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1. Risk prediction tools in cardiovascular disease prevention: A report from the ESC Prevention of CVD Programme led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP)

Author: Xavier Rossello, Jannick AN Dorresteijn, Arne Janssen, Ekaterini Lambrinou, Martijn Scherrenberg, Eric Bonnefoy-Cudraz, Mark Cobain, Massimo F Piepoli, Frank LJ Visseren, Paul Dendale, null This paper is a co-publication betw, Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), University Medical Center [Utrecht], Jessa Ziekenhuis [Hasselt], Cyprus University of Technology, Hasselt University (UHasselt), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Cardiologie Lyon (Hôpital Louis Pradel [CHU - HCL]), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Imperial College London, University of Southern California (USC), Rossello, Xavier/0000-0001-6783-8463, Rossello, Xavier, Dorresteijn, Jannick A. N., JANSSEN, Arne, Lambrinou, Ekaterini, SCHERRENBERG, Martijn, Bonnefoy-Cudraz, Eric, Cobain, Mark, Piepoli, Massimo F., Visseren, Frank L. J., DENDALE, Paul, CarMeN, laboratoire, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, Time Factors, Epidemiology, [SDV]Life Sciences [q-bio], Allied Health Personnel, Disease, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Medical and Health Sciences, 0302 clinical medicine, prevention, Risk Factors, cardiovascular disease, Preventive Health Services, Advanced and Specialised Nursing, 030212 general & internal medicine, Cardiovascular nursing, Societies, Medical, Aged, 80 and over, biology, risk assessment, General Medicine, Middle Aged, Prognosis, Risk prediction, 3. Good health, [SDV] Life Sciences [q-bio], Preventive cardiology, Europe, Primary Prevention, Medical–Surgical Nursing, Cardiovascular Diseases, Practice Guidelines as Topic, Female, patient, Cardiology and Cardiovascular Medicine, Risk assessment, Algorithms, Adult, Cardiovascular Nursing, medicine.medical_specialty, Critical Care, Clinical Decision-Making, Cardiology, Decision Support Techniques, 03 medical and health sciences, Predictive Value of Tests, Health Sciences, Medical–Surgical, medicine, Humans, Medical history, Intensive care medicine, Association (psychology), Aged, Advanced and Specialized Nursing, patient Keywords Risk prediction, Acca, Models, Statistical, business.industry, biology.organism_classification, Lifetime risk, business, Forecasting
Abstract: Risk assessment and risk prediction have become essential in the prevention of cardiovascular disease. Even though risk prediction tools are recommended in the European guidelines, they are not adequately implemented in clinical practice. Risk prediction tools are meant to estimate prognosis in an unbiased and reliable way and to provide objective information on outcome probabilities. They support informed treatment decisions about the initiation or adjustment of preventive medication. Risk prediction tools facilitate risk communication to the patient and their family, and this may increase commitment and motivation to improve their health. Over the years many risk algorithms have been developed to predict 10-year cardiovascular mortality or lifetime risk in different populations, such as in healthy individuals, patients with established cardiovascular disease and patients with diabetes mellitus. Each risk algorithm has its own limitations, so different algorithms should be used in different patient populations. Risk algorithms are made available for use in clinical practice by means of - usually interactive and online available - tools. To help the clinician to choose the right tool for the right patient, a summary of available tools is provided. When choosing a tool, physicians should consider medical history, geographical region, clinical guidelines and additional risk measures among other things. Currently, the website is the only risk prediction tool providing prediction algorithms for all patient categories, and its implementation in clinical practice is suggested/advised by the European Association of Preventive Cardiology. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this paper was produced within the framework of the ESC Prevention of Cardiovascular Disease Programme which is led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP). The ESC Prevention of Cardiovascular Disease Programme is supported by unrestricted educational grants. The authors received no financial support for the research, authorship, and/or publication of this article. Rossello, X (corresponding author), Ctr Nacl Invest Cardiovasc CNIC Carlos III, Melchor Fernandez Almagro 3, Madrid 28029, Spain. fjrossello@cnic.es
Published: 2020

2. Mutated olfactomedin 1 in the interphotoreceptor matrix of the mouse retina causes functional deficits and vulnerability to light damage

Author: Barbara M. Braunger, Herbert Jägle, Johanna Hausberger, Marcus Koch, Walter Paper, Bernd Rosenhammer, Cornelia Volz, and Ernst R. Tamm
Subjects: 0301 basic medicine, Histology, Light, genetic structures, Mutant, Interphotoreceptor matrix, Biology, Retina, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Photoreceptor Cells, Outer nuclear layer, Molecular Biology, Glycoproteins, Extracellular Matrix Proteins, medicine.diagnostic_test, Retinal, Cell Biology, Anatomy, eye diseases, Extracellular Matrix, Cell biology, Medical Laboratory Technology, 030104 developmental biology, medicine.anatomical_structure, chemistry, Rhodopsin, Mutation, biology.protein, Optic nerve, sense organs, 030217 neurology & neurosurgery, Electroretinography
Abstract: Olfactomedin 1 (OLFM1) is a secreted glycoprotein and member of the olfactomedin protein family, which is preferentially expressed in various areas throughout the central nervous system. To learn about the functional properties of OLFM1 in the eye, we investigated its localization in the mouse and pig eye. In addition, we analyzed the ocular phenotype of Olfm1 mutant mice in which 52 amino acids were deleted in the central part (M2 region) of OLFM1. OLFM1 was detected in cornea, sclera, retina, and optic nerve of both wild-type and Olfm1 mutant littermates. By immunohistochemistry and double labeling with the lectin peanut agglutinin, OLFM1 was found in the interphotoreceptor matrix (IPM) of mouse and pig retina where it was directly localized to the inner segments of photoreceptors. Western blotting confirmed the presence of the OLFM1 isoforms pancortin 1 (BMY) and pancortin 2 (BMZ) in the IPM. The retinal phenotype of Olfm1 mutant mice did not obviously differ from that of wild-type littermates. In addition, outer nuclear layer (ONL) and total retinal thickness were not different, and the same was true for the area of the optic nerve in cross sections. Functional changes were observed though by electroretinography, which showed significantly lower a- and b-wave amplitudes in Olfm1 mutant mice when compared to age-matched wild-type mice. When light damage experiments were performed as an experimental paradigm of photoreceptor apoptosis, significantly more TUNEL-positive cells were observed in Olfm1 mutant mice 30 h after light exposure. One week after light exposure, the ONL was significantly thinner in Olfm1 mutant mice than in wild-type littermates indicating increased photoreceptor loss. No differences were observed when rhodopsin turnover or ERK1/2 signaling was investigated. We conclude that OLFM1 is a newly identified IPM molecule that serves an important role for photoreceptor homeostasis, which is significantly compromised in the eyes of Olfm1 mutant mice.
Published: 2016

3. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE) : an international, randomised, placebo-controlled trial

Author: P J Devereaux, Emmanuelle Duceppe, Gordon Guyatt, Vikas Tandon, Reitze Rodseth, Bruce M Biccard, Denis Xavier, Wojciech Szczeklik, Christian S Meyhoff, Jessica Vincent, Maria Grazia Franzosi, Sadeesh K Srinathan, Jason Erb, Patrick Magloire, John Neary, Mangala Rao, Prashant V Rahate, Navneet K Chaudhry, Bongani Mayosi, Miriam de Nadal, Pilar Paniagua Iglesias, Otavio Berwanger, Juan Carlos Villar, Fernando Botto, John W Eikelboom, Daniel I Sessler, Clive Kearon, Shirley Pettit, Mukul Sharma, Stuart J Connolly, Shrikant I Bangdiwala, Purnima Rao-Melacini, Andreas Hoeft, Salim Yusuf, P.J. Devereaux, Shrikant I. Bangdiwala, Stuart Connolly, John Eikelboom, Janice Pogue, Daniel I. Sessler, Sara Di Diodato, Zora Gasic, Louise J. Mastrangelo, Sarah H. Molnar, Jennifer L. Swanson, Makayla L. Tosh, Jennifer R. Wells, Rafael Diaz, Clara K. Chow, Beatriz Gonzales, Skarlet Vásquez, Petr Jansky, Radovan Dušek, Christian S. Meyhoff, Pierre Coriat, Maria Wittmann, Gerald Yonga, Nandini Mathur, Elena Seletti, German Malaga, Bernadette A. Tumanan-Mendoza, Maria Pamela A. Tagle, Bruce M. Biccard, Pablo Alonso-Coello, Ekaterine Popova, Martin Shields, Yannick Le Manach, Paul Moayyedi, Sander van Zanten, Edith Fleischmann, Amit Garg, Kamilu Karaye, Edward McFalls, Alben Sigamani, Emilie Belley-Côté, Grzegorz Biedroń, Flavia Borges, Steffan Frosi Stella, Christian Haarmark Nielsen, Darryl P. Leong, Jessica Spence, Allen Tran, Katarzyna Wawrzycka-Adamczyk, Stephen S. Yang, Terence Yung, D. George Wyse, Davy Cheng, David E. Johnstone, George A. Wells, Philip Joseph, Ameen Patel, Krysten Gregus, Kelly Lawrence, Lindsay Doharris, David Conen, Jason Cheung, Jim Douketis, Douglas Wright, Spencer Wikkerink, William Dechert, Mohamed Panju, Khalid Azzam, Theodore Rapanos, Tomas Van Helder, Anjali Shroff, Jacqueline Hare, Biniam Kidane, Thang Nguyen, Larissa Leydier, Vanessa Bayaraa, Joel Parlow, Deborah A. DuMerton, Amar Thakrar, Jessica Shelley, Benoit Deligne, Roberta Daila Carling, Marko Mrkobrada, George K. Dresser, Michael J. Jacka, David Hornstein, Gerrit B. Winkelaar, Zoeb Hussain Haider, Pravina Prashant Lanjewar, Valsamma Varughese, Rajneesh Calton, Hemani Ahuja, Preetha George, Ambika Sharma, Keyur Sureshchandra Bhatt, Dhaval Odhavajibhai Mangukiya, Karshan Vira Nandaniya, Viral Vasantrai Parekh, Ashok Bhaskaran Pillai, Vidya P. Menon, Sanjay Channappa Desai, Ravinder Singh Sidhu, Sandeep Kumar Gupta, Robbie K. George, T.R. Gurunath, Leanne W. Drummond, Alexandra M. Torborg, Belinda S. Küsel, Prebashini Naidoo, Datshana P. Naidoo, Chantal Rajah, Zane Farina, Richard Peter von Rahden, Simphiwe Gumede, Chishala Chishala, Ettienne Coetzee, Robert A. Dyer, Johan Diedericks, Piotr Bielański, Bogusz Kaczmarek, Dorota Studzińska, Maciej Zaniewski, Marek Józef Libura, Tomasz Mikołaj Zacharias-Nalichowski, Aurelia A.S. Sega, Jakub Salwa, Mateusz Kózka, Jacek Górka, Anna Wludarczyk, Ilona Nowak-Kózka, Paweł Szczepan Grudzień, Jaroslaw W. Gucwa, Michał Piotr Słowiaczek, Paweł P.D. Dobosz, Ismail Gögenur, Jens Ravn Eriksen, Tine Borup, Tove Kirkegaard, Dan Isbye, Asger Sonne, Lars S. Rasmussen, Sofie Pedersen, Hannibal Troensegaard, Camilla L. Duus, Benedikte M. Halle, Ossian N. Gundel, Katrine F. Bernholm, Kristian Rønsholt Martinsen, Søren Pedersen, Theis S. Itenov, Elena Camio, Carles Vázquez, Silvia Matarin, Esther Cano, Jesús Álvarez-García, Inmaculada India, Aránzazu González-Osuna, Marc Vives, Elena Rosselló, Ana B. Serrano, Maurizio Turiel, Lorenzo Drago, Chiara Colombo, Federica Marra, Lucio Mos, Franco Arteni, Rosalba Lembo, Alessandro Ortalda, Simonetta Passarani, Zhirajr Mokini, Estevao Lanna Figueiredo, Gustavo Fonseca Werner, Joao Luiz Petriz, Lilia Nigro Maia, Ricardo R. Bergo, Dalton Bertolim Precoma, José Francisco Kerr Saraiva, Oscar Gomez Vilamajo, Eduardo Allegrini, Mariano Benzadón, Maria Leonor Parody, Ernesto A. Duronto, Adrián C. Ingaramo, Gustavo Adolfo Parra, Danny Novoa, Scott A. Miller, Sabu Thomas, Sudhakar P. Karlapudi, Mohamad H. Bourji, Subhash Banerjee, Anita Gupta, Isaac O. Opole, Michal Fischer, Victor Lecaros Mendoza, Eugenio Borja Reyes, Richard J. Pierson, Martin O. Shields, Vincent Piriou, Kai Zacharowski, Aida Rotta-Rotta, Main Paper, Sadeesh K. Srinathan, Prashant Rahate, Navneet Chaudhry, Bogani Mayosi, and Mike Sharma
Subjects: Male, medicine.medical_specialty, Myocardial Infarction, Placebo-controlled study, Hemorrhage, 030204 cardiovascular system & hematology, Placebo, Antithrombins, Dabigatran, law.invention, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Internal medicine, medicine, Humans, Perioperative Period, Stroke, Aged, Aged, 80 and over, business.industry, Hazard ratio, Proton Pump Inhibitors, Thrombosis, Venous Thromboembolism, General Medicine, Perioperative, Placebo Effect, medicine.disease, Troponin, Clinical trial, Treatment Outcome, Female, business, Omeprazole, medicine.drug
Abstract: Summary Background Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. Methods In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. Findings Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55–0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55–1·53; p=0·76). Interpretation Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication. Funding Boehringer Ingelheim and Canadian Institutes of Health Research.
Published: 2018

4. 'You Are Not Alone' Strategies for Addressing Mental Health and Health Promotion with a Refugee Women's Sewing Group

Author: Rebekah J. Salt, Emma L. Dotson, Margaret E. Costantino, and Bruce Paper
Subjects: Adult, Community-Based Participatory Research, Refugee, 050109 social psychology, Pilot Projects, Health Promotion, Social Environment, Health Services Accessibility, 03 medical and health sciences, Social support, 0302 clinical medicine, Quality of life (healthcare), Nursing, Intervention (counseling), Medicine, Vulnerable population, Humans, Mass Screening, 0501 psychology and cognitive sciences, 030212 general & internal medicine, Aged, Refugees, business.industry, Mental Disorders, fungi, 05 social sciences, food and beverages, Social environment, Social Support, Emigration and Immigration, Middle Aged, Mental health, Texas, Community Mental Health Services, Group Processes, Health promotion, Quality of Life, Health Resources, Female, Pshychiatric Mental Health, business
Abstract: Resettlement can be an uncertain time for refugees as they have often suffered life-threatening circumstances prior to flight from their countries, yet few resettlement programs screen for mental health. The purpose of this study was to pilot the Refugee Health Screener-15 (RHS-15) to assess mental health and the Pathways to Wellness intervention to identify internal and structural barriers affecting resettlement with a refugee women's sewing group. Community collaborations that create healthy social and physical environments through access to resources, economic opportunities, and social support promote a holistic approach to health and can improve quality of life for this vulnerable population.
Published: 2017

5. Changes in Default Alarm Settings and Standard In-Service are Insufficient to Improve Alarm Fatigue in an Intensive Care Unit: A Pilot Project

Author: Charles Reed, Azizeh K. Sowan, Albert Tarriela, Bruce Paper, and Tiffany Michelle Gomez
Subjects: Quality management, default alarm settings, Health Informatics, Human Factors and Ergonomics, intensive care unit, in-service, law.invention, 03 medical and health sciences, ALARM, Patient safety, 0302 clinical medicine, cardiac monitors, nursing, law, 030225 pediatrics, Intensive care, Alarm management, Medicine, survey, Nurse education, alarm fatigue, Original Paper, 030504 nursing, business.industry, Usability, medicine.disease, Intensive care unit, Medical emergency, 0305 other medical science, business
Abstract: Background: Clinical alarm systems safety is a national concern, specifically in intensive care units (ICUs) where alarm rates are known to be the highest. Interventional projects that examined the effect of changing default alarm settings on overall alarm rate and on clinicians’ attitudes and practices toward clinical alarms and alarm fatigue are scarce. Objective: To examine if (1) a change in default alarm settings of the cardiac monitors and (2) in-service nursing education on cardiac monitor use in an ICU would result in reducing alarm rate and in improving nurses’ attitudes and practices toward clinical alarms. Methods: This quality improvement project took place in a 20-bed transplant/cardiac ICU with a total of 39 nurses. We implemented a unit-wide change of default alarm settings involving 17 parameters of the cardiac monitors. All nurses received an in-service education on monitor use. Alarm data were collected from the audit log of the cardiac monitors 10 weeks before and 10 weeks after the change in monitors’ parameters. Nurses’ attitudes and practices toward clinical alarms were measured using the Healthcare Technology Foundation National Clinical Alarms Survey, pre- and postintervention. Results: Alarm rate was 87.86 alarms/patient day (a total of 64,500 alarms) at the preintervention period compared to 59.18 alarms/patient day (49,319 alarms) postintervention ( P =.01). At baseline, Arterial Blood Pressure (ABP), Pair Premature Ventricular Contractions (PVCs), and Peripheral Capillary Oxygen Saturation (SpO2) alarms were the highest. ABP and SpO2 alarms remained among the top three at the postproject period. Out of the 39 ICU nurses, 24 (62%) provided complete pre- and postproject survey questionnaires. Compared to the preintervention survey, no remarkable changes in the postproject period were reported in nurses’ attitudes. Themes in the narrative data were related to poor usability of cardiac monitors and the frequent alarms. The data showed great variation among nurses in terms of changing alarm parameters and frequency of replacing patients' electrodes. Despite the in-service, 50% (12/24) of the nurses specified their need for more training on cardiac monitors in the postproject period. Conclusions: Changing default alarm settings and standard in-service education on cardiac monitor use are insufficient to improve alarm systems safety. Alarm management in ICUs is very complex, involving alarm management practices by clinicians, availability of unit policies and procedures, unit layout, complexity and usability of monitoring devices, and adequacy of training on system use. The complexity of the newer monitoring systems requires urgent usability testing and multidimensional interventions to improve alarm systems safety and to attain the Joint Commission National Patient Safety Goal on alarm systems safety in critical care units. [JMIR Hum Factors 2016;3(1):e1]
Published: 2016

6. Comparison of a Barcode-Based Smartphone Application to a Questionnaire to Assess the Use of Cleaning Products at Home and Their Association with Asthma Symptoms

Author: Lemire, Pierre, Temam, Sofia, Quinot, Catherine, Sévin, Etienne, Remacle, Sophie, Supernant, Karine, Dumas, Orianne, Le Moual, Nicole, Eyriey, E., Licinia, A., Vellement, A., Pin, Isabelle, Hofmann, P., Hullo, Églantine, Llerena, Catherine, Morin, X., Morlot, A., Lepeule, Johanna, Lyon-Caen, Sarah, Philippat, Claire, Quentin, Joane, Siroux, Valérie, Slama, Rémy, Faraldo, Beatrice, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, MGEN Foundation for Public Health [Paris] (FESP-MGEN), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), EpiConcept [Paris], The Sepages Study Group., Fondation d’entreprise MGEN pour la santé publique (FESP MGEN), Anses-PNR-EST-2015-1-022/Ademe-1594C0091, Anses-PNR-EST-2017-1-101/Ademe-1762C0021 Seventh Framework Programme, FP7: FP7/2007-206, N308333-HELIX European Research Council, ERC: N 311765-E-DOHaD Agence Nationale de la Recherche, ANR: 14-CE21-0007-01, 19-CE36-0003-01, ANR 18-CE36-005, ANR-12-PDOC-0029-01, ANR-15-IDEX, ANR-15-IDEX-02 Institut National de la Santé et de la Recherche Médicale, Inserm Fondation de France: CLI-MATHES—00081169 Commissariat Général à l'Investissement, CGI Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, ANSES: PNR-EST-2018-1-264 Agir pour les Maladies Chroniques, Acknowledgments: We acknowledge the role of SEPAGES cohort study group: E. Eyriey, A. Licinia, A. Vellement (Groupe Hospitalier Mutualiste, Grenoble), I. Pin, P. Hofmann, E. Hullo, C. Llerena (Grenoble University Hospital, La Tronche), X. Morin (Clinique des Cèdres, Echirolles), A. Morlot (Clinique Belledonne, Saint-Martin d’Hères), J. Lepeule, S. Lyon-Caen, C. Philippat, I. Pin, J. Quentin, V. Siroux, R. Slama (Inserm, CNRS, University Grenoble Alpes IAB research center). We thank A. Benlakhryfa, L. Borges, Y. Gioria, clinical research assistants, J. Giraud, M. Marceau, M.-P. Martin, nurses, E. Charvet, A. Putod, midwives, M. Graca, K. Gridel, C. Pelini, fieldworkers, K. Guichardet, A. Levanic, C. Martel, E. Quinteiro neuropsychologists, the sta↵ from Grenoble Center for Clinical Investigation (CIC): J.-L. Cracowski, C. Cracowski, E. Hodaj, D. Abry, N. Gonnet and A. Tournier. A warm thank you also to M. Althuser, S. Althuser, F. Camus-Chauvet, P. Dusonchet, S. Dusonchet, L. Emery, P. Fabbrizio, P. Ho↵mann, D. Marchal André, X. Morin, E. Opoix, L. Pacteau, P. Rivoire, A. Royannais, C. Tomasella, T. Tomasella, D. Tournadre, P. Viossat, E. Volpi, S. Rey, E. Warembourg and clinicians from Grenoble University Hospital for their support in the recruitment of the study volunteers. We also thank A. Buchet, S.F. Caraby, J.-N. Canonica, J. Dujourdil, E. Eyriey, P. Hofmann, M. Jeannin, A. Licina, X. Morin, A. Nicolas, and all midwives from the four maternity wards of Grenoble urban areas. We thank B. Chevolon, C. Cornes, A.S. Gauchez, D. Guergour, P. Faure, J. Arnaud for thyroid hormones assessment. We thank the team of L. Chaperod (EFS) for its implication on the immunological aspects of the project. We thank G. Uzu (IRD) and J.-L. Ja↵rezo (CNRS) for their implication on PM oxidative potential assessment. We thank F.-X. Leupert, O. Bonnet and L. Goirand for the access to the birth certificate database from the Conseil Général de l’Isère. Sépages biospecimens are stored at Grenoble University Hospital (CHU-GA) biobank (bb-0033-00069), we would like to thank the whole CRB team, led by P. Mossuz and P. Lorimier, and in particular the technicians for the huge work of biospecimens processing and pooling: W. Jayar and L. Than, as well as G. Schummer. The Internet platform for secured data collection was developed by Epiconcept Paris (E. Sevin, S. Ployart, A. Polaert). SEPAGES data are stored thanks to Inserm RE-CO-NAI platform funded by Commissariat Général à l’Investissement, with the implication of Sophie de Visme (Inserm DSI). Many thanks to M.A. Charles, RE-CO-NAI coordinator, for her support. Finally, and importantly, we would like to express our sincere thanks to participants of the SEPAGES study. The authors are grateful for the help received from Ines Taarit and Mathias Clément to update the cleaning products ingredients database., Funding: The cohort was supported by the European Research Council (consolidator grant N 311765-E-DOHaD, PI, R. Slama), by the European Community’s Seventh Framework Programme (FP7/2007-206, grant N308333-HELIX, PI, M. Vrijheid), by ANR, the French Research Agency (PAPER project ANR-12-PDOC-0029-01, PI, J. Lepeule, SHALCOH project, 14-CE21-0007-01, PI, R. Slama, GUMME project, PI, R. Slama, ETAPE ANR 18-CE36-005, PI, J. Lepeule, EDeN project 19-CE36-0003-01, SYMER project, ANR-15-IDEX-02, PI, U. Schlattner, Mobil’Air project, ANR-15-IDEX, PI, S. Mathy, supported by University Grenoble-3Alpes), by ANSES (CNAP and HYPAXE projects, PI C. Philippat, PENDORE project, PNR-EST-2018-1-264, PI, V. Siroux), by Plan Cancer (Canc’Air project, PI, P. Guénel), by Association de Recherche sur le Cancer (ARC, PI, P. Guénel), by AGIR pour les maladies chroniques (PI, R. Slama and PRENAPAR project, V. Siroux), and Fonds de Recherche pour la Santé Respiratoire (FRSR, PI, I. Pin) and by Fondation de France (CLI-MATHES—00081169, J. Lepeule). We acknowledge the support of ANSES, Inserm and AGIR pour les maladies chroniques, for SEPAGES feasibility study. The support of 'SCUSI 2017' Région Auvergne-Rhône-Alpes programme is also acknowledged. COBANET-Sepages project was support by Anses and Ademe (COBANET: Anses-PNR-EST-2015-1-022/Ademe-1594C0091, PI: N Le Moual, CRESPINET: Anses-PNR-EST-2017-1-101/Ademe-1762C0021, PI: N Le Moual). Pierre Lemire benefited from a PhD scholarship of the University of Paris-Sud/Paris-Saclay, France., The cohort was supported by the European Research Council (consolidator grant N 311765-E-DOHaD, PI, R. Slama), by the European Community?s Seventh Framework Programme (FP7/2007-206, grant N308333-HELIX, PI, M. Vrijheid), by ANR, the French Research Agency (PAPER project ANR-12-PDOC-0029-01, PI, J. Lepeule, and EDeN project 19-CE36-0003-01, SYMER project, ANR-15-IDEX-02, PI, U. Schlattner, Mobil?Air project, ANR-15-IDEX, PI, S. Mathy, supported by University Grenoble-3Alpes), by ANSES (CNAP and HYPAXE projects, PI C. Philippat, PENDORE project, PNR-EST-2018-1-264, PI, V. Siroux), by Plan Cancer (Canc?Air project, PI, P. Gu?nel), by Association de Recherche sur le Cancer (ARC, PI, P. Gu?nel), by AGIR pour les maladies chroniques (PI, R. Slama and PRENAPAR project, V. Siroux), and Fonds de Recherche pour la Sant? Respiratoire (FRSR, PI, I. Pin) and by Fondation de France (CLIMATHES?00081169, J. Lepeule). We acknowledge the support of ANSES, Inserm and AGIR pour les maladies chroniques, for SEPAGES feasibility study. The support of ?SCUSI 2017? R?gion Auvergne-Rh?ne-Alpes programme is also acknowledged. COBANET-Sepages project was support by Anses and Ademe (COBANET: Anses-PNR-EST-2015-1-022/Ademe-1594C0091, PI: N Le Moual
Subjects: medicine.medical_specialty, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], lcsh:Medicine, Smartphone application, Logistic regression, Article, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Environmental health, Epidemiology, Odds Ratio, medicine, Humans, 030212 general & internal medicine, Association (psychology), smartphone application, Asthma, household cleaning products, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Asthma symptoms, Odds ratio, asthma, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Smartphone, business, Kappa, Disinfectants
Abstract: International audience; Household disinfectant and cleaning products (HDCPs) assessment is challenging in epidemiological research. We hypothesized that a newly-developed smartphone application was more objective than questionnaires in assessing HDCPs. Therefore, we aimed to compare both methods, in terms of exposure assessments and respiratory health effects estimates. The women of the SEPAGES birth cohort completed repeated validated questionnaires on HDCPs and respiratory health and used an application to report HDCPs and scan products barcodes, subsequently linked with an ingredients database. Agreements between the two methods were assessed by Kappa coefficients. Logistic regression models estimated associations of HDCP with asthma symptom score. The 101 participants (18 with asthma symptom score ≥1) scanned 617 different products (580 with available ingredients list). Slight to fair agreements for sprays, bleach and scented HDCP were observed (Kappa: 0.35, 0.25, 0.11, respectively). Strength of the associations between HDCP and asthma symptom score varied between both methods but all odds ratios (OR) were greater than one. The number of scanned products used weekly was significantly associated with the asthma symptom score (adjusted-OR [CI 95%]: 1.15 [1.00–1.32]). This study shows the importance of using novel tools in epidemiological research to objectively assess HDCP and therefore reduce exposure measurement errors.
Published: 2021

7. Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study

Author: François Jourda, Christophe Saint-Etienne, Luc Christiaens, Grégoire Rangé, Benoit Lattuca, Philippe Brunel, Paul Guedeney, Hervé Le Breton, Marie Hauguel-Moreau, Eric Vicaut, Anne Bellemain-Appaix, Jean-Louis Georges, Guillaume Cayla, Christophe Pouillot, Christophe Caussin, Gregory Ducrocq, Ziad Boueri, Farzin Beygui, Johanne Silvain, Thibault Lhermusier, Gilles Montalescot, Jean-Noël Labèque, Jean-Philippe Collet, Zuzana Motovska, Franck Boccara, Mohamad El Kasty, Raphaelle Dumaine, Jean-Guillaume Dillinger, Mikael Laredo, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de cardiologie [Chartres], Les hôpitaux de Chartres [Chartres], Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Hôpital de Bastia, Service de Cardiologie [Hôpital privé Dijon Bourgogne], Hôpital privé Dijon Bourgogne, Clinique Sainte Clotilde, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de cardiologie [CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de cardiologie [Centre Hospitalier de la Côte Basque, Bayonne], Centre Hospitalier de la Côte Basque, CHU Toulouse [Toulouse], Centre Hospitalier de Versailles André Mignot (CHV), Cardiology Department, Centre Hospitalier d'Antibes Juan les Pins, Antibes, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], 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), CHU Trousseau [APHP], Institut Mutualiste de Montsouris (IMM), Hôpital d'Auxerre, Partenaires INRAE, Grand Hôpital de l'Est Francilien (GHEF), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, AstraZeneca France Novartis Daiichi-Sankyo Bristol-Myers Squibb, BMS Eli Lilly and Company Bayer AstraZeneca France Boston Scientific Corporation, BSC Abbott Laboratories Medtronic Biotronik Fédération Française de Cardiologie, FFC, The ALPHEUS and the Bio-ALPHEUS studies are funded by the Fond de dotation ACTION ( www.action-fonds.org ) and a grant from AstraZeneca . The Bio-ALPHEUS study is also funded by the Institute of Cardiometabolism and Nutrition . The first draft of the paper was developed by Dr Silvain and Dr Montalescot, and all authors subsequently contributed to its development and final content and are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents. AstraZeneca reviewed the manuscript and was allowed to make suggestions, but final content was determined by the authors., Dr Silvain reports receiving consulting and lecture or travel support from AstraZeneca, Bayer HealthCare SAS, Biotronik, BPI France, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Terumo France SAS, Abbott Medical France SAS, and Zoll and is a stockholder of Pharmaseeds. Dr Cayla reports speaker or congress fees and has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. Dr Beygui reports receiving consulting and lecture fees from Astrazeneca, Bristol-Myers Squibb, Medtronic, Biosensors, Boston Scientific Institutional and research grants from Medtronic, Biosensors, Acist, and Boston scientific. Dr Rangé reports receiving speaker’s and/or consulting fees from Abbott. Dr Lattuca has received research grants from Biotronik, Boston Scientific, Daiichi-Sankyo, Fédération Française de Cardiologie, and Institute of CardioMetabolism and Nutrition, consultant fees from Daiichi-Sankyo and Eli Lilly, and lecture fees from AstraZeneca, Medtronic, and Novartis. Dr Collet reports receiving consulting and lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Fédération Française de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi-Aventis, and WebMD. Dr Dillinger reports receiving consulting and lecture fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, and Sanofi and grants from Bayer, Bristol-Myers Squibb/Pfizer, and Biosensors. Dr Boueri reports receiving consulting and lecture fees from Novartis and Astra Zeneca. Dr Boccara reports consulting or speaker fees from Amgen, Gilead, ViiV Healthcare, Amgen, Sanofi, MSD, and Servier outside the submitted work. Dr Christiaens reports consulting or speaker fees from Astra Zeneca. Dr Lhermusier reports consulting or speaker fees from Astra Zeneca, Boston Scientifics, and Abbott and a research grant from Astra Zeneca. Dr Georges reports consulting or speaker fees from AstraZeneca France, Sanofi-Aventis, Amgen, and Merck Sharpe and Dohme. Dr Bellemain-Appaix reports consulting or speaker fees from Astra Zeneca, Novartis, and Pfizer. Dr Saint-Etienne reports consulting or speaker fees from Abbott, Medtronic, Edwards, and Biotronik. Dr Motovska reports consulting or speaker fees from Astrazeneca. Dr Laredo reports fellowship grants from Medtronic, Biotronik, and Boston Scientific. Dr Ducrocq reports consulting or speaker fees from Amgen, Astra Zeneca, Bayer, BMS, Janssen, Sanofi, and Terumo, proctoring: Boston scientific, CEC: Novo Nordisk, and travel fees: Astra Zeneca, Bayer, and BMS. Dr Vicaut reports consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards, Pfizer, Sanofi, and Novartis. Dr Montalescot reports consulting or speaker fees from Abbott, AIM group, Amgen, Actelion, American College of Cardiology Foundation, Astrazeneca, Axis-Santé, Bayer, Boston-Scientific, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Fréquence Médicale, ICOM, Idorsia, Elsevier, Fédération Française de Cardiologie, Fréquence Médicale, Institute of Cardiometabolism and Nutrition, Lead-Up, Menarini, Medtronic, MSD, Novo-Nordisk, Pfizer, Quantum Genomics, Sanofi-Aventis, SCOR global life, Servier, and WebMD. Other authors have no conflict of interest to report., Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier d'Auxerre (CHA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord
Subjects: medicine.medical_specialty, Ticlopidine, medicine.medical_treatment, Myocardial Infarction, Coronary Disease, 030204 cardiovascular system & hematology, Coronary Angiography, Loading dose, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Aged, Aspirin, business.industry, Percutaneous coronary intervention, medicine.disease, Clopidogrel, 3. Good health, Conventional PCI, Cardiology, Purinergic P2Y Receptor Antagonists, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business, Ticagrelor, Platelet Aggregation Inhibitors, medicine.drug
Abstract: International audience; Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. Methods: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.
Published: 2020

8. The association between sedentary behavior and sarcopenia among adults aged ≥65 years in low-and middle-income countries

Author: Louis Jacob, Lee Smith, Deepti Adlakha, Mark A. Tully, Nicole E Blackburn, Ai Koyanagi, Paolo Caserotti, Pinar Soysal, Nicola Veronese, Guillermo Felipe López Sánchez, Davy Vancampfort, Anglia Ruskin University (ARU), University of Ulster, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Queen's University [Belfast] (QUB), University of Southern Denmark (SDU), Università degli studi di Palermo - University of Palermo, Institució Catalana de Recerca i Estudis Avançats (ICREA), National Institute on Aging, NIA: 08-CN-0020, OGHA 04034785, R01‐AG034479, R21‐AG034263, Y1-AG-1005, Y1‐AG‐1005–01, YA1323– 08‐CN‐0020, This paper uses data from WHO?s Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323? 08-CN-0020, Y1-AG-1005?01 and through research grants R01-AG034479 and R21-AG034263., Funding: This paper uses data from WHO’s Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323– 08‐CN‐0020, Y1‐AG‐1005–01 and through research grants R01‐AG034479 and R21‐AG034263., SOYSAL, PINAR, Smith, L., Tully, M., Jacob, L., Blackburn, N., Adlakha, D., Caserotti, P., Soysal, P., Veronese, N., Sánchez, G.F.L., Vancampfort, D., and Koyanagi, A.
Subjects: Male, Sarcopenia, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], lcsh:Medicine, WORLD-HEALTH-ORGANIZATION, Logistic regression, Continuous variable, older adult, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Gait, Public, Environmental & Occupational Health, Low- and middle-income countries, Hand Strength, Sedentary behavior, musculoskeletal system, 3. Good health, PREVALENCE, TIME, OBESITY, Older adults, Income, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Environmental Sciences & Ecology, Article, Odds, SKELETAL-MUSCLE MASS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Humans, OLDER-ADULTS, Aged, Science & Technology, business.industry, Public health, lcsh:R, Public Health, Environmental and Occupational Health, medicine.disease, body regions, PHYSICAL-ACTIVITY, Cross-Sectional Studies, Socioeconomic Factors, Ageing, Low and middle income countries, FAT, Sedentary Behavior, business, human activities, 030217 neurology & neurosurgery, Environmental Sciences, Demography, low- and middle-income countries, older adults, sarcopenia, sedentary behavior
Abstract: The present study aimed to assess the association between sedentary behavior and sarcopenia among adults aged &ge, 65 years. Cross-sectional data from the Study on Global Ageing and Adult Health were analyzed. Sarcopenia was defined as having low skeletal muscle mass and either a slow gait speed or a weak handgrip strength. Self-reported sedentary behavior was assessed as a continuous variable (hours per day) and also as a categorical variable (0&ndash, &lt, 4, 4&ndash, 8, 8&ndash, 11, &ge, 11 hours/day). Multivariable logistic regression was conducted to assess the association between sedentary behavior and sarcopenia. Analyses using the overall sample and country-wise samples were conducted. A total of 14,585 participants aged &ge, 65 years were included in the analysis. Their mean age was 72.6 (standard deviation, 11.5) years and 55% were females. Compared to sedentary behavior of 0&ndash, 4 hours/day, &ge, 11hours/day was significantly associated with 2.14 (95% CI = 1.06&ndash, 4.33) times higher odds for sarcopenia. The country-wise analysis showed that overall, a one-hour increase in sedentary behavior per day was associated with 1.06 (95% CI = 1.04&ndash, 1.10) times higher odds for sarcopenia, while the level of between-country heterogeneity was low (I2 = 12.9%). Public health and healthcare practitioners may wish to target reductions in sedentary behavior to aid in the prevention of sarcopenia in older adults.
Published: 2020

9. Fruit and vegetable consumption and sarcopenia among older adults in low- and middle-income countries

Author: Hans Oh, Louis Jacob, Ai Koyanagi, Lin Yang, Marco Solmi, Nicola Veronese, Lee Smith, Josep Maria Haro, Jae Il Shin, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institute on Aging, NIA: OGHA 04034785, PI15/00862, R01‐AG034479, R21‐AG034263, Y1‐AG‐1005–01, YA1323–08‐CN‐0020 European Regional Development Fund, FEDER: ERDF?FEDER, Acknowledgments: This paper uses data from WHO’s Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323–08‐CN‐0020, Y1‐AG‐1005–01 and through research grants R01‐AG034479 and R21‐AG034263. Ai Koyanagi’s work is supported by the PI15/00862 project, integrated into the National R + D + I and funded by the ISCIII‐General Branch Evaluation and Promotion of Health Research and the European Regional Development Fund (ERDF‐FEDER)., This paper uses data from WHO?s Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323?08?CN?0020, Y1?AG?1005?01 and through research grants R01?AG034479 and R21?AG034263. Ai Koyanagi?s work is supported by the PI15/00862 project, integrated into the National R + D + I and funded by the ISCIII?General Branch Evaluation and Promotion of Health Research and the European Regional Development Fund (ERDF?FEDER)., Koyanagi, A., Veronese, N., Solmi, M., Oh, H., Shin, J.I., Jacob, L., Yang, L., Haro, J.M., and Smith, L.
Subjects: Male, Future studies, Logistic regression, Persones grans, older people, Eating, 0302 clinical medicine, Vegetables, vegetable, fruit, low- and middle-income countries, older people, sarcopenia, vegetable, low- and middle-income countries, 030212 general & internal medicine, Aged, 80 and over, 2. Zero hunger, education.field_of_study, Nutrition and Dietetics, Hand Strength, Smoking, Age Factors, 3. Good health, Income, Female, lcsh:Nutrition. Foods and food supply, Alcohol Drinking, Population, lcsh:TX341-641, 030209 endocrinology & metabolism, Article, Odds, sarcopenia, 03 medical and health sciences, Sex Factors, medicine, Humans, education, Developing Countries, Exercise, Poverty, Hortalisses, Adult health, Aged, Consumption (economics), business.industry, Low‐ and middle‐income countries, fruit, medicine.disease, Fruita, Cross-Sectional Studies, Low and middle income countries, Fruit, Sarcopenia, Older people, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, human activities, Food Science, Demography
Abstract: Fruit and vegetable consumption may protect against sarcopenia but there are no studies on this topic from low- and middle-income countries (LMICs). Thus, we assessed this association among older adults from six LMICs. Community-based cross-sectional data of the Study on Global Aging and Adult Health were analyzed. Sarcopenia was defined as the presence of low skeletal muscle mass based on indirect population formula, and either slow gait or low handgrip strength. Quintiles of vegetable and fruit consumption were created based on the number of servings consumed on a typical day. Multivariable logistic regression analysis was conducted. The sample consisted of 14,585 individuals aged &ge, 65 years (mean (SD) age 72.6 (11.4) years, 55% females). Adjusted analyses showed that overall, compared to the lowest quintile (Q1), the highest quintile (Q5) of fruit consumption was associated with a 40% lower odds for sarcopenia (OR = 0.60, 95% CI = 0.42-0.84) but this association was largely driven by the strong association among females (e.g., Q5 vs. Q1 OR = 0.42, 95% CI = 0.24&minus, 0.73), with no significant associations found among males. Vegetable consumption was not significantly associated with sarcopenia. Future studies of longitudinal design may shed light on whether increasing fruit consumption among older females in LMICs may reduce risk for sarcopenia.
Published: 2020

10. Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells

Author: Emma Partiot, Nilda Vanesa Ayala-Nunez, Jacky G. Goetz, Gautier Follain, Judith R.E. Roels, Anita Eckly, Béatrice Uring-Lambert, Maxime Chazal, Raphael Gaudin, Gillian Hale, Frank M. J. Jacobs, Sandrine Bourdoulous, Orestis Faklaris, Sherif R. Zaki, Aurélie Hirschler, Nolwenn Jouvenet, Margot Carocci, Florian Bakoa, Sarah Cianférani, Christine Carapito, Frédéric Doussau, Brigid C. Bollweg, François Delalande, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Swammerdam Institute for Life Sciences, University of Amsterdam [Amsterdam] (UvA)-Center for Neurosciences, Génomique virale et vaccination, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion, Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), This work has received funding from the French State via the French National Research Agency (ANR) as part of the program Investissements d’avenir (IdEx Université de Strasbourg) to RG. This work was supported by an ATIP-AVENIR starting grant to RG. The research leading to these results has received funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program (FP7/2007–2013) under REA grant agreement no. PCOFUND-GA-2013-609102, through the PRESTIGE program coordinated by Campus France, and from the French Agency for Research on AIDS and Viral Hepatitis (ANRS), both attributed to NVAN. Experiments conducted by G.F. and J.G.G. were funded by Plan Cancer (OptoMetaTrap), Ligue contre le Cancer, Idex Attractivités (University of Strasbourg), and by institutional funds from INSERM and University of Strasbourg. G.F. was supported by a doctoral fellowship from Ligue Contre le Cancer. Mass spectrometry experiments were supported by the French Proteomic Infrastructure (ProFI, ANR-10-INBS-08-03). F.B. is a recipient of a PhD grant provided by ANRT (Association Nationale de la Recherche et de la Technologie). N.J. is funded by Agence Nationale pour la Recherche (ANR-16-CE15-0025-01), Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur. CDC contributions to this paper written and edited by G.L.H. and B.C.B. in their private capacity. No official support or endorsement by the Centers for Disease Control and Prevention, Department of Health and Human Services is intended, nor should be inferred. All authors read, provided feedback, and approved the paper. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 NL4-3 AD8 Infectious Molecular Clone (pNL(AD8)) from Dr. Eric O. Freed (cat# 11346)., ANR-16-CE15-0025,Viro-Storm,Mécanismes de production incontrôlée de cytokines au cours de l'infection virale(2016), European Project: 609102,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,PRESTIGE(2014), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), EFS-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), jouvenet, nolwenn, Mécanismes de production incontrôlée de cytokines au cours de l'infection virale - - Viro-Storm2016 - ANR-16-CE15-0025 - AAPG2016 - VALID, PRES Towards International Gain of Excellence - PRESTIGE - - EC:FP7:PEOPLE2014-09-01 - 2019-08-31 - 609102 - VALID, Equipe Direction scientifique, Sciences et Technologies de la Musique et du Son (STMS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Neuro-Immunologie Virale, Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de Photonique Quantique et Moléculaire (LPQM), Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-École normale supérieure - Cachan (ENS Cachan), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion (http://www.u949.inserm.fr/), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique, Département des Sciences Analytiques, Institut Pluridisciplinaire Hubert Curien, Strasbourg, France (LSMBO-DSA-IPHC), Centre National de la Recherche Scientifique (CNRS), Immunorhumathologie moléculaire, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Molecular Neuroscience (SILS, FNWI)
Subjects: Central Nervous System, 0301 basic medicine, MESH: Neurons, General Physics and Astronomy, MESH: Organoids, MESH: Monocytes, Monocytes, Zika virus, 0302 clinical medicine, MESH: Transendothelial and Transepithelial Migration, Cerebellum, MESH: Animals, lcsh:Science, MESH: Embryonic Stem Cells, ComputingMilieux_MISCELLANEOUS, Zebrafish, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Neurons, Multidisciplinary, Zika Virus Infection, Cell adhesion molecule, food and beverages, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Phenotype, 3. Good health, Cell biology, Organoids, Mechanisms of disease, medicine.anatomical_structure, MESH: Cell Survival, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Endothelium, Cell Survival, Science, MESH: Zika Virus, Biology, MESH: Endothelium, Article, General Biochemistry, Genetics and Molecular Biology, Virus, MESH: Cell Adhesion, 03 medical and health sciences, Virology, medicine, Animals, Humans, MESH: Central Nervous System, Cellular microbiology, Cell adhesion, MESH: Zebrafish, Embryonic Stem Cells, MESH: Humans, Monocyte, fungi, Transendothelial and Transepithelial Migration, Zika Virus, General Chemistry, biology.organism_classification, Embryonic stem cell, MESH: Cerebellum, Disease Models, Animal, 030104 developmental biology, lcsh:Q, MESH: Disease Models, Animal, Cell Adhesion Molecules, MESH: Female, 030217 neurology & neurosurgery
Abstract: Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention., Zika virus (ZIKV) can infect the central nervous system, but it is not clear how it reaches the brain. Here, Ayala-Nunez et al. show in ex vivo and in vivo models that ZIKV can hitch a ride in monocytes in a Trojan Horse manner to cross the endothelium and disseminate the virus.
Published: 2019

11. Genetic screens reveal mechanisms for the transcriptional regulation of tissue-specific genes in normal cells and tumors

