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1. Investing in the foundation of sustainable development: pathways to scale up for early childhood development

Author

Richter, Linda M, Daelmans, Bernadette, Lombardi, Joan, Heymann, Jody, Boo, Florencia Lopez, Behrman, Jere R, Lu, Chunling, Lucas, Jane E, Perez-Escamilla, Rafael, Dua, Tarun, Bhutta, Zulfiqar A, Stenberg, Karin, Gertler, Paul, Darmstadt, Gary L, and Committee, Paper 3 Working Group and the Lancet Early Childhood Development Series Steering

Subjects
Biomedical and Clinical Sciences, Health Sciences, Pediatric, Prevention, Generic health relevance, Quality Education, Child Development, Child Health Services, Child Protective Services, Child, Preschool, Developing Countries, Early Intervention, Educational, Financing, Government, Humans, Maternal Health Services, Politics, Poverty, Paper 3 Working Group and the Lancet Early Childhood Development Series Steering Committee, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals.

Published
2017

3. 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

4. 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

5. Baby Boy Jones Interactive Case-Based Learning Activity

Author

Bruce Paper, Linda Grace Solis, Bonnie Taylor, Elenice Valentim Carmona, and Lisa M. Cleveland

Subjects
E-learning (theory), education, Pilot Projects, Nursing Methodology Research, Infections, Education, User-Computer Interface, Pedagogy, Humans, Medicine, Nurse education, Education, Nursing, Internet, business.industry, Teaching, Infant, Newborn, Nurse educator, Problem-Based Learning, LPN and LVN, Pediatric Nursing, Innovative teaching, Nursing Education Research, Nursing Evaluation Research, Review and Exam Preparation, Neonatal nursing, Fundamentals and skills, Learning Management, Diffusion of Innovation, business, Limited resources, Computer-Assisted Instruction
Abstract

Faced with limited resources, nurse educators are challenged with transforming nursing education while preparing enough qualified nurses to meet future demand; therefore, innovative approaches to teaching are needed. In this article, we describe the development of an innovative teaching activity. Baby Boy Jones is a Web-delivered, case-based learning activity focused on neonatal infection. It was created using e-learning authoring software and delivered through a learning management system.

Published
2015

6. Development and Psychometric Evaluation of the Diabetes Self-Efficacy Scale

Author

Bruce Paper, Susan Grinslade, Hongjuan Jing, and Laurie Quinn

Subjects
Adult, Gerontology, Psychometrics, United Kingdom Prospective Diabetes Study, Population, Type 2 diabetes, Surveys and Questionnaires, Diabetes mellitus, medicine, Humans, education, General Nursing, Aged, Glycemic, Aged, 80 and over, Type 1 diabetes, education.field_of_study, business.industry, Reproducibility of Results, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Obesity, Self Efficacy, Self Care, Diabetes Mellitus, Type 2, Female, Factor Analysis, Statistical, business
Abstract

Background and Purpose: No scales measure self-efficacy in women with Type 2 diabetes. A scale was developed and tested. Methods: Items generated, content validity index (CVI) assessed by experts, the 2-part Diabetes Self-Efficacy Scale (DSLF-I and DSLF-II) was piloted with 62 women, administered to 208 women, and then readministered to 30 women to determine initial reliability. Factor analysis was conducted for construct validity. Discriminant, convergent, and predictive validity was examined. Results: The CVI index was 98%. Cronbach's alphas were 0.88 (DSLF-I) and 0.82 (DSLF-II; pilot) and 0.87 and 0.86, respectively (main study); test-retest correlation was .60 (DSLF-I) and .69 (DSLF-II). There were 3 factors that emerged: diabetes knowledge of self-care activity, diabetes diet self-care, and diabetes medication self-care. Conclusions: The Diabetes Self-Efficacy Scale demonstrates good initial reliability and validity.Keywords: instrument development; self-efficacy; diabetes mellitus Type 2; reliability; validity; factor analysisDiabetes mellitus affects 8.3% of the population in the United States, or 25.8 million people. More than 7 million people are estimated to be undiagnosed and unaware they have the disease (Center for Disease Control and Prevention [CDC], 2011). Approximately 90%-95% of persons with diabetes have Type 2 diabetes mellitus (T2DM). The San Antonio Heart Study revealed a rising incidence of T2DM, with age, ethnicity, and neighborhood as significant predictors of T2DM (Burke et al., 1999).Although T2DM affects all ethnic and gender groups, there is a disparate effect. For example, African Americans are 1.6 times more likely to have diabetes than Whites and are more likely to go undiagnosed American Diabetes Association (ADA, 2005a). Complications from T2DM are also more prevalent in minority populations (Carter, Pugh, & Monterosa, 1996). In addition, diabetic women, compared to diabetic men, have a significantly higher prevalence of cardiovascular disease and suffer greater adverse outcomes (D'Arrigo, 1999; Gu, Cowie, & Harris, 1999; Howard et al., 1998; Smitherman & Reis, 1997). Further, Sowers (1998) reported that the gender protectiveness for coronary heart disease (CHD) declines in women between the ages of 50 and 59 years, and that the loss of gender protectiveness increases the risk ratio for CHD to 3.5 for women with diabetes compared to 2.4 for men with diabetes (p. 618). Koerbel and Korytkowski (2003) stated that women with diabetes not only have greater risk for cardiovascular disease but they also suffer greater adverse outcomes. They cite several factors, which increase this risk in women: poorer glycemic control, elevated blood pressure and lipids, central obesity, increased depression and lower socioeconomic status. These factors contribute to increased morbidity and health care costs for women with diabetes. These data support the need for more research into prevention, detection, and cost-effective methods to effectively manage T2DM and prevent its complications in women.Maintenance of health and prevention of diabetic complications require significant changes in lifestyle management and adherence to a therapeutic diabetic regimen. Behavior change and adherence are not only difficult but are also often inadequate to maintain recommended glycemic control (Anderson, Fitzgerald, & Oh, 1993; Skelly, Marshall, Haughey, Davis, & Dunford, 1995). The importance of participation in diabetic self-care behavior in achieving glycemic control has been demonstrated by the Diabetes Control and Complications Trial Research Group (1993) for individuals with Type 1 diabetes mellitus (T1DM) and by the United Kingdom Prospective Diabetes Study Group (1998) for individuals with T2DM. This goal is accomplished through a therapeutic alliance among clients, family, and health care providers to promote self-care behaviors and therapeutic modalities (ADA, 2005b). Self-care behaviors include a combination of changing or modifying eating habits, maintaining weight or achieving weight loss, participating in a physical exercise program, self-monitoring of blood glucose, and/or taking oral or injectable medication. …

