. We thank the stakeholders of the ongoing SEAe project, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Oxford
Subjects: Japanese encephalitis virus, diagnosis, viruses, RT-qPCR, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, flavivirus, RNA
Abstract: International audience; Background: Japanese encephalitis virus (JEV) is a leading cause of central nervous system (CNS) infections in Asia and results in significant morbidity and mortality. JEV RNA is rarely detected in serum or cerebrospinal fluid (CSF), and diagnosis of JEV infection is usually based on serological tests that are frequently difficult to interpret. Unlike serum or CSF, urine is relatively easy to obtain, but, to date, there has been minimal work on the feasibility of testing urine for JEV RNA.Methods: We investigated the use of lysis buffer and a Microsep device to optimize urine storage for detection of JEV RNA by reverse transcription real-time polymerase chain reaction (RT-qPCR). The best of the studied methods was then evaluated in consecutive patients admitted to the hospital with suspected CNS infections in Laos.Results: We demonstrated degradation of JEV RNA in urine after even short storage periods at 4°C or -80°C. Although there was no advantage in using a Microsep concentration device alone, immediate addition of lysis buffer to fresh urine improved the detection of JEV RNA at the limit of detection.Conclusions: In 2 studies of 41 patients with acute encephalitis syndrome, 11 (27%) were positive for JEV IgM in CSF and/or serum, and 2 (4.9%) were JEV RT-qPCR positive from throat swabs. JEV RNA was not detected in any of these patients' urine samples. However, lysis buffer was only used during a prospective study, that is, for only 17/41 (41%) patient urine samples. Our findings suggest a need for larger studies testing urine for JEV RNA, with urine collected at different times from symptom onset, and using lysis buffer, which stabilizes RNA, for storage.
Published: 2019

21. Low Zika Virus Seroprevalence in Vientiane, Laos, 2003–2015

Author: Pastorino, B, Sengvilaipaseuth, O, Chanthongthip, A, Vongsouvath, M, Souksakhone, C, Mayxay, M, Thirion, L, Newton, P, De Lamballerie, X, Dubot-Pérès, A, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, National Blood Transfusion Centre [Vientiane, Laos] (Lao Red Cross), Institute of Research and Education Development [Vientiane, Lao People’s Democratic Republic], University of Health Sciences [Vientiane, Laos] (UHS), Nuffield Department of Clinical Medicine [Oxford], University of Oxford, This study was funded by the Wellcome Trust of Great Britain, the Institute of Research for Development, and Aix Marseille University, by the European Union’s Horizon 2020 Research and Innovation Programme EVAg under grant agreement No. 653316 and by the European Union`s Horizon 2020 Research and Innovation Programme under ZIKAlliance grant agreement No. 734548., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 734548,ZIKAlliance(2016), University of Oxford [Oxford], BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, and A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Adult, Male, Adolescent, Zika Virus Infection, Articles, Middle Aged, Young Adult, Laos, Seroepidemiologic Studies, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, Female, Sex Ratio, Aged
Abstract: International audience; Zika virus (ZIKV) has been presumed to be endemic in Southeast Asia (SEA), with a low rate of human infections. Although the first ZIKV evidence was obtained in the 1950s through serosurveys, the first laboratory-confirmed case was only detected in 2010 in Cambodia. The epidemiology of ZIKV in SEA remains uncertain because of the scarcity of available data. From 2016, subsequent to the large outbreaks in the Pacific and Latin America, several Asian countries started reporting increasing numbers of confirmed ZIKV patients, but no global epidemiological assessment is available to date. Here, with the aim of providing information on ZIKV circulation and population immunity, we conducted a seroprevalence study among blood donors in Vientiane, Laos. Sera from 359 asymptomatic consenting adult donors in 2003-2004 and 687 in 2015 were screened for anti-ZIKV IgG using NS1 ELISA assay (Euroimmun, Luebeck, Germany). Positive and equivocal samples were confirmed for anti-ZIKV-neutralizing antibodies by virus neutralization tests. Our findings suggest that ZIKV has been circulating in Vientiane over at least the last decade. Zika virus seroprevalence observed in the studied blood donors was low, 4.5% in 2003-2004 with an increase in 2015 to 9.9% (P = 0.002), possibly reflecting the increase of ZIKV incident cases reported over this period. We did not observe any significant difference in seroprevalence according to gender. With a low herd immunity in the Vientiane population, ZIKV represents a risk for future large-scale outbreaks. Implementation of a nationwide ZIKV surveillance network and epidemiological studies throughout the country is needed.
Published: 2019
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22. Economic evaluations of onchocerciasis interventions : a systematic review and research needs

Author: Turner, H, Walker, M, Pion, S, McFarland, D, Bundy, D, Basáñez, M, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford]-University of Oxford [Oxford], Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Royal Veterinary College [London], University of London [London], Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Emory University School of Medicine, Emory University [Atlanta, GA], London School of Hygiene and Tropical Medicine (LSHTM), University of Oxford-University of Oxford, University of Oxford, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Medical Research Council (MRC), and The Task Force for Global Health
Subjects: analyses coût-bénéfice, [SDV]Life Sciences [q-bio], onchocercose, river blindness, WILLINGNESS-TO-PAY, économie de la santé, rapport coût-efficacité, coût, 1117 Public Health and Health Services, évaluations économiques, elimination, cost elimination, Tropical Medicine, MIDDLE-INCOME COUNTRIES, NEGLECTED TROPICAL DISEASES, cost, health economics, cost-benefit analyses, élimination, Public, Environmental & Occupational Health, cécité des rivières, Science & Technology, COMMUNITY-DIRECTED TREATMENT, LOCAL IVERMECTIN DISTRIBUTION, cost effectiveness, economic evaluations, onchocerciasis, RIVER-BLINDNESS, GLOBAL BURDEN, INTEGRATED IMPLEMENTATION, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, DISABILITY WEIGHTS, COST-EFFECTIVENESS THRESHOLDS, Life Sciences & Biomedicine
Abstract: International audience; OBJECTIVE : To provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps.METHOD : A systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. No date or language stipulations were applied to the searches.RESULTS : We identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost-effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis-associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost-effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability-adjusted life year (DALY) averted of annual MDA varies between US$3 and US$30 (cost year variable).CONCLUSIONS : The cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond.
Published: 2019

23. The Prognostic Role of CD8 + T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score

Author: Mariana M Paraizo, Diancarlos P. Andrade, Ivy Zortéa S Parise, Enzo Lalli, Marco Volante, Heloisa Komechen, Mirvat Surakhy, Bonald C. Figueiredo, Marjorana Martini R Galvão, Marilza Leal Nascimento, Miriam L. Barbosa, Tatiana Ei-Jaick B Costa, Thiago Demetrius Woiski, Ana Luiza M. R. Fabro, Denise B Silva, José Antônio de Souza, Maria Helena C P Del-Valle, José Renato S. Barbosa, Mirna M O Figueiredo, Gislaine Custódio, Roberto Rosati, Melyssa Grignet Ribeiro, Lucia de Noronha, Gareth L. Bond, Guilherme A Parise, Pelé Pequeno Príncipe Research Institute [Curitiba, Brazil], Faculdades Pequeno Príncipe [Curitiba, Brazil], Hospital Infantil Joana Gusmão [Florianópolis, Brazil], Centro de Genética Molecular e Pesquisa do Câncer em Crianças [Curitiba, Brazil] (CEGEMPAC), Instituto de Pesquisa Pelé Pequeno Principe, Serviço de Anatomia Patológica [Curitiba, Brazil] (Hospital de Clínicas), Universidade Federal do Paraná (UFPR)-Hospital de Clínicas [Curitiba, Brazil], Departamento de Medicina [Curitiba, Brazil], Pontifícia Universidade Católica do Paraná (PUCPR), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Hospital Pequeno Príncipe [Curitiba, Brazil], Ciência Laboratório Médico Ltda [Florianópolis, Brazil], Hospital Infantil Joana de Gusmão [Florianópolis, Brazil], Department of Oncology [University of Turin], University of Turin, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Departamento de Saúde Coletiva [Curitiba, Brazil], Federal University of Paraná [Curitiba, Brazil], This work was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) Finance code 001, Conselho National de Desenvolvimento e Pesquisa (CNPq, Brazil), the Ludwig Institute for Cancer Research, and the CNRS EXPOGEN-CANCER. International Associated Laboratory (LIA)., Lalli, Enzo, University of Oxford, Università degli studi di Torino = University of Turin (UNITO), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, T cell, [SDV]Life Sciences [q-bio], Gastroenterology, behavioral disciplines and activities, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, children, Internal medicine, PD-L1, medicine, adrenocortical carcinoma, Adrenocortical carcinoma, Cytotoxic T cell, Cluster of differentiation, biology, business.industry, immune escape, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, [SDV] Life Sciences [q-bio], HLA, stomatognathic diseases, 030104 developmental biology, medicine.anatomical_structure, Oncology, nervous system, 030220 oncology & carcinogenesis, Ki-67, histopathology, biology.protein, Histopathology, business, human activities, CD8, psychological phenomena and processes
Abstract: Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 &plusmn, 2.3 y, mean age &plusmn, SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8+) cytotoxic T lymphocytes (CD8+-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8+-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8+-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8+ T cell recognition may provide insights for future pre-clinical studies.
Published: 2019

24. The role of birds at Çatalhöyük revealed by the analysis of eggshell

Author: Julia Best, Beatrice Demarchi, Roman Fischer, Jorune Sakalauskaite, Samantha Presslee, Department of Life Sciences and Systems Biology [University of Turin], University of Turin, Departments of Archaeology [York] (BioArch), University of York [York, UK], Biogéosciences [UMR 6282] [Dijon] (BGS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Department of Archaeology and Conservation, Cardiff University, Italian Ministry of Education, University and Research ('Young Researchers - Rita Levi Montalcini' programme) and the UK Engineering and Physical Sciences Research Council (EPSRC) under Grant [EP/I001514/1]., Università degli studi di Torino = University of Turin (UNITO), and Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Eggshell, Taxonomy, Birds, Morphology, Microscopy, Ancient proteins, Mass spectrometry, Çatalhöyük, Neolithic, Morphology, 010506 paleontology, Ancient proteins, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Zoology, Biology, Q1, 010502 geochemistry & geophysics, 01 natural sciences, Birds, Eggshell, Neolithic, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, 0105 earth and related environmental sciences, Earth-Surface Processes, Taxonomy, Microscopy, Osteology, Mass spectrometry, Çatalhöyük, Biological classification, 15. Life on land, Integrated approach, CC, Anseriformes, biology.organism_classification, Taxonomy (biology)
Abstract: 11 pages; International audience; The exceptional eggshell assemblage from Çatalhöyük was studied using an integrated approach combining morphology (by optical and scanning electron microscopy) and palaeoproteomics (by mass spectrometry). We provide taxonomic classification for 90 fragments, of which only 11 remain undetermined. The striking predominance of Anseriformes (probably including greylag geese, as well as ducks and swans) in all types of deposits examined, particularly middens and burial fills, suggests that these eggs were exploited as food and, at the same time, had a special significance for the inhabitants of the site. We detected the presence of crane eggshell in contexts associated with both the world of the living and the world of the dead (consistent with the well-known importance of this bird at Çatalhöyük), as well as the possible but infrequent occurrence of bustards and herons. Overall, we suggest that eggshell analysis, together with osteological data and the archaeological context, can provide the basis for a nuanced understanding of the relationship between humans and birds in the past.
Published: 2018

25. Serotype Distribution of Clinical Streptococcus pneumoniae Isolates before the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Cambodia

Author: Matthew R. Kasper, Vonthanak Saphonn, Arnaud Tarantola, Blandine Rammaert, Gavin W. Ford, Florence Komurian-Pradel, Paul Turner, Chadwick Y. Yasuda, Sok Touch, Alexandra Kerleguer, Christina Farris, Youlet By, Bertrand Guillard, Sirenda Vong, Laurence Borand, Buth Sokhal, Malin Inghammar, Jan Jacobs, Melina Messaoudi, Chanleakhena Phoeung, Thong Phe, Charles Mayaud, Ung Sam An, Sophie Goyet, Steven Newell, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Skane University Hospital [Lund], Fondation Mérieux, University of Health Science, US Naval Medical Research Unit n°2, Shihanouk Hospital Centre of HOPE, Médecine Interne et Maladies Infectieuses, CHU de Poitiers, Poitiers, France, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Cambodian National Laboratory of Public Health, Communicable Disease Department [Phnom Penh] (CDC MOH), Ministry of Health [Mozambique], Cambodia Oxford Medical Research, Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Institute of Tropical Medicine [Antwerp] (ITM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Tarantola, Arnaud
Subjects: Male, 0301 basic medicine, Serotype, [SDV]Life Sciences [q-bio], Drug resistance, medicine.disease_cause, Pneumococcal conjugate vaccine, Pneumococcal Vaccines, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Multiple, Bacterial, Medicine, 030212 general & internal medicine, Child, Aged, 80 and over, Articles, Middle Aged, Anti-Bacterial Agents, Bacterial Typing Techniques, 3. Good health, [SDV] Life Sciences [q-bio], Streptococcus pneumoniae, Infectious Diseases, Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.symptom, Cambodia, Bronchoalveolar Lavage Fluid, medicine.drug, Adult, Adolescent, 030106 microbiology, Serogroup, Mass Vaccination, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Antibiotic resistance, Virology, Multiplex polymerase chain reaction, Humans, Aged, Vaccines, Conjugate, business.industry, Sputum, Infant, Pneumonia, Pneumococcal, Laboratories, Hospital, medicine.disease, Pneumonia, Parasitology, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business
Abstract: International audience; Childhood vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in Cambodia in January 2015. Baseline data regarding circulating serotypes are scarce. All microbiology laboratories in Cambodia were contacted for identification of stored isolates ofStreptococcus pneumoniaefrom clinical specimens taken before the introduction of PCV13. Available isolates were serotyped using a multiplex polymerase chain reaction method. Among 166 identified isolates available for serotyping from patients with pneumococcal disease, 4% were isolated from upper respiratory samples and 80% were from lower respiratory samples, and 16% were invasive isolates. PCV13 serotypes accounted for 60% (95% confidence interval [CI] 52-67) of all isolates; 56% (95% CI 48-64) of noninvasive and 77% (95% CI 57-89) of invasive isolates. Antibiotic resistance was more common among PCV13 serotypes. This study of clinicalS. pneumoniaeisolates supports the potential for high reduction in pneumococcal disease burden and may serve as baseline data for future monitoring ofS. pneumoniaeserotypes circulation after implementation of PCV13 childhood vaccination in Cambodia.
Published: 2018