Author: Morgane Bourmaud, Anda Huna, Ikrame Naciri, Marthe Laisné, Pierre-Antoine Defossez, Selene Di Carlo, Nikhil Gupta, David Bernard, Lucie Peduto, Laure Ferry, Olivier Kirsh, Nadine Martin, Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stroma, inflammation et réparation tissulaire - Stroma, Inflammation and Tissue Repair, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Institutes of Health [EpiCALC 2013 to P.A.D. and D.B.], Institut National du Cancer [PLBio15–013 to P.A.D. and D.B.], Labex ‘Who am I?’ [ANR-11-LABX-0071 under ANR-11-IDEX-005–02, to P.A.D.], European Research Council [ERC648428-PERIF to L.P.], Fondation ARC [4th-year PhD scholarship to I.N., Programme Labellisé PGA1/RF20180206807 to P.A.D.], Fondation pour la Recherche Médicale [postdoctoral fellowship to A.H.]. The open access publication charge for this paper has been waived by Oxford University Press - NAR Editorial Board members are entitled to one free paper per year in recognition of their work on behalf of the journal., The authors thanks the Genomics Platform of Institut Curie for Nanostring analysis. The Nanostring platform of Institut Curie was initiated with the support of French grants (LabEx and EquipEx): ANR-10-IDEX-0001–02 PSL, ANR-11-LBX-0044 and « INCa-DGOS- 4654 » SIRIC11–002. We thank Valérie Doye, Stéphanie Bolhy, and Philippe Girard at Institut Jacques Monod for help with the Incucyte. Concerning the lentiviral vector production, we acknowledge Christophe Huret and the Paris Diderot Vectorology Platform of Paris Diderot University, Sorbonne Paris Cité, CNRS UMR 7216, Paris, France. We acknowledge the kind help of Elisabeth Brambilla with some experiments that do not appear in the submitted version of the manuscript. For the gift of reagents we acknowledge the kind contribution of Katrin Chua, Philippe Chavrier, Annabelle Decottignies, Sébastien Jauliac and Michael Kracht. Finally, we thank the following colleagues for useful discussions: Jean-Marc Vanacker, Robert Dante, Nathalie Théret, Saadi Khochbin, Céline Prunier, Céline Vallot, Claire Rougeulle, Isabelle Bernard-Pierrot, Slimane Ait-si-ali, Jonathan Weitzman, Valérie Lallemand-Mezger, ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), European Project: 648428,H2020,ERC-2014-CoG,PERIF(2015), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM), Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École pratique des hautes études (EPHE), Centre de Recherche en Cancérologie de Lyon (CRCL), Stroma, inflammation et réparation tissulaire, ATMEL [Rousset], Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), TOMASSO DEVERGE, Carina, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, and Perivascular cells at the crossroads of inflammation, regeneration and fibrosis - PERIF - - H20202015-11-01 - 2020-10-31 - 648428 - VALID
Subjects: Transcription, Genetic, [SDV]Life Sciences [q-bio], ADAM12 Protein, Triple Negative Breast Neoplasms, Biology, Protein Serine-Threonine Kinases, Cell Line, Transforming Growth Factor beta1, 03 medical and health sciences, 0302 clinical medicine, RNA interference, Cell Line, Tumor, Neoplasms, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, Genetics, Humans, Epigenetics, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Histone Acetyltransferases, Regulation of gene expression, 0303 health sciences, Gene regulation, Chromatin and Epigenetics, Chromatin, Cell biology, Gene Expression Regulation, Neoplastic, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Organ Specificity, Cancer cell, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA Interference, 030217 neurology & neurosurgery, Genetic screen, Signal Transduction
Abstract: International audience; The proper tissue-specific regulation of gene expression is essential for development and homeostasis in metazoans. However, the illegitimate expression of normally tissue-restricted genes-like testis- or placenta-specific genes-is frequently observed in tumors; this promotes transformation, but also allows immunotherapy. Two important questions are: how is the expression of these genes controlled in healthy cells? And how is this altered in cancer? To address these questions, we used an unbiased approach to test the ability of 350 distinct genetic or epigenetic perturbations to induce the illegitimate expression of over 40 tissue-restricted genes in primary human cells. We find that almost all of these genes are remarkably resistant to reactivation by a single alteration in signaling pathways or chromatin regulation. However, a few genes differ and are more readily activated; one is the placenta-expressed gene ADAM12, which promotes invasion. Using cellular systems, an animal model, and bioinformatics, we find that a non-canonical but druggable TGF-β/KAT2A/TAK1 axis controls ADAM12 induction in normal and cancer cells. More broadly, our data show that illegitimate gene expression in cancer is an heterogeneous phenomenon, with a few genes activatable by simple events, and most genes likely requiring a combination of events to become reactivated.
Published: 2019

12. Left Ventricle Quantification Challenge: A Comprehensive Comparison and Evaluation of Segmentation and Regression for Mid-Ventricular Short-Axis Cardiac MR Data

Author: Georgios Tziritas, Yeonggul Jang, Jin Ma, Fumin Guo, Quanzheng Li, Tiancong Hua, Xiang Li, Lihong Liu, Angélica Atehortúa, James R. Clough, Zhiqiang Hu, Eric Kerfoot, Vicente Grau, Enzo Ferrante, Matthew Ng, Guanyu Yang, Mireille Garreau, Alejandro Debus, Elias Grinias, Jiahui Li, Wufeng Xue, Shuo Li, Wenjun Yan, Ilkay Oksuz, Hao Xu, Shenzhen University, Beijing University of Posts and Telecommunications (BUPT), Peking University [Beijing], King‘s College London, Istanbul Technical University (ITÜ), University of Oxford [Oxford], University of Toronto, Massachusetts General Hospital [Boston], University of Crete [Heraklion] (UOC), Fudan University [Shanghai], Universidad Nacional de Colombia [Bogotà] (UNAL), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Information Biomédicale sino-français (CRIBS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), Yonsei University, Universidad Nacional del Litoral [Santa Fe] (UNL), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, University of Western Ontario (UWO), The paper is partially supported by the Natural Science Foundation of China under Grants 61801296. The workof Eric Kerfoot was supported by an EPSRC programmeGrant (EP/P001009/1) and the Wellcome EPSRC Centre for Medical Engineering at the School of Biomedical Engineering and Imaging Sciences, Kings College London (WT203148/Z/16/Z). The work of Angelica Atehortua was supported by Colciencias-Colombia, Grant No. 647 (2015 call for National PhD studies) and Université de Rennes 1. The work of Alejandro Debus was supported by the Santa Fe Science, Technology and Innovation Agency (AS ACTEI), Government of the Province of Santa Fe, through Project AC-00010-18,Resolution N 117/14., University of Oxford, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Short axis, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Computer science, Heart Ventricles, Magnetic Resonance Imaging, Cine, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Health Information Management, medicine, Humans, Segmentation, Electrical and Electronic Engineering, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, Ground truth, Cardiac cycle, business.industry, Heart, Pattern recognition, Image segmentation, Magnetic Resonance Imaging, Regression, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Computer Science Applications, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, medicine.anatomical_structure, Ventricle, 030220 oncology & carcinogenesis, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Cardiac phase, Biotechnology
Abstract: Automatic quantification of the left ventricle (LV) from cardiac magnetic resonance (CMR) images plays an important role in making the diagnosis procedure efficient, reliable, and alleviating the laborious reading work for physicians. Considerable efforts have been devoted to LV quantification using different strategies that include segmentation-based (SG) methods and the recent direct regression (DR) methods. Although both SG and DR methods have obtained great success for the task, a systematic platform to benchmark them remains absent because of differences in label information during model learning. In this paper, we conducted an unbiased evaluation and comparison of cardiac LV quantification methods that were submitted to the Left Ventricle Quantification (LVQuan) challenge, which was held in conjunction with the Statistical Atlases and Computational Modeling of the Heart (STACOM) workshop at the MICCAI 2018. The challenge was targeted at the quantification of 1) areas of LV cavity and myocardium, 2) dimensions of the LV cavity, 3) regional wall thicknesses (RWT), and 4) the cardiac phase, from mid-ventricle short-axis CMR images. First, we constructed a public quantification dataset Cardiac-DIG with ground truth labels for both the myocardium mask and these quantification targets across the entire cardiac cycle. Then, the key techniques employed by each submission were described. Next, quantitative validation of these submissions were conducted with the constructed dataset. The evaluation results revealed that both SG and DR methods can offer good LV quantification performance, even though DR methods do not require densely labeled masks for supervision. Among the 12 submissions, the DR method LDAMT offered the best performance, with a mean estimation error of 301 mm $^2$ for the two areas, 2.15 mm for the cavity dimensions, 2.03 mm for RWTs, and a 9.5% error rate for the cardiac phase classification. Three of the SG methods also delivered comparable performances. Finally, we discussed the advantages and disadvantages of SG and DR methods, as well as the unsolved problems in automatic cardiac quantification for clinical practice applications.
Published: 2021

13. Proteomic and Mechanistic Analysis of Spironolactone in Patients at Risk for HF

Author: Pierpaolo Pellicori, Blerim Mujaj, Stephane Heymans, Fozia Z Ahmed, N. Girerd, Ping Wang, Arantxa González, Hans-Peter Brunner-La-Rocca, Javier Díez, Franco Cosmi, Frank T. Edelmann, Mark R. Hazebroek, João Pedro Ferreira, Joe Cuthbert, Andrew L. Clark, Johannes Petutschnigg, Mamas A. Mamas, Roberto Latini, Job A J Verdonschot, John G.F. Cleland, Beatrice Mariottoni, Patrick Rossignol, Javed Khan, Jan A. Staessen, Burkert Pieske, Faiez Zannad, Anne Pizard, Stéphanie Grojean, Timothy Collier, Philippe Rouet, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], London School of Hygiene and Tropical Medicine (LSHTM), University of Manchester [Manchester], University of Hull [United Kingdom], Cortona Hospital, Universidad de Navarra [Pamplona] (UNAV), German Heart Institute Berlin, University of Glasgow, Mario Negri Institute, Center for Human Genetics, University of Leuven School of Medicine, SCHOOL of MEDICINE [Louvain], Université Catholique de Louvain = Catholic University of Louvain (UCL)-Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Author Disclosures HOMAGE was funded by a grant from the European Union 7th Framework Programme for Research and Technological Development (HEALTH-F7-305507 HOMAGE (EU FP7 305507 http://www.homage-hf.eu). Drs. Ferreira, Rossignol, Girerd, and Zannad are supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program (reference: ANR-15-RHUS-0004), the French PIA project 'Lorraine Université d’Excellence' (reference: ANR-15-IDEX-04-LUE), Contrat de Plan Etat Lorraine IT2MP, and FEDER Lorraine. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), DE CARVALHO, Philippe, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Heart OMics in AGEing - HOMAGE - - EC:FP7:HEALTH2013-02-01 - 2019-01-31 - 305507 - VALID, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and MUMC+: MA Med Staf Artsass Cardiologie (9)
Subjects: Male, Proteomics, [SDV]Life Sciences [q-bio], Adipokine, Inflammation, 030204 cardiovascular system & hematology, Pharmacology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Mineralocorticoid receptor, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Fibrosis, Renin–angiotensin system, Natriuretic Peptide, Brain, medicine, Humans, 030212 general & internal medicine, Aged, Mineralocorticoid Receptor Antagonists, Heart Failure, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, fibrosis, spironolactone, HEART-FAILURE INSIGHTS, medicine.disease, Brain natriuretic peptide, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, CARDIAC MATRIX BIOMARKERS, [SDV] Life Sciences [q-bio], renin-angiotensin-aldosterone system, chemistry, MYOCARDIAL-INFARCTION, inflammation, Heart failure, Spironolactone, SURVIVAL, EPLERENONE, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, heart failure prevention, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: OBJECTIVES This study sought to further understand the mechanisms underlying effect of spironolactone and assessed its impact on multiple plasma protein biomarkers and their respective underlying biologic pathways.BACKGROUND In addition to their beneficial effects in established heart failure (HF), mineralocorticoid receptor antagonists may act upstream on mechanisms, preventing incident HF. In people at risk for developing HF, the HOMAGE (Heart OMics in AGEing) trial showed that spironolactone treatment could provide antifibrotic and antiremodeling effects, potentially slowing the progression to HF.METHODS Baseline, 1-month, and 9-month (or last visit) plasma samples of HOMAGE participants were measured for protein biomarkers (n = 276) by using Olink Proseek-Multiplex cardiovascular and inflammation panels (Olink, Uppsala, Sweden). The effect of spironolactone on biomarkers was assessed by analysis of covariance and explored by knowledgebased network analysis. RESULTS A total of 527 participants were enrolled; 265 were randomized to spironolactone (25 to 50 mg/day) and 262 to standard care ("control"). The median (interquartile range) age was 73 years (69 to 79 years), and 26% were female. Spironolactone reduced biomarkers of collagen metabolism (e.g., COL1A1, MMP-2); brain natriuretic peptide; and biomarkers related to metabolic processes (e.g., PAPPA), inflammation, and thrombosis (e.g., IL17A, VEGF, and urokinase). Spironolactone increased biomarkers that reflect the blockade of the mineralocorticoid receptor (e.g., renin) and increased the levels of adipokines involved in the anti-inflammatory response (e.g., RARRES2) and biomarkers of hemostasis maintenance (e.g., tPA, UPAR), myelosuppressive activity (e.g., CCL16), insulin suppression (e.g., RETN), and inflammatory regulation (e.g., IL-12B).CONCLUSIONS Proteomic analyses suggest that spironolactone exerts pleiotropic effects including reduction in fibrosis, inflammation, thrombosis, congestion, and vascular function improvement, all of which may mediate cardiovascular protective effects, potentially slowing progression toward heart failure. (HOMAGE [Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure]; NCT02556450) (C) 2021 by the American College of Cardiology Foundation.
Published: 2021

14. The association between objective vision impairment and mild cognitive impairment among older adults in low- and middle-income countries

Author: Hans Oh, Ai Koyanagi, Guillermo F. López-Sánchez, Jae Il Shin, Yvonne Barnett, Lee Smith, Pinar Soysal, Louis Jacob, Laurie T. Butler, Nicola Veronese, Shahina Pardhan, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institute on Aging, NIA: 08-CN-0020, OGHA 04034785, R01-AG034479, R21-AG034263, Y1-AG-1005, YA1323, This paper uses data from WHO?s Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323?08-CN-0020, Y1-AG-1005?01 and through research grants R01-AG034479 and R21-AG034263., Smith, L., Shin, J.I., Jacob, L., López-Sánchez, G.F., Oh, H., Barnett, Y., Pardhan, S., Butler, L., Soysal, P., Veronese, N., Koyanagi, A., and SOYSAL, PINAR
Subjects: Male, Gerontology, China, Aging, medicine.medical_specialty, Visual acuity, genetic structures, Epidemiology, [SDV]Life Sciences [q-bio], Visual impairment, Vision impairment, Logistic regression, Odds, 03 medical and health sciences, 0302 clinical medicine, Prevalence, Humans, Medicine, Dementia, Cognitive Dysfunction, 030212 general & internal medicine, Association (psychology), Developing Countries, Aged, Low- and middle-income countries, business.industry, Mild cognitive impairment, medicine.disease, eye diseases, Smith L., Shin J. I. , Jacob L., López-Sánchez G. F. , Oh H., Barnett Y., Pardhan S., Butler L., Soysal P., Veronese N., et al., -The association between objective vision impairment and mild cognitive impairment among older adults in low- and middle-income countries.-, Aging clinical and experimental research, 2021, Vision impairment, Mild cognitive impairment, Older adults, Low- and middle-income countries, Epidemiology, Cross-Sectional Studies, Ageing, Older adults, Female, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Aim: The association between visual impairment and mild cognitive impairment (MCI) has not been investigated to date. Thus, we assessed this association among older adults from six low- and middle-income countries (LMICs) (China, India, Ghana, Mexico, Russia, and South Africa) using nationally representative datasets. Methods: Cross-sectional, community-based data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. Visual acuity was measured using the tumbling ElogMAR chart, and vision impairment (at distance and near) was defined as visual acuity worse than 6/18 (0.48 logMAR) in the better-seeing eye. The definition of MCI was based on the National Institute on Aging-Alzheimer’s Association criteria. Multivariable logistic regression was conducted. Results: Data on 32,715 individuals aged ≥ 50years [mean (SD) age 62.1 (15.6) years; 51.2% females] were analyzed. Compared to those without far or near vision impairment, those with near vision impairment but not far vision impairment (OR = 1.33; 95% CI = 1.16–1.52), and those with both far and near vision impairment (OR = 1.70; 95% CI = 1.27–2.29) had significantly higher odds for MCI. Only having far vision impairment was not significantly associated with MCI. Conclusions: Visual impairment is associated with increased odds for MCI among older adults in LMICs with the exception of far vision impairment only. Future longitudinal and intervention studies should examine causality and whether improvements in visual acuity, or early intervention, can reduce risk for MCI and ultimately, dementia. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.
Published: 2021

15. Urban environment and cognitive and motor function in children from four European birth cohorts

Author: Marina Vafeiadi, Raquel Soler-Blasco, Mariza Kampouri, Mònica Guxens, Martine Vrijheid, Johanna Lepeule, Llúcia González-Safont, Mark J. Nieuwenhuijsen, Mark Mon-Williams, John Wright, Rosie McEachan, Anne-Claire Binter, Claire Philippat, Jonathan Y. Bernard, Jordi Sunyer, Loreto Santa-Marina, Leda Chatzi, Lucia Alonso, Ainara Andiarena, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agency for science, technology and research [Singapore] (A*STAR), University of South-Eastern Norway (USN), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Jaume I, University of Crete [Heraklion] (UOC), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), University of Bradford, University of Southern California (USC), Universitat Pompeu Fabra [Barcelona] (UPF), Erasmus University Medical Center [Rotterdam] (Erasmus MC), This work was supported by funding from the European Community’s Seventh Framework Programme [FP7/2007–206 n◦308333, the HELIX project]. This INMA cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, PI041436, PI081151 incl. FEDER funds, FIS PI06/0867, FIS-PI09/00090, FIS and FIS-PI18/01142 incl. FEDER funds, FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI16/00118 and PI17/00663, FIS-FSE: 17/00260, Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, and CPII18/00018), from UE (FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1, and H2020 n◦824989), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), Alicia Koplowitz Foundation 2017, CIBERESP, Department of Health of the Basque Government (2013111089, 2009111069, 2013111089, 2015111065 and 2018111086), Provincial Government of Gipuzkoa (DFG06/002, DFG08/001, DFG15/221 and DFG 89/17) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu , Legazpi, Azkoitia y Azpeitia y Beasain). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the 'Centro de Excelencia Severo Ochoa 2019-2023' Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. The work was also supported by MICINN [MTM2015-68140- R] and Centro Nacional de Genotipado- CEGEN- PRB2- ISCIII (Spain). The Rhea project was financially supported by European projects, and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014, 'Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Collaboration for Applied Health Research and Care (CLAHRC) for Yorkshire and Humber (UK). The EDEN study was supported by Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A), and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programs (ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety and French National Agency for Food Security (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN), French-speaking association for the study of diabetes and metabolism (ALFEDIAM). Core support for Born in Bradford is also provided by the Wellcome Trust (WT101597MA, UK). Born in Bradford (BiB) is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, health professionals, schools and researchers who have made BiB happen. BiB receives funding from the ESRC/MRC, the Wellcome Trust (WT101597MA) and the National Institute for Health Research Yorkshire and Humber ARC (reference: NIHR20016). M. Mon-Williams was supported by a Fellowship from the Alan Turing Institute. Additional funding from the National Institute of Environmental Health Science supported Dr Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, and P30ES007048). The views expressed are those of the authors, and not necessarily those of the NHS or the NIHR. None of the funders were involved in designing the study, collecting the data, analyzing or interpreting the data, deciding to submit the article for publication, or the writing of the report., HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Singapore Institute for Clinical Sciences [Singapour] (SICS), Bradford Institute for Health Research [Bradford, UK], Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Leeds, Universitat de València (UV), Karolinska Institutet [Stockholm], Binter, Anne-Claire, Child and Adolescent Psychiatry / Psychology, Erasmus MC other, European Commission, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: Urban environment, 010501 environmental sciences, 01 natural sciences, 0302 clinical medicine, Cognition, Pregnancy, Cognició en els infants, 11. Sustainability, GE1-350, 030212 general & internal medicine, Children, Motor skill, ComputingMilieux_MISCELLANEOUS, Desenvolupament urbà, General Environmental Science, SDG 15 - Life on Land, 2. Zero hunger, education.field_of_study, Air Pollutants, 4. Education, motor function, Cohort, cohort, SDG 11 - Sustainable Cities and Communities, 3. Good health, Child, Preschool, Birth Cohort, Female, Cognitive function, Psychology, Population, Gross motor skill, 03 medical and health sciences, children, Urban planning, Air Pollution, medicine, Humans, education, Motor function, cognitive function, 0105 earth and related environmental sciences, Environmental Exposure, medicine.disease, urban environment, Confidence interval, Environmental sciences, Spain, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Particulate Matter, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Demography
Abstract: [EN]Background: The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children. Methods: We used data from 5403 mother-child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-exposure models using the Deletion-Substitution-Addition algorithm. Results: Higher greenness exposure within 300 m during pregnancy was associated with higher verbal abilities (1.5 points (95% confidence interval 0.4, 2.7) per 0.20 unit increase in greenness). Higher connectivity density within 100 m and land use diversity during pregnancy were related to lower verbal abilities. Childhood exposure to PM2.5 mediated 74% of the association between greenness during childhood and verbal abilities. Higher exposure to PM2.5 during pregnancy was related to lower fine motor function (-1.2 points (-2.1, -0.4) per 3.2 mu g/m3 increase in PM2.5). No associations were found with non-verbal abilities and gross motor function. Discussion: This study suggests that built environment, greenness, and air pollution may impact child cognitive and motor function at five years old. This study adds evidence that well-designed urban planning may benefit children's cognitive and motor development. Acknowledgements We are grateful to all the participating children, parents, practi-tioners and researchers in the four countries who took part in this study. This work was supported by funding from the European Community's Seventh Framework Programme [FP7/2007-206 n 308333; the HELIX project] . This INMA cohort was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds, FIS PI06/0867, FIS-PI09/00090, FIS and FIS-PI18/01142 incl. FEDER funds, FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI16/00118 and PI17/00663; FIS-FSE: 17/00260; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051, and CPII18/00018) , from UE (FP7-ENV-2011 cod 282957, HEALTH.2010.2.4.5-1, and H2020 n 824989) , Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundacio La marato de TV3 (090430) , Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249) , Alicia Koplowitz Foundation 2017, CIBERESP, Department of Health of the Basque Government (2013111089, 2009111069, 2013111089, 2015111065 and 2018111086) , Provincial Government of Gipuzkoa (DFG06/002, DFG08/001, DFG15/221 and DFG 89/17) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu , Legazpi, Azkoitia y Azpeitia y Beasain) . We acknowledge support from the Spanish Ministry of Science and Inno-vation and the State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S) , and support from the Generalitat de Catalunya through the CERCA Program. The work was also supported by MICINN [MTM2015-68140-R] and Centro Nacional de Genotipado-CEGEN-PRB2-ISCIII (Spain) . The Rhea project was financially supported by European projects, and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011-2014; "Rhea Plus": Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-15) . This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Collaboration for Applied Health Research and Care (CLAHRC) for Yorkshire and Humber (UK) . The EDEN study was supported by Foundation for medical research (FRM) , National Agency for Research (ANR) , National Institute for Research inPublic health (IRESP: TGIR cohorte sante 2008 program) , French Min-istry of Health (DGS) , French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) , and Human Nutrition Na-tional Research Programs, Paris-Sud University, Nestle, French National Institute for Population Health Surveillance (InVS) , French National Institute for Health Education (INPES) , the European Union FP7 pro-grams (ESCAPE, ENRIECO, Medall projects) , Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD) ) , French Agency for Environmental Health Safety and French National Agency for Food Security (now ANSES) , Mutuelle Generale de l'Education Nationale a complementary health insurance (MGEN) , French-speaking association for the study of diabetes and metabolism (ALFEDIAM) . Core support for Born in Bradford is also provided by the Wellcome Trust (WT101597MA, UK) . Born in Bradford (BiB) is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, health professionals, schools and researchers who have made BiB happen. BiB receives funding from the ESRC/MRC, the Wellcome Trust (WT101597MA) and the National Institute for Health Research York-shire and Humber ARC (reference: NIHR20016) . M. Mon-Williams was supported by a Fellowship from the Alan Turing Institute. Additional funding from the National Institute of Environmental Health Science supported Dr Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, and P30ES007048) . The views expressed are those of the authors, and not necessarily those of the NHS or the NIHR. None of the funders were involved in designing the study, collecting the data, analyzing or interpreting the data, deciding to submit the article for publication, or the writing of the report. Data sharing statement The HELIX data warehouse has been established as an accessible resource for collaborative research involving researchers external to the project. Access to HELIX data is based on approval by the HELIX Project Executive Committee and by the individual cohorts. Further details on the content of the data warehouse (data catalogue) and procedures for external access are described on the project website (http:// www.proj-ecthelix.eu/index.php/es/data-inventory) .
Published: 2022

16. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author: Eva Ardanaz, Agnetha Linn Rostgaard-Hansen, Alessio Naccarati, Elisabete Weiderpass, Pekka Keski-Rahkonen, Rudolf Kaaks, Tilman Kühn, Anna Winkvist, Jośe Mariá Huerta, H. B. Bueno-De-Mesquita, Guri Skeie, Pietro Ferrari, Krasimira Aleksandrova, Gabriel Perlemuter, Augustin Scalbert, Olatz Mokoroa, Giovanna Tagliabue, Marc J. Gunter, Kim Overvad, José Ramón Quirós, Agneta Kiss, Marie-Christine Boutron-Ruault, Yahya Mahamat-Saleh, Talita Duarte-Salles, Nivonirina Robinot, Anne Tjønneland, Antonia Trichopoulou, Julie A. Schmidt, Christina C. Dahm, Roel Vermeulen, Rosario Tumino, Núria Sala, Joseph A. Rothwell, Sophia Harlid, Magdalena Stepien, Klas Sjöberg, Vivian Viallon, Neil Murphy, Anna Karakatsani, Salvatore Panico, Nicholas J. Wareham, María José Sánchez, Francesca Mancini, Domenico Palli, Mazda Jenab, Elio Riboli, Bodil Ohlsson, Kay-Tee Khaw, 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), Institut National Du Cancer, INCa: 2014-1-RT-02-CIRC-1 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Cancer Research UK, CRUK: C570/A16491 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS National Research Council, NRC 6236 Hellenic Health Foundation, HHF Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, CIRC Associazione Italiana per la Ricerca sul Cancro, AIRC RD06/0020 Deutsche Krebshilfe World Cancer Research Fund, WCRF Cancerfonden Medical Research Council, MRC: MR/M012190/1, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA) (grant number 2014-1-RT-02-CIRC-1, PI: M. Jenab). The coordination of EPIC is financially supported by the European Commission (DG-SANCO), and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (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), and Statistics Netherlands (the Netherlands), and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 for EPIC-Norfolk and C570/A16491 for EPIC-Oxford) and the Medical Research Council (1000143 for EPIC-Norfolk and MR/M012190/1 for EPIC-Oxford) (UK). The funding sources had no influence on the design of the study, the collection, analysis, and interpretation of data, the writing of the report, and or the decision to submit the paper for publication. Disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, prospective observational cohort, Glycocholic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dehydroepiandrosterone sulfate, Internal medicine, Biomarkers, Tumor, medicine, Humans, Metabolomics, Prospective Studies, Aged, Hepatitis, business.industry, Liver Neoplasms, Cancer, Feeding Behavior, hepatocellular carcinoma, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, untargeted metabolomics, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Female, business, Metabolic Networks and Pathways, Chromatography, Liquid, Cohort study
Abstract: International audience; Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
Published: 2020

17. The Flemmingsome reveals an ESCRT-to-membrane coupling via ALIX/syntenin/syndecan-4 required for completion of cytokinesis

Author: Quentin Giai Gianetto, Neetu Gupta-Rossi, Mariette Matondo, Stéphane Frémont, Frédérique Cuvelier, Audrey Salles, Julia Chamot-Rooke, Hervé Ménager, Florine Milin, Sandrine Schmutz, Cyril Addi, Murielle Rocancourt, Magalie Duchateau, Arnaud Echard, Thibaut Douché, Adrien Presle, Pascale Zimmermann, Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Institut Pasteur [Paris], Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Plateforme de Protéomique / Proteomics platform, Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), This work has been supported by Institut Pasteur, CNRS, and ANR (AbCyStem, Cytosign) to A.E. C.A. received a fellowship from the Doctoral School Complexité du Vivant ED515, contrat n° 2412/2016 and AMX. A.P. received a fellowship from the Doctoral School Complexité du Vivant ED515, contrat n°2611 bis/2016 and Fondation ARC pour la recherche sur le cancer (DOC20190508876)., We thank R. Basto, G. Hickson, J. Mathieu, J.-R. Huyhn, R. Shaughnessy, M. Serres, and T. Wai for critical reading of the paper, the Echard Lab members for helpful discussions, the Recombinant antibodies platform (TAb-IP, Institut Curie, Paris) and the DSHB (University of Iowa) for antibodies. GFP-MKLP2 cells were from the Hyman Lab MPI-MCBG Dresden45., UTechS PBI is part of the France–BioImaging infrastructure network (FBI) supported by the French National Research Agency (ANR-10-INSB-04, Investments for the Future), and acknowledges support from ANR/FBI and the Région Ile-de-France (program 'Domaine d’Intérêt Majeur-Malinf') for the use of the Zeiss LSM 780 Elyra PS1 microscope. We thank P.H. Commere from the Utechs CB, Institut Pasteur for FACS sorting., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Salles, Audrey
Subjects: 0301 basic medicine, Syntenins, SYNDECAN, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Cell Cycle Proteins, Plasma protein binding, ABSCISSION, 0302 clinical medicine, ALIX, SYNTENIN, lcsh:Science, Multidisciplinary, Chemistry, MOLECULAR-MECHANISMS, Transmembrane protein, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, Midbody, Science & Technology - Other Topics, MACHINERY, LATE STEPS, Protein Binding, Cell division, Science, BIOGENESIS, SCISSION, HIV Budding, Endosomes, macromolecular substances, General Biochemistry, Genetics and Molecular Biology, ESCRT, Article, 03 medical and health sciences, Abscission, Humans, Cytokinesis, Organelles, MIDBODY, Science & Technology, Endosomal Sorting Complexes Required for Transport, Calcium-Binding Proteins, Cell Membrane, General Chemistry, 030104 developmental biology, Membrane protein, Syndecan-4, lcsh:Q, 030217 neurology & neurosurgery, HeLa Cells
Abstract: Cytokinesis requires the constriction of ESCRT-III filaments on the side of the midbody, where abscission occurs. After ESCRT recruitment at the midbody, it is not known how the ESCRT-III machinery localizes to the abscission site. To reveal actors involved in abscission, we obtained the proteome of intact, post-abscission midbodies (Flemmingsome) and identified 489 proteins enriched in this organelle. Among these proteins, we further characterized a plasma membrane-to-ESCRT module composed of the transmembrane proteoglycan syndecan-4, ALIX and syntenin, a protein that bridges ESCRT-III/ALIX to syndecans. The three proteins are highly recruited first at the midbody then at the abscission site, and their depletion delays abscission. Mechanistically, direct interactions between ALIX, syntenin and syndecan-4 are essential for proper enrichment of the ESCRT-III machinery at the abscission site, but not at the midbody. We propose that the ESCRT-III machinery must be physically coupled to a membrane protein at the cytokinetic abscission site for efficient scission, uncovering common requirements in cytokinesis, exosome formation and HIV budding., ESCRT filaments drive the final abscission between two daughter cells but how they physically interact with the membrane is unclear. Using proteomics, the authors show that syndecan-4/syntenin/ALIX couples the ESCRT machinery to the abscission site and thus promotes efficient abscission.
Published: 2020

18. Mixture modeling for identifying subtypes in disease course mapping

Author: Stanley Durrleman, Pierre-Emmanuel Poulet, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This research has received funding from the program 'Investissements d’avenir' ANR-10-IAIHU-06. This work was also funded in part by the French government under management of Agence Nationale de la Recherche as part of the 'Investissements d’avenir' program, reference ANR-19-P3IA-0001 (PRAIRIE 3IA Institute)., Aasa Feragen, Stefan Sommer, Julia Schnabel, Mads Nielsen, ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This paper is funded in part by grant number 678304 (ERC), 826421 (TVB-Cloud) from H2020 programme, and ANR-10-IAIHU-06 (IHU ICM), ANR-19-P3IA-0001 (PRAIRIE) and ANR-19-JPW2-000 (E-DADS) from ANR., Poulet, Pierre-Emmanuel, PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Computer science, Population, Stochastic approximation, Machine learning, computer.software_genre, 01 natural sciences, Synthetic data, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], Alzheimer's disease subtypes, mixed-effect models, 0101 mathematics, Cognitive decline, mixture models, education, Cluster analysis, Non-linear mixed-effect model, ComputingMilieux_MISCELLANEOUS, Mixture model, Ground truth, education.field_of_study, MCMC-SAEM, business.industry, Contrast (statistics), Disease course mapping, Disease progression modelling, [STAT.ML] Statistics [stat]/Machine Learning [stat.ML], Artificial intelligence, business, computer, [STAT.ME]Statistics [stat]/Methodology [stat.ME], 030217 neurology & neurosurgery
Abstract: International audience; Disease modeling techniques summarize the possible trajectories of progression from multimodal and longitudinal data. These techniques often assume that individuals form a homogeneous cluster, thus ignoring possible disease subtypes within the population. We extend a non-linear mixed-effect model used for disease course mapping with a mixture framework. We jointly estimate model parameters and subtypes with a tempered version of a stochastic approximation of the Expectation Maximisation algorithm. We show that our model recovers the ground truth parameters from synthetic data, in contrast to the naive solution consisting in post hoc clustering of individual parameters from a one-class model. Applications to Alzheimer's disease data allows the unsupervised identification of disease subtypes associated with distinct relationship between cognitive decline and progression of imaging and biological biomarkers.
Published: 2021

19. The impact of diabetes on heart failure development: the cardio-renal-metabolic connection

Author: Paul Valensi, Jean-Michel Halimi, Erwan Donal, Sara Pinto, Gaëtan Prévost, Jonchère, Laurent, Service d'endocrinologie diabétologie, nutrition (Hôpital Jean Verdier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, CHU Rouen, Normandie Université (NU), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], For this review paper the authors did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau
Subjects: medicine.medical_specialty, GLP1-receptor agonists, Endocrinology, Diabetes and Metabolism, Population, heart failure, 030209 endocrinology & metabolism, Type 2 diabetes, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Renal Insufficiency, Chronic, education, Intensive care medicine, Contraindication, [SDV.IB] Life Sciences [q-bio]/Bioengineering, education.field_of_study, business.industry, Diabetes, General Medicine, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Natural history, Diabetes Mellitus, Type 2, Heart failure, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, SGLT2 inhibitors, chronic kidney disease, coronary artery disease, Kidney disease
Abstract: Heart failure (HF) and chronic kidney disease (CKD) are often associated in type 2 diabetes (T2D), aggravate each other and exert synergistic effects to increase the risk of cardiac and renal events. The risks of renal worsening in HF patients and HF in CKD patients need to be evaluated to tailor preventive therapy. The recent CV and renal trials enriched our knowledge about the natural history of HF and CKD in T2D and provided evidence for the benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in HF and renal decline prevention. SGLT-2is are the best choice in patients with HFrEF to improve CV prognosis and HF-related outcomes and also to prevent kidney-related outcomes, and in CKD patients to slow down renal failure and also reduce hospitalization for HF and CV death. In both situations the number of patients to treat in order to prevent such events in one patient is lower than in the general T2D population at high CV risk. GLP1-receptor agonists could be an alternative in a patient who is intolerant or has a contraindication to SGLT-2is. A tight collaboration between diabetologists, nephrologists and cardiologists should be encouraged for a holistic and effective strategy to reduce the burden of cardio-renal-metabolic interaction.
Published: 2021

20. Protocol for a randomized pilot study (FIRST STEPS): implementation of the Incredible Years-ASLD® program in Spanish children with autism and preterm children with communication and/or socialization difficulties

Author: Fátima Valencia, Inmaculada Navas, Maria Elias, Laia Villalta, Marina Romero-González, Almudena Ramírez, Alexandra Garriz, Elena Urbiola, [Valencia,F, Urbiola,E, Garriz,A] Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Romero-González,M, Navas,I, Ramírez,A] Maternity Hospital, Hospital Regional Universitario de Málaga, Málaga, Spain. [Romero-González,M, Ramírez,A] Department of Brain Health, CIMES, Faculty of Medicine-IBIMA, UMA, Málaga, Spain. [Elías,M, Villalta,L] Department of Psychiatry and Psychology, Hospital Sant Joan de Déu de Barcelona, L’Hospitalet de Llobregat, Spain. [Villalta,L] Children and Adolescent Mental Health Research Group, Research Institute Sant Joan de Déu, Esplugues de Llobregat, Spain., and This paper reports on independent research financially supported by the Alicia Koplowitz Foundation.
Subjects: Parents, Medicine (General), Information Science::Information Science::Communication [Medical Subject Headings], Autism Spectrum Disorder, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Family::Family Relations::Parenting [Medical Subject Headings], Psychological intervention, Medicine (miscellaneous), Pilot Projects, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Study Protocol, 0302 clinical medicine, Randomized controlled trial, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Multicenter Studies as Topic [Medical Subject Headings], law, Autistic children, Medicine, Multicenter Studies as Topic, Pharmacology (medical), Child, Child development, Randomized Controlled Trials as Topic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic [Medical Subject Headings], Parenting, Communication, 05 social sciences, Pilot, Autism spectrum disorder, Child, Preschool, Premature Birth, 050104 developmental & child psychology, Clinical psychology, medicine.medical_specialty, Parenting intervention, Pilotos, Psychiatry and Psychology::Mental Disorders::Mental Disorders Diagnosed in Childhood::Child Development Disorders, Pervasive::Autistic Disorder [Medical Subject Headings], ASD, Desarrollo infantil, 03 medical and health sciences, R5-920, Complex intervention, Intervention (counseling), Humans, 0501 psychology and cognitive sciences, Persons::Persons::Age Groups::Child [Medical Subject Headings], Autistic Disorder, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Pilot Projects [Medical Subject Headings], Infants autistes, business.industry, Public health, Trastorno del espectro del autismo, Socialization, medicine.disease, Mental health, Responsabilidad parental, Desenvolupament infantil, Preterm children, Spain, randomized controlled trial, Autism, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Socialization [Medical Subject Headings], Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Obstetric Labor Complications::Obstetric Labor, Premature::Premature Birth [Medical Subject Headings], business, Persons::Persons::Parents [Medical Subject Headings], Persons::Persons::Age Groups::Child::Child, Preschool [Medical Subject Headings], 030217 neurology & neurosurgery, Nacimiento prematuro
Abstract: Abstract Having access to parenting interventions in the early years is key to improve the developmental outcomes of children with neurodevelopmental problems. The Incredible Years® (IY) Parent Program is a group intervention that has demonstrated efficacy in terms of reducing stress in parents, as well as improving behavioral, emotional, and social outcomes in children. The program has been recently adapted for families of children with autism or language delays (IY-ASLD®). This intervention has not yet been implemented in the Spanish Public Health System, where there is a scarcity of evidence-based interventions being offered to families with young children presenting neurodevelopmental problems. The main aims of this study are to determine the feasibility of implementing the IY-ASLD® program within Spanish Child Mental Health Services and to examine parents’ acceptability and satisfaction with the intervention. As a secondary objective, we aim to evaluate its preliminary effectiveness in terms of reducing parental stress and behavioral difficulties in their children. The FIRST STEPS study is a multicenter, pilot randomized controlled trial comparing the IY-ASLD® program with a treatment-as-usual (TAU) condition. Approximately 70 families of children with autism spectrum disorder (ASD) and preterm children with communication and/or socialization difficulties (aged 2–5 years) will be recruited. Families will be assessed prior to randomization and after the intervention. Due to the COVID-19 pandemic, the intervention will consist of 22 weekly online sessions (approximately 6 months). The FIRST STEPS pilot trial will demonstrate the feasibility and acceptability of reliably implementing the IY-ASLD® program within the Spanish Public Health System. The results of this study could represent the first step to inform policymakers in Spain when designing evidence-based healthcare pathways for families of children presenting ASD symptoms or neurodevelopmental difficulties at early stages. Trial registration ClinicalTrials.gov NCT04358484. Registered on 04 April 2020
Published: 2021

21. Family, social and cultural determinants of long-lasting insecticidal net (LLIN) use in Madagascar: secondary analysis of three qualitative studies focused on children aged 5–15 years

Author: Andry Andrianasolo, Ammy Fiadanana Njatosoa, Chiarella Mattern, Bakoly Rahaivondrafahitra, Christophe Rogier, Mauricette Andriamananjara, Aina Harimanana, Thomas Kesteman, Dolorès Pourette, Elliot Rakotomanana, Jocelyn Razafindrakoto, Emma Raboanary, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Unité de Recherche sur le Paludisme [Antananarivo, Madagascar], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Oxford University Clinical Research Unit [Hanoi] (OUCRU), Population Services International Madagascar [Antananarivo], Population Services International [Washington], Ministère de la Santé Publique [Antananarivo, Madagascar], U.S. President’s Malaria Initiative [Antananarivo] (PMI), U.S. President's Malaria Initiative [Atlanta, GA,], Institut international des sciences sociales [Antananarivo] (IISS), Primum Vitare, The publication process of this paper has been funded by USAID through the Research, Innovation, Surveillance and Evaluation (RISE) programme., Institut de Recherche pour le Développement (IRD), and Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité)
Subjects: Male, medicine.medical_specialty, Mosquito Control, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, LLIN use, 030231 tropical medicine, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Ethnic group, Qualitative property, [SHS]Humanities and Social Sciences, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Environmental health, parasitic diseases, medicine, Madagascar, Humans, lcsh:RC109-216, 030212 general & internal medicine, Children over five, Insecticide-Treated Bednets, Child, Disease burden, Research, Public health, [SHS.ANTHRO-SE]Humanities and Social Sciences/Social Anthropology and ethnology, medicine.disease, 3. Good health, Malaria, Infectious Diseases, Geography, Child, Preschool, Mosquito net, Female, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Thematic analysis, Sociocultural factors, Qualitative research
Abstract: BackgroundAlthough it is accepted that long-lasting insecticidal net (LLIN) use is an effective means to prevent malaria, children aged 5 to 15 years do not appear to be sufficiently protected in Madagascar; the malaria prevalence is highest in this age group. The purpose of this research is to summarize recent qualitative studies describing LLIN use among the Malagasy people with a focus on children aged 5–15 years.MethodsQualitative data from three studies on malaria conducted between 2012 and 2016 in 10 districts of Madagascar were analysed. These studies cover all malaria epidemiological profiles and 10 of the 18 existing ethnic groups in Madagascar. A thematic analysis was conducted on the collected data from semi-structured interviews, direct observation data, and informal interviews.ResultsA total of 192 semi-structured interviews were conducted. LLINs are generally perceived positively because they protect the health and well-being of users. However, regional representations of mosquito nets may contribute to LLIN lower use by children over 5 years of age including the association between married status and LLIN use, which leads to the refusal of unmarried young men to sleep under LLINs; the custom of covering the dead with a mosquito net, which leads to fear of LLIN use; and taboos governing sleeping spaces for siblings of opposite sexes, which leads to LLIN shortages in households. Children under 5 years of age are known to be the most vulnerable age group for acquiring malaria and, therefore, are prioritized for LLIN use when there are limited supplies in households. In contrast, children over 5 years of age, who are perceived to be at less risk for malaria, often sleep without LLINs.ConclusionsPerceptions, social practices and regional beliefs regarding LLINs and vulnerability to malaria contribute to the nonuse of LLINs among children over 5 years of age in Madagascar. Modifying LLIN policies to account for these factors may increase LLIN use in this age group and reduce disease burden.
Published: 2021

22. Association between food insecurity and depression among older adults from low- and middle-income countries

Author: Lee Smith, Yvonne Barnett, Igor Grabovac, Hans Oh, Louis Jacob, Nicola Veronese, Lin Yang, Ai Koyanagi, Guillermo F. López-Sánchez, Jae Il Shin, Pinar Soysal, Daragh T. McDermott, SOYSAL, PINAR, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institute on Aging, NIA: 08-CN-0020, OGHA 04034785, R01-AG034479, R21-AG034263, Y1-AG-1005, YA1323 Faculty of Science, Agriculture and Engineering, Newcastle University, SAgE, This paper uses data from WHO's Study on global AGEing and adult health (SAGE). SAGE is supported by the US National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323?08-CN-0020, Y1-AG-1005?01 and through research grants R01-AG034479 and R21-AG034263., Smith, L., Il Shin, J., McDermott, D., Jacob, L., Barnett, Y., López-Sánchez, G.F., Veronese, N., Yang, L., Soysal, P., Oh, H., Grabovac, I., and Koyanagi, A.
Subjects: Male, China, Psychological intervention, India, Logistic regression, Ghana, Odds, Russia, 03 medical and health sciences, South Africa, 0302 clinical medicine, older adults, Environmental health, food insecurity, Prevalence, Medicine, Humans, low- and middle-income countries, Association (psychology), Developing Countries, Mexico, Depression (differential diagnoses), Aged, 2. Zero hunger, business.industry, 1. No poverty, Middle Aged, Mental health, Confidence interval, 3. Good health, 030227 psychiatry, Food insecurity, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, low- and middle-income countrie, depression, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Smith L., Il Shin J., McDermott D., Jacob L., Barnett Y., López-Sánchez G. F. , Veronese N., Yang L., Soysal P., Oh H., et al., -Association between food insecurity and depression among older adults from low- and middle-income countries.-, Depression and anxiety, 2021, 030217 neurology & neurosurgery
Abstract: Background:\ud \ud To examine the association between self‐reported food insecurity and depression in 34,129 individuals aged ≥50 years from six low‐ and middle‐income countries (LMICs) (China, Ghana, India, Mexico, Russia, and South Africa).\ud \ud Methods:\ud \ud Cross‐sectional, community‐based, nationally representative data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. Self‐reported past 12‐month food insecurity was assessed with two questions on frequency of eating less and hunger due to lack of food. Questions based on the World Mental Health Survey version of the Composite International Diagnostic Interview were used for the endorsement of past 12‐month DSM‐IV depression. Multivariable logistic regression analysis and meta‐analysis were conducted to assess associations.\ud \ud Results:\ud \ud In total, 34,129 individuals aged ≥50 years [mean (SD) age, 62.4 (16.0) years; 52.1% females] were included in the analysis. Overall, the prevalence of moderate and severe food insecurity was 6.7% and 5.1%, respectively, while the prevalence of depression was 6.0%. Meta‐analyses based on countrywise estimates showed that overall, moderate food insecurity (vs. no food insecurity) is associated with a nonsignificant 1.69 (95% confidence interval [CI] = 0.82–3.48) times higher odds for depression, while severe food insecurity is significantly associated with 2.43 (95% CI = 1.65–3.57) times higher odds for depression.\ud \ud Conclusions:\ud \ud In this large representative sample of older adults from six LMICs, those with severe food insecurity were over two times more likely to suffer from depression (compared with no food insecurity). Utilizing lay health counselors and psychological interventions may be effective mechanisms to reduce depression among food‐insecure populations. Interventions to address food insecurity (e.g., supplemental nutrition programs) may reduce depression at the population level but future longitudinal studies are warranted.
Published: 2021

23. A review of current treatment strategies for infective endocarditis

Author: Ines Lakbar, David Luque Paz, Pierre Tattevin, CHU Pontchaillou [Rennes], CHU Toulouse [Toulouse], ARN régulateurs bactériens et médecine (BRM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This paper was not funded., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Microbiology (medical), Oral treatment, medicine.medical_specialty, Prosthesis-Related Infections, Time Factors, empirical treatment, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibiotics, Heart Valve Diseases, review, Microbiology, antibiotics, 03 medical and health sciences, 0302 clinical medicine, enterococci, Virology, medicine, Endocarditis, Animals, Humans, 030212 general & internal medicine, Intensive care medicine, staphylococci, treatment, business.industry, HACEK, oral treatment, Endocarditis, Bacterial, medicine.disease, 3. Good health, Anti-Bacterial Agents, Empirical treatment, Infectious Diseases, streptococci, Infective endocarditis, Heart Valve Prosthesis, Treatment strategy, business
Abstract: International audience; Introduction Infective endocarditis is one of the most difficult-to-treat infectious diseases. Areas covered We restricted this review to the anti-infective treatment of the main bacteria responsible for infective endocarditis, i.e. staphylococci, streptococci, enterococci, and Gram-negative bacilli, including HACEK. Specific topics of major interest in treatment strategy are covered as well, including empirical treatment, oral switch, and treatment duration. We searched in the MEDLINE database to identify relevant studies, trials, reviews, or meta-analyses until May 2020. Expert opinion The use of aminoglycosides for the treatment of endocarditis has been dramatically reduced over the last 20 years. It should be administered once daily, and no longer than 2 weeks. For staphylococcal endocarditis, recent data reinforced the role of anti-staphylococcal penicillins, for methicillin-susceptible isolates (alternative, cefazolin), and vancomycin for methicillin-resistant isolates (alternative, daptomycin). For staphylococcal prosthetic-valve endocarditis, these treatments will be reinforced by the addition of gentamicin during the first 2 weeks, and rifampin throughout the whole treatment duration, i.e. 6 weeks. The optimal duration of antibacterial treatment is 4 weeks for most native valve endocarditis, and 6 weeks for prosthetic-valve endocarditis. The oral switch is safe in patients stabilized after the initial intravenous course.
Published: 2021