Published
2015

7. '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

8. Sulphated Oligosaccharides as Inhibitors of Hyaluronidases from Bovine Testis, Bee Venom andStreptococcus agalactiae

Author

Günther Bernhardt, Christian Käsbauer, Sunnhild Salmen, Dieter H. Paper, Armin Buschauer, and Julia Hoechstetter

Subjects
Male, Hyaluronoglucosaminidase, Oligosaccharides, Pharmaceutical Science, Venom, Biology, medicine.disease_cause, Streptococcus agalactiae, Analytical Chemistry, Inhibitory Concentration 50, chemistry.chemical_compound, Hyaluronidase, Hyaluronate lyase, Testis, Drug Discovery, Hyaluronic acid, medicine, Animals, Humans, Enzyme Inhibitors, Pharmacology, chemistry.chemical_classification, Plants, Medicinal, Plant Extracts, Sulfates, Organic Chemistry, Neomycin, Bees, Oligosaccharide, Bee Venoms, Enzyme, Complementary and alternative medicine, chemistry, Biochemistry, Molecular Medicine, Cattle, Phytotherapy, medicine.drug
Abstract

Potent and specific inhibitors of hyaluronidases, a group of enzymes preferentially catalysing the hydrolysis of hyaluronic acid, are not known so far. Such compounds could be useful as pharmacological tools for studying the physiological and pathophysiological role of both hyaluronan and hyaluronidases. The effects of sulphated and non-sulphated structurally different oligosaccharides on bovine testicular hyaluronidase, hyaluronidase from bee venom and hyaluronate lyase from Streptococcus agalactiae (hylB (4755)) were studied with the Morgan-Elson reaction. Several active compounds were identified within a series of sulphated beta-(1,4)-galacto-oligosaccharides. The determined IC (50) values of these sulphated oligosaccharides ranged from 4 microM to 630 microM for all hyaluronan-degrading enzymes. Sulphated oligosaccharides like verbascose, planteose and neomycin showed comparable inhibition on all hyaluronidases, thereby possessing 100 - 500 times the activity of the widely accepted hyaluronidase inhibitor apigenin.

Published
2005

9. Comparison of the antiinflammatory effects ofDrosera rotundifolia andDrosera madagascariensis in the HET-CAM assay

Author

Liselotte Krenn, Michaela Kremser, Elisabeth Karall, and D. H. Paper

Subjects
Drosera madagascariensis, Drosera, Flavonoid, Chick Embryo, Pharmacognosy, law.invention, chemistry.chemical_compound, Allantois, law, Botany, Animals, Humans, Inflammation, Pharmacology, chemistry.chemical_classification, Dose-Response Relationship, Drug, biology, Traditional medicine, Plant Extracts, Anti-Inflammatory Agents, Non-Steroidal, Plant Components, Aerial, biology.organism_classification, Drosera rotundifolia, chemistry, Polyphenol, Biological Assay, Phytotherapy, Ellagic acid
Abstract

The antiinflammatory effects of ethanol and aqueous extracts from Drosera rotundifolia and from Drosera madagascariensis were compared in vivo in the HET-CAM assay. Both extracts from D. rotundifolia and the ethanol extract from D. madagascariensis showed remarkable efficacy at doses of 500 microg/pellet. The inhibition of the inflammation by the extracts was stronger than that by 50 microg hydrocortisone/pellet. In contrast, there was only a very weak effect observed at a dose of 500 microg/pellet of the water extract from D. madagascariensis. The chemical analyses of the extracts showed that the effect cannot be attributed to naphthoquinones, but might be due to flavonoids. Ellagic acid obviously plays an important role in the antiangiogenic effect of the Drosera extracts.