26. Molecular epidemiology of dengue viruses in three provinces of Lao PDR, 2006-2010

Author: Saythong Inthalath, Audrey Dubot-Pérès, Phouthalavanh Souvannasing, Koukeo Phommasone, Manivanh Vongsouvath, Géraldine Piorkowski, Raphaëlle Klitting, Paul N. Newton, Cécile Baronti, Mayfong Mayxay, Onanong Sengvilaipaseuth, Bountoy Sibounheuang, Phouvieng Douangdala, Anisone Chanthongthip, Soulignasack Thongpaseuth, Xavier de Lamballerie, Josée Castonguay-Vanier, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Health Sciences [Vientiane, Laos] (UHS), Luang Namtha Provincial Hospital, Salavan Provincial Hospital, University of Oxford [Oxford], HAL AMU, Administrateur, Graduate School, AII - Infectious diseases, APH - Global Health, and APH - Methodology
Subjects: RNA viruses, 0301 basic medicine, Serotype, Viral Diseases, Veterinary medicine, viruses, Artificial Gene Amplification and Extension, Dengue virus, Pathology and Laboratory Medicine, medicine.disease_cause, Polymerase Chain Reaction, Dengue Fever, Dengue fever, Dengue, Database and Informatics Methods, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemiology, Medicine and Health Sciences, Ethnicities, Child, Data Management, Molecular Epidemiology, Denv serotypes, lcsh:Public aspects of medicine, virus diseases, Phylogenetic Analysis, Middle Aged, 3. Good health, Phylogenetics, Phylogeography, Infectious Diseases, Laos, Medical Microbiology, Child, Preschool, Viral Pathogens, Epidemiological Monitoring, Viruses, Lao People, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Topography, Medical, Seasons, Pathogens, Sequence Analysis, Research Article, Neglected Tropical Diseases, Adult, Computer and Information Sciences, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Adolescent, Bioinformatics, lcsh:RC955-962, 030231 tropical medicine, Sequence Databases, Biology, Serogroup, Research and Analysis Methods, Microbiology, Young Adult, 03 medical and health sciences, Extraction techniques, medicine, Humans, Evolutionary Systematics, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Taxonomy, Evolutionary Biology, Biology and life sciences, Flaviviruses, Molecular epidemiology, Organisms, Public Health, Environmental and Occupational Health, Outbreak, lcsh:RA1-1270, Reverse Transcriptase-Polymerase Chain Reaction, Dengue Virus, biochemical phenomena, metabolism, and nutrition, Tropical Diseases, medicine.disease, RNA extraction, Biological Databases, 030104 developmental biology, People and Places, Population Groupings, Sequence Alignment
Abstract: Few data on dengue epidemiology are available for Lao PDR. Here, we provide information on the complexity of dengue epidemiology in the country, demonstrating dynamic circulation that varies over space and time, according to serotype. We recruited 1,912 consenting patients presenting with WHO dengue criteria at Mahosot Hospital, Vientiane (central Laos), between 2006 and 2010. Between 2008 and 2010, 1,413 patients with undifferentiated fever were also recruited at Luang Namtha (LNT) Provincial Hospital (northern Laos) and 555 at Salavan (SV) Provincial Hospital (southern Laos). We report significant variations in Dengue virus (DENV) circulation between the three sites. Peaks of DENV infection were observed in the rainy seasons, although 11% of confirmed cases in the provinces and 4.6% in the capital were detected during the dry and cool seasons (between December and February). Four DENV serotypes were detected among the 867 RT-PCR positive patients: 76.9% DENV-1, 9.6% DENV-2, 7.7% DENV-4 and 5.3% DENV-3. DENV-1 was the predominant serotype throughout the study except in LNT in 2008 and 2009 when it was DENV-2. Before July 2009, DENV-2 was not detected in SV and only rarely detected in Vientiane. DENV-3 and DENV-4 were commonly detected in Vientiane, before 2008 for DENV-4 and after 2009 for DENV-3. The phylogenetic analyses of DENV envelope sequences suggest concurrent multiple introductions of new strains as well as active DENV circulation throughout Laos and with neighboring countries. It is therefore of great importance to develop and strengthen a year-round nation-wide surveillance network in order to collect data that would allow anticipation of public health issues caused by the occurrence of large dengue outbreaks., Author summary Dengue is a mosquito-borne disease that can be caused by 4 viruses. It is a flu-like disease but can sometime be more severe and cause hemorrhage or death. An estimated 390 million people are infected every year, mainly in the Western Pacific and in South-East Asia. In Laos, where our study was conducted from 2006 to 2010, little was known on the circulation of the different dengue viruses. A total of 1,912 patients were recruited at Mahosot Hospital, Vientiane (central Laos), 1,413 patients at Luang Namtha Provincial Hospital (northern Laos) and 555 at Salavan Provincial Hospital (southern Laos). Although most Dengue virus infections were detected during rainy seasons (where mosquitoes are the most active) in all three provinces, some patients were also infected during the dryer months. All 4 dengue viruses were detected with different distributions: mostly type 1 in the capital and in the South, and type 1 and 2 in equal proportion in the north. Type 3 and 4 were not detected in Luang Namtha and rarely in Salavan. Comparison of Dengue virus sequences from Laos with sequences collected worldwide showed an active year-round circulation of dengue within Laos and with neighboring countries. It is hence of great importance to develop and strengthen a year-round nation-wide surveillance network in order to collect data that would allow anticipation of public health issues caused by the occurrence of large dengue outbreaks.
Published: 2018

27. Detection and Characterization of Homologues of Human Hepatitis Viruses and Pegiviruses in Rodents and Bats in Vietnam

Author: Van Nguyen, D, Van Nguyen, C, Bonsall, D, Ngo, T, Carrique-Mas, J, Pham, A, Bryant, J, Thwaites, G, Baker, S, Woolhouse, M, Simmonds, P, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre for Immunity, Infection and Evolution, University of Edinburgh, Van Nguyen, Dung [0000-0001-9390-9990], Apollo - University of Cambridge Repository, University of Oxford [Oxford], University of Oxford [Oxford]-University of Oxford [Oxford], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Wellcome Trust
Subjects: 0301 basic medicine, Rodent, Hepacivirus, lcsh:QR1-502, Genome, lcsh:Microbiology, Hepatitis, Chiroptera, Zoonoses, Rhizomys, homologues, Public Health Surveillance, Viral, Phylogeny, biology, Transmission (medicine), 3. Good health, Infectious Diseases, Vietnam, Hepatitis, Viral, Animal, rodents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, bats, pegiviruses, hepatitis viruses, [SDV.IMM]Life Sciences [q-bio]/Immunology, RNA, Viral, 0605 Microbiology, Human, Hepatitis, Viral, Human, Pegivirus, Rodentia, Genome, Viral, Article, 03 medical and health sciences, Phylogenetics, Virology, biology.animal, Journal Article, Animals, Humans, Animal, Bamboo rat, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, RNA
Abstract: International audience; Rodents and bats are now widely recognised as important sources of zoonotic virus infections in other mammals, including humans. Numerous surveys have expanded our knowledge of diverse viruses in a range of rodent and bat species, including their origins, evolution, and range of hosts. In this study of pegivirus and human hepatitis-related viruses, liver and serum samples from Vietnamese rodents and bats were examined by PCR and sequencing. Nucleic acids homologous to human hepatitis B, C, E viruses were detected in liver samples of 2 (1.3%) of 157 bats, 38 (8.1%), and 14 (3%) of 470 rodents, respectively. Hepacivirus-like viruses were frequently detected (42.7%) in the bamboo rat, Rhizomys pruinosus, while pegivirus RNA was only evident in 2 (0.3%) of 638 rodent serum samples. Complete or near-complete genome sequences of HBV, HEV and pegivirus homologues closely resembled those previously reported from rodents and bats. However, complete coding region sequences of the rodent hepacivirus-like viruses substantially diverged from all of the currently classified variants and potentially represent a new species in the Hepacivirus genus. Of the viruses identified, their routes of transmission and potential to establish zoonoses remain to be determined.
Published: 2018

28. Assessing the epidemiological effect of wolbachia for dengue control

Author: Scott Leslie O'Neill, Neil M. Ferguson, Thomas W. Scott, Louis Lambrechts, Peter A. Ryan, Scott C. Weaver, Cameron P. Simmons, Elizabeth A. McGraw, Scott A. Ritchie, Eva Harris, Eng Eong Ooi, Edward C. Holmes, Interactions Virus-Insectes (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], MRC Centre for Outbreak Analysis and Modelling [London], Imperial College London, Division of Infectious Diseases and Vaccinology, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, School of Biological Sciences [Clayton], Monash University [Clayton], Duke-National University of Singapore Graduate Medical School, School of Public Health and Tropical Medicine and Rehabilitative Sciences, James Cook University (JCU), Fogarty International Center, National Institutes of Health [Bethesda] (NIH), Department of Entomology and Nematology, University of California [Davis] (UC Davis), University of California-University of California, Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Centre for Tropical Medicine, Nossal Institute of Global Health, University of Melbourne, Institute for Human Infections and Immunity and Department of Pathology, The University of Texas Medical Branch (UTMB), This work was supported by a grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative of the Bill & Melinda Gates Foundation, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of California (UC)-University of California (UC), and University of Oxford
Subjects: and promotion of well-being, Dengue virus, medicine.disease_cause, Dengue fever, Dengue, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Aedes, Seroepidemiologic Studies, Epidemiology, 2.2 Factors relating to the physical environment, Aetiology, Randomized Controlled Trials as Topic, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, 3. Good health, Human morbidity, Mosquito control, Infectious Diseases, Research Design, Medical Microbiology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Public Health and Health Services, Wolbachia, Infection, medicine.medical_specialty, Clinical Sciences, Computational biology, Microbiology, Virus, Article, Rare Diseases, parasitic diseases, medicine, Animals, Humans, Pest Control, Biological, 3.2 Interventions to alter physical and biological environmental risks, Prevention, Dengue Virus, biology.organism_classification, medicine.disease, Biological, Prevention of disease and conditions, Virology, Insect Vectors, Vector-Borne Diseases, Emerging Infectious Diseases, Good Health and Well Being, Geographical cluster, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pest Control, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; Dengue viruses cause more human morbidity and mortality than any other arthropod-borne virus. Dengue prevention relies mainly on vector control; however, the failure of traditional methods has promoted the development of novel entomological approaches. Although use of the intracellular bacterium wolbachia to control mosquito populations was proposed 50 years ago, only in the past decade has its use as a potential agent of dengue control gained substantial interest. Here, we review evidence that supports a practical approach for dengue reduction through field release of wolbachia-infected mosquitoes and discuss the additional studies that have to be done before the strategy can be validated and implemented. A crucial next step is to assess the efficacy of wolbachia in reducing dengue virus transmission. We argue that a cluster randomised trial is at this time premature because choice of wolbachia strain for release and deployment strategies are still being optimised. We therefore present a pragmatic approach to acquiring preliminary evidence of efficacy through various complementary methods including a prospective cohort study, a geographical cluster investigation, virus phylogenetic analysis, virus surveillance in mosquitoes, and vector competence assays. This multipronged approach could provide valuable intermediate evidence of efficacy to justify a future cluster randomised trial.
Published: 2015
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29. Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice

Author: Pierre Fenaux, Louise C. Strong, Anita Langerød, Nicole Concin, B. Leroy, Patricia Ashton-Prolla, Gareth L. Bond, Sharon A. Savage, Mandy L. Ballinger, Davide Rossi, Robert Zeillinger, Lawrence A. Donehower, Gianluca Gaidano, Thorsten Zenz, Eva Hellström-Lindberg, Šárka Pospíšilová, Wafik S. El-Deiry, Patricia N. Tonin, Kim E. Nichols, Pierre Hainaut, Joseph F. Fraumeni, Fanny Baran-Marszak, Jeffrey N. Myers, Phuong L. Mai, Jacqueline Lehmann-Che, Ute M. Moll, Peter E.M. Taschner, David Malkin, Antony W. Braithwaite, Richard Iggo, Thierry Soussi, Sorbonne Université (SU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ludwig Institute for Cancer Research, University of Oxford [Oxford], Nuffield Department of Clinical Medicine [Oxford], University of Otago [Dunedin, Nouvelle-Zélande], The University of Sydney, Innsbruck Medical University [Austria] (IMU), Baylor College of Medicine (BCM), Baylor University, Fox Chase Cancer Center, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Oslo University Hospital [Oslo], Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Institut Bergonié [Bordeaux], UNICANCER, Université de Bordeaux (UB), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), The Hospital for sick children [Toronto] (SickKids), University of Toronto, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), The University of Texas M.D. Anderson Cancer Center [Houston], St Jude Children's Research Hospital, Masaryk University [Brno] (MUNI), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), McGill University = Université McGill [Montréal, Canada], University of Vienna [Vienna], University of Heidelberg, Medical Faculty, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Leiden University, International Prevention Research Institute (IPRI), Institut Albert Bonniot, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Cancer Center Karolinska [Karolinska Institutet] (CCK), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Gestionnaire, Hal Sorbonne Université, University of Oxford, and Innsbruck Medical University = Medizinische Universität Innsbruck (IMU)
Subjects: 0301 basic medicine, Cancer Research, Alternative splicing, Cancer, Genetic Variation, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Gene mutation, Biology, medicine.disease, Bioinformatics, Germline, 3. Good health, 03 medical and health sciences, Exon, 030104 developmental biology, Breast cancer, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Li–Fraumeni syndrome, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], humans, neoplasms
Abstract: Accurate assessment of TP53 gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li–Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants reveals that the two newly discovered exons of the gene, exons 9β and 9γ, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrange-ments in intron 1 of TP53 are associated with LFS and are frequently observed in sporadic osteosarcoma. In this context of constantly growing genomic data, we discuss how screening strategies must be improved when assessing TP53 status in clinical samples. Finally, we discuss how TP53 alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports. Cancer Res; 77(6); 1250–60. ©2017 AACR.
Published: 2017

30. An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid

Author: Wong, Vanessa K., Baker, Stephen, Connor, Thomas R., Pickard, Derek, Page, Andrew J., Dave, Jayshree, Murphy, Niamh, Holliman, Richard, Sefton, Armine, Millar, Michael, Dyson, Zoe A., Dougan, Gordon, Holt, Kathryn E., Parkhill, Julian, Feasey, Nicholas A., Kingsley, Robert A., Thomson, Nicholas R., Keane, Jacqueline A., Weill, François- Xavier, Le Hello, Simon, Hawkey, Jan, Edwards, David, Harris, Simon R., Cain, Amy K., Hadfield, James, Hart, Peter J., Thieu, Nga Tran Vu, Klemm, Elizabeth, Breiman, Robert F., Watson, Conall H., Edmunds, W. John, Kariuki, Samuel, Gordon, Melita A., Heyderman, Robert S., Okoro, Chinyere, Jacobs, Jan, Lunguya, Octavie, Msefula, Chisomo, Chabalgoity, Jose A., Kama, Mike, Jenkins, Kylie, Dutta, Shanta, Marks, Florian, Campos, Josefina, Thompson, Corinne, Obaro, Stephen, MacLennan, Calman A., Dolecek, Christiane, Keddy, Karen H., Smith, Anthony M., Parry, Christopher M., Karkey, Abhilasha, Dongol, Don, Basnyat, Buddha, Arjyal, Amit, Mulholland, E. Kim, Campbell, James I., Dufour, Muriel, Bandaranayake, Don, Toleafoa, Take N., Singh, Shalini Pravin, Hatta, Mochammad, Newton, Paul, Dance, David, Davong, Viengmon, Onsare, Robert S., Isaia, Lupeoletalalelei, Thwaites, Guy, Wijedoru, Lalith, Crump, John A., de Pinna, Elizabeth, Nair, Satheesh, Nilles, Eric J., Thanh, Duy Pham, Turner, Paul, Soeng, Sona, Valcanis, Mary, Powling, Joan, Dimovski, Karolina, Hogg, Geoff, Farrar, Jeremy, Mather, Alison E., Amos, Ben, Addenbrooke's Hospital, Cambridge University NHS Trust, The Wellcome Trust Sanger Institute [Cambridge], London School of Hygiene and Tropical Medicine (LSHTM), University of Oxford [Oxford], Cardiff University, Barts Health NHS Trust [London, UK], Centre for Sytems Genomics, University of Melbourne, Department of Engineering [Cambridge], University of Cambridge [UK] (CAM), Liverpool School of Tropical Medicine (LSTM), University of Liverpool, Institute of Food Research [Norwich], Institute for Astronomy [Honolulu], University of Hawai‘i [Mānoa] (UHM), Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris], Atmospheric Chemistry Observations and Modeling Laboratory (ACOML), National Center for Atmospheric Research [Boulder] (NCAR), INM-8, Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Global Disease Detection Division, Centers for Disease Control and Prevention, Department of Applied Mathematics and Theoretical Physics (DAMTP), University College of London [London] (UCL), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut National de Recherche Biomédicale [Kinshasa] (INRB), University of Malawi, Universidad de la República [Montevideo] (UCUR), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Department of Mathematics and Statistics [Toronto], York University [Toronto], Department of Mathematical Sciences [Varanasi], Banaras Hindu University [Varanasi] (BHU), Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Public Health England [London], Nuffield Department of Clinical Medicine [Oxford], This work was supported by a number of organizations. The Wellcome Trust Sanger Institute authors were funded by Wellcome Trust Award #098051. V.K.W. was supported by the Wellcome Trust (#098051) and the National Institute of HealthResearch (NIHR) Cambridge Biomedical Research Centre (BRC). N.F. was supported by the Wellcome Trust Research Fellowship #WT092152MA. N.F., R.S.H. and this work were supported by a strategic award from the Wellcome Trust for the MLW ClinicalResearch Programme (#101113/Z/13/Z). C.P. was funded by The Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme, supported by the Wellcome Trust of Great Britain (Major Overseas Programmes—Thailand Unit CoreGrant), the European Society for Paediatric Infectious Diseases and University of Oxford-Li Ka Shing Global Health Foundation. D.D., P.N. and V.D. were supported by the Wellcome Trust (core grant #089275/H/09/Z). Z.A.D. was supported by the WellcomeTrust (Strategic award #106158). K.E.H. was supported by the NHMRC of Australia (fellowship #1061409) and the Victorian Life Sciences Computation Initiative (VLSCI, grant #VR0082). C.A.M. was supported by a Clinical Research Fellowship fromGlaxoSmithKline and PJH by a UK Medical Research Council PhD studentship. This work forms part of an EU FP7 Marie Curie Actions Industry Academia Partnerships and Pathways (IAPP) Consortium Programme, entitled GENDRIVAX (Genome-drivenvaccine development for bacterial infections), involving the Wellcome Trust Sanger Institute, KEMRI Nairobi and Novartis Vaccines Institute for Global Health. The Institut Pasteur (IP) authors were funded by the IP, the Institut de Veille Sanitaire and by theFrench Government ‘Investissement d’Avenir’ programme (Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, grant #ANR-10-LABX-62-IBEID). C.H.W. was supported by the UK Medical Research Council (MRC, MR/J003999/1).C.O. was supported by Society in Science, The Branco Weiss Fellowship, administered by the ETH Zurich. A.K.C. was supported by the MRC (#G1100100/1). J.J. was supported by the antibiotic resistance surveillance project in DR Congo, funded by Project 2.01 of the Third Framework Agreement between the Belgian Directorate General of Development Cooperation and the Institute of Tropical Medicine, Antwerp, Belgium. F.M. was supported by a research grant from the Bill and Melinda Gates Foundation. J.A.C. was supported by the joint US National Institutes of Health-National Science Foundation Ecology and Evolution of Infectious Disease program (#R01 TW009237) and the UK Biotechnology and Biological Sciences Research Council (BBSRC, BB/J010367/1), and by UK BBSRC Zoonoses in Emerging Livestock Systems awards #BB/L017679, #BB/L018926 and #BB/L018845. S.K. was supported by the NIH Grant Number R01 AI099525-02. S.B. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (#100087/Z/12/Z). S.O. was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health (#R01AI097493). C.D. was supported by the University of Oxford-Li Ka Shing Global Health Programme. A.E.M. was supported by a Biotechnology and Biological Sciences Research Councilaward (#BB/M014088/1). P.T. was supported by the Wellcome Trust of Great Britain (Major Overseas Programmes—Thailand Unit Core Grant) and University of Oxford-Li Ka Shing Global Health Foundation., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Dyson, Zoe A [0000-0002-8887-3492], Holt, Kathryn E [0000-0003-3949-2471], Apollo - University of Cambridge Repository, University of Oxford, Biotechnology and Biological Sciences Research Council (BBSRC), Institut Pasteur [Paris] (IP), and Universidad de la República [Montevideo] (UDELAR)
Subjects: 0301 basic medicine, DNA, Bacterial, Genotype, Science, Population, General Physics and Astronomy, Biology, Salmonella typhi, complex mixtures, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Typhoid fever, Article, 03 medical and health sciences, medicine, Cluster Analysis, Humans, Typhoid Fever, education, Genotyping, Phylogeny, Genetics, education.field_of_study, Multidisciplinary, Geography, business.industry, Haplotype, Subclade, General Chemistry, Sequence Analysis, DNA, medicine.disease, bacterial infections and mycoses, 3. Good health, Biotechnology, 030104 developmental biology, Haplotypes, Microbial genetics, bacteria, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations., Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi). This study examines ∼2,000 clinical isolates of S. Typhi to show highly structured/geographically restricted genomes except rapidly disseminating H58 subclade, and design a genotyping framework for tracking the disease.
Published: 2016

31. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa

Author: Ben Amos, Roxanne Alter, Samuel Kariuki, Elizabeth de Pinna, Robert F. Breiman, Anthony M. Smith, Calman A. MacLennan, Nicholas A. Feasey, Peter J. Hart, Stephen K. Obaro, Gordon Dougan, Chinyere K. Okoro, Huda Munir, Melita A. Gordon, Andrew J. Page, Vanessa K. Wong, Octavie Lunguya, Paul D. Fey, Simon Le Hello, Robert S. Heyderman, Chisomo L. Msefula, Robert S. Onsare, Kathryn E. Holt, Florian Marks, Derek Pickard, Karen H. Keddy, Stephen Baker, François-Xavier Weill, Satheesh Nair, Grace Olanipekun, Jan Jacobs, The Wellcome Trust Sanger Institute [Cambridge], Addenbrooke's Hospital, Cambridge University NHS Trust, Bio21 Molecular Science & Biotechnology Institute [Melbourne] (School of Chemistry), Faculty of Science [Melbourne], University of Melbourne-University of Melbourne, University of Melbourne, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], London School of Hygiene and Tropical Medicine (LSHTM), Department of Epidemiology, International Vaccine Institute (IVI), International Foundation Against Infectious Diseases in Nigeria (IFAIN), Department of Medical Microbiology, Aminu Kano Teaching Hospital, University of Nebraska Medical Center, University of Nebraska System, Liverpool School of Tropical Medicine (LSTM), Centre National de Référence - National Reference Center Escherichia coli, Shigella et Salmonella (CNR-ESS), Institut Pasteur [Paris], Institut National de Recherche Biomédicale [Kinshasa] (INRB), St. George’s, University of London, Kenya Medical Research Institute (KEMRI), Global Disease Detection Division, Centers for Disease Control and Prevention, Emory Global Health Institute [Atlanta] (EGHI), Emory University [Atlanta, GA], University of Liverpool, University College of London [London] (UCL), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Malawi, National Institute for Communicable Diseases [Johannesburg] (NICD), St Augustine’s Hospital, Division of Pediatric Infectious Diseases, University of Nebraska System-University of Nebraska System, University of Abuja, Bingham University, This work was supported by a number of organizations. The Wellcome Trust Sanger Institute authors were funded by Wellcome Trust Award 098051, NAF was supported by the Wellcome Trust Research Fellowship WT092152MA. NAF, RSH and this work were supported by a strategic award from the Wellcome Trust for the MLW Clinical Research Programme (101113/Z/13/Z). KEH was supported by the NHMRC of Australia (fellowship #1061409) and the Victorian Life Sciences Computation Initiative (VLSCI) (grant #VR0082). CAM was supported by a Clinical Research Fellowship from GlaxoSmithKline and PJH by a UK Medical Research Council PhD studentship. This work forms part of an EU FP7 Marie Curie Actions Industry Academia Partnerships and Pathways (IAPP) Consortium Programme, entitled GENDRIVAX (Genome-driven vaccine development for bacterial infections), involving the Wellcome Trust Sanger Institute, KEMRI Nairobi and Novartis Vaccines Institute for Global Health. The Institut Pasteur (IP) authors were funded by the IP, the Institut de Veille Sanitaire, and by the French Government 'Investissement d'Avenir' program(Integrative Biology of Emerging Infectious Diseases' Laboratory of Excellence, grant no. ANR-10-LABX-62-IBEID). CO was supported by Society in Science, The Branco Weiss Fellowship, administered by the ETH Zurich. JJ was supported by the antibioticresistance surveillance project in DR Congo, funded by Project 2.01 of the Third Framework Agreement between the Belgian Directorate General of Development Cooperation and the Institute of Tropical Medicine, Antwerp, Belgium. FM was supported by a research grant from the Bill & Melinda Gates Foundation. The findings and conclusions contained within this publication are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. SK was supported by the NIH Grant Number R01 AI099525-02. SB is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society(100087/Z/12/Z). SO was supported by the National Institute Of Allergy And Infectious Diseases (NIAID) of the National Institutes of Health (#R01AI097493). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis,decision to publish, or preparation of the manuscript., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Baker, Stephen [0000-0003-1308-5755], Marks, Florian [0000-0002-6043-7170], Dougan, Gordon [0000-0003-0022-965X], Apollo - University of Cambridge Repository, University of Oxford, Institut Pasteur [Paris] (IP), and Ryan, E
Subjects: 0301 basic medicine, Bacterial Diseases, Veterinary medicine, Salmonella typhi, Pathology and Laboratory Medicine, Global Health, Salmonella Typhi, Geographical Locations, 0302 clinical medicine, Salmonella, Epidemiology, Global health, Medicine and Health Sciences, Typhoid, Medicine, Public and Occupational Health, Clade, Mammals, lcsh:Public aspects of medicine, International Typhoid Consortium, 3. Good health, Bacterial Pathogens, Europe, Infectious Diseases, Medical Microbiology, Vertebrates, Pathogens, Research Article, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Nigeria, Microbiology, complex mixtures, Typhoid fever, wa_110, 03 medical and health sciences, Antibiotic resistance, Enterobacteriaceae, Environmental health, Microbial Control, Animals, Microbial Pathogens, QR355, Pharmacology, Bacteria, business.industry, qw_138, wc_270, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, lcsh:RA1-1270, medicine.disease, bacterial infections and mycoses, R1, United Kingdom, 030104 developmental biology, Carriage, Parasitology, Amniotes, People and Places, Africa, Cats, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antimicrobial Resistance, business
Abstract: Background The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid., Author Summary Typhoid fever, a serious bloodstream infection caused by the bacterium Salmonella Typhi, is a major cause of disease and death around the world. There have been limited data on the epidemiology of typhoid in many countries in sub-Saharan African, including Nigeria. Recent evidence, however, showed that typhoid was an important cause of bacteraemia in children residing in two regions of Nigeria. Here, we analyzed the whole genome sequences of 128 S. Typhi isolates from two studies in order to elucidate the population structure and characterize the genetic components of antimicrobial resistance. We found that the multiple S. Typhi genotypes identified were closely related to other S. Typhi from neighboring regions of Africa and that multidrug resistance (MDR) was common among these isolates, and in many cases was associated with the IncHI1 plasmid known to cause MDR typhoid. These results provide evidence that typhoid was established in Nigeria as a result of several independent introductions into the country and that there has been extensive exchange of S. Typhi in and around the region of West Africa. This study emphasizes the importance of surveillance to improve our understanding of the epidemiology of typhoid, which is needed to underpin public health measures to reduce the spread of disease and facilitate patient management.
Published: 2016

32. Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases

Author: Chowdhury, Rasheduzzaman, Leung, Ivanhoe K. H., Tian, Ya-Min, Abboud, Martine I., Ge, Wei, Domene, Carmen, Cantrelle, François-Xavier, Landrieu, Isabelle, Hardy, Adam P., Pugh, Christopher W., Ratcliffe, Peter J., Claridge, Timothy D. W., Schofield, Christopher J., University of Oxford [Oxford], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), CNRS, Université de Lille, Chemistry Research Laboratory [Oxford, UK], Nuffield Department of Clinical Medicine [Oxford], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], University of Oxford, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Science, ComputingMilieux_MISCELLANEOUS
Abstract: The response to hypoxia in animals involves the expression of multiple genes regulated by the αβ-hypoxia inducible transcription factors (HIFs). The hypoxia sensing mechanism involves oxygen limited hydroxylation of prolyl-residues in the N- and C-terminal oxygen dependent degradation domains (NODD and CODD) of HIFα isoforms, as catalyzed by prolyl hydroxylases (PHD 1-3). Prolyl hydroxylation promotes binding of HIFα to the von Hippel-Lindau protein (VHL)-elongin B/C complex, so signaling for proteosomal degradation of HIFα. We reveal that certain PHD2 variants linked to familial erythrocytosis and cancer are highly selective for CODD or NODD. Crystalline and solution state studies coupled to kinetic and cellular analyses reveal how wildtype and variant PHDs achieve ODD selectivity via different dynamic interactions involving loop and C-terminal regions. The results inform on how HIF target gene selectivity is achieved and will be of use in developing selective PHD inhibitors.
Published: 2016

33. Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change

Author: Giovanna Tagliabue, Ingegerd Johansson, José María Huerta, Domenico Palli, Anne Tjønneland, Petra H.M. Peeters, Aurelio Barricarte, Anne M. May, Göran Hallmans, Francesca L. Crowe, Madlen Schütze, Daphne L. van der A, Françoise Clavel-Chapelon, Birgit Teucher, George Makrygiannis, Thorkild I. A. Sørensen, Jonas Manjer, Isabelle Romieu, Laudina Rodríguez, H. B. Bueno-de-Mesquita, Veronique Chajes, Kim Overvad, Guy Fagherazzi, Nadia Slimani, Karen Margrete Due, Nicholas J. Wareham, Dimosthenis Zylis, Heiner Boeing, Pilar Amiano, Kay-Tee Khaw, Claus Dethlefsen, Amalia Mattiello, Marianne Uhre Jakobsen, Rudolf Kaaks, Jytte Halkjær, Marie-Christine Boutron-Ruault, Elisabet Wirfält, Esther Molina-Montes, Noémie Travier, Elio Riboli, Antonia Trichopoulou, [Jakobsen,MU] Department of Clinical Epidemiology. [Jakobsen,MU, Dethlefsen,C, Due,KM, Overvad,K] Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg. [Jakobsen,MU, Overvad,K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Slimani,N, Chajès,V, Romieu,I] Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [May,AM, Peeter,PHM] Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht. [May,AM, van der A,DL, Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Sørensen,TIA] Institute of Preventive Medicine, Copenhagen University Hospital. [Halkjær,J, Tjønneland,A] The Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M, Fagherazzi,G] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy. Paris South University, Villejuif, France. [Teucher,B, Kaaks,R] German Cancer Research Center, Department of Cancer Epidemiology, Heidelberg. [Boeing,H, Schütze,M, Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Zylis,D] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School. [Trichopoulou,A, Zylis,D, Makrygiannis,G] Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples. [Tagliabue,G] Cancer Registry and Environmental Epidemiology Division, National Cancer Institute, Milan, Italy. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands. [Rodríguez,L] Public Health and Participation Directorate, Health and Health Care Services Council, Asturias. [Travier,N] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, IDIBELL, Barcelona. [Molina-Montes,E] Andalusian School of Public Health, Granada. [Molina-Montes,E, Huerta,JM, Barricarte,A, Amiano,P] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia. [Barricarte,A] Public Health Institute of Navarra, Pamplona. [Amiano,P] Public Health Division of Gipuzkoa, Basque Government, Spain. [Manjer,J] Department of Surgery, Skåne University Hospital Malmö, Lund University. [Wirfält,E] Department of Clinical Sciences in Malmö/Nutrition Epidemiology, Lund University, Malmö. [Johansson,I] Department of Odontology, Umeå University. [Hallmans,G] Department of Public Health and Clinical Medicine, Umeå University, Nutritional Research, Umeå, Sweden. [Khaw,K] Clinical Gerontology Unit, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge. [Wareham, NJ] MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge. [Crowe,F] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford. [Riboli,E, Peeters, PHM] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK., This work is part of the project Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of Home and Obesity (PANACEA), which is supported by the European Union in the framework of the Public Health Programmme (Contract 2005328). The work was further supported by the European Commission: Public Health and Consumer Protection Directorate 1993–2004, Research Directorate-General 2005, Ligue contre le Cancer, Société 3M, Mutuelle Générale de l’Education Nationale, Institut National de la Santé de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany), Danish Cancer Society (Denmark), ISCIII (RETICC RD06/0020) of the Spanish Ministry of Health, the participating regional governments and institutions (Spain), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, The Wellcome Trust (UK), Greek Ministry of Health, Greek Ministry of Education, Hellenic Ministry of Health, Stavros Niarchos Foundation, and the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer, National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch Zorg Onderzoek Nederland (ZON), World Cancer Research Fund (WCRF) (The Netherlands), and and Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Västerbotten (Sweden). This work is also part of the project Hepatic and Adipose Tissue and Functions in the Metabolic Syndrome (HEPADIP, www.hepadip.org), which is supported by the European Commission as an Integrated Project under the 6th Framework Programme (Contract LSHM-CT-2005-018734) and part of the research program of the Danish Obesity Research Centre (DanORC, www.danorc.dk), which is supported by the Danish Council for Strategic Research (Contract 2101-06-0005).
Subjects: Male, Health (social science), 030309 nutrition & dietetics, Obesidad, Ácidos grasos omega-3, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Estudios prospectivos, Fosfolípidos, Modelos lineales, Prospective Studies, Masculino, Prospective cohort study, Phospholipids, chemistry.chemical_classification, 0303 health sciences, education.field_of_study, Weight change, Femenino, Middle Aged, n-3 fatty acids, Humanos, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Female, Original Article, lipids (amino acids, peptides, and proteins), Cohort study, Polyunsaturated fatty acid, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Phospholipid, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, 03 medical and health sciences, Chemicals and Drugs::Lipids::Fats::Dietary Fats::Dietary Fats, Unsaturated::Fatty Acids, Omega-3 [Medical Subject Headings], Physiology (medical), Internal medicine, Fatty Acids, Omega-3, Omega-3 fatty acids, medicine, Humans, Obesity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Linear Models [Medical Subject Headings], Chemicals and Drugs::Lipids::Phospholipids [Medical Subject Headings], education, Mediana edad, business.industry, Body Weight, Peso corporal, Body weight, Confidence interval, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Endocrinology, Check Tags::Female [Medical Subject Headings], chemistry, Linear Models, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight [Medical Subject Headings], sense organs, business
Abstract: Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. METHOD A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. RESULTS The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. CONCLUSION The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population. Yes
Published: 2016