24. Impact of Geographic Region on the COMMANDER-HF Trial

Author: João Pedro Ferreira, John G.F. Cleland, Carolyn S.P. Lam, Dirk J. van Veldhuisen, William M. Byra, David A. La Police, Stefan D. Anker, Mandeep R. Mehra, Céline Leroy, Valerie Eschwege, Marie Toussaint-Hacquard, Patrick Rossignol, Barry Greenberg, Faiez Zannad, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Glasgow, National Heart Centre Singapore (NHCS), Duke-National University of Singapore Graduate Medical School, University Medical Center Groningen [Groningen] (UMCG), Janssen Research & Development, Berlin-Brandenburg Center for Regenerative Therapies, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Brigham and Women's Hospital [Boston], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of California [San Diego] (UC San Diego), University of California, Funding Support and Author Disclosures The COMMANDER-HF trial was supported by Janssen Research and Development. Drs. Ferreira, Rossignol, and Zannad are supported by Reseau Hospitalo-Universitaire Fight-HF, a public grant overseen by the French National Research Agency as part of the second 'Investissements d’Avenir' program (reference: ANR-15-RHUS-0004) and by the French Investments for the Future Program project 'Lorraine Université d’Excellence' (reference: ANR-15-IDEX-04-LUE). The biobanking for rivaroxaban dosages is managed by Biological Resource Center Lorrain BB-0033-00035. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), and Cardiovascular Centre (CVC)
Subjects: Latin Americans, [SDV]Life Sciences [q-bio], Psychological intervention, heart failure, 030204 cardiovascular system & hematology, Lower risk, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Stroke, rivaroxaban, Clinical Trials as Topic, Rivaroxaban, business.industry, Patient Selection, Stroke Volume, medicine.disease, 3. Good health, Latin America, [SDU]Sciences of the Universe [physics], Cardiology and Cardiovascular Medicine, business, Regional differences, Demography, medicine.drug, regional differences
Abstract: OBJECTIVES This study sought to compare patient characteristics, outcomes, and treatment effects among regions in the COMMANDER-HF trial.BACKGROUND Globalization of cardiovascular trials increases generalizability. However, regional differences may also introduce heterogeneity in results.METHODS Incidence rates and interactions with treatment were recorded in pre-specified regions: Eastern Europe, Western Europe and South Africa, North America, Asia-Pacific, and Latin America.RESULTS Most patients (n = 3,224; 64.2%) were from Eastern Europe; 458 (9.1%) were from Western Europe and South Africa; 149 (3.0%) were from North America; 733 (14.6%) were from Asia-Pacific; and 458 (9.1%) were from Latin America. Compared with patients from Eastern Europe, patients from Western Europe and South Africa, North America, and Asia-Pacific were older and more likely to have coronary interventions and cardiac devices. Patients from Eastern Europe had the lowest event rates. For the primary outcome of myocardial infarction (MI), stroke, or all-cause death, event rates (100/year) were 11.6 in Eastern Europe (10.8 to 12.5); 19.5 (16.5 to 23.0) in Western Europe and South Africa; 14.2 (10.5 to 19.2) in North America; 17.7 (15.4 to 20.3) in Asia-Pacific; and 18.6 (15.6 to 22.1) in Latin America. There was a lower incidence of bleeding in Eastern Europe. Blood concentrations of rivaroxaban (Xarelto, Titusville, New Jersey) at 4 weeks were undetectable in 21% patients from Eastern Europe (n = 128) compared to 5% in other regions (n = 42). There was no evidence of treatment-by-region heterogeneity for the primary outcome (interaction(p) = 0.14), but a favorable effect on the secondary outcome of MI, stroke, or cardiovascular death was observed in Western Europe and South Africa, North America, and Latin America but not in Eastern Europe and Asia-Pacific (interaction(p) = 0.017).CONCLUSIONS In the COMMANDER-HF study, patients from Eastern Europe had a lower risk profile and fewer cardiovascular and bleeding events, possibly related to lower treatment adherence. Those differences might have influenced the effect of rivaroxaban therapy. (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure [COMMANDER HF]; NCT01877915) (c) 2021 by the American College of Cardiology Foundation.
Published: 2021

25. Prospective Cohort Study of Infective Endocarditis in People Who Inject Drugs

Author: David R. Murdoch, Nuria Fernández-Hidalgo, Eugene Athan, Juan M. Pericàs, José M. Miró, Tomáš Freiberger, Pierre Tattevin, Emanuele Durante-Mangoni, Francisco Nacinovich, Marta Hernández-Meneses, Vivian H. Chu, Zeina A. Kanafani, Jacob Strahilevitz, Jaume Llopis, Cristiane da Cruz Lamas, Margaret M. Hannan, University of Barcelona, Deakin University [Burwood], University of Otago [Dunedin, Nouvelle-Zélande], American University of Beirut [Beyrouth] (AUB), Masaryk University [Brno] (MUNI), Hadassah Hebrew University Medical Center [Jerusalem], Universitat Autònoma de Barcelona (UAB), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Duke University [Durham], This study was supported by the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (# E26/202.782/2015 to Dr. Lamas), Red Española de Investigación en Patología Infecciosa (V-2003-REDC14A-O), and Fondo de Investigaciones Sanitarias de la Seguridad Social (FIS 00-0475) (Dr. Miro). Dr. Miro has received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, for 2017 to 2021. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., Pericas, J. M., Llopis, J., Athan, E., Hernandez-Meneses, M., Hannan, M. M., Murdoch, D. R., Kanafani, Z., Freiberger, T., Strahilevitz, J., Fernandez-Hidalgo, N., Lamas, C., Durante-Mangoni, E., Tattevin, P., Nacinovich, F., Chu, V. H., Miro, J. M., and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Male, medicine.medical_specialty, Staphylococcus aureus, cardiac surgery, [SDV]Life Sciences [q-bio], infective endocarditi, Human immunodeficiency virus (HIV), 030204 cardiovascular system & hematology, Logistic regression, medicine.disease_cause, Global Health, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Substance Abuse, Intravenous, Aged, Prosthetic valve, people who inject drug, Endocarditis, business.industry, Public health, Incidence, HIV, Middle Aged, medicine.disease, 3. Good health, Cardiac surgery, people who inject drugs, Infective endocarditis, opioid crisis, Female, infective endocarditis, opioid crisi, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: International audience; Background - Infective endocarditis (IE) in people who inject drugs (PWID) is an emergent public health problem. Objectives - The purpose of this study was to investigate IE in PWID and compare it with IE in non-PWID patients. Methods - Two prospective cohort studies (ICE-PCS and ICE-Plus databases, encompassing 8,112 IE episodes from 2000 to 2006 and 2008 to 2012, with 64 and 34 sites and 28 and 18 countries, respectively). Outcomes were compared between PWID and non-PWID patients with IE. Logistic regression analyses were performed to investigate risk factors for 6-month mortality and relapses amongst PWID. Results - A total of 7,616 patients (591 PWID and 7,025 non-PWID) were included. PWID patients were significantly younger (median 37.0 years [interquartile range: 29.5 to 44.2 years] vs. 63.3 years [interquartile range: 49.3 to 74.0 years]; p
Published: 2021

26. Tracking Animal Reservoirs of Pathogenic Leptospira: The Right Test for the Right Claim

Author: Koussay Dellagi, Patrick Mavingui, Pablo Tortosa, Yann Gomard, Steve Michael Goodman, Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), Direction Internationale de l'Institut Pasteur, Institut Pasteur [Paris] (IP), Association Vahatra [Antananarivo, Madagascar], Field Museum of Natural History [Chicago, USA], The sampling of Mormopterus acetabulosus on Mauritius was supported by a grant from European Research Development Fund (ERDF) 'Pathogènes associés à la Faune Sauvage Océan Indien' #31189. Original serological data presented in this paper were obtained under a grant from ERDF known as InterregV ECOSPIR 'Eco-épidemiologie des leptospires endémiques de l’Océan Indien: des bactéries à risque pour les populations humaines?' (number RE6875)., Tortosa, Pablo, Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), and Institut Pasteur [Paris]
Subjects: Leptospira, 030231 tropical medicine, Zoology, Context (language use), Biology, Article, Microbiology, Serology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Direct agglutination test, medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, One Health, 030304 developmental biology, 0303 health sciences, animal reservoir, MAT, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Immunology and Microbiology, 030306 microbiology, Zoonosis, Public Health, Environmental and Occupational Health, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Gold standard (test), medicine.disease, biology.organism_classification, Leptospirosis, 3. Good health, Chronic infection, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: Leptospirosis, caused by a pathogenic Leptospira bacteria, is the most prevalent zoonosis worldwide and in this context has been extensively investigated through a One Health framework. Diagnosis of human leptospirosis includes molecular and serological tools, with serological Microscopic Agglutination Test (MAT) still being considered as a gold standard. Mammals considered as biological reservoirs include species or populations that are able to maintain chronic infection and shed the bacteria via their urine in the environment. Leptospira bacteria are often investigated using the same diagnosis tool, serological MAT. However, MAT testing of putative animal reservoirs can lead to mis-interpretations as it can signal previous infection and not necessarily bring in robust information regarding the capacity of such sero-positive animals to maintain chronic infection. We use previously published data and present new results on introduced and endemic small mammals to show that MAT should not be used for the identification of reservoirs. By contrast, serological data are informative on the level of exposure of animals occupying a specific environment. Finally, we present a sequential methodology to investigate human leptospirosis in a One Health framework that associates molecular detection in humans and animals, together with MAT of human samples using Leptospira isolates obtained from reservoir animals occurring in the same environment.
Published: 2021

27. Association between food insecurity and fall-related injury among adults aged ≥65 years in low- and middle-income countries: The role of mental health conditions

Author: Jae Il Shin, Igor Grabovac, Louis Jacob, Lee Smith, Guillermo F. López-Sánchez, Yvonne Barnett, Pinar Soysal, Hans Oh, Nicola Veronese, Ai Koyanagi, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, Dr. Antoni Pujadas, This paper uses data from WHO's Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785 , YA1323-08-CN-0020 , Y1-AG-1005-01 and through research grants R01-AG034479 and R21-AG034263 ., SOYSAL, PINAR, Smith, L., Shin, J.I., López-Sánchez, G.F., Veronese, N., Soysal, P., Oh, H., Grabovac, I., Barnett, Y., Jacob, L., and Koyanagi, A.
Subjects: Male, Aging, Health (social science), Low- and middle-income countries, Psychological intervention, Logistic regression, Food Supply, Odds, 03 medical and health sciences, Older adults, 0302 clinical medicine, Fall-related injury, Environmental health, Prevalence, Humans, Medicine, 030212 general & internal medicine, Developing Countries, Depression (differential diagnoses), Aged, 2. Zero hunger, 030214 geriatrics, Food insecurity, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Confounding, Cognition, MESH: Accidental Falls, Aged, Cross-Sectional Studies, Developing Countries, Female, Food Insecurity, Food Supply, Humans, Male, Mental Health, Prevalence, Mental health, 3. Good health, Cross-Sectional Studies, Mental Health, Low- and middle-income countrie, Anxiety, Accidental Falls, Female, Geriatrics and Gerontology, medicine.symptom, business, Gerontology, The role of mental health conditions.-, Archives of gerontology and geriatrics, cilt.96, ss.104438, 2021 [Smith L., Shin J. I. , López-Sánchez G. F. , Veronese N., Soysal P., Oh H., Grabovac I., Barnett Y., Jacob L., Koyanagi A., -Association between food insecurity and fall-related injury among adults aged ≥65 years in low- and middle-income countries]
Abstract: Purpose:\ud \ud We investigated the association between food insecurity and fall-related injury among older adults from six low- and middle-income countries (LMICs), and the extent to which this association is mediated by mental health.\ud \ud Methods:\ud \ud Cross-sectional, community-based, nationally representative data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. Past 12-month food insecurity was assessed with two questions on frequency of eating less and hunger due to lack of food. Fall-related injury referred to those that occurred in the past 12 months. Multivariable logistic regression analysis and mediation analysis were conducted to assess associations.\ud \ud Results:\ud \ud Data on 14,585 adults aged ≥65 years [mean (SD) age 72.5 (11.5) years; 54.9% females] were analyzed. After adjustment for potential confounders, severe food insecurity (versus no food insecurity) was associated with 1.95 (95%CI = 1.11–3.41) times higher odds for fall-related injury. Moderate food insecurity was not significantly associated with fall-related injury (OR = 1.34; 95%CI = 0.81–2.25). The mediation analysis showed that 37.3%, 21.8%, 17.7%, and 14.0% of the association between severe food insecurity and fall-related injury was explained by anxiety, sleep problems, depression, and cognition, respectively.\ud \ud Conclusion:\ud \ud Severe food insecurity was associated with higher odds for injurious falls among older adults in LMICs, and a large proportion of this association may be explained by mental health complications. Interventions to improve mental health among those who are food insecure and a strong focus on societal and government efforts to reduce food insecurity may contribute to a decrease in injurious falls.
Published: 2021

28. A high-resolution downscaled CMIP5 projections dataset of essential surface climate variables over the globe coherent with theERA5 reanalysis for climate change impact assessments

Author: Thomas Noël, Mathieu Vrac, Guillaume Levavasseur, Dimitri Defrance, Harilaos Loukos, the Climate Data Factory, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Extrèmes : Statistiques, Impacts et Régionalisation (ESTIMR), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Pierre-Simon-Laplace (IPSL (FR_636)), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Fondation de l'École Polytechnique, FX Centre National de la Recherche Scientifique, CNRS, The activities described in this paper were funded by the Copernicus Climate Change Service. ECMWF implements the Copernicus Climate Change Service and the Copernicus Atmosphere Monitoring Service on behalf of the European Commission. To process the data, this study benefited from the IPSL mesocenter ESPRI facility that is supported by CNRS , SU , and Ecole Polytechnique partly funded by IS-ENES3 project. We also thank the Institut Pierre Simon Laplace for assistance with the Synda software and the Deutsches Klimarechenzentrum for the Quality Assurance tool., The Climate Data Factory, Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Science (General), [SDV]Life Sciences [q-bio], Computer applications to medicine. Medical informatics, R858-859.7, Climate change, Wind speed, Q1-390, 03 medical and health sciences, 0302 clinical medicine, Downscaling, CMIP5, Impact modeling, Precipitation, Adaptation, Data Article, 030304 developmental biology, Projections, 0303 health sciences, Multidisciplinary, Impact assessment, 13. Climate action, Greenhouse gas, Climatology, Environmental science, ERA5, Climate model, High-resolution, 030217 neurology & neurosurgery, Quantile
Abstract: International audience; A high-resolution climate projections dataset is obtained by statistically downscaling climate projections from the CMIP5 experiment using the ERA5 reanalysis from the Copernicus Climate Change Service. This global dataset has a spatial resolution of 0.25°x 0.25°, comprises 21 climate models and includes 5 surface daily variables at monthly resolution: air temperature (mean, minimum, and maximum), precipitation, and mean near-surface wind speed. Two greenhouse gas emissions scenarios are available: one with mitigation policy (RCP4.5) and one without mitigation (RCP8.5). The downscaling method is a Quantile Mapping method (QM) called the Cumulative Distribution Function transform (CDF-t) method that was first used for wind values and is now referenced in dozens of peer-reviewed publications. The data processing includes quality control of metadata according to the climate modeling community standards and value checking for outlier detection.
Published: 2021

29. Dichotomous metabolic networks govern human ILC2 proliferation and function

Author: Carys A. Croft, James P. Di Santo, Antonia Cama, Solenne Marie, Carmen Buchrieser, Davide Topazio, Olimpia Musumeci, Valerie Dardalhon, Laura Surace, Naomi Taylor, Jean-Marc Doisne, Vincent Guillemot, Natalia Petrosemoli, Pedro Escoll, Ido Amit, Anna Thaller, Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Otolaryngology, Ospedale 'Giuseppe Mazzini' di Teramo, Department of Maxillofacial and Otolaryngology, Hospital 'Floraspe Renzetti', Department of Immunology [Rehovot, Israël], Weizmann Institute of Science [Rehovot, Israël], Department of Clinical and Experimental Medicine [Messina, Italy], University of Messina, The Innate Immunity Unit is supported by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur, the Agence National pour le Recherche (ANR) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (695467, ILC_REACTIVITY). A.T. is supported by European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 765104. C.B.’s group was supported by the Fondation pour la Recherche Médicale (FRM) grant no. EQU201903007847 and the grant no. ANR-10-LABX-62-IBEID. L.S. was supported by an SNSF-Early PostDoc. Mobility fellowship and a Marie Curie grant (H2020- MSCA-IF-2017)., We thank all the members of the Innate Immunity Unit for helpful discussions, the Centre de Recherche Translationnelle and the logistic department of Institut Pasteur. We thank the CB-UTechS platform for cytometry support and the Imagopole-CiTech (part of France-BioImaging supported by ANR grant no. ANR-10-INSB-04-01, Conseil de la Region Ile-de-France, FRM) for technical support., The study was conceptualized by L.S. and J.P.D. Experiments were coordinated by L.S. FACS and subsequent analyses were performed by L.S., C.A.C., A.T., J.-M.D. and S.M. Confocal microscopy analysis was performed by P.E., C.B. and L.S. Bioinformatic analyses were performed by N.P. and V.G. RNA-seq experiments were conducted by I.A. O.M., V.D., N.T., D.T. and A.C. provided resources. L.S. and J.P.D. wrote the paper. Funding was acquired by L.S. and J.P.D., and the study was supervised by J.P.D., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 695467,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ILC_REACTIVITY(2016), European Project: 765104,MATURE-NK, European Project: 796004,BIF-SCV, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED BioSPC), Université Sorbonne Paris Cité (USPC)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Hospital 'Giuseppe Mazzini'
Subjects: Letter, Mitochondrial Diseases, Lymphocyte Activation, 0302 clinical medicine, Immunology and Allergy, Glycolysis, Receptor, Tissue homeostasis, Cells, Cultured, 0303 health sciences, MESH: Cytokines, Innate lymphoid cell, MESH: Energy Metabolism, MESH: Arginine, MESH: Mitochondrial Diseases, MESH: Case-Control Studies, Cell biology, Mitochondria, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, MESH: Immunity, Innate, MESH: Cells, Cultured, MESH: Interleukin-33, MESH: Mitochondria, Immunology, Innate lymphoid cells, Oxidative phosphorylation, Biology, MESH: Phenotype, Arginine, 03 medical and health sciences, Th2 Cells, MESH: Th2 Cells, MESH: Cell Proliferation, Humans, MESH: Lymphocyte Activation, PI3K/AKT/mTOR pathway, 030304 developmental biology, Cell Proliferation, MESH: Humans, Interleukins, Metabolism, Interleukin-33, Immunity, Innate, Metabolic pathway, Case-Control Studies, Energy Metabolism, Amino Acids, Branched-Chain, 030215 immunology, MESH: Amino Acids, Branched-Chain
Abstract: Group 2 innate lymphoid cells (ILC2s) represent innate homologs of type 2 helper T cells (TH2) that participate in immune defense and tissue homeostasis through production of type 2 cytokines. While T lymphocytes metabolically adapt to microenvironmental changes, knowledge of human ILC2 metabolism is limited, and its key regulators are unknown. Here, we show that circulating ‘naive’ ILC2s have an unexpected metabolic profile with a higher level of oxidative phosphorylation (OXPHOS) than natural killer (NK) cells. Accordingly, ILC2s are severely reduced in individuals with mitochondrial disease (MD) and impaired OXPHOS. Metabolomic and nutrient receptor analysis revealed ILC2 uptake of amino acids to sustain OXPHOS at steady state. Following activation with interleukin-33 (IL-33), ILC2s became highly proliferative, relying on glycolysis and mammalian target of rapamycin (mTOR) to produce IL-13 while continuing to fuel OXPHOS with amino acids to maintain cellular fitness and proliferation. Our results suggest that proliferation and function are metabolically uncoupled in human ILC2s, offering new strategies to target ILC2s in disease settings., ILC2 metabolism has been largely unexplored. Di Santo and colleagues examine metabolic profiles from naive and cytokine-activated ILC2s and find that IL-33-triggered ILC2s rely on distinct metabolic pathways to sustain proliferation and function.
Published: 2021
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30. Relationship between Physical Activity, Oxidative Stress, and Total Plasma Antioxidant Capacity in Spanish Children from the GENOBOX Study

Author: María D. Mesa, Rosaura Leis, Augusto Anguita-Ruiz, Azahara I. Rupérez, Concepción M. Aguilera, Luis A. Moreno, Angel Gil, Francisco Jesus Llorente-Cantarero, Francisco Javier Aguilar-Gómez, Gloria Bueno, Rocío Vázquez-Cobela, Mercedes Gil-Campos, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, [Llorente-Cantarero,FJ] Department of Specific Didactics, Faculty of Education, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Llorente-Cantarero,FJ, Leis,R, Bueno,G, Anguita-Ruiz,A, Vázquez-Cobela,R, Moreno,LA, Gil,A, Aguilera,CM, Gil-Campos,M] CIBEROBN, (Physiopathology of Obesity and Nutrition) Institute of Health Carlos III (ISCIII), Madrid, Spain. [Aguilar-Gomez FJ, Gil-Campos,M] Metabolism and Investigation Unit, Reina Sofía University Hospital, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Leis,R, Vázquez-Cobela,R] Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Pediatric Department, University of Santiago de Compostela, Clinic University Hospital of Santiago, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain. [Bueno,G] Pediatric Endocrinology Unit, Clinic University Hospital Lozano Blesa, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain. [Bueno,G, Rupérez,AI, Moreno,LA] GENUD Research Group, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria (IIS) Aragón, University of Zaragoza, Zaragoza, Spain. [Anguita-Ruiz,A, Mesa,MA, Aguilera,CM] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Armilla, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Instituto de Investigación Biosanitaria ibs Granada, 18014 Granada, Spain., This research was funded by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/02042, PI11/02059, PI11/01425, and PI16/00871, PI16/01301, PI16/01205) and RETIC (Redes temáticas de investigación cooperativa) (Red SAMID RD12/0026/0015). The authors also acknowledge Instituto de Salud Carlos III for personal funding of A.A.R: Contratos i-PFIS: doctorados IIS-empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048). Á.G. was funded by the Research Plan of the Vice-Rectorate of Research and Transfer of the University of Granada, Spain This paper will be included in F.J.A. doctorate, under the 'Biomedicine Program' at the University of Córdoba, Spain.
Subjects: Antioxidant, Isoprostane, 8-hydroxy-2′-deoxyguanosine, Physiology, medicine.medical_treatment, Clinical Biochemistry, Physical fitness, physical activity, medicine.disease_cause, Biochemistry, Acelerometría, chemistry.chemical_compound, 0302 clinical medicine, Accelerometry, oxidative stress, 030212 general & internal medicine, Isoprostane F2α, Plasma total antioxidant capacity, Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings], Health Care::Health Care Economics and Organizations::Organizations::International Agencies::United Nations::World Health Organization [Medical Subject Headings], Total plasma, plasma total antioxidant capacity, Estrés oxidativo, Ejercicio físico, isoprostane F2, Antioxidant capacity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Titrimetry::Colorimetry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniques::Enzyme-Linked Immunosorbent Assay [Medical Subject Headings], 8-Hidroxi-2'-Desoxicoguanosina, medicine.medical_specialty, Physical activity, Article, 03 medical and health sciences, Internal medicine, isoprostane F2α, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Antioxidants [Medical Subject Headings], medicine, accelerometry, Pysical activity, Molecular Biology, Redox homeostasis, business.industry, lcsh:RM1-950, 030229 sport sciences, Cell Biology, 8-hydroxy-20-deoxyguanosine, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Physical Fitness [Medical Subject Headings], lcsh:Therapeutics. Pharmacology, chemistry, Oxidative stress, business
Abstract: The World Health Organization has recommended performing at least 60 min a day of moderate-to-vigorous physical activity (MVPA) and reducing sedentarism in children and adolescents to offer significant health benefits and mitigate health risks. Physical fitness and sports practice seem to improve oxidative stress (OS) status during childhood. However, to our knowledge, there are no data regarding the influence of objectively-measured physical activity (PA) and sedentarism on OS status in children and adolescents. The present study aimed to evaluate the influence of moderate and vigorous PA and sedentarism on OS and plasma total antioxidant capacity (TAC) in a selected Spanish population of 216 children and adolescents from the GENOBOX study. PA (light, moderate, and vigorous) and sedentarism (i.e., sedentary time (ST)) were measured by accelerometry. A Physical Activity-Sedentarism Score (PASS) was developed integrating moderate and vigorous PA and ST levels. Urinary 8-hydroxy-20-deoxyguanosine (8-OHdG) and isoprostane F2 (F2-IsoPs), as markers of OS, were determined by ELISA; and TAC was estimated by colorimetry using an antioxidant kit. A higher PASS was associated with lower plasma TAC and urinary 8-OHdG and F2-IsoPs, showing a better redox profile. Reduced OS markers (8-OHdG and F2-IsoPs) in children with higher PASS may diminish the need of maintaining high concentrations of antioxidants in plasma during rest to achieve redox homeostasis., Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI11/02042 PI11/02059 PI11/01425 PI16/00871 PI16/01301 PI16/01205, RETIC (Redes temáticas de investigación cooperativa) Red SAMID RD12/0026/0015, Instituto de Salud Carlos III European Commission IFI17/00048, Research Plan of the Vice-Rectorate of Research and Transfer of the University of Granada, Spain
Published: 2021