Published
2005

10. Hypoglycemic, anticomplement and anti-HIV activities of Spathodea campanulata stem bark

Author

G. Laekeman, E. De Clercq, A. J. Vlietinck, Myriam Witvrouw, Gerhard Franz, G. Niyonzima, B. Van Poel, Luc Pieters, and D. H. Paper

Subjects
Blood Glucose, Anti-HIV Agents, Pharmaceutical Science, Decoction, In Vitro Techniques, Biology, Pharmacology, Plant Epidermis, Mice, Complement Inactivator Proteins, Column chromatography, Drug Discovery, medicine, Animals, Humans, Hypoglycemic Agents, Gabon, Stem bark, Glucose tolerance test, Plants, Medicinal, medicine.diagnostic_test, Plant Extracts, Anti hiv, Glucose Tolerance Test, biology.organism_classification, Complementary and alternative medicine, Molecular Medicine, Spathodea, Female
Abstract

Spathodea campanulata stem bark decoction (SCD) has shown hypoglycemic activity in mice. It was separated by column chromatography into different fractions, which were evaluated for their hypoglycemic, anticomplement and anti-HIV activities. The most polar fraction exerted by far the most prominent effect in different biological models.

Published
1999

11. Natural Products as Angiogenesis Inhibitors

Author

D. H. Paper

Subjects
Adult, Angiogenesis, Pharmaceutical Science, Inflammation, Endogeny, Biology, Analytical Chemistry, Neovascularization, Pathogenesis, Drug Discovery, medicine, Animals, Humans, Pharmacology, Molecular Structure, Neovascularization, Pathologic, Plant Extracts, Organic Chemistry, Cancer, medicine.disease, Angiogenesis inhibitor, Complementary and alternative medicine, Immunology, Cancer research, Molecular Medicine, medicine.symptom, Wound healing
Abstract

Angiogenesis is a strictly controlled process in the healthy, adult human body. It is regulated by a variety of endogenous angiogenic and angiostatic factors. It is only switched on, e.g., during wound healing. Pathological angiogenesis occurs, for example, in cancer, chronic inflammation, or atherosclerosis. Angiogenesis inhibitors are able to interfere with various steps of angiogenesis, like basement destruction of blood vessels, proliferation and migration of endothelial cells, or the lumen formation. Among the known angiogenesis inhibitors compounds derived from natural sources, like flavonoids, sulphated carbohydrates, or triterpenoids are playing a prominent role.

Published
1998

12. Elevated amounts of myocilin in the aqueous humor of transgenic mice cause significant changes in ocular gene expression

Author

Paul Russell, Walter Paper, Ernst R. Tamm, Dietrich A. Stephan, Sebastian Heersink, Rudolf Fuchshofer, and Markus Kroeber

Subjects
Genetically modified mouse, DNA, Complementary, genetic structures, Transgene, Blotting, Western, Mice, Transgenic, Biology, Article, Gene product, Aqueous Humor, Cellular and Molecular Neuroscience, Mice, Trabecular Meshwork, Gene expression, medicine, Animals, Humans, Eye Proteins, Gene, Myocilin, Cells, Cultured, Glycoproteins, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, Reverse Transcriptase Polymerase Chain Reaction, Molecular biology, Sensory Systems, eye diseases, Ophthalmology, Cytoskeletal Proteins, medicine.anatomical_structure, Gene Expression Regulation, Trabecular meshwork, sense organs
Abstract

Myocilin is a 55-57kDa secreted glycoprotein and member of the olfactomedin family, which is mutated in some forms of primary open-angle glaucoma. To assess the effects of elevated amounts of myocilin on aqueous humor outflow dynamics in an in vivo system, transgenic betaB1-crystallin-MYOC mice have been developed that strongly overexpress myocilin in their eyes. The transgenic overexpression of myocilin results in an almost five-fold increase of secreted normal myocilin in the aqueous humor of betaB1-crystallin-MYOC mice. In the present study, we wanted to use betaB1-crystallin-MYOC as a tool to identify the response of ocular tissues to the presence of higher than normal amounts of myocilin, and to identify changes in gene expression that could help to shed light on the functional in vivo properties of myocilin. RNA was isolated from ocular tissues of betaB1-crystallin-MYOC mice and wild-type littermates. Changes in gene expression were determined by hybridization of gene microarrays and confirmed by real time RT-PCR and Western blotting. The expression of genes that had been found to be differentially regulated in betaB1-crystallin-MYOC mice was further analyzed in cultured human trabecular meshwork (HTM) cells treated with recombinant myocilin. Although betaB1-crystallin-MYOC mice do not have an obvious phenotype, a statistically significant up- and downregulation of several distinct genes was found when compared to gene expression in wild-type littermates. Among the genes that were found to be differentially regulated were Wasl, Ceacam1, and Spon2, which are involved in cell adhesion and cell-matrix interactions. Differences in expression were also found for Six1 which encodes for a transcription factor, and for Pftk1 whose gene product is a cdc2-related protein kinase. The expression of these genes was also found to be regulated in vitro in HTM cells treated with recombinant myocilin. Substantially higher amounts in ocular tissues of betaB1-crystallin-MYOC mice were found for connexin 46 and alphaB-crystallin. In addition, several genes that encode for olfactomedin proteins showed distinct changes in expression. Olfml3 was significantly downregulated, while Lphn1, Lphn2, and Lphn3 were significantly upregulated. Our findings support a role for myocilin in modulating cellular adhesion, and suggest functional processes that involve other proteins of the olfactomedin family.