34. The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk

Author: Olga M. Sinilnikova, Rudolf Kaaks, Pilar Amiano, Anne Tjønneland, José Ramón Quirós, Eiliv Lund, Daniele Campa, Carla H. van Gils, Göran Hallmans, Kay-Tee Khaw, H. Bas Bueno-de-Mesquita, Anika Hüsing, Sabina Rinaldi, Nicholas J. Wareham, Nathalie Chabbert-Buffet, Kim Overvad, Eva Ardanaz, Sabine Rohrmann, Vittorio Krogh, Federico Canzian, Giovanna Masala, Françoise Clavel-Chapelon, María Dolores Chirlaque, Per Lenner, Carlotta Sacerdote, Esther Molina-Montes, Guy Fagherazzi, Jakob Stegger, James McKay, N. Charlotte Onland-Moret, Salvatore Panico, Rosario Tumino, Afshan Siddiq, Birgit Teucher, Timothy J. Key, Erifili Oustoglou, Ruth C. Travis, Veronique Chajes, Dimosthenis Zylis, Ulla Vogel, Antonia Trichopoulou, Elio Riboli, Nadia Slimani, Heiner Boeing, Núria Sala, Eva Fisher, Wareham, Nicholas [0000-0003-1422-2993], Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, Campa, D, Hüsing, A, Mckay, Jd, Sinilnikova, O, Vogel, U, Tjønneland, A, Overvad, K, Stegger, J, Clavel Chapelon, F, Chabbert Buffet, N, Fagherazzi, G, Trichopoulou, A, Zylis, D, Oustoglou, E, Rohrmann, S, Teucher, B, Fisher, E, Boeing, H, Masala, G, Krogh, V, Sacerdote, C, Panico, Salvatore, Tumino, R, Onland Moret, Nc, van Gils, Ch, Bueno de Mesquita, Hb, Lund, E, Chirlaque, Md, Sala, N, Quirós, Jr, Ardanaz, E, Amiano, P, Molina Montes, E, Hallmans, G, Lenner, P, Travis, Rc, Key, Tj, Wareham, N, Khaw, Kt, Rinaldi, S, Slimani, N, Chajes, V, Siddiq, A, Riboli, E, Kaaks, R, Canzian, F., and [Campa D, Hüssing A, Rohrmann S, Teucher B, Kaaks R, Canzian F] German Cancer Research Center (DKFZ), Heidelberg, Germany. [McKay JD, Slimani N, Chajes V] International Agency for Research on Cancer, Lyon, France. [Sinilnikova O] Hospices Civils de Lyon/Centre Léon Bérard, UMR5201 CNRS-Université Claude Bernard, Lyon, France. [Vogel U] National Food Institute Technical University of Denmark, Denmark. [Tjønneland A] Danish Cancer Society, Copenhagen, Denmark. [Overvad K] Aarhus University Hospital, Aalborg, Denmark. [Stegger J] Department of Cardiology, Cardiovascular Research Centre, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Clavel-Chapelon F, Chabbert-Buffet N, Fagherazzi G] Institut Gustave Roussy, Villejuif, France. [Trichopoulou A, Zylis D] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou A, Oustoglou E] Hellenic Health Foundation, Athens, Greece. [Fisher E, Boeing H] German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. [Masala G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Krogh V] Istituto Nazionale dei Tumori (IRCCS), Milan, Italy. [Sacerdote C] CPO Piemonte, Turin, Italy. [Panico S] Department of Clinical and Experimental Medicine Federico II University, Naples, Italy. [Tumino R] Azienda Ospedaliera 'Civile M.P.Arezzo' Ragusa, Italy. [Onland-Moret NC, van Gils CH] Julius Center, University Medical Center, Utrecht, The Netherlands. [Bueno-de-Mesquita HB] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. [Lund E] Institute of Community Medicine University of Tromsø, Tromsø, Norway. [Chirlaque MD] Murcia Regional Health Council, Murcia, Spain. [Sala N] Catalan Institute of Oncology, Barcelona, Spain. [Quirós JR] Consejería de Salud y Servicios Sanitarios Principado de Asturias, Oviedo, Spain. [Ardanaz E] Public Health Institute of Navarra, Pamplona, Spain. [Amiano P] Public Health Department of Gipuzkoa, San Sebastian, Spain. [Molina-Montes E] Andalusian School of Public Health, Granada, Spain. [Chirlaque MD, Amiano P, Molina-Montes E] CIBER de Epidemiología y Salud Pública (CIBERESP), Spain. [Hallmans G, Lenner2 P] Umeå University, Umeå, Sweden. [Travis RC, Key TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK OX3 7LF. [Wareham N, Khaw KT] University of Cambridge, Cambridge, UK. [Siddiq A, Riboli E] Imperial College, London, UK.
Subjects: Oncology, Aging, Cancer Research, Genome-wide association study, 32 Biomedical and Clinical Sciences, Body Mass Index, Cohort Studies, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [Medical Subject Headings], 0302 clinical medicine, 2.1 Biological and endogenous factors, membrane protein, POPULATION, Cancer, 2. Zero hunger, 2 Aetiology, 0303 health sciences, education.field_of_study, Intracellular Signaling Peptides and Proteins, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 4203 Health Services and Systems, 3. Good health, Índice de masa muscular, INSIG2 protein, Adipose Tissue, Neoplasias de la mama, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins [Medical Subject Headings], Female, Life Sciences & Biomedicine, Cohort study, Research Article, Adult, Risk, medicine.medical_specialty, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, Genotype, Estudios de cohortes, Population, Polimorfismo Genético, COMMON GENETIC VARIANT, PHENOTYPES, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Breast Neoplasms, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, lcsh:RC254-282, Estudio de Asociación del Genoma Completo, 03 medical and health sciences, Breast cancer, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], SDG 3 - Good Health and Well-being, Clinical Research, Internal medicine, Breast Cancer, POLYGENIC CONTRIBUTION, medicine, Genetics, Humans, signal peptide, Neoplasm Invasiveness, Obesity, human, education, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Nutrition, Aged, Science & Technology, Polymorphism, Genetic, Models, Genetic, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Prevention, Case-control study, 42 Health Sciences, Membrane Proteins, DNA, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], medicine.disease, 3211 Oncology and Carcinogenesis, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Biometry::Anthropometry::Body Mass Index [Medical Subject Headings], VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Case-Control Studies, Immunology, INSIG2 protein, human, business, Body mass index, Genome-Wide Association Study
Abstract: Background The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC). Methods we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk. Results and Conclusions In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.
Published: 2016

35. The polyserine domain of the lysyl-5 hydroxylase Jmjd6 mediates subnuclear localization

Author: Alexander Wolf, Monica Mantri, Muhammad Mukram Mohamed Mackeen, Heinrich Leonhardt, Christopher J. Schofield, Lothar Schermelleh, Astrid Heim, Benedikt M. Kessler, Erika Fichter, Angelika Böttger, Catherine Vénien-Bryan, Udo Müller, Gregory Dadie, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München-German Research Center for Environmental Health, Helmholtz-Zentrum München (HZM), Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, University of Oxford [Oxford], Department of Biology II, Ludwig Maximilians University, Munich, Department of Biology II, Department of Biochemistry, University of Oxford, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Henry Wellcome Building for Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Helmholtz Zentrum München = German Research Center for Environmental Health, University of Oxford, Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), and Nuffield Department of Clinical Medicine [Oxford]
Subjects: Jumonji Domain-Containing Histone Demethylases, Nucleolus, Immunoprecipitation, RNA Splicing, Lysine, Biology, Biochemistry, Cell Line, Hydroxylation, 03 medical and health sciences, chemistry.chemical_compound, Microscopy, Electron, Transmission, Humans, Electrophoresis, Gel, Two-Dimensional, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, 0303 health sciences, Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase, 030302 biochemistry & molecular biology, Alternative splicing, Fluorescence recovery after photobleaching, Cell Biology, Cell biology, chemistry, Cell culture, RNA splicing, Chromatography, Gel, Cell Nucleolus, Fluorescence Recovery After Photobleaching, HeLa Cells
Abstract: International audience; Jmjd6 (jumonji-domain-containing protein 6) is an Fe(II)- and 2OG (2-oxoglutarate)-dependent oxygenase that catalyses hydroxylation of lysine residues in proteins involved in premRNA splicing. Jmjd6 plays an essential role in vertebrate embryonic development and has been shown to modulate alternative splicing in response to hypoxic stress. In the present study we show that an alternatively spliced version of Jmjd6 lacking the polyS (polyserine) domain localizes to the nucleolus, predominantly in the fibrillar centre. Jmjd6 with the polyS domain deleted also interacts with nucleolar proteins. Furthermore, coimmunoprecipitation experiments and F2H (fluorescent 2-hybrid) assays demonstrate that Jmjd6 homo-oligomerization occurs in cells. In correlation with the observed variations in the subnuclear distribution of Jmjd6, the structure of Jmjd6 oligomers in vitro changes in the absence of the polyS domain, possibly reflecting the role of the polyS domain in nuclear/nucleolar shuttling of Jmjd6. Key words: Fe(II)- and 2-oxoglutarate-dependent oxygenase, JmjC, lysine hydroxylation, nucleolus, polyserine domain, pre-mRNA splicing
Published: 2016

36. Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G

Author: Benjamin E. Willcox, Kouhei Tsumoto, Mitsunori Shiroishi, Marco Colonna, Veronique M. Braud, Katsumi Maenaka, Izumi Kumagai, P. Anton van der Merwe, E. Yvonne Jones, Azure T Makadzange, Yasuo Shirakihara, David S.J. Allan, Sarah Rowland-Jones, Kimie Amano, Division of Structural Biology, Kyushu University [Fukuoka]-Medical Institute of Bioregulation, Department of Biomolecular Engineering, Graduate School of Engineering-Tohoku University [Sendai], Structural Biology Center, National Institute of Genetics (NIG), Department of Pathology and Immunology, Washington University School of Medicine, Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Cancer Research UK Receptor Structure Group, Wellcome Trust Centre for Human Genetics, Sir William Dunn School of Pathology [Oxford], and Ministry of Education, Sports, Culture, and Technology of Japan, the 2000th year Joint Research Project of Sokendai, Nakajima Foundation, Cancer Research UK, Medical Research Council
Subjects: Models, Molecular, Protein Conformation, MESH: Sequence Homology, Amino Acid, MESH: Membrane Glycoproteins, Leukocyte Immunoglobulin-like Receptor B1, MESH: Amino Acid Sequence, Protein tyrosine phosphatase, CD8-Positive T-Lymphocytes, MESH: Base Sequence, Leukocyte immunoglobulin-like receptors, MESH: Histocompatibility Antigens Class I, MESH: Recombinant Proteins, MESH: Protein Conformation, 0302 clinical medicine, HLA Antigens, HLA-G, Immunoreceptor tyrosine-based activation motif, Receptors, Immunologic, MESH: Antigens, CD, MESH: HLA Antigens, 0303 health sciences, Membrane Glycoproteins, Multidisciplinary, MESH: Kinetics, biology, Biological Sciences, MESH: CD8-Positive T-Lymphocytes, Recombinant Proteins, MESH: Surface Plasmon Resonance, Cell biology, Killer Cells, Natural, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoreceptor tyrosine-based inhibitory motif, MESH: Models, Molecular, MESH: Killer Cells, Natural, DNA, Complementary, CD8 Antigens, Molecular Sequence Data, MESH: Binding, Competitive, In Vitro Techniques, Binding, Competitive, 03 medical and health sciences, Antigens, CD, Cell surface receptor, MHC class I, Humans, Amino Acid Sequence, MESH: Receptors, Immunologic, 030304 developmental biology, HLA-G Antigens, Binding Sites, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Sequence Homology, Amino Acid, Histocompatibility Antigens Class I, MESH: DNA, Complementary, Surface Plasmon Resonance, Molecular biology, Kinetics, MESH: Binding Sites, biology.protein, MESH: Antigens, CD8, 030215 immunology
Abstract: Ig-like transcript 4 (ILT4) (also known as leukocyte Ig-like receptor 2, CD85d, and LILRB2) is a cell surface receptor expressed mainly on myelomonocytic cells, whereas ILT2 (also known as leukocyte Ig-like receptor 1, CD85j, and LILRB1) is expressed on a wider range of immune cells including subsets of natural killer and T cells. Both ILTs contain immunoreceptor tyrosine-based inhibitory receptor motifs in their cytoplasmic tails that inhibit cellular responses by recruiting phosphatases such as SHP-1 (Src homology 2 domain containing tyrosine phosphatase 1). Although these ILTs have been shown to recognize a broad range of classical and nonclassical human MHC class I molecules (MHCIs), their precise binding properties remain controversial. We have used surface plasmon resonance to analyze the interaction of soluble forms of ILT4 and ILT2 with several MHCIs. Although the range of affinities measured was quite broad (Kd= 2–45 μM), some interesting differences were observed. ILT2 generally bound with a 2- to 3-fold higher affinity than ILT4 to the same MHCI. Furthermore, ILT2 and ILT4 bound to HLA-G with a 3- to 4-fold higher affinity than to classical MHCIs, suggesting that ILT/HLA-G recognition may play a dominant role in the regulation of natural killer, T, and myelomonocytic cell activation. Finally, we show that ILT2 and ILT4 effectively compete with CD8 for MHCI binding, raising the possibility that ILT2 modulates CD8+T cell activation by blocking the CD8 binding as well as by recruiting inhibitory molecules through its immunoreceptor tyrosine-based inhibitory receptor motif.
Published: 2016