31. Is loneliness associated with mild cognitive impairment in low- and middle-income countries?

Author: Laurie T. Butler, Ai Koyanagi, Mike Trott, Karel Kostev, Louis Jacob, Yvonne Barnett, Lauren R. Godier-McBard, Erica L Bettac, Lee Smith, Jodie Bloska, Nicola Veronese, Helen Odell-Miller, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), US National Institute on Aging through OGHA 04034785, Y1‐AG‐1005–01, YA1323–08‐CN‐0020R01 AG034479/AG/NIA NIH HHS/United StatesR21 AG034263/AG/NIA NIH HHS/United States, This paper uses data from WHO's Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323–08‐CN‐0020, Y1‐AG‐1005–01 and through research grants R01‐AG034479 and R21‐AG034263., Smith L., Bloska J., Jacob L., Barnett Y., Butler L., Trott M., Odell-Miller H., Veronese N., Kostev K., Bettac E.L., Godier-McBard L., and Koyanagi A.
Subjects: China, Logistic regression, multi-country, Odds, loneliness, 03 medical and health sciences, 0302 clinical medicine, mild cognitive impairment, MESH: Aged, China/epidemiology, Cognitive Dysfunction/epidemiology, Cross-Sectional Studies, Developing Countries, Humans, Loneliness, Middle Aged, Prevalence, medicine, Dementia, Cognitive Dysfunction, low- and middle-income countries, Risk factor, Cognitive impairment, Aged, 030214 geriatrics, business.industry, medicine.disease, Confidence interval, 3. Good health, Psychiatry and Mental health, Low and middle income countries, loneliness, low- and middle-income countries, mild cognitive impairment, multi-country, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Geriatrics and Gerontology, medicine.symptom, business, Demography
Abstract: Background: Loneliness may be a risk factor for mild cognitive impairment but studies on this topic are scarce, particularly from low- and middle-income countries (LMICs). Therefore, the aim of the present study was to investigate the association between loneliness and mild cognitive impairment (MCI) in six LMICs (China, Ghana, India, Mexico, Russia and South Africa). Methods: Cross-sectional, community-based, nationally representative data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. The definition of MCI was based on the National Institute on Ageing-Alzheimer's Association criteria. Multivariable logistic regression analysis and meta-analysis were conducted to assess associations. Results: The final analytical sample consisted of 19,092 and 13,623 individuals aged 50–64 years (middle-aged adults) and ≥65 years (older adults), respectively. Among the middle-aged, overall, loneliness was associated with a non-significant 1.43 (95% confidence interval [CI]=0.93–2.21) times higher odds for MCI although significant associations were observed in China (OR=1.51; 95%CI=1.08–2.09) and South Africa (OR=3.87; 95%CI=1.72–8.71). As for older adults, overall, there was a significant association between loneliness and MCI (OR=1.52; 95%CI=1.12–2.07). Conclusion: In this large representative sample of middle-aged and older adults from multiple LMICs, findings suggest that loneliness is associated with MCI. It may be prudent to consider reducing loneliness in low-economic settings to aid in the prevention of MCI and ultimately dementia.
Published: 2021

32. Does Infant-Directed Speech Help Phonetic Learning? A Machine Learning Investigation

Author: Reiko Mazuka, Emmanuel Dupoux, Bogdan Ludusan, RIKEN Center for Brain Science [Wako] (RIKEN CBS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Universität Bielefeld = Bielefeld University, Department of Psychology and Neuroscience, Duke University [Durham], Apprentissage machine et développement cognitif (CoML), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de sciences cognitives et psycholinguistique (LSCP), CIFAR program in Learning in Machines & Brains CIFAR LMB program, The research reported in this paper was partly funded by JSPS Grant-in-Aid for Scientific Research (16H06319, 20H05617) and MEXT Grant-in-Aid on Innovative Areas #4903 (Co-creative Language Evolution), 17H06382 to R. Mazuka. The work of E. Dupoux in his EHESS role was supported by the European Research Council (ERC-2011-AdG-295810 BOOTPHON) the Agence Nationale pour la Recherche (ANR-10-LABX-0087 IEC, ANR-10-IDEX0001-02 PSL*, ANR-19-P3IA-0001 PRAIRIE 3IA Institute), and CIFAR (Learning in Machines and Brain). Part of the work was conducted while E. Dupoux was a visiting scientist at DeepMind and Facebook. B. Ludusan was also supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 799022., ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), ANR-17-EURE-0017,FrontCog,Frontières en cognition(2017), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), European Project: 295810,EC:FP7:ERC,ERC-2011-ADG_20110406,BOOTPHON(2012), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)
Subjects: Functional role, Adult, Computer science, Cognitive Neuroscience, Experimental and Cognitive Psychology, Machine learning, computer.software_genre, Infant-directed speech, 050105 experimental psychology, Read speech, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], Artificial Intelligence, Robustness (computer science), Phonetics, Concept learning, Vowel, Humans, Speech, 0501 psychology and cognitive sciences, Speech variability, Hyperarticulation, business.industry, 05 social sciences, Phonetic learning, Infant, Reading, Speech Perception, Artificial intelligence, business, computer, Adult-directed speech, 030217 neurology & neurosurgery
Abstract: A prominent hypothesis holds that by speaking to infants in infant-directed speech (IDS) as opposed to adult-directed speech (ADS), parents help them learn phonetic categories. Specifically, two characteristics of IDS have been claimed to facilitate learning: hyperarticulation, which makes the categories more separable, and variability, which makes the generalization more robust. Here, we test the separability and robustness of vowel category learning on acoustic representations of speech uttered by Japanese adults in ADS, IDS (addressed to 18- to 24-month olds), or read speech (RS). Separability is determined by means of a distance measure computed between the five short vowel categories of Japanese, while robustness is assessed by testing the ability of six different machine learning algorithms trained to classify vowels to generalize on stimuli spoken by a novel speaker in ADS. Using two different speech representations, we find that hyperarticulated speech, in the case of RS, can yield better separability, and that increased between-speaker variability in ADS can yield, for some algorithms, more robust categories. However, these conclusions do not apply to IDS, which turned out to yield neither more separable nor more robust categories compared to ADS inputs. We discuss the usefulness of machine learning algorithms run on real data to test hypotheses about the functional role of IDS. © 2021 The Authors. Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society (CSS).
Published: 2020

33. Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations

Author: Lance H. Rodan, Rebecca C. Spillmann, Harley T. Kurata, Shawn M. Lamothe, Jasmine Maghera, Rami Abou Jamra, Anna Alkelai, Stylianos E. Antonarakis, Isis Atallah, Omer Bar-Yosef, Frédéric Bilan, Kathrine Bjorgo, Xavier Blanc, Patrick Van Bogaert, Yoav Bolkier, Lindsay C. Burrage, Björn U. Christ, Jorge L. Granadillo, Patricia Dickson, Kirsten A. Donald, Christèle Dubourg, Aviva Eliyahu, Lisa Emrick, Kendra Engleman, Michaela Veronika Gonfiantini, Jean-Marc Good, Judith Kalser, Chiara Kloeckner, Guus Lachmeijer, Marina Macchiaiolo, Francesco Nicita, Sylvie Odent, Emily O’Heir, Xilma Ortiz-Gonzalez, Marta Pacio-Miguez, María Palomares-Bralo, Loren Pena, Konrad Platzer, Mathieu Quinodoz, Emmanuelle Ranza, Jill A. Rosenfeld, Eliane Roulet-Perez, Avni Santani, Fernando Santos-Simarro, Ben Pode-Shakked, Cara Skraban, Rachel Slaugh, Andrea Superti-Furga, Isabelle Thiffault, Richard H. van Jaabrsveld, Marie Vincent, Hong-Gang Wang, Pia Zacher, Mercedes E. Alejandro, Mahshid S. Azamian, Carlos A. Bacino, Ashok Balasubramanyam, Hsiao-Tuan Chao, Gary D. Clark, William J. Craigen, Hongzheng Dai, Shweta U. Dhar, Lisa T. Emrick, Alica M. Goldman, Neil A. Hanchard, Fariha Jamal, Lefkothea Karaviti, Seema R. Lalani, Brendan H. Lee, Richard A. Lewis, Ronit Marom, Paolo M. Moretti, David R. Murdock, Sarah K. Nicholas, James P. Orengo, Jennifer E. Posey, Lorraine Potocki, Susan L. Samson, Daryl A. Scott, Alyssa A. Tran, Tiphanie P. Vogel, Michael F. Wangler, Shinya Yamamoto, Christine M. Eng, Pengfei Liu, Patricia A. Ward, Edward Behrens, Matthew Deardorff, Marni Falk, Kelly Hassey, Kathleen Sullivan, Adeline Vanderver, David B. Goldstein, Heidi Cope, Allyn McConkie-Rosell, Kelly Schoch, Vandana Shashi, Edward C. Smith, Jennifer A. Sullivan, Queenie K.-G. Tan, Nicole M. Walley, Pankaj B. Agrawal, Alan H. Beggs, Gerard T. Berry, Lauren C. Briere, Laurel A. Cobban, Matthew Coggins, Cynthia M. Cooper, Elizabeth L. Fieg, Frances High, Ingrid A. Holm, Susan Korrick, Joel B. Krier, Sharyn A. Lincoln, Joseph Loscalzo, Richard L. Maas, Calum A. MacRae, J. Carl Pallais, Deepak A. Rao, Edwin K. Silverman, Joan M. Stoler, David A. Sweetser, Melissa Walker, Chris A. Walsh, Cecilia Esteves, Emily G. Kelley, Isaac S. Kohane, Kimberly LeBlanc, Alexa T. McCray, Anna Nagy, Surendra Dasari, Brendan C. Lanpher, Ian R. Lanza, Eva Morava, Devin Oglesbee, Guney Bademci, Deborah Barbouth, Stephanie Bivona, Olveen Carrasquillo, Ta Chen Peter Chang, Irman Forghani, Alana Grajewski, Rosario Isasi, Byron Lam, Roy Levitt, Xue Zhong Liu, Jacob McCauley, Ralph Sacco, Mario Saporta, Judy Schaechter, Mustafa Tekin, Fred Telischi, Willa Thorson, Stephan Zuchner, Heather A. Colley, Jyoti G. Dayal, David J. Eckstein, Laurie C. Findley, Donna M. Krasnewich, Laura A. Mamounas, Teri A. Manolio, John J. Mulvihill, Grace L. LaMoure, Madison P. Goldrich, Tiina K. Urv, Argenia L. Doss, Maria T. Acosta, Carsten Bonnenmann, Precilla D’Souza, David D. Draper, Carlos Ferreira, Rena A. Godfrey, Catherine A. Groden, Ellen F. Macnamara, Valerie V. Maduro, Thomas C. Markello, Avi Nath, Donna Novacic, Barbara N. Pusey, Camilo Toro, Colleen E. Wahl, Eva Baker, Elizabeth A. Burke, David R. Adams, William A. Gahl, May Christine V. Malicdan, Cynthia J. Tifft, Lynne A. Wolfe, John Yang, Bradley Power, Bernadette Gochuico, Laryssa Huryn, Lea Latham, Joie Davis, Deborah Mosbrook-Davis, Francis Rossignol, null Ben Solomon, John MacDowall, Audrey Thurm, Wadih Zein, Muhammad Yousef, Margaret Adam, Laura Amendola, Michael Bamshad, Anita Beck, Jimmy Bennett, Beverly Berg-Rood, Elizabeth Blue, Brenna Boyd, Peter Byers, Sirisak Chanprasert, Michael Cunningham, Katrina Dipple, Daniel Doherty, Dawn Earl, Ian Glass, Katie Golden-Grant, Sihoun Hahn, Anne Hing, Fuki M. Hisama, Martha Horike-Pyne, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Christina Lam, Kenneth Maravilla, Heather Mefford, J. Lawrence Merritt, Ghayda Mirzaa, Deborah Nickerson, Wendy Raskind, Natalie Rosenwasser, C. Ron Scott, Angela Sun, Virginia Sybert, Stephanie Wallace, Mark Wener, Tara Wenger, Euan A. Ashley, Gill Bejerano, Jonathan A. Bernstein, Devon Bonner, Terra R. Coakley, Liliana Fernandez, Paul G. Fisher, Laure Fresard, Jason Hom, Yong Huang, Jennefer N. Kohler, Elijah Kravets, Marta M. Majcherska, Beth A. Martin, Shruti Marwaha, Colleen E. McCormack, Archana N. Raja, Chloe M. Reuter, Maura Ruzhnikov, Jacinda B. Sampson, Kevin S. Smith, Shirley Sutton, Holly K. Tabor, Brianna M. Tucker, Matthew T. Wheeler, Diane B. Zastrow, Chunli Zhao, William E. Byrd, Andrew B. Crouse, Matthew Might, Mariko Nakano-Okuno, Jordan Whitlock, Gabrielle Brown, Manish J. Butte, Esteban C. Dell’Angelica, Naghmeh Dorrani, Emilie D. Douine, Brent L. Fogel, Irma Gutierrez, Alden Huang, Deborah Krakow, Hane Lee, Sandra K. Loo, Bryan C. Mak, Martin G. Martin, Julian A. Martínez-Agosto, Elisabeth McGee, Stanley F. Nelson, Shirley Nieves-Rodriguez, Christina G.S. Palmer, Jeanette C. Papp, Neil H. Parker, Genecee Renteria, Rebecca H. Signer, Janet S. Sinsheimer, Jijun Wan, Lee-kai Wang, Katherine Wesseling Perry, Jeremy D. Woods, Justin Alvey, Ashley Andrews, Jim Bale, John Bohnsack, Lorenzo Botto, John Carey, Laura Pace, Nicola Longo, Gabor Marth, Paolo Moretti, Aaron Quinlan, Matt Velinder, Dave Viskochil, Pinar Bayrak-Toydemir, Rong Mao, Monte Westerfield, Anna Bican, Elly Brokamp, Laura Duncan, Rizwan Hamid, Jennifer Kennedy, Mary Kozuira, John H. Newman, John A. PhillipsIII, Lynette Rives, Amy K. Robertson, Emily Solem, Joy D. Cogan, F. Sessions Cole, Nichole Hayes, Dana Kiley, Kathy Sisco, Jennifer Wambach, Daniel Wegner, Dustin Baldridge, Stephen Pak, Timothy Schedl, Jimann Shin, Lilianna Solnica-Krezel, Eric Rush, Geoffrey S. Pitt, Ping Yee Billie Au, Boston Children's Hospital, University of Alberta, Universität Leipzig [Leipzig], Geneva University Hospital (HUG), Tel Aviv University [Tel Aviv], Service Génétique Médicale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Baylor College of Medicine (BCM), Baylor University, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Lausanne University Hospital, Centre de référence Maladies Rares CLAD-Ouest [Rennes], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Children’s Hospital of Philadelphia (CHOP ), Hospital Universitario La Paz, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Duke University [Durham], University of Kansas Medical Center [Lawrence], University of Missouri System, Children's Mercy Hospital [Kansas City], Weill Cornell Medicine [New York], University of Calgary, Research reported in this paper was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under award number(s) (U01HG007709 [Baylor College of Medicine] and U01HG007672 [Duke University to V.S.]). Additional funding for this project was under award number 1RO1HD090132-01A1 (Cornell University to G.P.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional funding was provided by a Canadian Institutes of Health Research Grant (MOP-97988 to H.T.K.), and a Rowland and Muriel Haryett Fellowship (University of Alberta, to S.M.L.) and a fellowship from the Ministry of Education and Research of the Community of Madrid to M.P.M. (B2017/BMD-3721), and microgrant from the Rare Disease Foundation (P.Y.B.A. and H.T.K.). Sequencing and analysis was supported by the National Human Genome Research Institute grants UM1 HG008900 and R01 HG009141. K.A.D., B.C., and E.O. were supported the National Institute of Mental Health U01 MH119689., Universität Leipzig, Columbia University Medical Center (CUMC), Columbia University [New York], Tel Aviv University (TAU), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Unité de recherche de l'institut du thorax (ITX-lab), University of Kansas Medical Center [Kansas City, KS, USA], Weill Cornell Medicine [Cornell University], and Cornell University [New York]
Subjects: Ataxia, Calcium Channels, L-Type, Long QT syndrome, Timothy syndrome, Bioinformatics, Article, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Intellectual disability, medicine, Missense mutation, Humans, Autistic Disorder, Genetics (clinical), 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, medicine.disease, Hypotonia, Long QT Syndrome, Phenotype, Autism, Syndactyly, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; Purpose:CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results:Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.Conclusion:We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome.
Published: 2020

34. Physical functional performance and prognosis in patients with heart failure: a systematic review and meta-analysis

Author: Antonio Cuesta-Vargas, Ricardo Gómez-Huelgas, María Rosa Bernal-López, Iván José Fuentes-Abolafio, Brendon Stubbs, Luis M. Pérez-Belmonte, [Fuentes-Abolafio,IJ, Cuesta-Vargas,AI] Department of Physiotherapy, Faculty of Health Science, University of Malaga, The Institute of Biomedical Research in Malaga (IBIMA), Clinimetric Group FE-14, Malaga, Spain. [Stubbs,B] Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, UK. [Stubbs,B] Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK. [Stubbs,B] Positive Ageing Research Intitute (PARI), Faculty of Health Social Care and Education, Anglia Ruskin University, Chelmsford, UK. [Pérez-Belmonte,LM, Bernal-López,MR, Gómez-Huelgas,R] Internal Medicine Department, Instituto de Investigación Biomédica de Malaga (IBIMA), Regional University Hospital of Málaga, Málaga, Spain. [Pérez-Belmonte,LM] Unidad de Neurofisiología Cognitiva, Centro de Investigaciones Médico Sanitarias (CIMES), Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Campus de Excelencia Internacional (CEI) Andalucía Tech, Málaga, Spain. [Pérez-Belmonte,LM] Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. [Bernal-López,MR, Gómez-Huelgas,R] CIBER Fisio-patología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain. [Cuesta-Vargas,AI] School of Clinical Sciences, Faculty of Health at the Queensland University of Technology, Brisbane, Queensland, Australia., and Brendon Stubbs is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR). Brendon Stubbs is part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. Brendon Stubbs is also supported by the Maudsley Charity, King’s College London and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. This paper presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions. María Rosa Bernal-López was supported by 'Miguel Servet Type I' program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER.
Subjects: Male, lcsh:Diseases of the circulatory (Cardiovascular) system, Hospitalización, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], Walking, 030204 cardiovascular system & hematology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Physical functional performance, Hospitalisation, Medicine, 030212 general & internal medicine, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise::Walking [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Aged, 80 and over, Insuficiencia cardíaca, Pronóstico, Middle Aged, Prognosis, Cardiac surgery, Hospitalization, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Hospitalization [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of Tests [Medical Subject Headings], Meta-analysis, Female, Gait Analysis, Cardiology and Cardiovascular Medicine, Research Article, medicine.medical_specialty, Check Tags::Male [Medical Subject Headings], Walk Test, Functional tests, Heart failure, CINAHL, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Humans, In patient, Mortality, Aged, Angiology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Cardiovascular::Heart Function Tests::Exercise Test [Medical Subject Headings], business.industry, Diseases::Cardiovascular Diseases::Heart Diseases::Heart Failure [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Evidence-based medicine, medicine.disease, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Gait [Medical Subject Headings], Functional Status, Check Tags::Female [Medical Subject Headings], lcsh:RC666-701, Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Mortalidad, Physical therapy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Observational study, business, Rendimiento físico funcional
Abstract: Background Patients with Heart Failure (HF) show impaired functional capacities which have been related to their prognosis. Moreover, physical functional performance in functional tests has also been related to the prognosis in patients with HF. Thus, it would be useful to investigate how physical functional performance in functional tests could determine the prognosis in patients with HF, because HF is the leading cause of hospital admissions for people older than 65 years old. This systematic review and meta-analysis aims to summarise and synthesise the evidence published about the relationship between physical functional performance and prognosis in patients with HF, as well as assess the risk of bias of included studies and the level of evidence per outcome. Methods Major electronic databases, such as PubMed, AMED, CINAHL, EMBASE, PEDro, Web of Science, were searched from inception to March 2020 for observational longitudinal cohort studies (prospective or retrospective) examining the relationship between physical functional performance and prognosis in patients with HF. Results 44 observational longitudinal cohort studies with a total of 22,598 patients with HF were included. 26 included studies reported a low risk of bias, and 17 included studies showed a moderate risk of bias. Patients with poor physical functional performance in the Six Minute Walking Test (6MWT), in the Short Physical Performance Battery (SPPB) and in the Gait Speed Test showed worse prognosis in terms of larger risk of hospitalisation or mortality than patients with good physical functional performance. However, there was a lack of homogeneity regarding which cut-off points should be used to stratify patients with poor physical functional performance from patients with good physical functional performance. Conclusion The review includes a large number of studies which show a strong relationship between physical functional performance and prognosis in patients with HF. Most of the included studies reported a low risk of bias, and GRADE criteria showed a low and a moderate level of evidence per outcome.
Published: 2020

35. Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa : a population-level self-controlled case-series study