Published
2008

13. Detained adolescents' attitudes about pregnancy and parenthood

Author

Bruce Paper, Patricia J. Kelly, and Janna Lesser

Subjects
Male, Parents, Adolescent, Population, Logistic regression, Developmental psychology, Pregnancy, medicine, Juvenile, Pediatric Nurse Practitioner, Humans, Justice (ethics), education, education.field_of_study, people.profession, medicine.disease, Juvenile detention, Health promotion, Cross-Sectional Studies, Adolescent Behavior, Pediatrics, Perinatology and Child Health, Female, Psychology, people, Attitude to Health
Abstract

Introduction The purpose of this study was to examine attitudes and behaviors associated with parenthood and pregnancy among adolescents in the juvenile justice system. Method A cross-sectional survey of attitudes and behaviors about parenthood was conducted with 300 adolescents residing in three juvenile detention centers. Results Data revealed high rates of risky behaviors that resulted in parenthood/pregnancy and generally positive attitudes about being an adolescent parent. Positive attitudes about parenthood (P = .000) and lower self-efficacy to not have sex (P = .021) were significantly correlated with having been pregnant or having fathered a child. Logistic regression showed positive attitudes about parenthood and the combination of drinking and driving together were significant predictors of pregnancy (P ≤ .05). Discussion Pediatric nurse practitioners working with adolescents in the juvenile justice system who routinely provide prevention counseling and implement health promotion programs must take into account the reality that many adolescents in this population are or will become parents and do not consider pregnancy as an outcome to be necessarily avoided. Moving beyond primary and secondary prevention strategies to implement programs to prevent second pregnancies and enhance parenting skills will provide needed health benefits to these adolescent parents.

Published
2007

14. Can you recognize and respond to von Willebrand disease?

Author

Renee Paper

Subjects
Advanced and Specialized Nursing, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Estrogens, Assessment and Diagnosis, Emergency Nursing, LPN and LVN, Critical Care Nursing, Bioinformatics, medicine.disease, Nurse's Role, Antifibrinolytic Agents, Hemostatics, Patient Care Planning, von Willebrand Diseases, Patient Education as Topic, Adaptation, Psychological, Von Willebrand disease, Medicine, Humans, Deamino Arginine Vasopressin, Blood Coagulation Tests, business, Progesterone
Published
2003

15. Antenatal manifestation of congenital pancreatoblastoma in a fetus with Beckwith-Wiedemann syndrome

Author

G. P. e. l. i. z. z. o., . G. Conoscenti, Vesce, Fortunato, Guerrini, . P., Cavazzini AUTHOR CORRECTIONS: Two of the author names in the above paper, . L., published in the April issue of Prenatal Diagnosis, The correct names are Fortunato Vesce, were supplied e. r. r. o. n. e. o. u. s. l. y., and The authors would like to apologise for any inconvenience caused, Pietro G. u. e. r. r. i. n. i.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Pediatrics, medicine.medical_specialty, Pathology, Pancreatic disease, Beckwith-Wiedemann Syndrome, Pregnancy, High-Risk, Pancreatoblastoma, Beckwith–Wiedemann syndrome, Prenatal diagnosis, Ultrasonography, Prenatal, Pregnancy, Neoplasms, medicine, complications/pathology/ultrasonography, Humans, Prenatal, Cyst, Tomography, Genetics (clinical), Ultrasonography, Fetus, business.industry, Infant, Newborn, Obstetrics and Gynecology, Infant, complications/surgery/ultrasonography, Neoplasms, Germ Cell and Embryonal, Middle Aged, medicine.disease, complications/pathology/ultrasonography, Female, Humans, Infant, Newborn, Maternal Age, Middle Aged, Neoplasms, Germ Cell and Embryonal, complications/surgery/ultrasonography, Pancreatic Neoplasms, complications/surgery/ultrasonography, Pregnancy, Pregnancy, High-Risk, Tomography, X-Ray Computed, Treatment Outcome, Ultrasonography, Newborn, Uniparental disomy, X-Ray Computed, Pancreatic Neoplasms, medicine.anatomical_structure, Treatment Outcome, Female, High-Risk, Pancreas, business, Tomography, X-Ray Computed, Maternal Age
Abstract

Antenatal detection of an isolated abdominal cyst was found to be a pancreatoblastoma in a female fetus with Beckwith-Wiedemann syndrome. Prenatal and post-natal features and management of this very rare tumour are discussed. Molecular investigation disclosed a mosaic paternal 11p15 uniparental disomy in the tumoral cells. The prognosis of a congenital pancreatoblastoma is good if complete surgical excision is achieved. However, the association with Beckwith-Wiedemann syndrome requires a prolonged follow-up because of the increased risk of developing malignant tumours.

Published
2003

16. Becoming a partner in your healthcare

Author

R, Paper

Subjects
Physician-Patient Relations, Communication, Personal Autonomy, Quality of Life, Humans, Guidelines as Topic, Hemophilia A
Abstract

Chronic disorders such as haemophilia and von Willebrand disease can rob people of a feeling of control over their lives. Added to this is often a feeling of confusion or intimidation when dealing with the healthcare system. People may begin to feel like victims of their disorders and of the healthcare system. The healthcare system defines people who are in receipt of care as patients. The word patient comes from the Latin word patiens, which means to suffer, endure, allow, permit or undergo. Even the term implies a sense of victimization. People who become partners in their care and view the receipt and delivery of healthcare as a service wherein they are the consumer and the doctor or clinician is the provider, will feel more in control and will likely have better outcomes than people who assume the more traditional role of 'patient'.