37. Diet quality scores and prediction of all-cause, cardiovascular and cancer mortality in a pan-european cohort study

Author: Lassale, Camille, Gunter, Marc J., Romaguera, Dora, Peelen, Linda M., Van der Schouw, Yvonne T., Beulens, Joline W. J., Freisling, Heinz, Muller, David C., Ferrari, Pietro, Huybrechts, Inge, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Affret, Aurelie, Overvad, Kim, Dahm, Christina C., Olsen, Anja, Roswall, Nina, Tsilidis, Konstantinos K., Katzke, Verena A., Kuehn, Tilman, Buijsse, Brian, Quiros, Jose-Ramon, Sanchez-Cantalejo, Emilio, Etxezarreta, Nerea, Maria Huerta, Jose, Barricarte, Aurelio, Bonet, Catalina, Khaw, Kay-Tee, Key, Timothy J., Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Boer, Jolanda M. A., Sonestedt, Emily, Nilsson, Lena Maria, Renstrom, Frida, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Moons, Karel G. M., Riboli, Elio, Tzoulaki, Ioanna, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Lassale, Camille, Gunter, Marc J, Romaguera, Dora, Peelen, Linda M, Van der Schouw, Yvonne T, Beulens, Joline W. J, Freisling, Heinz, Muller, David C, Ferrari, Pietro, Huybrechts, Inge, Fagherazzi, Guy, Boutron Ruault, Marie Christine, Affret, Aurélie, Overvad, Kim, Dahm, Christina C, Olsen, Anja, Roswall, Nina, Tsilidis, Konstantinos K, Katzke, Verena A, Kühn, Tilman, Buijsse, Brian, Quirós, José Ramón, Sánchez Cantalejo, Emilio, Etxezarreta, Nerea, Huerta, José María, Barricarte, Aurelio, Bonet, Catalina, Khaw, Kay Tee, Key, Timothy J, Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno de Mesquita, H. Ba, Boer, Jolanda M. A, Sonestedt, Emily, Nilsson, Lena Maria, Renström, Frida, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Moons, Karel G. M, Riboli, Elio, Tzoulaki, Ioanna, [Lassale,C, Gunter,MJ, Romaguera,D, Tsilidis,KK, Riboli,E, Tzoulaki,I] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain. [Romaguera,D, Quirós,J, Sánchez-Cantalejo,E, Etxezarreta,N, Huerta,JM, Barricarte,A, Bonet,C] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Peelen,LM, Schouw,ITV, Beulens,JWJ, Moons,KGM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.[Freisling,H, Muller,DC, Ferrari,P, Huybrechts,I] International Agency for Research on Cancer, Lyon, France. [Fagherazz,G, Boutron-Ruault,M, Affret,A] Institut National de la Santé et de la Recherche Médicale, Center for Research in Epidemiology and Population, Health, Villejuif, France. Institut Gustave Roussy, Villejuif, France. Paris South University, Unité Mixte de Recherche, Villejuif, France. [Overvad,K, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Olsen,A, Roswall,N] Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Tsilidis,KK] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany. [Katzke,VA, Kühn,T] Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke German Institute of Human Nutrition, Potsdam, Germany. [Buijsse,B] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Quirós,R] Public Health Directorate, Asturias, Oviedo, Spain. [Sánchez-Cantalejo,E] Andalusian School of Public Health, Granada, Spain. [Etxezarreta,N] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Bonet,C] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Cambridge, United Kingdom. [Key,J] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. [Trichopoulou,A, Bamia,C, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Department of Preventive and Predictive Medicine, Foundation of the Carlo Besta Neurological Institute, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic MP Arezzo' Hospital, Ragusa, Italy. [Fasanelli,F] Human Genetics Foundation, Turin, Italy. [Bueno-de-Mesquita,HB, Boer,JMA] Center for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, Netherlands. [Sonestedt,E] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [Nilsson,LM, Renström,F] Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Weiderpass,E, Skeie,G, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland., Funding: The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/ A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: Male, humanos, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Social Sciences, Índice de masa corporal, Global Health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, distribución por sexos, Mathematical and Statistical Techniques, Sociology, Risk Factors, Neoplasms, Medicine and Health Sciences, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity [Medical Subject Headings], Public and Occupational Health, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], Estado Nutricional, estudios de cohortes, mediana edad, Factores de Riesgo, neoplasias, Medicine(all), Nutrition and Dietetics, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Agricultural and Biological Sciences(all), dieta, Agriculture, Public Health, Global Health, Social Medicine and Epidemiology, Estudios Prospectivos, Plants, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Neoplasias, Näringslära, Cardiovascular Diseases, Hábitos alimenticios, estilo de vida, Physical Sciences, Medicine, Dieta, Female, Statistics (Mathematics), Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], General Science & Technology, Science, Estudios de cohortes, European Continental Ancestry Group, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], enfermedades cardiovasculares, Crops, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research and Analysis Methods, White People, Education, Fruits, Age Distribution, distribución por edades, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Anatomy::Cardiovascular System [Medical Subject Headings], Journal Article, factores de riesgo, Humans, Statistical Methods, Sex Distribution, Life Style, Educational Attainment, Nutrition, Sistema cardiovascular, Biochemistry, Genetics and Molecular Biology(all), Organisms, Biology and Life Sciences, Physical Activity, Nutrients, Actividad motora, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior::Food Habits [Medical Subject Headings], Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Hábito de Fumar, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, grupo de ascendencia continental europea, Mathematics, Forecasting, Crop Science
Abstract: Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors., The coordination of EPIC is financially supported by the European Commission (D-GSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC- Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Published: 2016

38. Selectivity, Cocrystal Structures, and Neuroprotective Properties of Leucettines, a Family of Protein Kinase Inhibitors Derived from the Marine Sponge Alkaloid Leucettamine B

Author: Claude Cochet, Guillaume Burgy, François Carreaux, Meera Soundararajan, Panagis Filippakopoulos, Anselm Erich Oberholzer, Emilie Durieu, Laurent Meijer, Jean Pierre Bazureau, Ralf S. Schmid, Florent Delhommel, Jonathan M. Elkins, Donald C. Lo, Tania Tahtouh, Laurence H. Pearl, Stefan Knapp, Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Models, Molecular, DYRK1B, DYRK1A, Crystallography, X-Ray, 01 natural sciences, Chromatography, Affinity, Rats, Sprague-Dawley, CLK1, Amyloid beta-Protein Precursor, Mice, chemistry.chemical_compound, Drug Discovery, 0303 health sciences, Cell Death, Molecular Structure, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Kinase, Chemistry, Pyramidal Cells, Imidazoles, Brain, Stereoisomerism, Protein-Tyrosine Kinases, Recombinant Proteins, Porifera, Neuroprotective Agents, Biochemistry, Molecular Medicine, Protein Binding, Glutamic Acid, Dioxoles, In Vitro Techniques, Protein Serine-Threonine Kinases, Cell Line, Structure-Activity Relationship, 03 medical and health sciences, Alkaloids, Animals, Humans, Protein kinase A, Protein Kinase Inhibitors, 030304 developmental biology, Protein-Serine-Threonine Kinases, 010405 organic chemistry, Cyclin-Dependent Kinase 2, Cyclin-dependent kinase 2, Tyrosine phosphorylation, Rats, 0104 chemical sciences, biology.protein
Abstract: International audience; DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases) are implicated in the onset and development of Alzheimer's disease and Down syndrome. The marine sponge alkaloid leucettamine B was recently identified as an inhibitor of DYRKs/CLKs. Synthesis of analogues (leucettines) led to an optimized product, leucettine L41. Leucettines were cocrystallized with DYRK1A, DYRK2, CLK3, PIM1, and GSK-3β. The selectivity of L41 was studied by activity and interaction assays of recombinant kinases and affinity chromatography and competition affinity assays. These approaches revealed unexpected potential secondary targets such as CK2, SLK, and the lipid kinase PIKfyve/Vac14/Fig4. L41 displayed neuroprotective effects on glutamate-induced HT22 cell death. L41 also reduced amyloid precursor protein-induced cell death in cultured rat brain slices. The unusual multitarget selectivity of leucettines may account for their neuroprotective effects. This family of kinase inhibitors deserves further optimization as potential therapeutics against neurodegenerative diseases such as Alzheimer's disease.
Published: 2012

39. Mapping of the Fibroblast Growth Factors in Human White Adipose Tissue

Author: Peter Arner, Jean Galitzky, Ingrid Dahlman, Niklas Mejhert, Mikael Rydén, Keith N. Frayn, Lennart Blomqvist, Amanda T. Pettersson, Clara Bambace, Anne Bouloumié, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Surgery, Department of Clinical Science, Karolinska Institutet [Stockholm]-Danderyds Hospital, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, This work was supported by several grants from the Swedish Heart and Lung Foundation, the Swedish Research Council, the Swedish Diabetes Foundation, Storstockholms Diabetesfo¨ rening, Torsten och Ragnar So¨ derberg Foundation, Novo Nordisk Foundation, the European Union (HEPADIP, LSHM-CT-2005- 018734), ADAPT (HEALTH-F2-2008-201100), COST action (BM0602), NordForsk (SYSDIET-070014), and the Swedish Medical Association., European Project: 32591,HEPADIP, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, and Hepatic and adipose tissue and functions in the metabolic syndrome - HEPADIP - 32591 - OLD
Subjects: MESH: Heparin, FGF21, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, White adipose tissue, Fibroblast growth factor, Polymerase Chain Reaction, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adipocyte, Abdomen, FGF, MESH: Obesity, Oligonucleotide Array Sequence Analysis, 2. Zero hunger, 0303 health sciences, integumentary system, Chromosome Mapping, MESH: Enzyme-Linked Immunosorbent Assay, adipose tissue, MESH: Adipose Tissue, White, embryonic structures, MESH: Fibroblast Growth Factors, medicine.medical_specialty, Adipose Tissue, White, Enzyme-Linked Immunosorbent Assay, 030209 endocrinology & metabolism, Biology, MESH: Abdomen, 03 medical and health sciences, FGF9, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, RNA, Messenger, obesity, MESH: Overweight, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, Heparin, Biochemistry (medical), MESH: Polymerase Chain Reaction, FGF18, Overweight, FGF1, Fibroblast Growth Factors, PPAR gamma, MESH: PPAR gamma, chemistry, MESH: Oligonucleotide Array Sequence Analysis, MESH: Chromosome Mapping
Abstract: Context: Fibroblast growth factors (FGFs) regulate the development of white adipose tissue (WAT). However, the secretion and cellular origin of individual FGFs in WAT as well as the influence of obesity are unknown. Objective: Our objective was to map FGFs in human sc WAT, the cellular source, and association with obesity. Design: Secretion, mRNA, and circulatory levels of FGFs in human abdominal sc WAT from nonobese and obese donors were examined by microarray, real-time quantitative PCR, and ELISA. The activity of FGFs in cultured human adipocytes was determined by phosphorylation assays. Results: Expression of five FGFs (FGF1, FGF2, FGF7, FGF9, and FGF18) and FGF homologous factor (FHF2) was identified in WAT. Only FGF1 was released in a time-dependent manner from sc WAT, and fat cells were the major source of FGF1 secretion. FGF1 expression increased and FGF2 decreased during adipocyte differentiation. Furthermore, FGF1 was not secreted into the circulation. Although FGF1 levels were 2-fold increased in obesity, they were unaltered by weight reduction. Only FGF1 and FGF2 induced a marked concentration-dependent phosphorylation of p44/42 in cultured human adipocytes. Conclusions: Of the investigated FGFs, only FGF1 is secreted from sc WAT and predominantly so from the adipocyte fraction. The activity in adipocyte cultures and lack of secretion into the circulation suggest that FGF1 acts as an auto- or paracrine factor. FGF1 levels are increased in obesity but unaffected by weight reduction, suggesting a primary defect in obese individuals. In conclusion, FGF1 may play a superior role among the FGFs in sc WAT and obesity development.
Published: 2010

40. Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation

Author: Jaime Soto, Joelle Rode, Alejandro Llanos-Cuentas, Juan Miguel Pascale, Afif Ben Salah, Astrid C. Erber, Mourad Mokni, Liliana López Carvajal, Lise Grout, Byron Arana, Nidia Rizzo Molina, Vahid Mashayekhi, Iván D. Vélez, Max Grogl, Ermias Diro, Olga Zerpa, Marina Boni, Endalamaw Gadisa, Nancy G. Saravia, Mamoudou Cisse, Ali Khamesipour, Florian Vogt, Soner Uzun, Edgar M. Carvalho, Houda Chebli, Mohammad Sami Nahzat, Badre Eddine Lmimouni, Piero Olliaro, Farhad Handjani, Gláucia Fernandes Cota, Yusuf Özbel, José Antonio Ruiz-Postigo, Gustavo Adolfo Sierra Romero, Ege Üniversitesi, WHO-TDR Suisse, WHO-TDR Suisse-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], U.S. Naval Medical Research Unit No. 6 (NAMRU-6), Drugs for Neglected Diseases initiative Latin America (DNDi), Drugs for Neglected Diseases Initiative, Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Direction de l’Epidémiologie et de Lutte contre les Maladies (DELM), Université Polytechnique de Bobo-Dioulasso (UPB), University of Gondar - Université de Gondar, Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), Armauer Hansen Research Institute (AHRI), Shiraz University (Shiraz University ), Tehran University of Medical Sciences (TUMS), Instituto de Medicina Tropical 'Alexander von Humboldt' (IMT AvH), Universidad Peruana Cayetano Heredia (UPCH), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Mohammed V, Hôpital La Rabta [Tunis], National Malaria & Leishmaniasis Control Program [Kabul] (NMLCP), Laboratoire d'Epidémiologie Médicale, Institut Pasteur de Tunis, Institut Pasteur de Tunis, Ege university, Instituto Conmemorativo Gorgas de Estudios de la Salud [Panamá], Universidad del Valle de Guatemala, Universidade de Brasilia [Brasília] (UnB), Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Fundación Nacional de Dermatología [Santa Cruz] (FUNDERMA), Akdeniz University, Imam Reza Hospital [Iran], Institute of Tropical Medicine [Antwerp] (ITM), and Instituto Medico la Floresta [Caracas]
Subjects: Species Delimitation, Standardization, Speciation, [SDV]Life Sciences [q-bio], Terapéutica, Psychological intervention, Iran, Pathology and Laboratory Medicine, Geographical locations, MESH: Antiprotozoal Agents/therapeutic use, 0302 clinical medicine, Zoonoses, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Amphotericin, Leishmaniasis, MESH: Treatment Outcome, Protozoans, Ulcers, Leishmania, Clinical Trials as Topic, Pharmaceutics, Antimicrobials, lcsh:Public aspects of medicine, Eukaryota, Drugs, MESH: Leishmaniasis, Cutaneous/drug therapy, 3. Good health, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Systematic review, Ensayos Clínicos como Asunto, Drug therapy, Clinical evaluation, Brazil, purl.org/pe-repo/ocde/ford#3.03.06 [https], Research Article, Neglected Tropical Diseases, medicine.medical_specialty, Evolutionary Processes, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Antiprotozoal Agents, Leishmaniasis, Cutaneous, Standardized test, Mycology, Therapeutics, Microbiology, 03 medical and health sciences, Signs and Symptoms, Drug Therapy, Cutaneous leishmaniasis, Diagnostic Medicine, Microbial Control, Parasitic Diseases, Species delimitation, Humans, Medical physics, Pharmacology, Evolutionary Biology, Antifungals, Protozoan Infections, MESH: Humans, business.industry, Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, lcsh:RA1-1270, South America, Tropical Diseases, medicine.disease, Parasitic Protozoans, Clinical trial, Leishmaniasis Cutánea, Clinical research, Lesions, MESH: Clinical Trials as Topic/standards, People and places, business
Abstract: WOS: 000424022700022, PubMed ID: 29329311, Introduction Progress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL and NWCL). Materials and methods Using a previously published guidance paper on CL treatment trial methodology as the reference, consensus was sought on key parameters including core eligibility and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7 countries, 11 trial sites) during two separate meetings. Results Findings and level of consensus within and between OWCL and NWCL sites are presented and discussed. In addition, CL trial site characteristics and capacities are summarized. Conclusions The consensus reached allows standardization of future clinical research across OWCL and NWCL sites. We encourage CL researchers to adopt and adapt as required the proposed parameters and outcomes in their future trials and provide feedback on their experience. The expertise afforded between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL and faster approval of candidate treatments., World Health OrganizationWorld Health Organization [001]
Published: 2018

41. Super-resolution microscopy in Neurosciences: zoom in on synapses – Laurent

Author: Hell, Stefan, Sahl, Steffen, Bates, Mark, Zhuang, Xiaowei, Heintzmann, Rainer, Booth, Martin J, Bewersdorf, Joerg, Shtengel, Gleb, Hess, Harald, Tinnefeld, Philipp, Honigmann, Alf, Jakobs, Stefan, Testa, Ilaria, Cognet, Laurent, Lounis, Brahim, Ewers, Helge, Davis, Simon J, Eggeling, Christian, Klenerman, David, Willig, Katrin, Vicidomini, Giuseppe, Castello, Marco, Diaspro, Alberto, Cordes, Thorben, Sahl, Steffen J, Tinnefeld, Philip, Willig, Katrin I, Max Planck Institute for Biophysical Chemistry (MPI-BPC), Max-Planck-Gesellschaft, Howard Hughes Medical Institute (HHMI), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Department of Engineering Science, University of Oxford [Oxford], Institute for Molecular Biophysics, University of Maine, Janelia Farm Research Campus, Institute of Physical and Theoretical Chemistry [Braunschweig], Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], Braunschweig Integrated Centre of Systems Biology [Braunschweig] (BRICS), Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig]-Helmholtz Centre for Infection Research (HZI), Laboratory for Emerging Nanotechnology (LENA), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Department of NanoBiophotonics [Göttingen], Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Laboratoire Photonique, Numérique et Nanosciences (LP2N), Université de Bordeaux (UB)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), Freie Universität Berlin, Nuffield Department of Clinical Medicine [Oxford], MRC Human Immunology Unit, The Weatherall Institute of Molecular Medicine, University of Oxford [Oxford]-University of Oxford [Oxford], Department of Chemistry [Cambridge, UK], University of Cambridge [UK] (CAM), Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany, Nanoscopy, Nanophysics, IstitutoItaliano di Tecnologia, Via Morego, 30, 16163, Genoa, Italy, University of Groningen, LP2N_A3, and LP2N_G1
Subjects: [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]
Abstract: International audience; Far-field optical microscopy using focused light is an important tool in a number of scientific disciplines including chemical, (bio)physical and biomedical research, particularly with respect to the study of living cells and organisms. Unfortunately, the applicability of the optical microscope is limited, since the diffraction of light imposes limitations on the spatial resolution of the image. Consequently the details of, for example, cellular protein distributions, can be visualized only to a certain extent. Fortunately, recent years have witnessed the development of 'super-resolution' far-field optical microscopy (nanoscopy) techniques such as stimulated emission depletion (STED), ground state depletion (GSD), reversible saturated optical (fluorescence) transitions (RESOLFT), photoactivation localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), structured illumination microscopy (SIM) or saturated structured illumination microscopy (SSIM), all in one way or another addressing the problem of the limited spatial resolution of far-field optical microscopy. While SIM achieves a two-fold improvement in spatial resolution compared to conventional optical microscopy, STED, RESOLFT, PALM/STORM, or SSIM have all gone beyond, pushing the limits of optical image resolution to the nanometer scale. Consequently, all super-resolution techniques open new avenues of biomedical research. Because the field is so young, the potential capabilities of different super-resolution microscopy approaches have yet to be fully explored, and uncertainties remain when considering the best choice of methodology. Thus, even for experts, the road to the future is sometimes shrouded in mist. The super-resolution optical microscopy roadmap of Journal of Physics D: Applied Physics addresses this need for clarity. It provides guidance to the outstanding questions through a collection of short review articles from experts in the field, giving a thorough discussion on the concepts underlying super-resolution optical microscopy, the potential of different approaches, the importance of label optimization (such as reversible photoswitchable proteins) and applications in which these methods will have a significant impact.
Published: 2015

42. Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri

Author: Duy Pham Thanh, Lothar H. Wieler, Claire Jenkins, François-Xavier Weill, Malika Gouali, Anthony M. Smith, Thomas R. Connor, Ishrat J. Azmi, Wanderley Dias da Silveira, Kaisar A. Talukder, Torsten Semmler, Kate S. Baker, Dong Wook Kim, Alejandro Cravioto, Nicholas R. Thomson, Julian Parkhill, Stephen Baker, Shah M. Faruque, Karen H. Keddy, Clare R. Barker, School of Biosciences [Cardiff], Cardiff University, Pathogen Genomics [Cambridge], The Wellcome Trust Sanger Institute [Cambridge], Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris], Centre for Food and Water borne diseases, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), National Institute for Communicable Diseases [Johannesburg] (NICD), Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], University of Campinas [Campinas] (UNICAMP), Robert Koch Institute [Berlin] (RKI), Centre for Infection Medicine, Institute of Microbiology and Epizootics, Public Health England [London], Global Evaluative Sciences, Department of Pharmacy, School of Pharmacy, TRC, KSB, JP and NRT were all funded by the Wellcome Trust, grant number 098051. CRB was funded by a Wellcome Trust/NISCHR ISSF project at Cardiff University. The Bioinformatics analysis performed at Cardiff used resources funded by the MRC (Grant ref: MR/L015080/1) and Cardiff University (storage funded by the Cardiff University Research Infrastructure Fund). FXW and MG are funded by the Institut Pasteur, the Institut de Veille Sanitaire, and by the French Government ‘Investissement d'Avenir’ program (Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, grant no. ANR-10-LABX-62-IBEID). DWK was supported by the grant 2012R1A2A2A01009741 from National Research Foundation (NRF) of Korea., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP), University of Oxford, and Universidade Estadual de Campinas = University of Campinas (UNICAMP)
Subjects: MESH: Sequence Analysis, DNA, MESH: Shigella flexneri/genetics, MESH: Global Health, medicine.disease_cause, Global Health, MESH: Genome, Bacterial, MESH: Dysentery, Bacillary/epidemiology, Shigella flexneri, genomic, Shigella, MESH: Genetic Variation, Biology (General), 2. Zero hunger, 0303 health sciences, Molecular Epidemiology, Microbiology and Infectious Disease, Phylogenetic tree, biology, General Neuroscience, General Medicine, 6. Clean water, 3. Good health, Phylogeography, MESH: Phylogeography, Medicine, Research Article, Virulence Factors, QH301-705.5, Science, Molecular Sequence Data, MESH: Dysentery, Bacillary/microbiology, Genomics, Serogroup, General Biochemistry, Genetics and Molecular Biology, Microbiology, 03 medical and health sciences, dysentery, Spatio-Temporal Analysis, MESH: Spatio-Temporal Analysis, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, medicine, genomics, MESH: Virulence Factors/genetics, Humans, MESH: Molecular Epidemiology, 030304 developmental biology, Dysentery, Bacillary, MESH: Shigella flexneri/classification, Whole genome sequencing, MESH: Humans, MESH: Molecular Sequence Data, General Immunology and Microbiology, Molecular epidemiology, 030306 microbiology, QK, E. coli, other, Genetic Variation, pathogen evolution, Sequence Analysis, DNA, MESH: Serogroup, biology.organism_classification, Pathogenicity island, Colonisation, Epidemiology and Global Health, Evolutionary biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genome, Bacterial
Abstract: Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the S. flexneri PGs we identify geographically restricted sub-lineages that appear to have persistently colonised regions for many decades to over 100 years. Although we found abundant evidence of antimicrobial resistance (AMR) determinant acquisition, our dataset shows no evidence of subsequent intercontinental spread of antimicrobial resistant strains. The pattern of colonisation and AMR gene acquisition suggest that S. flexneri has a distinct life-cycle involving local persistence. DOI: http://dx.doi.org/10.7554/eLife.07335.001, eLife digest Dysentery is a disease in which the intestine becomes inflamed due to infection by bacteria, viruses or other microbes. Of the bacteria that can cause dysentery, bacteria called Shigella are most often responsible. Humans can acquire Shigella through contaminated food or water. Over the last century, improvements to sanitation combined with access to clean drinking water and better food hygiene have decreased the number of cases of dysentery in many countries. However, the disease continues to be common in low-income countries, especially in young children. One species of Shigella bacteria, called S. flexneri, causes far more cases of dysentry than other species of Shigella. Across the world, there are many different strains of S. flexneri, but it is not clear how these strains are related to each other, or how variable the genes that they carry are—known as genetic diversity. Here, Connor, Barker, Baker et al. used a technique called whole genome sequencing to map the evolutionary relationships of over 300 S. flexneri samples collected from around the globe over the past 100 years. This revealed that the bacterial strains can be split into seven groups that each have distinct geographic ranges and combinations of genes that enable the bacteria to infect humans. Many of the strains of bacteria within these groups seem to have colonized, and remained in, quite small geographic areas over long periods of time. This is different to other Shigella species, which appear to have spread between continents far more frequently over much shorter timescales. Connor, Barker, Baker et al.'s findings reveal that S. flexneri is more diverse than other Shigella bacteria, and suggest that the ability of strains to persist in local areas may have contributed to the species' long-term success. These results point towards the importance of the provision of clean water in the fight against S. flexneri, and underline the need for a greater understanding of how disease-causing bacteria colonize and interact with the local environment. DOI: http://dx.doi.org/10.7554/eLife.07335.002
Published: 2015

43. High prevalence of Tropheryma whipplei in Lao kindergarten children

Author: Paul N. Newton, Bountoy Sibounheuang, Didier Raoult, Mayfong Mayxay, Florence Fenollar, Alpha Kabinet Keita, Audrey Dubot-Pérès, Koukeo Phommasone, Manivanh Vongsouvath, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Nuffield Department of Clinical Medicine [Oxford], University of Oxford [Oxford], Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahidol University [Bangkok]-Mahosot Hospital, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), and University of Oxford
Subjects: AFRICA, Veterinary medicine, SENEGAL, lcsh:Arctic medicine. Tropical medicine, Genotype, POLYMERASE-CHAIN-REACTION, lcsh:RC955-962, Tropheryma, Real-Time Polymerase Chain Reaction, DISEASE, SALIVA, Tropheryma whipplei, Feces, Prevalence, Humans, Child, Genotyping, High prevalence, Schools, biology, Whipple Disease, STOOL, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, Genetic Variation, lcsh:RA1-1270, biology.organism_classification, Virology, 3. Good health, Infectious Diseases, Carriage, Laos, WHIPPELII DNA, BACTERIUM, Child, Preschool, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: Background Tropheryma whipplei is a bacterium commonly found in feces of young children in Africa, but with no data from Asia. We estimated the prevalence of T. whipplei carriage in feces of children in Lao PDR (Laos). Methods/Principal Findings Using specific quantitative real-time PCR, followed by genotyping for each positive specimen, we estimated the prevalence of T. whipplei in 113 feces from 106 children in Vientiane, the Lao PDR (Laos). T. whipplei was detected in 48% (51/106) of children. Those aged ≤4 years were significantly less frequently positive (17/52, 33%) than older children (34/54, 63%; p< 0.001). Positive samples were genotyped. Eight genotypes were detected including 7 specific to Laos. Genotype 2, previously detected in Europe, was circulating (21% of positive children) in 2 kindergartens (Chompet and Akad). Genotypes 136 and 138 were specific to Chompet (21% and 15.8%, respectively) whereas genotype 139 was specific to Akad (10.55%). Conclusions/Significance T. whipplei is a widely distributed bacterium, highly prevalent in feces of healthy children in Laos. Further research is needed to identify the public health significance of this finding., Author Summary Tropheryma whipplei is a common bacterium carried in feces of young children. Here, using specific PCR, we estimated the prevalence of T. whipplei in 113 feces from 106 children in Vientiane, the Lao PDR (Laos). T. whipplei was detected in 48% (51/106) of children. Eight genotypes were detected, including 7 specific to Laos. Genotype 2, previously detected in Europe, was circulating (21% of positive children) in 2 kindergartens (Chompet and Akad). Genotypes 136 and 138 were specific to Chompet (21% and 15.8%, respectively), whereas genotype 139 was specific to Akad (10.55%). Long regarded as a rare bacterium, now we can affirm that T. whipplei is a widely distributed bacterium, highly prevalent in feces including those from children in Vientiane.
Published: 2015

44. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data

Author: Ouédraogo J-B., Bertrand Lell, Sanjeev Krishna, Ogobara K. Doumbo, Mbaye Pene, Emiliana Tjitra, Ric N. Price, I Van den Broek, Jennifer A. Flegg, Christian Nsanzabana, Faucher J-F., Jean-René Kiechel, Sue J. Lee, Nicholas J. White, Issaka Zongo, Adoke Yeka, Sodiomon B. Sirima, Halidou Tinto, Michel Vaillant, Etard J-F., K Sylla, Sarah G. Staedke, Andreas Mårtensson, Louis K. Penali, Meghna Desai, Martin M Meremikwu, M A Adjuik, Elizabeth A. Ashley, Peter W. Gething, Sally Hamour, Claude Rwagacondo, Clarissa Moreira, Moses R. Kamya, François Bompart, Julie Thwing, Prabin Dahal, Armedy Ronny Hasugian, Elizabeth Juma, Francesco Grandesso, Hasifa Bukirwa, Loretxu Pinoges, Vincent Jullien, Philip J. Rosenthal, Simon I. Hay, Ndiaye J-L., Raquel González, Bhawna Sharma, D Sow, Anup Anvikar, Neena Valecha, E Espié, Frank Smithuis, Didier Menard, Philippe Deloron, Carol Hopkins Sibley, Peter G. Kremsner, M S Ba, Anders Björkman, Albert Same-Ekobo, Todd D. Swarthout, G Diap, Taylor Wrj., Michael Nambozi, Georgina S Humphreys, Caterina I. Fanello, Tine Rck., Karen I. Barnes, Carolyn Nabasumba, Achille Massougbodji, Hervé Ei Menan, Jeff Smith, A Seck, Patrice Piola, Babacar Faye, Richard Allan, Philippe J Guerin, Corine Karema, Frederic Nikiema, Ambrose O. Talisuna, Véronique Sinou, E A Temu, Lyda Osorio, Gaye O, Piero Olliaro, Francine Ntoumi, Michel Cot, Grant Dorsey, Maryline Bonnet, Hubert Barennes, Birgit Schramm, Umberto D'Alessandro, Kasia Stepniewska, Elisabeth Baudin, Steffen Borrmann, Abdoulaye Djimde, Bernards Ogutu, Guthmann J-P., L M Ibrahim, Francesco Checchi, Fabrice A. Somé, Valerie Lameyre, Clara Menéndez, Quique Bassat, Philippe Brasseur, Cally Roper, Joel Tarning, WorldWide Antimalarial Resistance Network (WWARN), University of Washington [Seattle], National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Epicentre [Paris] [Médecins Sans Frontières], Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Centre Muraz [Bobo-Dioulasso, Burkina Faso], Universitat de Barcelona (UB), Karolinska Institutet [Stockholm], Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Centre Lillois d’Études et de Recherches Sociologiques et Économiques - UMR 8019 (CLERSÉ), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (LSHTM), Institut de Recherche pour le Développement (IRD), University of Oxford-Churchill Hospital Oxford Centre for Haematology, Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Département d'épidémiologie des affections parasitaires (DEAP), Université de Bamako-Malaria Research and Training Center (MRTC)-Facultés de Médecine, de Pharmacie et d'Odonto-Stomatologie-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC), Malaria Research and Training Centre, Université de Bamako-Faculty of Medicine, Pharmacy, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Mahidol Oxford Tropical Medicine Research Unit, University of Oxford-Mahidol University [Bangkok], Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), WorldWide Antimalarial Resistance Network (WWARN) (WWARN), University of Oxford, Università degli Studi di Milano = University of Milan (UNIMI), Institut de Veille Sanitaire (INVS), Institute for Health Metrics and Evaluation [University of Washington], Pharmacologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), University of Tübingen, Division of Cellular and Molecular Medicine, St George's University of London, Sanofi-Aventis R&D, SANOFI Recherche, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Department of Microbiology, Tumour and Cell biology [Stockholm, Sweden] (Malaria Research), Faculté des Sciences de la Santé de Cotonou (Faculté des Sciences de la Santé de Cotonou), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Centre de recherche et de Diagnostic sur le Sida [Abidjan, Côte d'Ivoire] (CeDreS), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), Institut Pasteur du Cambodge, Universidad de la República [Montevideo] (UDELAR), Nuffield Department of Clinical Medicine [Oxford], Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], Tropical Diseases Research Center (TDRC), Université Marien Ngouabi, Kenya Medical Research Institute (KEMRI), WHO-TDR Suisse, WHO-TDR Suisse-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Universidad del Valle [Cali] (Univalle), Institut de Recherche en Sciences de la Santé Bobo Dioulasso (INSSA), Université Polytechnique Nazi Boni Bobo-Dioulasso (UNB), World Wide Antimalarial Resistance Network [West Africa] (WWARN-West Africa Regional Centre), University of Washington [Seattle]-University of Washington [Seattle], Institut Pasteur de Madagascar, Global Health Division, Menzies School of Health Research, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Service de Parasitologie-Mycologie Médicale, Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Université de Bordeaux Ségalen [Bordeaux 2], WWARN is funded by a Bill and Melinda Gates Foundation grant., The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, We thank the patients and all the staff who participated in these clinical trials at all the sites and the WWARN team for technical and administrative support., Université de Washington Seattle, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, University of Oxford [Oxford]-University of Oxford [Oxford], Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), University of California [San Francisco] (UCSF), University of California, University of Oxford [Oxford]-Mahidol University [Bangkok], Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], Università degli Studi di Milano [Milano] (UNIMI), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], University of Abomey Calavi (UAC), Universidad de la República [Montevideo] (UCUR), Université de Washington Seattle-Université de Washington Seattle, and Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, Artemether/lumefantrine, Artesunate, Infektionsmedicin, MESH: Africa, Pharmacology, Gastroenterology, MESH: Dose-Response Relationship, Drug, Efficacy, chemistry.chemical_compound, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Recurrence, Risk Factors, Malaria, Falciparum, MESH: Treatment Outcome, MESH: Middle Aged, MESH: Malaria, Falciparum, Artesunate/amodiaquine, Hazard ratio, General Medicine, Middle Aged, Artemisinins, 3. Good health, Drug Combinations, Dosing, Treatment Outcome, Female, medicine.drug, Research Article, medicine.medical_specialty, Infectious Medicine, Fixed-dose combination, Plasmodium falciparum, Amodiaquine, Antimalarials, Internal medicine, MESH: Artemisinins, medicine, Humans, MESH: Amodiaquine, MESH: Drug Combinations, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Antimalarials, MESH: Male, MESH: Recurrence, Malaria, chemistry, Drug resistance, Africa, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Commentary, business, MESH: Female
Abstract: Background Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P
Published: 2015

45. Blocked angiogenesis in Galectin-3 null mice does not alter cellular and behavioral recovery after middle cerebral artery occlusion stroke