Author: Arran Hamlet, Hanaya Raad, Tini Garske, Katy A. M. Gaythorpe, Kévin Jean, Daniel R Hogan, Tewodaj Mengistu, Judith E. Mueller, Mounia N. Hocine, Heather Whitaker, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Imperial College London, École des Hautes Études en Santé Publique [EHESP] (EHESP), Chercheur indépendant, Public Health England [London], This work was carried out as part of the Vaccine Impact Modelling Consortium (www.vaccineimpact.org), but the views expressed are those of the authors and not necessarily those of the Consortium or its funders. The funders were given the opportunity to review this paper prior to publication, but the final decision on the content of the publication was taken by the authors. Dr Jean, Mr Hamlet, Dr Gaythorpe, and Dr Garske acknowledge joint Centre funding from the UK Medical Research Council and Department for International Development (MR/R015600/1) and report grant from The Bill & Melinda Gates Foundation (grant number OPP1157270). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), and Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: medicine.medical_specialty, Disease surveillance, business.industry, Public health, 030231 tropical medicine, Yellow fever, Outbreak, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Epidemiology, Pandemic, Cohort, medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, business, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Cohort study
Abstract: Introduction The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, by how much PMVCs are associated with a decreased risk of outbreak to occur has not yet been quantified. Methods and Findings We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for, the SCCS method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The location and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the relative incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, outbreaks occurred during the pre-PMVC period in 26 (79%) provinces versus 7 (21%) occurring in the post-PMVC period. At the province level, the post-PMVC period was associated with a 86% reduction (95% Confidence interval 66% to 94%, p-value A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever or possibly improved disease surveillance. Conclusion In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention. AUTHOR SUMMARY Why Was This Study Done? Yellow fever is a mosquito-borne vaccine-preventable disease that may cause large urban outbreaks, especially in tropical African regions. Since 2006, Preventive Mass Vaccination Campaigns (PMVCs) have been implemented in many African provinces. These are large scale vaccination campaigns targeting all or most age group in a specific area. The preventive impact PMVCs may have on the risk of yellow fever outbreak has not been quantified yet. What Did the Researchers Do and Find? We used the self-controlled case series (SCCS) method to assess the association between PMVCs and outbreak risk at the province level over 34 African countries between 2005 and 2018. Using this method, we compared pre- and post-PMVC period are compared within each province individually, thus controlling for all possible confounders that do not vary in time, especially the fact that provinces indicated for PMVCs are generally those considered at highest baseline risk of yellow fever (ie confounding by indication). At the province level, we estimated that implementation of PMVCs was associated with an 86% reduction (66% to 94%) in the risk of yellow fever outbreak. Results from a complete cohort analysis provided less reliable results than the SCCS method, likely because of confounding by indication that was not entirely controlled for by adjusting on known drivers of yellow fever. We further estimated that all PMVCs conducted between 2006 and 2018 in Africa may have reduced the total number of yellow fever outbreaks by 34% (22% to 45%). What Do These Findings Mean? These results provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. These results may encourage rapid re-scheduling of yellow fever PMVCs that have been postponed due to the COVID-19 pandemic. The SCCS design may be advantageously applied at the population level to assess the impact of public health interventions.
Published: 2020

36. Towards a European Health Union: Time to Level Up

Author: Alberto Alemanno, Ecole des Hautes Etudes Commerciales (HEC Paris), and HEC Paris Research Paper Series
Subjects: EU health, Public administration, 0302 clinical medicine, Emergency Regulation, 030212 general & internal medicine, 050207 economics, media_common, Precautionary principle, 050208 finance, 030503 health policy & services, 05 social sciences, Cost-benefit analysis, EU law, Risk regulation, 3. Good health, Risk vs risk, JEL: K - Law and Economics/K.K3 - Other Substantive Areas of Law/K.K3.K32 - Environmental, Health, and Safety Law, [SHS.GESTION]Humanities and Social Sciences/Business administration, Health law, 0305 other medical science, Safety Research, tradeoffs, medicine.medical_specialty, Public health law, Economic policy, Supply chain, JEL: K - Law and Economics/K.K3 - Other Substantive Areas of Law, 03 medical and health sciences, Politics, Blueprint, Political science, 0502 economics and business, medicine, media_common.cataloged_instance, European Union, European union, Worst-case scenarios, Risk Regulation, Suppression, business.industry, Public health, JEL: K - Law and Economics/K.K3 - Other Substantive Areas of Law/K.K3.K33 - International Law, COVID-19, Consumer protection, Coronavirus, Agriculture, business, Law
Abstract: The European response to COVID-19 has revealed an inconvenient truth. Despite having integrated public health concerns across all its policies – be it agriculture, consumer protection, or security –, the Union cannot directly act to save people’s lives. Only member states can do so. Yet when they adopted unilateral measures to counter the spread of the virus, those proved not only ineffective but also disruptive on vital supply chains, by ultimately preventing the flow of essential goods and people across the Union. These fragmented efforts in tackling cross-border health threats have almost immediately prompted political calls for the urgent creation of a European Health Union. Yet this call raises more questions than answers. With the aim to offer a rigorous and timely blueprint to decision-makers and the public at large, this Special Issue of the European Journal of Risk Regulation contextualizes such a new political project within the broader constitutional and institutional framework of EU public health law and policy. By introducing the Special, this paper argues that unless the envisaged Health Union will tackle the root causes of what prevented the Union from effectively responding to COVID-19 – the divergent health capacity across the Union –, it might fall short of its declared objective of strengthening the EU’resilience for cross-border health threats.
Published: 2020

37. Interdisciplinary Research in Artificial Intelligence: Challenges and Opportunities

Author: Remy Kusters, Dusan Misevic, Hugues Berry, Antoine Cully, Yann Le Cunff, Loic Dandoy, Natalia Díaz-Rodríguez, Marion Ficher, Jonathan Grizou, Alice Othmani, Themis Palpanas, Matthieu Komorowski, Patrick Loiseau, Clément Moulin Frier, Santino Nanini, Daniele Quercia, Michele Sebag, Françoise Soulié Fogelman, Sofiane Taleb, Liubov Tupikina, Vaibhav Sahu, Jill-Jênn Vie, Fatima Wehbi, Centre de Recherche Interdisciplinaire / Center for Research and Interdisciplinarity [Paris, France] (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Imperial College London, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Flowing Epigenetic Robots and Systems (Flowers), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), École Nationale Supérieure de Techniques Avancées (ENSTA Paris), Laboratoire Images, Signaux et Systèmes Intelligents (LISSI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Performance analysis and optimization of LARge Infrastructures and Systems (POLARIS), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'Informatique de Grenoble (LIG), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Nokia Bell Labs [Cambridge], TAckling the Underspecified (TAU), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Recherche en Informatique (LRI), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hub France IA, Nokia Bell Labs [Paris-Saclay], Scool (Scool), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Thanks to the Bettencourt Schueller Foundation long term partnership, the workshop that gave rise to this paper was partially supported by the funding from CRI Research Collaboratory, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Unité d'Informatique et d'Ingénierie des Systèmes (U2IS), École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École Nationale Supérieure de Techniques Avancées (ENSTA Paris), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Big Data, 0301 basic medicine, [SCCO.COMP]Cognitive science/Computer science, [INFO.INFO-NE]Computer Science [cs]/Neural and Evolutionary Computing [cs.NE], [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], 03 medical and health sciences, 0302 clinical medicine, Political science, Health care, Computer Science (miscellaneous), auditability, education, lcsh:T58.5-58.64, Ai education, business.industry, lcsh:Information technology, interdisciplinary science, Precision medicine, artificial intelligence, Transparency (behavior), ethics, Variety (cybernetics), 030104 developmental biology, [INFO.INFO-MA]Computer Science [cs]/Multiagent Systems [cs.MA], Perspective, Artificial intelligence, business, interpretability, 030217 neurology & neurosurgery, Information Systems
Abstract: The use of artificial intelligence (AI) in a variety of research fields is speeding up multiple digital revolutions, from shifting paradigms in healthcare, precision medicine and wearable sensing, to public services and education offered to the masses around the world, to future cities made optimally efficient by autonomous driving. When a revolution happens, the consequences are not obvious straight away, and to date, there is no uniformly adapted framework to guide AI research to ensure a sustainable societal transition. To answer this need, here we analyze three key challenges to interdisciplinary AI research, and deliver three broad conclusions: 1) future development of AI should not only impact other scientific domains but should also take inspiration and benefit from other fields of science, 2) AI research must be accompanied by decision explainability, dataset bias transparency as well as development of evaluation methodologies and creation of regulatory agencies to ensure responsibility, and 3) AI education should receive more attention, efforts and innovation from the educational and scientific communities. Our analysis is of interest not only to AI practitioners but also to other researchers and the general public as it offers ways to guide the emerging collaborations and interactions toward the most fruitful outcomes.
Published: 2020

38. Current use of inotropes in circulatory shock

Author: Michael R. Pinsky, Maria Cronhjort, Thomas Kaufmann, Rupert M Pearse, Ludhmila Abrahão Hajjar, Daniel A. Reuter, Jean Louis Vincent, Daniel De Backer, Martin W. Dünser, Maurizio Cecconi, Xavier Monnet, Iwan C. C. van der Horst, Vanina Siham Kanoore Edul, Bernard Cholley, Claude Martin, Thomas Scheeren, Yasser Sakr, Philippe Vignon, Didier Payen, Olfa Hamzaoui, Bernd Saugel, E. Christiaan Boerma, Pierre Squara, Alexandre Mebazaa, Geert Koster, Djillali Annane, Andrea Morelli, Arnaldo Dubin, Marc Leone, Pierre Asfar, Mervyn Singer, Anthony C. Gordon, Jan Bakker, Antoine Vieillard-Baron, Giovanni Landoni, Michael Sander, Michelle S Chew, Jean-Louis Teboul, Simon T. Vistisen, Glenn Hernandez, Peter Radermacher, Jacques Duranteau, Bruno Levy, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), RS: Carim - V04 Surgical intervention, Intensive Care, MUMC+: MA Medische Staf IC (9), MUMC+: MA Intensive Care (3), University of Groningen [Groningen], University Medical Center Groningen [Groningen] (UMCG), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Columbia University Medical Center (CUMC), Columbia University [New York], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical Centre Leeuwarden, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Linköping University (LIU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], Centre Hospitalier Interrégional Edith Cavell (CHIREC), Universidad Nacional de la Plata [Argentine] (UNLP), Johannes Kepler University Linz [Linz] (JKU), Kepler University Hospital, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Imperial College London, Universidade de São Paulo = University of São Paulo (USP), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pontificia Universidad Católica de Chile (UC), Hospital Juan A. Fernandez [Buenos Aires, Argentina], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Hôpital Nord [CHU - APHM], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre de Référence de l’Hypertension Pulmonaire Sévère [CHU Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], William Harvey Research Institute, Barts and the London Medical School, Queen Mary University of London (QMUL), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Universitätsklinikum Ulm - University Hospital of Ulm, University Medical Center Rostock, Jena University Hospital [Jena], Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University College of London [London] (UCL), Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Aarhus University Hospital, European Society of Intensive Care Medicine, ESICM, This work has received the endorsement of the European Society of Intensive Care Medicine. The authors would like to thank Hannah Wunsch and Anders Perner, who provided their expertise as experts but abstained from being listed as co-author of this paper., HAL UVSQ, Équipe, NIHR, Scheeren, T. W. L., Bakker, J., Kaufmann, T., Annane, D., Asfar, P., Boerma, E. C., Cecconi, M., Chew, M. S., Cholley, B., Cronhjort, M., De Backer, D., Dubin, A., Dunser, M. W., Duranteau, J., Gordon, A. C., Hajjar, L. A., Hamzaoui, O., Hernandez, G., Kanoore Edul, V., Koster, G., Landoni, G., Leone, M., Levy, B., Martin, C., Mebazaa, A., Monnet, X., Morelli, A., Payen, D., Pearse, R. M., Pinsky, M. R., Radermacher, P., Reuter, D. A., Sakr, Y., Sander, M., Saugel, B., Singer, M., Squara, P., Vieillard-Baron, A., Vignon, P., Vincent, J. -L., van der Horst, I. C. C., Vistisen, S. T., and Teboul, J. -L.
Subjects: Inotrope, PDE-inhibitors, Levosimendan, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, GUIDELINES, 0302 clinical medicine, Catecholamines, CARDIAC-OUTPUT SYNDROME, Septic shock, Inotropes, Cardiogenic shock, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Acute circulatory failure, 3. Good health, [SDV] Life Sciences [q-bio], Shock (circulatory), Sepsis, Resuscitation, Vasoactive agents, Cardiac output, medicine.symptom, Life Sciences & Biomedicine, CRITICALLY-ILL PATIENTS, medicine.drug, medicine.medical_specialty, Anestesi och intensivvård, Medicina, Context (language use), VASOPRESSORS, 1117 Public Health and Health Services, 03 medical and health sciences, Critical Care Medicine, acute circulatory failure, cardiac output, cardiogenic shock, catecholamines, inotropes, levosimendan, resuscitation, sepsis, septic shock, vasoactive agents, General & Internal Medicine, Anesthesiology, medicine, Intensive care medicine, METAANALYSIS, Science & Technology, Anesthesiology and Intensive Care, business.industry, Research, 1103 Clinical Sciences, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Guideline, medicine.disease, DYSFUNCTION, CARDIOGENIC-SHOCK, Dobutamine, business
Abstract: Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. Results: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). Conclusion: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes., La lista completa de autores que integran el documento puede consultarse en el archivo., Facultad de Ciencias Médicas
Published: 2020

39. Study Protocol: A Cross-Sectional Examination of Socio-Demographic and Ecological Determinants of Nutrition and Disease Across Madagascar

Author: Christopher D. Golden, Benjamin L. Rice, Hervet J. Randriamady, Arisoa Miadana Vonona, Jean Frederick Randrianasolo, Ambinintsoa Nirina Tafangy, Mamy Yves Andrianantenaina, Nicholas J. Arisco, Gauthier N. Emile, Faustin Lainandrasana, Robuste Fenoarison Faraniaina Mahonjolaza, Hermann Paratoaly Raelson, Vololoniaina Ravo Rakotoarilalao, Anjaharinony Andry Ny Aina Rakotomalala, Alex Dominique Rasamison, Rebaliha Mahery, M. Luciano Tantely, Romain Girod, Akshaya Annapragada, Amy Wesolowski, Amy Winter, Daniel L. Hartl, James Hazen, C. Jessica E. Metcalf, Harvard T.H. Chan School of Public Health, Madagascar Health and Environmental Research [Maroantsetra, Madagascar] (MAHERY), Princeton University, Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Harvard University [Cambridge], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Catholic Relief Services [Antananarivo, Madagascar] (CRS), Catholic Relief Services [Baltimore] (CRS), and We are grateful for the support from the United States Agency for International Development (Grant No. AID-FFP-A-14-00008) implemented by Catholic Relief Services (CRS) in consortium with four local implementing partners in Madagascar. The views and opinions expressed in this paper are those of the authors and not necessarily the views and opinions of the United States Agency for International Development. We also thank the Wellcome Trust Our Planet, Our Health program (grant 106866/Z/15/Z) for providing funding to CM for this research.
Subjects: Environmental change, infectious disease, [SDV]Life Sciences [q-bio], Population, malaria, Distribution (economics), planetary health, Disease, migration, MESH: Madagascar, 03 medical and health sciences, 0302 clinical medicine, MESH: Cross-Sectional Studies, Environmental health, MESH: Child, disease ecology, MESH: Family Characteristics, MESH: Ecosystem, 030212 general & internal medicine, Clinical Study Protocol, education, Disease burden, 2. Zero hunger, education.field_of_study, Food security, MESH: Humans, business.industry, seasonality, 030503 health policy & services, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, food security, 15. Life on land, MESH: Nutritional Status, MESH: Male, General Social Survey, Geography, 13. Climate action, micronutrient nutrition, Observational study, Public Health, 0305 other medical science, business, MESH: Female
Abstract: International audience; Madagascar has experienced significant environmental change since 1960, particularly through forest clearing for agricultural expansion. Climatic patterns are undergoing change in Madagascar as well, with increasing temperatures, droughts, and cyclonic activity. The impact of these environmental and climatic changes will pose threats to food availability, income generation, and local ecosystems, with significant potential effects on the spatial and temporal distribution of disease burden. This study seeks to describe the health status of a large sample of geographically and socially diverse Malagasy communities through multiple clinical measurements, detailed social surveys, and paired data on regional variation in local ecologies. With an increased understanding of the current patterns of variation in human health and nutrition, future studies will be better able to identify associations with climate and anticipate and mitigate the burdens expected from larger, longer-term changes. Our mixed-method approach included an observational cross-sectional study. Research subjects were men, women, and children from 1,125 households evenly distributed across 24 communities in four ecologically and socio-demographically distinct regions of Madagascar. For these 1,125 households, all persons of both sexes and all ages therein (for a total of 6,292 individuals) were recruited into the research study and a total of 5,882 individuals were enrolled. Through repeated social survey recalls and focus group meetings, we obtained social and demographic data, including broad categories of seasonal movements, and characterized the fluctuation of income generation, food production and dietary consumption. Through collection of clinical and biological samples for both point-of-care diagnoses and laboratory analyses, we obtained detailed occurrence (and importantly co-occurrence) data on micronutrient nutritional, infectious disease, and non-communicable disease status. Our research highlights the highly variable social, cultural, and environmental contexts of health conditions in Madagascar, and the tremendous inter-regional, inter-community, and intra-community variation in nutritional and disease status. More than 30% of the surveyed population was afflicted by anemia and 14% of the population had a current malaria infection. This type of rich metadata associated with a suite of biological samples and nutritional and disease outcome data should allow disentangling some of the underlying drivers of ill health across the changing landscapes of Madagascar.
Published: 2020

40. Variation in Anopheles distribution and predictors of malaria infection risk across regions of Madagascar

Author: Marcia C. Castro, Gauthier N. Emile, Romain Girod, Christopher D. Golden, Benjamin L. Rice, Hervet J. Randriamady, Nicholas J. Arisco, Luciano Michaël Tantely, Harvard T.H. Chan School of Public Health, Harvard University [Cambridge], Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Madagascar Health and Environmental Research [Maroantsetra, Madagascar] (MAHERY), and We are grateful for the support from the United States Agency for International Development (Grant AID-FFP-A-14-00,008) implemented by Catholic Relief Services (CRS) in consortium with four local implementing partners in Madagascar. The views and opinions expressed in this paper are those of the authors and not necessarily the views and opinions of the United States Agency for International Development. GeoStore funds provided by Airbus Defense & Space (Grant AH08211501).
Subjects: Male, Environmental change, Range (biology), [SDV]Life Sciences [q-bio], Distribution (economics), MESH: Madagascar, 0302 clinical medicine, MESH: Aged, 80 and over, Risk Factors, Planetary health, MESH: Demography, MESH: Risk Factors, MESH: Child, Disease ecology, MESH: Animals, MESH: Ecosystem, 030212 general & internal medicine, Child, Land use change, Aged, 80 and over, MESH: Aged, 2. Zero hunger, MESH: Middle Aged, biology, Multilevel model, Anopheles, Middle Aged, MESH: Infant, Infectious Diseases, Geography, MESH: Young Adult, Child, Preschool, Female, MESH: Mosquito Vectors, Adult, MESH: Socioeconomic Factors, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, 030231 tropical medicine, MESH: Malaria, Mosquito Vectors, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, Young Adult, MESH: Cross-Sectional Studies, Deforestation, Environmental health, Vector-borne disease, parasitic diseases, medicine, Madagascar, Animals, Humans, lcsh:RC109-216, Socioeconomic status, Ecosystem, Aged, Demography, MESH: Adolescent, MESH: Humans, business.industry, Research, MESH: Child, Preschool, MESH: Animal Distribution, Infant, MESH: Adult, 15. Life on land, medicine.disease, biology.organism_classification, MESH: Male, Malaria, Cross-Sectional Studies, Socioeconomic Factors, Parasitology, business, Animal Distribution, MESH: Female
Abstract: Background Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset. Methods The objectives were to assess (1) the ecological correlates of malaria vector breeding through larval surveys, and (2) the socioeconomic, demographic, and ecological risk factors for malaria infection in four ecologically distinct regions of rural Madagascar. Risk factors were determined using multilevel models for the four regions included in the study. Results The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity. Conclusions Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.
Published: 2020

41. The interplay between innate lymphoid cells and T cells

Author: Gayetri Ramachandran, Rachel Golub, Marie Cherrier, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), M.C. is supported by INSERM and Association François Aupetit dedicated to patients suffering from IBD. R.G. work is supported by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Université de Paris, and ANR project NASHILCCD8 (#18-CE15-0024-01)., We thank Serge van de Pavert for critical discussions and for review of the paper., ANR-18-CE15-0024,NASHILCCD8,Contribution des ILC et des cellules T CD8 à la stéatose hépatique non alcoolique et à sa progression vers l'hépatocarcinome.(2018), Vougny, Marie-Christine, APPEL À PROJETS GÉNÉRIQUE 2018 - Contribution des ILC et des cellules T CD8 à la stéatose hépatique non alcoolique et à sa progression vers l'hépatocarcinome. - - NASHILCCD82018 - ANR-18-CE15-0024 - AAPG2018 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Cell type, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Context (language use), Cell Communication, Biology, Gut flora, Adaptive Immunity, Lymphocyte Activation, Substrate Specificity, Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Immune system, T-Lymphocyte Subsets, Immunology and Allergy, Animals, Humans, skin and connective tissue diseases, Immunity, Cellular, Innate lymphoid cell, Cell Differentiation, Acquired immune system, biology.organism_classification, Immunity, Innate, body regions, 030104 developmental biology, Gene Expression Regulation, Host-Pathogen Interactions, [SDV.IMM]Life Sciences [q-bio]/Immunology, Neuroscience, Immunologic Memory, Function (biology), Homeostasis, Biomarkers, 030215 immunology, Signal Transduction
Abstract: International audience; ILCs and T cells are closely related functionally but they significantly differ in their ability to circulate, expand, and renew. Cooperation and reciprocal functional regulation suggest that these cell types are more complementary than simply redundant during immune responses. How ILCs shape T-cell responses is strongly dependent on the tissue and inflammatory context. Likewise, indirect regulation of ILCs by adaptive immunity is induced by environmental cues such as the gut microbiota. Here, we review shared requirements for the development and function of both cell types and divergences in the orchestration of prototypic immune functions. We discuss the diversity of functional interactions between T cells and ILCs during homeostasis and immune responses. Identifying the location and the nature of the tissue microenvironment in which these interactions are taking place may uncover the remaining mysteries of their close encounters.
Published: 2020

42. Clinical and epidemiological characteristics of 1420 European patients with mild‐to‐moderate coronavirus disease 2019

Author: Lechien, Jerome R., Chiesa‐Estomba, Carlos M., Place, Sammy, Van Laethem, Yves, Cabaraux, Pierre, Mat, Quentin, Huet, Kathy, Plzak, Jan, Horoi, Mihaela, Hans, Stéphane, Rosaria Barillari, Maria, Cammaroto, Giovanni, Fakhry, Nicolas, Martiny, Delphine, Ayad, Tareck, Jouffe, Lionel, Hopkins, Claire, Saussez, Sven, Blecic, Serge, De Siati, Daniele R., Leich, Pierre, Souchay, Christel, Rossi, Camelia, Journe, Fabrice, Hsieh, Julien, Ris, Laurence, El Afia, Fahd, Harmegnies, Bernard, Distinguin, Lea, Chekkoury‐Idrissi, Younes, Circiu, Marta, Lavigne, Philippe, Lopez Delgado, Irene, Calvo‐Henriquez, Christian, Falanga, Chiara, Coppee, Frederique, Le Bon, Serge Daniel, Rodriguez, Alexandra, Dequanter, Didier, Cornelis, Jean‐Philippe, Vergez, Sebastien, Koenen, Lukas, Giuditta, Mannelli, Molteni, Gabriele, Tucciarone, Manuel, Radulesco, Thomas, Khalife, Mohamad, Fourneau, Anne‐Francoise, Cherifi, Soraya, Manto, Mario, Michel, Justin, Mannelli, Giuditta, Cantarella, Giovanna, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), We would like to thank Bayesia (BayesiaLab?, Chang?, France) for the Network Analysis, Jean-Louis Vincent and Michel Van Haeverbeek for the review of the paper or their useful comments, the heads of the Hospitals, which have been involved in the study, for their help in the rapid conduction of the study and the agreement of ethics committees, the European Press/Media (i.e. Le Monde, La Libre, Le Soir, MediQuality, MedScape, and Le Specialiste) for their help in the spread of the information about the study, and FRMH & UMONS for the grant and the support., Lechien, J. R., Chiesa-Estomba, C. M., Place, S., Van Laethem, Y., Cabaraux, P., Mat, Q., Huet, K., Plzak, J., Horoi, M., Hans, S., Barillari, M. R., Cammaroto, G., Fakhry, N., Martiny, D., Ayad, T., Jouffe, L., Hopkins, C., Saussez, S., Blecic, S., De Siati, D. R., Leich, P., Souchay, C., Rossi, C., Journe, F., Hsieh, J., Ris, L., El Afia, F., Harmegnies, B., Distinguin, L., Chekkoury-Idrissi, Y., Circiu, M., Lavigne, P., Lopez Delgado, I., Calvo-Henriquez, C., Falanga, C., Coppee, F., Le Bon, S. D., Rodriguez, A., Dequanter, D., Cornelis, J. -P., Vergez, S., Koenen, L., Giuditta, M., Molteni, G., Tucciarone, M., Radulesco, T., Khalife, M., Fourneau, A. -F., Cherifi, S., Manto, M., Michel, J., Mannelli, G., and Cantarella, G.
Subjects: 0301 basic medicine, myalgia, Male, medicine, Original, [SDV]Life Sciences [q-bio], coronavirus, symptoms, Disease, epidemiological, 030204 cardiovascular system & hematology, patients, clinical, Olfaction Disorders, Taste Disorders, 0302 clinical medicine, Epidemiology, Sore throat, Prevalence, Nose, Age Factors, Headache, Middle Aged, 3. Good health, Europe, medicine.anatomical_structure, COVID-19, Female, patient, medicine.symptom, Symptom Assessment, Coronavirus Infections, Sex characteristics, Adult, medicine.medical_specialty, Pneumonia, Viral, 03 medical and health sciences, Betacoronavirus, Sex Factors, Throat, Internal medicine, Internal Medicine, Humans, Pandemics, covid‐19, rhinorrhea, business.industry, SARS-CoV-2, Bayes Theorem, Myalgia, coronaviru, 030104 developmental biology, business
Abstract: International audience; Background: The clinical presentation of European patients with mild-to-moderate COVID-19 infection is still unknown. Objective: To study the clinical presentation of COVID-19 in Europe. Methods: Patients with positive diagnosis of COVID-19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analysing the relationship between outcomes. Results: A total of 1,420 patients completed the study (962 females, 30.7% of healthcare workers). The mean age of patients was 39.17 ± 12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by 45.4%. The mean duration of COVID-19 symptoms of mild-to-moderate cured patients was 11.5 ± 5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate COVID-19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. Conclusion: The clinical presentation of mild-to-moderate COVID-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate COVID-19 that needs to be recognized as such by the WHO.
Published: 2020
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43. Retinal findings in pediatric patients with Usher syndrome Type 1 due to mutations in MYO7A gene