Published
2002

17. Synthetic 2-aroylindole derivatives as a new class of potent tubulin-inhibitory, antimitotic agents

Author

Heinz-Herbert Fiebig, Markus Frieser, Siavosh Mahboobi, Harald Hufsky, Thomas Beckers, D. H. Paper, Jutta Bürgermeister, Herwig Pongratz, Frank-D. Böhmer, Jörg Hockemeyer, Angelika M. Burger, Alexei Lyssenko, and Silke Baasner

Subjects
G2 Phase, Indoles, Transplantation, Heterologous, Mice, Nude, Mitosis, Angiogenesis Inhibitors, Antineoplastic Agents, In Vitro Techniques, GTP Phosphohydrolases, HeLa, chemistry.chemical_compound, Mice, Structure-Activity Relationship, Biopolymers, Microtubule, Allantois, Tubulin, Drug Discovery, Tumor Cells, Cultured, Animals, Humans, Cytotoxicity, Melanoma, biology, Chorion, Cell cycle, biology.organism_classification, Nocodazole, Biochemistry, chemistry, biology.protein, Molecular Medicine, Antimitotic Agent, Cattle, Drug Screening Assays, Antitumor
Abstract

A new class of simple synthetic antimitotic compounds based on 2-aroylindoles was discovered. (5-Methoxy-1H-2-indolyl)-phenylmethanone (1) as well as analogous 3-fluorophenyl- (36) and 3-methoxyphenyl (3) derivatives displayed high cytotoxicity of IC(50) = 20 to 75 nM against the human HeLa/KB cervical, SK-OV-3 ovarian, and U373 astrocytoma carcinoma cell lines. The inhibition of proliferation correlated with the arrest in the G2/M phase of the cell cycle. In in vitro assays with tubulin isolated from bovine brain, in general antiproliferative activity correlated with inhibition of tubulin polymerization. Thus, the antimitotic activity of 2-aroylindoles is explained by interference with the mitotic spindle apparatus and destabilization of microtubules. In contrast to colchicine, vincristine, nocodazole, or taxol, 1 did not significantly affect the GTPase activity of beta-tubulin. Interestingly, selected compounds inhibited angiogenesis in the chorioallantoic membrane (CAM) assay. In xenograft experiments, 1 was highly active after oral administration at 200 mg/kg against the human amelanocytic melanoma MEXF 989 in athymic nude mice. We conclude, that 2-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.

Published
2001

18. Gynaecological complications in women with bleeding disorders

Author

Paper R

Subjects
medicine.medical_specialty, business.industry, General surgery, Pregnancy Complications, Hematologic, Hemorrhage, Hematology, General Medicine, Coagulation Protein Disorders, Hemophilia A, Surgery, von Willebrand Diseases, Pregnancy, medicine, Humans, Female, business, Genital Diseases, Female, Genetics (clinical)
Published
2000

19. Acid-sensitive polyethylene glycol conjugates of doxorubicin: preparation, in vitro efficacy and intracellular distribution

Author

Luigi Messori, Peter Schumacher, Pierluigi Orioli, Felix Kratz, Clemens Unger, Heinz H. Fiebig, Thomas Roth, D. H. Paper, Paula C.A. Rodrigues, Rolf Mülhaupt, and Ulrich Beyer

Subjects
Clinical Biochemistry, Pharmaceutical Science, Antineoplastic Agents, Polyethylene glycol, Biochemistry, Polyethylene Glycols, chemistry.chemical_compound, Drug Stability, Amide, Drug Discovery, PEG ratio, medicine, Tumor Cells, Cultured, Animals, Humans, Doxorubicin, Molecular Biology, Maleimide, Tumor Stem Cell Assay, Organic Chemistry, DNA, Hydrogen-Ion Concentration, chemistry, Doxorubicin Preparation, Microscopy, Fluorescence, Biophysics, Molecular Medicine, Cattle, Drug carrier, Ethylene glycol, medicine.drug
Abstract

Coupling anticancer drugs to synthetic polymers is a promising approach of enhancing the antitumor efficacy and reducing the side-effects of these agents. Doxorubicin maleimide derivatives containing an amide or acid-sensitive hydrazone linker were therefore coupled to alpha-methoxy-poly(ethylene glycol)-thiopropionic acid amide (MW 20000 Da), alpha,omega-bis-thiopropionic acid amide poly(ethylene glycol) (MW 20000 Da) or alpha-tert-butoxy-poly(ethylene glycol)-thiopropionic acid amide (MW 70000 Da) and the resulting polyethylene glycol (PEG) conjugates isolated through size-exclusion chromatography. The polymer drug derivatives were designed as to release doxorubicin inside the tumor cell by acid-cleavage of the hydrazone bond after uptake of the conjugate by endocytosis. The acid-sensitive PEG conjugates containing the carboxylic hydrazone bonds exhibited in vitro activity against human BXF T24 bladder carcinoma and LXFL 529L lung cancer cells with IC70 values in the range 0.02-1.5 microm (cell culture assay: propidium iodide fluorescence or colony forming assay). In contrast, PEG doxorubicin conjugates containing an amide bond between the drug and the polymer showed no in vitro activity. Fluorescence microscopy studies in LXFL 529 lung cancer cells revealed that free doxorubicin accumulates in the cell nucleus whereas doxorubicin of the acid-sensitive PEG doxorubicin conjugates is primarily localized in the cytoplasm. Nevertheless, the acid-sensitive PEG doxorubicin conjugates retain their ability to bind to calf thymus DNA as shown by fluorescence and visible spectroscopy studies. Results regarding the effect of an acid-sensitive PEG conjugate of molecular weight 20000 in the chorioallantoic membrane (CAM) assay indicate that this conjugate is significantly less embryotoxic than free doxorubicin although antiangiogenic effects were not observed.