Author: Nicola J. Lewis, Alastair M. Buchan, Christopher C. Young, Keith J. Brooks, Micaela M Jenkins, Francis G. Szele, Françoise Poirier, Osama Al-Dalahmah, Department of Physiology, Anatomy and Genetics, University of Oxford, University of Oxford [Oxford], Nuffield Department of Clinical Medicine [Oxford], Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and National Institutes of Health RO1 NS-42253, MRC UK and Foundation Leducq, Rhodes Scholarship
Subjects: Male, Vascular Endothelial Growth Factor A, Time Factors, Angiogenesis, Galectin 3, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Subependymal zon, Cerebral Ventricles, Mice, chemistry.chemical_compound, 0302 clinical medicine, Ischemia, Gliosis, Stroke, Migration, Mice, Knockout, 0303 health sciences, Neovascularization, Pathologic, Mental Disorders, Neurogenesis, Brain, Infarction, Middle Cerebral Artery, Vascular endothelial growth factor, medicine.anatomical_structure, Neurology, Galectin-3, Cerebral cortex, Cerebrovascular Circulation, Neural repair, Brain Infarction, medicine.medical_specialty, Doublecortin Protein, Subventricular zone, Neuroprotection, lcsh:RC321-571, 03 medical and health sciences, Internal medicine, medicine, Animals, cardiovascular diseases, Middle cerebral artery occlusion, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, business.industry, Recovery of Function, medicine.disease, Disease Models, Animal, Endocrinology, Gene Expression Regulation, chemistry, nervous system, Angiogenesis Inducing Agents, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Angiogenesis is thought to decrease stroke size and improve behavioral outcomes and therefore several clinical trials are seeking to augment it. Galectin-3 (Gal-3) expression increases after middle cerebral artery occlusion (MCAO) and has been proposed to limit damage 3days after stroke. We carried out mild MCAO that damages the striatum but spares the cerebral cortex and SVZ. Gal-3 gene deletion prevented vascular endothelial growth factor (VEGF) upregulation after MCAO. This inhibited post-MCAO increases in endothelial proliferation and angiogenesis in the striatum allowing us to uniquely address the function of angiogenesis in this model of stroke. Apoptosis and infarct size were unchanged in Gal-3(-/-) mice 7 and 14days after MCAO, suggesting that angiogenesis does not affect lesion size. Microglial and astrocyte activation/proliferation after MCAO was similar in wild type and Gal-3(-/-) mice. In addition, openfield activity, motor hemiparesis, proprioception, reflex, tremors and grooming behaviors were essentially identical between WT and Gal-3(-/-) mice at 1, 3, 7, 10 and 14days after MCAO, suggesting that penumbral angiogenesis has limited impact on behavioral recovery. In addition to angiogenesis, increased adult subventricular zone (SVZ) neurogenesis is thought to provide neuroprotection after stroke in animal models. SVZ neurogenesis and migration to lesion were overall unaffected by the loss of Gal-3, suggesting no compensation for the lack of angiogenesis in Gal-3(-/-) mice. Because angiogenesis and neurogenesis are usually coordinately regulated, identifying their individual effects on stroke has hitherto been difficult. These results show that Gal-3 is necessary for angiogenesis in stroke in a VEGF-dependant manner, but suggest that angiogenesis may be dispensable for post-stroke endogenous repair, therefore drawing into question the clinical utility of augmenting angiogenesis.
Published: 2014

46. Spatial distribution of G6PD deficiency variants across malaria-endemic regions

Author: Howes, Rosalind E, Dewi, Mewahyu, Piel, Frédéric B, Monteiro, Wuelton M, Battle, Katherine E, Messina, Jane P, Sakuntabhai, Anavaj, Satyagraha, Ari W, Williams, Thomas N, Baird, J, Hay, Simon I, Spatial Ecology and Epidemiology Group, Department of Zoology, Eijkman-Oxford Clinical Research Unit, Evolutionary Ecology of Infectious Disease Group, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, University of the State of Amazonas, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Eijkman Institute for Molecular Biology [Jakarta], Kenya Medical Research Institute (KEMRI), Department of Medicine, Imperial College London, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and University of Oxford [Oxford]
Subjects: Spatial Analysis, Genetic variants, Research, Glucose-6-phosphate dehydrogenase deficiency, Genetic Variation, Haemolysis, Malaria elimination, Primaquine, Global Health, Risk Assessment, Plasmodium viva, Antimalarials, Infectious Diseases, Glucosephosphate Dehydrogenase Deficiency, Gene Frequency, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Malaria, Vivax, Humans, Parasitology, Topography, Medical, Spatial distribution, Malaria, Falciparum, Plasmodium vivax, G6PD
Abstract: International audience; BACKGROUND: Primaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax. It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission. However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquine's widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis. The risk of such an outcome varies widely among G6PD gene variants. METHODS: A literature review was conducted to identify surveys of G6PD variant frequencies among representative population groups. Informative surveys were assembled into two map series: (1) those showing the relative proportions of the different variants among G6PDd individuals; and (2) those showing allele frequencies of G6PD variants based on population surveys without prior G6PDd screening. RESULTS: Variants showed conspicuous geographic patterns. A limited repertoire of variants was tested for across sub-Saharan Africa, which nevertheless indicated low genetic heterogeneity predominated by the G6PD A-202A mutation, though other mutations were common in western Africa. The severe G6PD Mediterranean variant was widespread across western Asia. Further east, a sharp shift in variants was identified, with high variant heterogeneity in the populations of China and the Asia-Pacific where no single variant dominated. CONCLUSIONS: G6PD variants exhibited distinctive region-specific distributions with important primaquine policy implications. Relative homogeneity in the Americas, Africa, and western Asia contrasted sharply with the heterogeneity of variants in China, Southeast Asia and Oceania. These findings will inform rational risk assessments for primaquine in developing public health strategies for malaria control and elimination, and support the future development of regionally targeted policies. The major knowledge gaps highlighted here strongly advocate for further investigation of G6PD variant diversity and their primaquine-sensitivity phenotypes.
Published: 2013

47. Meat consumption and mortality--results from the European Prospective Investigation into Cancer and Nutrition

Author: Pietro Ferrari, Dagrun Engeset, Timothy J. Key, Kuanrong Li, Anne Tjønneland, Kim Overvad, José María Huerta, H. Bas Bueno-de-Mesquita, Christine L. Parr, Guri Skeie, Pilar Amiano, Kay-Tee Khaw, Teresa Norat, Göran Hallmans, Anne C. Vergnaud, Isabelle Romieux, Fulvio Ricceri, M. Luisa Redondo, Dimitirios Trichopoulos, Rosario Tumino, Veronika Fedirko, Françoise Clavel-Chapelon, Elio Riboli, Androniki Naska, Rikke Egeberg, Nicholas J. Wareham, Marianne Uhre Jakobsen, Emily Sonestedt, Heiner Boeing, Aurelio Barricarte, Salvatore Panico, Max Leenders, Manuela M. Bergmann, Laura Nailler, Isabel Drake, Paula Jakszyn, Marie-Christine Boutron-Ruault, Domenico Palli, Sabine Rohrmann, Vittorio Krogh, Antonia Trichopoulou, María José Sánchez, Jakob Linseisen, Petra H.M. Peeters, Ingegerd Johansson, Francesca L. Crowe, Rudolf Kaaks, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, University of Zurich, Rohrmann, Sabine, [Rohrmann,S] Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland. [Rohrmann,S., Li,K, Kaaks,R, Linseisen,J] Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany. [Overvad,K, Jakobsen,MU] Section of Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.[Bueno-de-Mesquita, HB, Leenders,M] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Egeberg,R, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Nailler,L, Boutron-Ruault,MC, Clavel-Chapelon,F] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy, Villejuif, France. [Nailler,L, Clavel-Chapelon,F] Paris South University, UMRS, Villejuif, France. [Krogh,V] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Panico,S] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civile - M.P.Arezzo' Hospital, Ragusa, Italy. [Ricceri,F] HuGeF - Human Genetics Foundation - Torino, Torino, Italy. [Bergmann,MM, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge UK. [Wareham,NJ] Medical Research Council (MRC) Epidemiology Unit, Cambridge UK. [Crowe,FL, Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. [Naska,A, Trichopoulou,A] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston MA, USA.Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Peeters,PHM] Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands. [Peeters,PHM, Norat,T, Vergnaud,AC, Riboli,E] School of Public Health, Imperial College, London, UK. [Engeset,D, Skeie,G] Department of Community Medicine, University of Tromsø, Tromsø, Norway. [Parr,CL] Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway. [Jakszyn,P] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sánchez,MJ, Huerta,JM] Andalusian School of Public Health, Granada, Spain. [Sánchez,MJ, Barricarte,A, Amiano,P] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Redondo,ML] Public Health Directorate Asturias, Oviedo, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, San Sebastian, Spain. [Drake,I, Sonestedt,E] Department of Clinical Sciences, Lund University, Malmö, Sweden. [Hallmans,G] Department of Public Health and Clinical Medicine, Nutrition Research, Umeå University, Umeå, Sweden. [Johansson,I] Department of Odontology, Cariology, Umeå University, Umeå, Sweden. [Fedirko,V, Romieux,I, Ferrari,P] International Agency for Research on Cancer (IARC), Lyon, France. [Linseisen,J] Institute of Epidemiology, Helmholtz Centre Munich, Neuherberg, Germany., Europe Against Cancer Program of the European Commission (SANCO), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RCESP exp. C03/09, Spain, Cancer Research UK, Medical Research Council, United Kingdom, Stroke Association, United Kingdom, British Heart Foundation, Department of Health, United Kingdom, Food Standards Agency, United Kingdom, Wellcome Trust, United Kingdom, the Hellenic Health Foundation and the Stavros Niarchos Foundation, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy, Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Nordforsk the Norwegian Cancer Society, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l’Education Nationale (MGEN), France, 3M Co, France, Gustave Roussy Institute (IGR), France, and General Councils of France, BMC, Ed., Division of Cancer Epidemiology and Prevention, Universität Zürich [Zürich] = University of Zurich (UZH)-Institute of Social and Preventive Medicine, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Section of Epidemiology, Aarhus University [Aarhus], Department of Gastroenterology and Hepatology, University Medical Centre, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Danish Cancer Society Research Center, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Department of Clinical and Experimental Medicine, University of Naples Federico II = Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, HuGeF - Human Genetics Foundation - Torino, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Epidemiology Unit, Medical Research Council, Cancer Epidemiology Unit, University of Oxford, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School [Athens], Hellenic Health Foundation, Harvard School of Public Health, Bureau of Epidemiologic Research, Academy of Athens, Julius Center, University Medical Center [Utrecht], School of Public Health, Imperial College London, Department of Community Medicine, University of Tromsø (UiT), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO), Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Murcia Regional Health Council, Public Health Directorate Asturias, Navarre Public Health Institute, Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Clinical Sciences, Lund University [Lund], Department of Public Health and Clinical Medicine, Umeå University, Department of Odontology, Cariology, International Agency for Cancer Research (IACR), Institute of Epidemiology, Helmholtz Centre Munich, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli studi di Napoli Federico II, University of Oxford [Oxford], Rohrmann, S, Overvad, K, Bueno de Mesquita, Hb, Jakobsen, Mu, Egeberg, R, Tj?nneland, A, Nailler, L, Boutron Ruault, Mc, Clavel Chapelon, F, Krogh, V, Palli, D, Panico, Salvatore, Tumino, R, Ricceri, F, Bergmann, Mm, Boeing, H, Li, K, Kaaks, R, Khaw, Kt, Wareham, Nj, Crowe, Fl, Key, Tj, Naska, A, Trichopoulou, A, Trichopoulos, D, Leenders, M, Peeters, Ph, Engeset, D, Parr, Cl, Skeie, G, Jakszyn, P, S?nchez, Mj, Huerta, Jm, Redondo, Ml, Barricarte, A, Amiano, P, Drake, I, Sonestedt, E, Hallmans, G, Johansson, I, Fedirko, V, Romieux, I, Ferrari, P, Norat, T, Vergnaud, Ac, Riboli, E, and Linseisen, J.
Subjects: Male, 030309 nutrition & dietetics, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis [Medical Subject Headings], Review, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], 2700 General Medicine, DISEASE, COLORECTAL-CANCER, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Diet, Meat, Mortality, Cohort, Europe, Cardiovascular, Cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys [Medical Subject Headings], 0302 clinical medicine, Neoplasms, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Medicine(all), RISK, CALIBRATION, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, cardiovascular, Diabetes, Hazard ratio, food and beverages, cohort, General Medicine, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Nutrition Surveys, Neoplasias, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, Cardiovascular Diseases, Red meat, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Enfermedades cardiovasculares, Life Sciences & Biomedicine, Geographicals::Geographic Locations::Americas::North America::United States [Medical Subject Headings], CERTIFICATES, Research Article, Cohort study, Technology, Industry, Agriculture::Food and Beverages::Food::Meat [Medical Subject Headings], Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Processed meat, Estudios de cohortes, Check Tags::Male [Medical Subject Headings], 610 Medicine & health, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, VEGETARIANS, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, cancer, Humans, ddc:610, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Cardiovascular Diseases [Medical Subject Headings], Aged, Science & Technology, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Feeding Behavior, medicine.disease, mortality, Survival Analysis, United States, Surgery, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, RED MEAT, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Commentary, 21-YEAR FOLLOW-UP, business, Body mass index, Demography
Abstract: Background Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. Results As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. Conclusions The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
Published: 2013