Author: Jaume Català-Mora, Olaia Subirà, Jesús Díaz-Cascajosa, J.M. Caminal, M. A. Claveria, Joan Prat, Natalia Coll-Alsina, Noel Padrón-Pérez, Christine Petit, Crystel Bonnet, L’Hospitalet de Llobregat [Barcelona, Spain], Hospital Sant Joan de Déu [Barcelona], Syndrome de Usher et autres atteintes rétino-cochléaires, Institut de la Vision, 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 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 National de la Santé et de la Recherche Médicale (INSERM), ED 515 - Complexité du vivant, Université Pierre et Marie Curie - Paris 6 (UPMC), Génétique et Physiologie de l'Audition, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), This work received no funding, We thank the families HEALTH-F2-2010-242013 (TREATRUSH). We also thank Bradley Londres for editing and improving the use of English in this document and Dr. Anne Kurtenbach for her critical review and comments of this paper., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Collège de France - Chaire Génétique et physiologie cellulaire
Subjects: Male, medicine.medical_specialty, Visual acuity, Adolescent, genetic structures, MYO7A, Usher syndrome, [SDV]Life Sciences [q-bio], Visual Acuity, Retina, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ophthalmology, Medicine, Humans, Fluorescein Angiography, External limiting membrane, Child, Melanosome, Retrospective Studies, Retinal pigment epithelium, business.industry, Usher Syndrome Type 1, Retinal, medicine.disease, eye diseases, medicine.anatomical_structure, chemistry, Child, Preschool, Myosin VIIa, Mutation, 030221 ophthalmology & optometry, Female, sense organs, medicine.symptom, business, Usher Syndromes, 030217 neurology & neurosurgery, Tomography, Optical Coherence
Abstract: International audience; Purpose: To describe retinal alterations detected by swept-source optical coherence tomography (SS-OCT) in paediatric patients with Usher syndrome type 1 (USH1) and to compare these findings to previously published reports.Methods: Thirty-two eyes from 16 patients (11 males and 5 females) with a genetic diagnosis of USH1 because of MYO7A mutations underwent SS-OCT. Patients ranged in age from 4 to 17 years (mean, 11,13 ± 4,29). The subfoveal and macular area were analysed with SS-OCT at 1050 nm using 12 radial scans of 12.0 mm. Structural abnormalities were evaluated and correlated with best-corrected visual acuity (BCVA).Results: The most common qualitative retinal abnormality was external layer damage in macular area. Specific alterations included external limiting membrane loss/disruption (27 eyes; 84.4%), disruption of the Myoid zone (27 eyes; 84.4%); Ellipsoid zone disruption (28 eyes; 87.5%), and loss of the outer segments (29 eyes; 90.6%). The damage of the retinal pigment epithelium was divided according to the loss of the different layers: phagosome zone (30 eyes; 93.8%), melanosome zone (29 eyes; 90.6%) and mitochondria zone (0 eyes; 0%). The presence of cystoid macular oedema (CMO) was significantly correlated with alterations in photoreceptors. Disruption or absence of the myoid and ellipsoid zones of the photoreceptors were the only variables independently associated with decreased BCVA.Conclusions: The findings of this study suggest that the physiopathologic basis of early-stage Usher syndrome (USH) may be changes in the outer retinal layer, particularly the photoreceptors, which in turn may cause alterations-such as CMO-in the inner retinal layers. Accordingly, monitoring the condition of photoreceptors during follow-up may be advisable for the early detection of pathologic changes.
Published: 2020

44. The nicotinic receptor alpha5 coding polymorphism rs16969968 as a major target in disease: Functional dissection and remaining challenges

Author: Uwe Maskos, Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Sorbonne Université (SU)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), he author has received funding to carry out the work of his laboratory described in the Review article, as indicated in the published papers. No funding has been received that is directly relevant to this Review article. The author has no conflict of interest to declare., and Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, human genetics, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, Disease, Receptors, Nicotinic, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Biochemistry, nicotine addiction, drug discovery, 03 medical and health sciences, Cellular and Molecular Neuroscience, [SCCO]Cognitive science, 0302 clinical medicine, single nucleotide polymorphism, Animals, Humans, nicotinic acetylcholine receptor, Genetic association, [SCCO.NEUR]Cognitive science/Neuroscience, Human genetics, 3. Good health, schizophrenia, Nicotinic acetylcholine receptor, 030104 developmental biology, Nicotinic agonist, positive allosteric modulator, Genome-wide Association Studies, 030217 neurology & neurosurgery
Abstract: International audience; Nicotinic acetylcholine receptors (nAChRs) are major signalling molecules in the central and peripheral nervous system. Over the last decade, they have been linked to a number of major human psychiatric and neurological conditions, like smoking, schizophrenia, Alzheimer's disease and many others. Human Genome-Wide Association Studies (GWAS) have robustly identified genetic alterations at a locus of chromosome 15q to several of these diseases. In this review, we discuss a major coding polymorphism in the alpha5 subunit, referred to as α5SNP, and its functional dissection in vitro and in vivo. Its presence at high frequency in many human populations lends itself to pharmaceutical intervention in the context of 'positive allosteric modulators' (PAMs). We will present the prospects of this novel treatment, and the remaining challenges to identify suitable molecules.
Published: 2020

45. Les professionnels de santé face à la pandémie de la maladie à coronavirus (COVID-19) : quels risques pour leur santé mentale ?

Author: Nefize Yalin, Frank Bellivier, Alessandro Colasanti, Bruno Étain, Tim Mantingh, Paul R. A. Stokes, Jean-Pierre Kahn, Chantal Henry, Marion Leboyer, Rashmi Patel, Allan H. Young, King‘s College London, Bethlem Royal Hospital [London], Brighton and Sussex Medical School (BSMS), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Fondation FondaMental [Créteil], IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Psychothérapique de Nancy [Laxou] (CPN), This paper represents independent research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Authors from France acknowledge the support provided by INSERM (Research Protocol C0829), Assistance Publique des Hôpitaux de Paris (Research Protocol GAN12)., Etain, Bruno, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: MESH: United Kingdom, Identification, MESH: Protective Devices, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, 0302 clinical medicine, MESH: Risk Factors, MESH: Bipolar Disorder, London, Medicine, MESH: Tobacco, Psychotic illness, MESH: Workload, education.field_of_study, MESH: Sleep Wake Disorders, Mania, Psychiatry and Mental health, Clinical Psychology, Characteristics, MESH: Stress Disorders, Post-Traumatic, MESH: Young Adult, Cohort, cardiovascular system, behavior and behavior mechanisms, France, medicine.symptom, MESH: Uncertainty, MESH: Occupational Diseases, medicine.medical_specialty, MESH: Pandemics, Clinical variables, MESH: Sleep, Bipolar disorder, Population, MESH: Social Support, MESH: Mania, Unipolar mania, behavioral disciplines and activities, 03 medical and health sciences, MESH: Infectious Disease Transmission, Patient-to-Professional, MESH: Severe Acute Respiratory Syndrome, mental disorders, Humans, MESH: SARS-CoV-2, education, Psychiatry, MESH: Work Schedule Tolerance, MESH: Helplessness, Learned, MESH: Humans, business.industry, MESH: Influenza Pandemic, 1918-1919, MESH: Retrospective Studies, MESH: London, medicine.disease, United Kingdom, MESH: Quantitative Trait Loci, MESH: Prospective Studies, 030227 psychiatry, MESH: France, Case register, MESH: Suicide, MESH: Pneumonia, Viral, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Matched group, RC0321, MESH: Resilience, Psychological, business, 030217 neurology & neurosurgery
Abstract: Background: Unipolar mania is a putative subtype of bipolar disorder (BD) in which individuals experience recurrent manic but not major depressive episodes. Few studies of unipolar mania have been conducted in developed countries and none in the UK. This study aimed to identify and characterise people with unipolar mania in the UK and France. \ud \ud Methods: People with unipolar mania were ascertained using a South London UK electronic case register and a French BD case series. Each unipolar mania group was compared to a matched group of people with BD who have experienced depressive episodes. \ud \ud Results: 17 people with unipolar mania were identified in South London and 13 in France. The frequency of unipolar mania as a percentage of the BD clinical population was 1.2% for the South London cohort and 3.3% for the French cohort. In both cohorts, people with unipolar mania experienced more manic episodes than people with BD, and in the French cohort were more likely to experience a psychotic illness onset and more psychiatric admissions. Treatment characteristics of people with unipolar mania were similar to people with BD except that the unipolar mania group was less likely to be treated with antidepressants. \ud \ud Limitations: The relatively small number of people with unipolar mania identified by this study limits its power to detect differences in clinical variables. \ud \ud Conclusions: People with unipolar mania can be identified in France and the UK, and they may experience a higher frequency of manic episodes but have similar treatment characteristics to people with BD.
Published: 2020

46. Evolution and characteristics of the use of valproate in women of childbearing age with bipolar disorder: Results from the FACE-BD cohort

Author: Nicolas Mazer, Christine Passerieux, Bruno Etain, Valerie Aubin, S Gard, Joséphine Loftus, Raoul Belzeaux, Pierre-Michel Llorca, F Poinso, Thomas Schwitzer, Ludovic Samalin, Paul Roux, Bruno Aouizerate, A. Pelletier, Ophélia Godin, Emmanuel Haffen, Emilie Olié, Caroline Dubertret, Raymund Schwan, Marion Leboyer, C. Henry, P. Courtet, Thierry Bougerol, Franck Bellivier, Mircea Polosan, L Encely, Djamila Bennabi, Fondation FondaMental [Créteil], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Psychiatrie et de Médecine Addictologique [AP-HP, GH Saint-Louis-Lariboisière-F.Widal], AP-HP Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal, GHU Paris Psychiatrie et Neurosciences, Service de Psychiatrie [CHU Mondor], Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Princesse Grace de Monaco (CHPG), Monaco, Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Psychothérapique de Nancy-Unité D, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital psychiatrique de Nancy, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Charles Perrens, Ministère des Affaires Sociales et de la Santé ANR-10-COHO-10-01 Institut National de la Santé et de la Recherche Médicale, Inserm Assistance Publique - Hôpitaux de Paris, AP-HP, This multicenter, cross-sectional study included patients recruited into the FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders) cohort between June 2009 and June 2018. The FACE-BD cohort is based on a French national network of 12 BD Expert Centers (Besançon, Bordeaux, Clermont-Ferrand, Créteil, Colombes, Grenoble, Marseille, Monaco, Montpellier, Nancy, Paris and Versailles). This network was set up by the FondaMental Foundation ( www.fondation-fondamental.org ) and funded by the French Ministry of Research and the French Ministry of Health to build an infrastructure and to provide resources to follow clinical cohorts and comparative-effectiveness research on a patient population. This cohort and the clinical variables have been extensively described in a previous paper ( Henry et al., 2015 )., This work was funded by AP-HP (Assistance Publique des Hôpitaux de Paris), by the Fondation FondaMental (RTRS Santé Mentale), by the Investissements d'Avenir program, by the ANR under reference ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01, and by INSERM (Institut National de la Santé et de la Recherche Médicale). This funding source had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication., Aix Marseille Université (AMU), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), and Centre hospitalier Charles Perrens [Bordeaux]
Subjects: Adult, Pediatrics, medicine.medical_specialty, Adolescent, Bipolar disorder, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Logistic regression, National cohort, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Anticonvulsant, Humans, 030212 general & internal medicine, Medical prescription, Women of childbearing age, ComputingMilieux_MISCELLANEOUS, Valproate, business.industry, Valproic Acid, Middle Aged, medicine.disease, 3. Good health, Affect, Psychiatry and Mental health, Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Childbearing age, Cohort, Female, business, 030217 neurology & neurosurgery
Abstract: International audience; Background: Valproate is associated with teratogenic and neurodevelopmental effects. Several agencies have restricted the conditions of its prescription in bipolar disorders (BD). We aimed to assess the evolution of valproate prescription and the clinical profile of BD women of childbearing age receiving valproate. Methods: Based on a large national cohort, we included all BD women 16–50 years old. Sociodemographic, clinical and pharmacological data were recorded. Logistic regression analyses were used to describe variables associated with valproate prescription. Results: Of the 1018 included women 16–50 years old, 26.9% were treated with valproate with a mean daily dosage of 968 mg. The prevalence of BD women using valproate was 32.6% before May 2015 and 17.3% after May 2015 (p
Published: 2020

47. The European Response to COVID19: From Regulatory Emulation to Regulatory Coordination?

Author: Alberto Alemanno, Haldemann, Antoine, Groupement de Recherche et d'Etudes en Gestion à HEC (GREGH), Ecole des Hautes Etudes Commerciales (HEC Paris)-Centre National de la Recherche Scientifique (CNRS), and HEC Research Paper Series
Subjects: Risk analysis, medicine.medical_specialty, Scrutiny, Coronavirus disease 2019 (COVID-19), International trade, Precautionary principle, JEL: K - Law and Economics/K.K3 - Other Substantive Areas of Law, Competence (law), 03 medical and health sciences, 0302 clinical medicine, Emergency Regulation, Political science, 050602 political science & public administration, medicine, media_common.cataloged_instance, 030212 general & internal medicine, European union, Worst-case scenarios, media_common, Emulation, Risk Regulation, Suppression, business.industry, Public health, JEL: K - Law and Economics/K.K3 - Other Substantive Areas of Law/K.K3.K33 - International Law, 05 social sciences, Cost-benefit analysis, EU law, COVID-19, Articles, 0506 political science, Coronavirus, Flatten the Curve, Action (philosophy), Risk vs risk, JEL: K - Law and Economics/K.K3 - Other Substantive Areas of Law/K.K3.K32 - Environmental, Health, and Safety Law, [SHS.GESTION]Humanities and Social Sciences/Business administration, business, [SHS.GESTION] Humanities and Social Sciences/Business administration, Safety Research, Law, tradeoffs
Abstract: COVID-19 is a matter of common European interest since its very first detection on the continent. Yet this pandemic outbreak has largely been handled as an essentially national matter.This article makes a first attempt at unpacking how such fragmented, uncoordinated national responses to COVID19 came into being under the EU legal order. To do so, it systematizes the European response into separate stages. Phase 1 – the emergency – has been characterized by the adoption of national emergency risk management measures that, albeit country specific, were inspired by a common objective of pandemic suppression, i.e. to reduce disease transmission and thereby diminishing pressure on health services, under the by now well-known ‘flatten the curve’ imperative. Phase 2 – the lifting – is about the attempt at relaxing some of the national risk responses in a coordinated fashion to avoid creating negative spillovers or distortions – be they sanitary and/or financial – across the Union.The article argues that contrary to conventional wisdom the resulting uncoordinated EU response to Covid-19 shouldn’t be seen as the inevitable consequence of the EU’s limited competence in public health. Against this backdrop, it strives to define the regulatory policy framework that might be governing the next phases of the European risk management response to this pandemic as they will emerge from a widely undefined yet unescapable dialectic between the Union and its member states. Ultimately, it predicts that by testing the outer limits of the EU public health competence COVID-19 is set to go down in history as a major catalyst in the advancement of EU health emergency action.
Published: 2020

48. Otolaryngological complications of hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring

Author: Francois Bobin, Jerome R. Lechien, Sven Saussez, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], and C. Knuts (native speaker (United States)) for the proofreading of the paper. Published with written consent of the patient.
Subjects: Impedance–pH monitoring, Medicine (General), medicine.medical_specialty, Laryngology, [SDV]Life Sciences [q-bio], education, Case Report, complication, Case Reports, 030204 cardiovascular system & hematology, Ph monitoring, 03 medical and health sciences, Laryngopharyngeal reflux, R5-920, 0302 clinical medicine, medicine, otorhinolaryngologic diseases, Nose, health care economics and organizations, business.industry, pH monitoring, Reflux, General Medicine, respiratory system, medicine.disease, digestive system diseases, testing, 3. Good health, laryngopharyngeal, medicine.anatomical_structure, 030220 oncology & carcinogenesis, impedance, Medicine, lipids (amino acids, peptides, and proteins), Radiology, reflux, business
Abstract: Probe of pH study may kink in the esophagus leading to nasal symptoms during the removal.
Published: 2020

49. The coming age of flavonoids in the treatment of diabetic complications

Author: Gema Marín-Royo, Carmen Gomez-Guerrero, Lucas Opazo-Ríos, Luna Jimenez-Castilla, Jesús Egido, Teresa Caro-Ordieres, Juan Antonio Moreno, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD), [Caro-Ordieres,T] Research Discovery and Innovation Department, FAES FARMA, S.A, Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Leioa (Bizkaia), Spain. [Marín-Royo,G, Opazo-Ríos,L, Jiménez-Castilla,L, Gómez-Guerrero,C, Egido,J] Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autonoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. [Moreno,JA] Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain. [Moreno,JA] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Moreno,JA] Hospital Universitario Reina Sofía, Córdoba, Spain., and This paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130, PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness. No other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Subjects: medicine.medical_specialty, Microvascular complications, Nefropatías Diabéticas, Medicina, Terapéutica, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics [Medical Subject Headings], lcsh:Medicine, Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Nephropathies [Medical Subject Headings], Review, Diabetic nephropathy, Therapeutics, Controlled studies, Chemicals and Drugs::Heterocyclic Compounds::Pyrans::Benzopyrans::Chromones::Flavonoids [Medical Subject Headings], Unmet needs, 03 medical and health sciences, Diabetes mellitus, 0302 clinical medicine, medicine, Flavonoides, Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings], Intensive care medicine, Diseases::Cardiovascular Diseases [Medical Subject Headings], Beneficial effects, Enfermedades Cardiovasculares, 030304 developmental biology, Flavonoids, Inflammation, 0303 health sciences, Inflamación, Diseases::Endocrine System Diseases::Diabetes Mellitus [Medical Subject Headings], business.industry, lcsh:R, Diabetes, General Medicine, medicine.disease, Cardiovascular disease, Clinical trial, Clinical research, Tolerability, Oxidative stress, 030220 oncology & carcinogenesis, business, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Estrés Oxidativo
Abstract: Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding therapies to prevent or retard the progression of diabetic complications remains an unmet need due to the complexity of mechanisms involved, which include inflammation, oxidative stress and angiogenesis, among others. Flavonoids are natural antioxidant compounds that have been shown to possess anti-diabetic properties. Moreover, increasing scientific evidence has demonstrated their potential anti-inflammatory and anti-oxidant effects. Consequently, the use of these compounds as anti-diabetic drugs has generated growing interest, as is reflected in the numerous in vitro and in vivo studies related to this field. Therefore, the aim of this review is to assess the recent pre-clinical and clinical research about the potential effect of flavonoids in the amelioration of diabetic complications. In brief, we provide updated information concerning the discrepancy between the numerous experimental studies supporting the eficacy of flavonoids on diabetic complications and the lack of appropriate and well-designed clinical trials. Due to the well-described beneficial effects on different mechanisms involved in diabetic complications, the excellent tolerability and low cost, future randomized controlled studies with compounds that have adequate bioavailability should be evaluated as add-on therapy on well-established anti-diabetic drugs, This paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130, PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness.
Published: 2020

50. Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women

Author: Agnès Fournier, Marc J. Gunter, Gianluca Severi, Manon Cairat, Laure Dossus, Marie Al Rahmoun, Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France, International Agency for Cancer Research (IACR), 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), Institut Gustave Roussy (IGR), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Ligue Contre le Cancer Mutuelle Générale de l'Education Nationale, MGEN Institut Gustave-Roussy Institut National de la Santé et de la Recherche Médicale, Inserm, Ligue Contre le Cancer (support for the E3N cohort and PhD fellowship to Manon Cairat). Acknowledgements Disclaimer, and The research was carried out using data from the Inserm (French National Institutes for Health and Medical Research) E3N cohort, which was established and maintained with the support of the Mutuelle Générale de l’Education Nationale (MGEN), Gustave Roussy, and the French League against Cancer (LNCC). We are grateful to the study participants for their continued participation and to medical practitioners for providing pathology reports. We also thank all members of the E3N-EPIC study group, in particular Rafika Chaït, Ghizlane Esselma, Marie Fangon, Pascale Gerbouin-Rérolle, Lyan Hoang, Roselyn Gomes and the data management team, and Amandine Gelot for data management and/or technical assistance. The work reported in this paper was performed during Agnès Fournier’s term as a Visiting Scientist at the International Agency for Research on Cancer.
Subjects: medicine.medical_specialty, Proton pump inhibitors, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Comorbidity, Lower risk, lcsh:RC254-282, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Surveys and Questionnaires, Internal medicine, medicine, Humans, Medical history, Prospective Studies, Prospective cohort study, Aged, Proportional Hazards Models, 030304 developmental biology, 0303 health sciences, Aspirin, business.industry, Proportional hazards model, Incidence, Incidence (epidemiology), Anti-Inflammatory Agents, Non-Steroidal, Hazard ratio, Nonsteroidal anti-inflammatory drugs, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Postmenopausal women, 3. Good health, Postmenopause, 030220 oncology & carcinogenesis, Female, France, business, Research Article, Cohort study
Abstract: BackgroundAlthough anti-inflammatory agents could theoretically have anticancer properties, results from cohort studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer (BC) risk are inconsistent.MethodsWe investigated the association between NSAID use and BC incidence in the French E3N prospective cohort, which includes 98,995 women born between 1925 and 1950 and insured by a health insurance plan that covers mostly teachers. Self-reported information on lifestyle and medical history has been collected biennially by questionnaires and matched with data from a drug reimbursement database covering the period 2004–2014. Women who self-reported current NSAID use in the 2000 or 2002 questionnaires or with at least two reimbursements in any previous 3-month period were defined as exposed to NSAIDs. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with BC risk.ResultsIn the current analysis, 62,512 postmenopausal women were followed between 2004 and 2014 (9 years on average, starting at a mean age of 63 years; 2864 incident BC). In multivariable models, there was no statistically significant association between NSAID use and BC risk [HR = 1.00 (0.92–1.08), compared with non-exposed women]. The NSAID-BC associations did not differ by NSAID types, BC subtypes, risk factors, and comorbidities, nor by duration and dose of use. However, a statistically significant interaction was observed by proton pump inhibitor (PPI) drug use (Pinteraction = 0.01) whereby a decreased risk of BC with NSAID use was only observed among women who also used PPI before.ConclusionOnly women who used NSAIDs after having used PPI had a lower risk of BC. This result is novel and requires replication in other studies.
Published: 2020

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