Published
2000

20. Selective inhibition of cell proliferation and DNA synthesis by the polysulphated carbohydrate l-carrageenan

Author

Walter Woodrow Burns, Richard Hoffman, and D. H. Paper

Subjects
Male, Cancer Research, TGF alpha, Angiogenesis, medicine.medical_treatment, Basic fibroblast growth factor, Antineoplastic Agents, Breast Neoplasms, Biology, Toxicology, Carrageenan, chemistry.chemical_compound, medicine, Tumor Cells, Cultured, Humans, Pharmacology (medical), Endothelium, Cells, Cultured, Pharmacology, DNA synthesis, Cell growth, Growth factor, Prostatic Neoplasms, DNA, DNA, Neoplasm, Molecular biology, Growth Inhibitors, Endothelial stem cell, Oncology, chemistry, Biochemistry, Cell culture, Depression, Chemical, Female, Fibroblast Growth Factor 2, Cell Division
Abstract

l-Carrageenan is a polysulphated carbohydrate that antagonises some heparin-binding growth factors. We assessed the effect of l-carrageenan on the proliferation of a panel of cell lines, some of which require heparin-binding growth factors for mitogenesis. The importance of growth factor antagonism for the anti-proliferative activity was also determined. Cell proliferation was determined by cell counts and a tetrazolium dye (MTT) assay, and DNA synthesis was determined by thymidine incorporation. The proliferation of the basic fibroblast growth factor (bFGF)-dependent endothelial cell line FBHE was inhibited by daily administration of l-carrageenan in a dose-dependent manner [concentration inhibiting cell growth by 50% (IC50 value), approx. 0.5 microgram/ml]. However, excess bFGF did not reverse the inhibitory effect. DNA synthesis was completely inhibited by concentrations of l-carrageenan that nonetheless allowed significant protein synthesis to occur. The proliferation of the androgen-dependent prostate-carcinoma cell line LNCaP was also inhibited by l-carrageenan (IC50 value, 5.5 micrograms/ml) and the cells were arrested at the G1/S boundary. l-Carrageenan inhibited DNA synthesis in MCF-7 cells stimulated by bFGF and transforming growth factor alpha (TGF alpha) but not in those stimulated by insulin-like growth factor 1 (IGF-1). Blocking IGF-1-mediated DNA synthesis with anti-IGF-1 receptor antibody alpha IR3 enhanced the inhibitory activity of l-carrageenan against MCF-7 cells grown in serum. A number of other transformed and non-transformed cell lines were either partially inhibited or not inhibited by l-carrageenan. l-Carrageenan had low anti-coagulant activity. l-Carrageenan is a selective anti-proliferative agent and warrants further investigation for anti-angiogenic therapy (in view of its activity against endothelial cells) and for the treatment of androgen-dependent prostate cancer.

Published
1995

21. Use of sulfonated primers to detect and type papillomavirus in cell cultures and cervical biopsies

Author

Michael Friedman, Israel Nur, and Thierry Paper

Subjects
Sexually transmitted disease, Biopsy, Molecular Sequence Data, Cervix Uteri, Biology, Polymerase Chain Reaction, Sensitivity and Specificity, law.invention, chemistry.chemical_compound, law, Primer dimer, Genetics, Humans, DNA Probes, HPV, Papillomaviridae, Polymerase chain reaction, Electroblotting, Cells, Cultured, Base Sequence, DNA–DNA hybridization, General Medicine, Virology, Molecular biology, Blotting, Southern, Poly C, chemistry, Oligodeoxyribonucleotides, Recombinant DNA, Female, Primer (molecular biology), Ethidium bromide, Sulfur, Plasmids
Abstract

Human papillomavirus (HPV) was detected by using two sets of deoxyribonucleotide primers for differentiating between 'low-risk' types (HPV11 and HPV6) and 'high-risk' (hri) types (HPV16, HPV18 and HPV33). A new application of the Chemiprobe method for labeling DNA was used to detect products of the polymerase chain reaction (PCR) from 36 cervical biopsies. This method, first demonstrated by Uchimura et al. (submitted), is based on the sulfonation of a polycytidylic acid tail of 5-20 monomers attached to the 5' end of either one or both of the PCR primers. This procedure can increase the sensitivity of detection of PCR products more than 100-fold with respect to ethidium bromide (EtdBr) staining. Various methods were used to detect hri HPV DNA in the 36 clinical samples. The number of positive results obtained was as follows, two by Southern-blot hybridization; five by PCR amplification followed by electrophoresis and detection of products by EtdBr staining; six by PCR amplification using one or two sulfonated C-tailed primers followed by electroblotting and immunoenzymatic visualization; and five by hybridization of sulfonated genomic viral recombinant with a PCR product immobilized on a membrane. The yield of the PCR product was significantly greater when one of the primers was C-tailed than when both or neither of the primers were C-tailed. PCR employing sulfonated C-tailed oligo primers is very specific and sensitive, and the entire procedure can be employed as a nonradioactive substitute for radioactive dot-blot or Southern-blot hybridization procedures, routinely used for detection of HPV in clinical samples.