48. Macronutrient Composition of the Diet and Prospective Weight Change in Participants of the EPIC-PANACEA Study

Author: Göran Hallmans, Tonje Braaten, Anne M. May, Rudolf Kaaks, Françoise Clavel-Chapelon, Androniki Naska, Heinz Freisling, Amalia Mattiello, Marianne Uhre Jakobsen, Florence Perquier, Anne Tjønneland, Emily Sonestedt, Petra H.M. Peeters, Heiner Boeing, Jytte Halkjær, Birgit Teucher, Kay-Tee Khaw, Dora Romaguera, Eiliv Lund, Aurelio Barricarte, Rosario Tumino, Marie-Christine Boutron-Ruault, Anne-Claire Vergnaud, Nadia Slimani, Antonia Trichopoulou, Francesca L. Crowe, Pilar Amiano, Nicholas J. Wareham, Laudina Rodríguez, Kim Overvad, Fulvio Ricceri, María Dolores Chirlaque, Isabel Drake, Franco Berrino, Elio Riboli, Domenico Palli, Esther Molina-Montes, Philippos Orfanos, Guri Skeie, H. Bas Bueno-de-Mesquita, Traci Mouw, Teresa Norat, Daphne L. van der A, Antonio Agudo, Isabelle Romieu, Ingeged Johansson, Brian Buijsse, [Vergnaud,AC, Norat,T, Mouw,T, Romaguera,D, Riboli,E, Peeters,PHM] Department of Epidemiology & Public Health, Imperial College London, London, United Kingdom. [May,AM, Peeters,PHM] Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands. [May,AM, Bueno-de-Mesquita,HB, van der A,HD] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, IDIBELL, Barcelona, Spain. [Wareham,N] Medical Research Council, Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. [Romieu,I, Freisling,H, Slimani,N] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Perquier,F, Boutron-Ruault,MC, Clavel-Chapelon,F] Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Palli,D] Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy. [Berrino,F] Epidemiology and Prevention Unit, IRCCS Foundation, National Cancer Institute, Milan, Italy. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, ‘‘Civile M.p.Arezzo’’ Hospital, Ragusa, Italy. [Ricceri,F] Human Genetics Foundation, HuGeF, Turin, Italy. [Rodríguez,L] Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain. [Molina-Montes,E] Andalusian School of Public Health, Granada, Spain. [Amiano,P] Public Health Department of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain and Biodonostia [sic]. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Molina-Montes,E, Amiano,P, Barricarte,A, Chirlaque,MD] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Authority, Murcia, Spain. [Crowe,FL] Cancer Epidemiology Unit Nuffield Department of Clinical Medicine University of Oxford, Oxford, United Kingdom. [Orfanos,P, Naska,A, Trichopoulou,A] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. Hellenic Health Foundation, Athens, Greece. [Teucher,B, Kaaks,R] Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Boeing,H, Buijsse,B] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. [Johansson,I] Department of Odontology, Umea University, Umea, Sweden. [Hallmans,G] Department of Public Health and Clinical Medicine, Nutritional Research, Umea University, Umea, Sweden. [Drake,I, Sonestedt,E] Department of Clinical Sciences in Malmö, Nutrition Epidemiology, Lund University, Malmö, Sweden. [Jakobsen, MU, Overvad,K] Department of Epidemiology School of Public Health Aarhus University, Aarhus, Denmark. [Overvad,K] Department of Cardiology Center for Cardiovascular Research Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Tjønneland,A, Halkjær,J] Danish Cancer Society Research Center, Copenhagen, Denmark. [Skeie,G, Braaten,T, Lund,E] Institute of Community Medicine, University of Tromsø, Tromsø, Norway., This publication arises from the project PANACEA, which has received funding from the European Union, in the framework of the Public Health Programme (project number: 2005328). The work was further financially supported by the European Commission: Public Health and Consumer Protection Directorate 1993–2004, Research Directorate-General 2005-.’’, Ligue contre le Cancer, Societe´ 3M, Mutuelle Ge´ne´ rale de l9Education Nationale, Institut National de la Sante´ et de la Recherche Me´dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany), Danish Cancer Society (Denmark), Health Research Fund (FIS) of the Spanish Ministry of Health, The participating regional governments and institutions (Spain), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (United Kingdom), Greek Ministry of Health and Social Solidarity, Hellenic Health Foundation and Stavros Niarchos Foundation (Greece), Italian Association for Research on Cancer, National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands), Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Va¨sterbotten (Sweden), and Norwegian Research Council (Norway).
Subjects: PROTEIN-INTAKE, Non-Clinical Medicine, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Body Weight Changes::Weight Gain [Medical Subject Headings], Obesidad, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Weight Gain, Social and Behavioral Sciences, Proteínas en la Dieta, Ingestión de Energía, Body Mass Index, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Morbid obesity, 0302 clinical medicine, Surveys and Questionnaires, Aumento de Peso, Medicine, Poisson Distribution, Prospective Studies, Cuestionarios, lcsh:Science, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight [Medical Subject Headings], LOW-FAT DIET, 0303 health sciences, Anthropometry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Questionnaires [Medical Subject Headings], Geographicals::Geographic Locations::Europe [Medical Subject Headings], LOW-CARBOHYDRATE, Humanos, 3. Good health, Näringslära, Carbohidratos en la Dieta, Cohort, Science & Technology - Other Topics, Dieta, Dietary Proteins, Factores de riesgo, Anciano, Chemicals and Drugs::Carbohydrates::Dietary Carbohydrates [Medical Subject Headings], Obesitat mòrbida, CONTROLLED-TRIAL, VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, 03 medical and health sciences, Dietary Carbohydrates, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Aged, Survey Research, Science & Technology, MULTIDISCIPLINARY SCIENCES, lcsh:R, Weight change, medicine.disease, Obesity, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], ENERGY-INTAKE, Anthropology, Linear Models, RISK-FACTORS, lcsh:Q, Physiological Processes, Body mass index, EUROPEAN COUNTRIES, Demography, Índice de Masa Corporal, Gerontology, Anatomy and Physiology, 030309 nutrition & dietetics, lcsh:Medicine, Overweight, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Dietary Proteins [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, Mediana Edad, Risk Factors, 030212 general & internal medicine, Prospective cohort study, 2. Zero hunger, Nutrition and Dietetics, Multidisciplinary, Adulto, Estudios Prospectivos, Middle Aged, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Energy Intake [Medical Subject Headings], Europe, Glycemic index, Distribución de Poisson, medicine.symptom, Europa, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Statistical Distributions::Poisson Distribution [Medical Subject Headings], GLYCEMIC-INDEX, Research Article, Adult, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Clinical Research Design, Modelos Lineales, UNITED-STATES, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Linear Models [Medical Subject Headings], Nutrition, Health Care Policy, business.industry, Health Risk Analysis, Diet, PHYSICAL-ACTIVITY, Sobrepeso, Energy Intake, Energy Metabolism, business, Weight gain
Abstract: Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND The effect of the macronutrient composition of the usual diet on long term weight maintenance remains controversial. METHODS 373,803 subjects aged 25-70 years were recruited in 10 European countries (1992-2000) in the PANACEA project of the EPIC cohort. Diet was assessed at baseline using country-specific validated questionnaires and weight and height were measured at baseline and self-reported at follow-up in most centers. The association between weight change after 5 years of follow-up and the iso-energetic replacement of 5% of energy from one macronutrient by 5% of energy from another macronutrient was assessed using multivariate linear mixed-models. The risk of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to initial Body Mass Index. RESULTS A higher proportion of energy from fat at the expense of carbohydrates was not significantly associated with weight change after 5 years. However, a higher proportion of energy from protein at the expense of fat was positively associated with weight gain. A higher proportion of energy from protein at the expense of carbohydrates was also positively associated with weight gain, especially when carbohydrates were rich in fibre. The association between percentage of energy from protein and weight change was slightly stronger in overweight participants, former smokers, participants ≥60 years old, participants underreporting their energy intake and participants with a prudent dietary pattern. Compared to diets with no more than 14% of energy from protein, diets with more than 22% of energy from protein were associated with a 23-24% higher risk of becoming overweight or obese in normal weight and overweight subjects at baseline. CONCLUSION Our results show that participants consuming an amount of protein above the protein intake recommended by the American Diabetes Association may experience a higher risk of becoming overweight or obese during adult life. Yes
Published: 2013

49. Novel immunomodulators from hard ticks selectively reprogramme human dendritic cell responses

Author: Chrisoula Kouremenou, Lena F. Burger, Oliwia Rysnik, Juraj Majtan, Alejandro Cabezas Cruz, Stephen G. Preston, Miles A. Nunn, Guido C. Paesen, Jonathan M. Austyn, Maylin Chiong Guzman, Patricia A. Nuttall, Nuffield Department of Surgical Sciences, University of Oxford [Oxford], John Radcliffe Hospital, Department of Zoology, Eszterházy Károly College, Institute of Zoology, Ilia State University [Tbilisi], Nuffield Department of Clinical Medicine [Oxford], Institute of Parisitology, University of South Bohemia, Institute of Parasitology, Animal Biotechnology Division, National Dairy Research Institute, Centre for Ecology and Hydrology, Natural Environment Research Council (NERC), Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, Wellcome Trust Centre for Human Genetics, Natural Environment Research Council (CEH010021 ), European Union (LSHB-CT-2004-512074), and Austyn, Jonathan M
Subjects: tique, Cellular differentiation, [SDV]Life Sciences [q-bio], Antigen Processing and Recognition, Adaptive Immunity, Monocytes, 0302 clinical medicine, Ticks, Cytotoxic T cell, Biology (General), Immune Response, 0303 health sciences, biology, Cell Differentiation, immunomodulator, Acquired immune system, Innate Immunity, Recombinant Proteins, 3. Good health, Cell biology, Rhipicephalus, Host-Pathogen Interaction, medicine.anatomical_structure, Cytokines, Research Article, QH301-705.5, T cell, Immune Cells, Immunology, Antigen-Presenting Cells, Immune Suppression, Microbiology, Vector Biology, Arthropod Proteins, Cell Line, Immune Activation, 03 medical and health sciences, Immune system, immunomodulateur, Virology, Genetics, medicine, Animals, Humans, Immunologic Factors, Salivary Proteins and Peptides, Molecular Biology, Biology, Immunity to Infections, 030304 developmental biology, Inflammation, Innate immune system, Immunity, Immunoregulation, Immune Defense, Dendritic cell, Dendritic Cells, RC581-607, biology.organism_classification, Biology and Microbiology, Gene Expression Regulation, Immune System, Parasitology, Immunologic diseases. Allergy, 030215 immunology
Abstract: Hard ticks subvert the immune responses of their vertebrate hosts in order to feed for much longer periods than other blood-feeding ectoparasites; this may be one reason why they transmit perhaps the greatest diversity of pathogens of any arthropod vector. Tick-induced immunomodulation is mediated by salivary components, some of which neutralise elements of innate immunity or inhibit the development of adaptive immunity. As dendritic cells (DC) trigger and help to regulate adaptive immunity, they are an ideal target for immunomodulation. However, previously described immunoactive components of tick saliva are either highly promiscuous in their cellular and molecular targets or have limited effects on DC. Here we address the question of whether the largest and globally most important group of ticks (the ixodid metastriates) produce salivary molecules that specifically modulate DC activity. We used chromatography to isolate a salivary gland protein (Japanin) from Rhipicephalus appendiculatus ticks. Japanin was cloned, and recombinant protein was produced in a baculoviral expression system. We found that Japanin specifically reprogrammes DC responses to a wide variety of stimuli in vitro, radically altering their expression of co-stimulatory and co-inhibitory transmembrane molecules (measured by flow cytometry) and their secretion of pro-inflammatory, anti-inflammatory and T cell polarising cytokines (assessed by Luminex multiplex assays); it also inhibits the differentiation of DC from monocytes. Sequence alignments and enzymatic deglycosylation revealed Japanin to be a 17.7 kDa, N-glycosylated lipocalin. Using molecular cloning and database searches, we have identified a group of homologous proteins in R. appendiculatus and related species, three of which we have expressed and shown to possess DC-modulatory activity. All data were obtained using DC generated from at least four human blood donors, with rigorous statistical analysis. Our results suggest a previously unknown mechanism for parasite-induced subversion of adaptive immunity, one which may also facilitate pathogen transmission., Author Summary Dendritic cells (DC) are specialised cells of the vertebrate immune system. DC can sense different types of infectious agents and parasites, and both trigger and help regulate the specific types of immunity needed to eliminate them. We have discovered that the largest and globally most important group of hard ticks produce a unique family of proteins in their saliva that selectively targets DC, radically altering functions that would otherwise induce robust immune responses; these proteins also prevent DC developing from precursor cells. The production of these salivary molecules may help to explain two highly unusual features of these hard ticks compared with other blood-feeding parasites: their ability to feed continuously on their vertebrate hosts for considerable lengths of time (7 days or more) without eliciting potentially damaging immune responses, and their capacity to transmit possibly the greatest variety of pathogens of any type of invertebrate.
Published: 2013

50. Development and Validation of a Risk Score Predicting Substantial Weight Gain over 5 Years in Middle-Aged European Men and Women

Author: Philippos Orfanos, Lefkos T. Middleton, Vittorio Krogh, Kuanrong Li, J. Ramón Quirós, Sven Knüppel, Birgit Teucher, Eva Ardanaz, Heiner Boeing, Anne M. May, Laureen Dartois, Guy Fagherazzi, Domenico Palli, Peter Wallström, Bo Hedblad, Jytte Halkjær, Rosario Tumino, Annika Steffen, José María Huerta, María José Sánchez, Amalia Mattiello, Nicholas J. Wareham, Kim Overvad, H. Bas Bueno-de-Mesquita, Kay-Tee Khaw, Daphne L. van der A, Antonia Trichopoulou, Miren Dorronsoro, Anne Tjønneland, Paolo Vineis, Thorkild I. A. Sørensen, Dimitrios Trichopoulos, Noémie Travier, Petra H.M. Peeters, Francesca L. Crowe, [Steffen,A, Knüppel,S, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Sørensen,TIA] Instiute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals – Part of Copenhagen University Hospital, The Capital Region, Denmark. [Travier,N] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health, Granada, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Sánchez,MJ, Huerta,JM, Ardanaz,E] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Dorronsoro,M] Basque Regional Health Department and Ciberesp – Biodonostia, San Sebastian, Spain. [Teucher,B, Li,K] Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Bueno-de-Mesquita,HB, A,D] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Mattiello,A] Dipartimento di Medicina Clinica e Chirurgia, Frederico II University, Naples, Italy. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, ‘‘Civile – M.P.Arezzo’’ Hospital, Ragusa, Italy. [Krogh,V] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Vineis,P] HuGeF Foundation Torino, Italy. [Trichopoulou,A, Orfanos,P, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. [Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Hedblad,B] Department of Clinical Sciences in Malmö, Clinical Research Centre, Skane University Hospital, Malmö, Sweden. [Wallström,P] Nutrition Epidemiology Research Group, Department of Clinical Sciences, Lund University, Malmö, Sweden. [Overvad,K] Section of Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Halkjær,J, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Fagherazzi,G, Dartois,L] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy, Villejuif, France. Paris South University, Villejuif, France. [Crowe,F] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom. [Khaw,K] Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom. [Wareham,N] Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. [Vineis,P, Middleton,L] School of Public Health, Imperial College, London, United Kingdom. [May,AM, Peeters,PHM] Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands. [Peeters,PHM] Department of Epidemiology and Public Health, Imperial College London, London, United Kingdom., This publication arises from a collaboration of two EU projects, the Diet, Obesity and Genes (DiOGenes) project and the Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of Home and Obesity (PANACEA) project. DiOGenes is a pan-European study within the EU Sixth Framework Programme for Research and Technological Development (2005-2009) (FOOD-CT-2005-513946, http://www.diogenes.eu.org). PANACEA received funding from the EU in the framework of the Public Health Programme (project 2005328). This work was further supported by the European Commission: Public Health and Consumer Protection Directorate 1993–2004, the Research Directorate-General 2005, the Ligue contre le Cancer, the Societe´ 3M, the Mutuelle Ge´ne´ rale de l’Education Nationale, and the Institut National de la Sante´ et de la Recherche Me´ dicale, German Cancer Aid, the German Cancer Research Center, and the Federal Ministry of Education and Research (Germany), the Danish Cancer Society (Denmark), Health Research Fund (FIS) of the Spanish Ministry of Health RTICC ’Red Tema´tica de Investigacio´n Cooperativa en Ca´ncer (grant number C03/10, R06/0020), the participating regional governments and institutions of Spain, Cancer Research United Kingdom, the Medical Research Council, the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency, and the Wellcome Trust (United Kingdom), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, the Dutch Zorg Onderzoek Nederland, and the World Cancer Research Fund (Netherlands), and the Swedish Cancer Society, the Swedish Scientific Council, and the Regional Government of Skane. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects: Male, Gerontology, Research Validity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards Models [Medical Subject Headings], Non-Clinical Medicine, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Body Weight Changes::Weight Gain [Medical Subject Headings], Epidemiology, lcsh:Medicine, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Weight Gain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Mediana Edad, 0302 clinical medicine, Risk Factors, Positive predicative value, Aumento de Peso, Cardiac and Cardiovascular Systems, Prospective Studies, 030212 general & internal medicine, Masculino, lcsh:Science, Factores de Riesgo, education.field_of_study, Multidisciplinary, Framingham Risk Score, Nutrition and Dietetics, Adulto, Femenino, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Epidemiology of Aging, Estudios Prospectivos, Middle Aged, Research Assessment, Humanos, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Medicine, Female, Public Health, medicine.symptom, Europa, Research Article, Adult, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Clinical Research Design, Science Policy, Anciano, Population, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, External validity, 03 medical and health sciences, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Humans, Obesity, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Statistical Methods, education, Aged, Proportional Hazards Models, Nutrition, Health Care Policy, Receiver operating characteristic, business.industry, Proportional hazards model, lcsh:R, Health Risk Analysis, Check Tags::Female [Medical Subject Headings], lcsh:Q, Modelos de Riesgos Proporcionales, business, Weight gain, Demography
Abstract: Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population. METHODS We used lifestyle and nutritional data from 53°758 individuals followed for a median of 5.4 years from six centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) to develop a risk score to predict substantial weight gain (SWG) for the next 5 years (derivation sample). Assuming linear weight gain, SWG was defined as gaining ≥ 10% of baseline weight during follow-up. Proportional hazards models were used to identify significant predictors of SWG separately by EPIC center. Regression coefficients of predictors were pooled using random-effects meta-analysis. Pooled coefficients were used to assign weights to each predictor. The risk score was calculated as a linear combination of the predictors. External validity of the score was evaluated in nine other centers of the EPIC study (validation sample). RESULTS Our final model included age, sex, baseline weight, level of education, baseline smoking, sports activity, alcohol use, and intake of six food groups. The model's discriminatory ability measured by the area under a receiver operating characteristic curve was 0.64 (95% CI = 0.63-0.65) in the derivation sample and 0.57 (95% CI = 0.56-0.58) in the validation sample, with variation between centers. Positive and negative predictive values for the optimal cut-off value of ≥ 200 points were 9% and 96%, respectively. CONCLUSION The present risk score confidently excluded a large proportion of individuals from being at any appreciable risk to develop SWG within the next 5 years. Future studies, however, may attempt to further refine the positive prediction of the score. Yes
Published: 2013

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