Published
1991

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. The challenge of West Nile virus in Europe: knowledge gaps and research priorities

Author

Sebastian Ulbert, Norbert Nowotny, Ana Moreno, Luisa Barzon, N. Pardigon, Penelope Koraka, Antonio Tenorio, Miguel Ángel Jiménez-Clavero, Jordi Figuerola, Paolo Cordioli, Niek N. Sanders, Byron E. E. Martina, Annapaola Rizzoli, Fondazione Edmund Mach - Edmund Mach Foundation [Italie] (FEM), Centro de Investigacion en Sanidad Animal (INIA-CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Universita degli Studi di Padova, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'Bruno Ubertini' (IZSLER), Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Veterinary Medicine [Vienna] (Vetmeduni), Sultan Qaboos University (SQU), Institut Pasteur [Paris], Universiteit Gent = Ghent University [Belgium] (UGENT), Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Instituto de Salud Carlos III [Madrid] (ISC), This paper is the product of a cooperative action promoted by the Coordinators and delegates of the EU funded projects on West Nile virus under the 7th European Programme, in particular the EuroWestNile project (www.eurowestnile.org, GA n. 261391), the EDENext project (www.edenext.eu , GA n. 261504) the Wings project (www.west-nile-shield-project.eu , GA n. 261426), and the Vectorie project (www.vectorie.eu , GA n. 261466). This study was partially funded by EU grant FP7-261504 EDENext and is catalogued by the EDENext Steering Committee as EDENext 142 (http://www.edenext.eu). AR was partially funded by the Autonomous Province of Trento grant LExEM (http://www.lexem.eu). The contents of this publication are the sole responsibility of the authors and don't necessarily reflect the views of the European Commission., This paper is dedicated to the memory of our wonderful colleague and friend, Dr Paolo Cordioli, who recently passed away. We thank the European Centre for Disease Prevention and Control (ECDC) for supporting this initiative and for promoting a stronger integration between public health and research in Europe. We also thank Dr Jolanta Kolodziejek of the Institute of Virology, University of Veterinary Medicine Vienna for establishing the phylogenetic trees and Matteo Marcantonio of the GIS/RS platform at the Edmund Mach Foundation for preparing the map in Figure 1, European Project: 261391,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EUROWESTNILE(2011), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), European Project: 261426,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,WINGS(2011), European Project: 261466,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,VECTORIE(2010), Virology, Università degli Studi di Padova = University of Padua (Unipd), Institut Pasteur [Paris] (IP), Universiteit Gent = Ghent University (UGENT), and Publica

Subjects
Health Knowledge, Attitudes, Practice, Veterinary medicine, Economic growth, WNV STRAINS, Epidemiology, viruses, MESH: Health Knowledge, Attitudes, Practice, medicine.disease_cause, Disease Outbreaks, EXPERIMENTAL-INFECTION, ENVELOPE PROTEIN, Neuroinvasive disease, Medicine and Health Sciences, MESH: Genetic Variation, MESH: Disease Outbreaks, MESH: Phylogeny, Phylogeny, media_common, EARLY WARNING SYSTEM, biology, SUBSTITUTION, AMINO-ACID, 3. Good health, Europe, MESH: Research, Geography, Population Surveillance, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, West Nile virus, SPARROWS PASSER-DOMESTICUS, media_common.quotation_subject, Ecology (disciplines), MESH: Population Surveillance, SDG 3 - Good Health and Well-being, Virology, medicine, Humans, media_common.cataloged_instance, Veterinary Sciences, European union, TIME RT-PCR, Settore VET/06 - PARASSITOLOGIA E MALATTIE PARASSITARIE DEGLI ANIMALI, MESH: West Nile virus, MESH: West Nile Fever, MESH: Humans, Research, LINEAGE 1 STRAIN, Public Health, Environmental and Occupational Health, Genetic Variation, Outbreak, biology.organism_classification, USUTU VIRUS, Early warning system, MESH: Europe, CULEX-PIPIENS MOSQUITOS, Usutu virus, West Nile Fever, Diversity (politics)
Abstract

West Nile virus (WNV) is continuously spreading across Europe, and other continents, i.e. North and South America and many other regions of the world. Despite the overall sporadic nature of outbreaks with cases of West Nile neuroinvasive disease (WNND) in Europe, the spillover events have increased and the virus has been introduced into new areas. The high genetic diversity of the virus, with remarkable phenotypic variation, and its endemic circulation in several countries, require an intensification of the integrated and multidisciplinary research efforts built under the 7th Framework Programme of the European Union (FP7). It is important to better clarify several aspects of WNV circulation in Europe, including its ecology, genomic diversity, pathogenicity, transmissibility, diagnosis and control options, under different environmental and socio-economic scenarios. Identifying WNV endemic as well as infection-free areas is becoming a need for the development of human vaccines and therapeutics and the application of blood and organs safety regulations. This review, produced as a joint initiative among European experts and based on analysis of 118 scientific papers published between 2004 and 2014, provides the state of knowledge on WNV and highlights the existing knowledge and research gaps that need to be addressed with high priority in Europe and neighbouring countries.

Published
2015

29. 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

30. The use of genetic tests to diagnose and manage patients with myeloproliferative and myeloproliferative/myelodysplastic neoplasms, and related disorders

Author

Catherine Cargo, Mamta Garg, Adam J. Mead, Anna L. Godfrey, Nicholas C.P. Cross, and Paper, A British Society for Haematology Good Practice

Subjects
medicine.medical_specialty, Receptor, Platelet-Derived Growth Factor alpha, Oncogene Proteins, Fusion, Mutation, Missense, Severity of Illness Index, Receptors, Colony-Stimulating Factor, Humans, Point Mutation, Medicine, Eosinophilia, Genetic Testing, mRNA Cleavage and Polyadenylation Factors, Biological Products, Myeloproliferative Disorders, business.industry, Disease Management, Bone Marrow Examination, Exons, Hematology, Janus Kinase 2, Prognosis, Dermatology, Clone Cells, Proto-Oncogene Proteins c-kit, Molecular Diagnostic Techniques, Myelodysplastic Syndromes, medicine.symptom, Calreticulin, business, Receptors, Thrombopoietin, Forecasting
Published
2021

31. Anthropometric deficits and the associated risk of death by age and sex in children aged 6–59 months: A meta‐analysis

Author

Susan Thurstans, Stephanie V. Wrottesley, Bridget Fenn, Tanya Khara, Paluku Bahwere, James A. Berkley, Robert E. Black, Erin Boyd, Michel Garenne, Sheila Isanaka, Natasha Lelijveld, Christine M. McDonald, Andrew Mertens, Martha Mwangome, Kieran S. O'Brien, Heather Stobaugh, Sunita Taneja, Keith P. West, Saul Guerrero, Marko Kerac, André Briend, Mark Myatt, London School of Hygiene and Tropical Medicine (LSHTM), SOUtenabilité et RésilienCE (SOURCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Recherche pour le Développement (IRD [France-Nord]), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-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 Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-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), Epicentre [Paris] [Médecins Sans Frontières], United States Agency for International Development, USAID, Irish Aid: HQPU/2021/ENN, This paper is made possible by the generous support of the American people through the United States Agency for International Development (USAID), and by funding from Irish Aid (grant number (HQPU/2021/ENN). The contents are entirely the responsibility of its authors and do not necessarily reflect the views of USAID or the United States Government or represent or reflect Irish Aid policy., Tampere University, and Clinical Medicine

Subjects
Male, Adolescent, wasting, Thinness, underweight, 3123 Gynaecology and paediatrics, Clinical Research, Prevalence, Humans, sex, Child, Growth Disorders, Pediatric, Nutrition and Dietetics, Anthropometry, Nutrition & Dietetics, Wasting Syndrome, Prevention, Malnutrition, stunting, Public Health, Environmental and Occupational Health, Infant, Obstetrics and Gynecology, mortality, Good Health and Well Being, age, Pediatrics, Perinatology and Child Health, Female, Zero Hunger, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6–59 months by age and sex. We categorised children into younger (6–23 months) and older (24–59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < −2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.

Published
2022

32. A dynamic neural field model of multimodal merging: application to the ventriloquist effect

Author

Simon Forest, Jean-Charles Quinton, Mathieu Lefort, Statistique pour le Vivant et l’Homme (SVH), Laboratoire Jean Kuntzmann (LJK), Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Institut National de Recherche en Informatique et en Automatique (Inria)-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), Systèmes Cognitifs et Systèmes Multi-Agents (SyCoSMA), 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), Project AMPLIFIER, funded by the French region Auvergne-Rhône-Alpes in the context of the 'Pack Ambition Recherche' initiative., Most of the computations presented in this paper were performed using the GRICAD infrastructure (https://gricad.univ-grenoble-alpes.fr), which is supported by Grenoble research communities., ANR-11-LABX-0025,PERSYVAL-lab,Systemes et Algorithmes Pervasifs au confluent des mondes physique et numérique(2011), and ANR-14-CE25-0006,GAG,Jeux et graphes(2014)

Subjects
Superior Colliculi, Arts and Humanities (miscellaneous), Cognitive Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, Visual Perception, Humans, Bayes Theorem, Computer Simulation, [INFO.INFO-NE]Computer Science [cs]/Neural and Evolutionary Computing [cs.NE], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Photic Stimulation, Probability
Abstract

Multimodal merging encompasses the ability to localize stimuli based on imprecise information sampled through individual senses such as sight and hearing. Merging decisions are standardly described using Bayesian models that fit behaviors over many trials, encapsulated in a probability distribution. We introduce a novel computational model based on dynamic neural fields able to simulate decision dynamics and generate localization decisions, trial by trial, adapting to varying degrees of discrepancy between audio and visual stimulations. Neural fields are commonly used to model neural processes at a mesoscopic scale—for instance, neurophysiological activity in the superior colliculus. Our model is fit to human psychophysical data of the ventriloquist effect, additionally testing the influence of retinotopic projection onto the superior colliculus and providing a quantitative performance comparison to the Bayesian reference model. While models perform equally on average, a qualitative analysis of free parameters in our model allows insights into the dynamics of the decision and the individual variations in perception caused by noise. We finally show that the increase in the number of free parameters does not result in overfitting and that the parameter space may be either reduced to fit specific criteria or exploited to perform well on more demanding tasks in the future. Indeed, beyond decision or localization tasks, our model opens the door to the simulation of behavioral dynamics, as well as saccade generation driven by multimodal stimulation.

Published
2022

33. Uses and perceptions of medications among French older adults: results from the 2020 French Health Barometer survey

Author

Anh Thi-Quynh Tran, Noémie Soullier, Joël Ankri, Marie Herr, Laure Carcaillon-Bentata, 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, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale, Inserm, The authors are grateful to the French Health Barometer team of the French National Public Health Agency for their work and support. They also thank Solène Drusch, PhD Candidate at Université Paris-Saclay, UVSQ, INSERM, CESP, Anti-infective evasion and pharmacoepidemiology, for reviewing preliminary version of this paper., This study received no external funding. The French Health Barometer survey was funded by the French National Public Health Agency., and HAL UVSQ, Équipe

Subjects
[SDV]Life Sciences [q-bio], Self Medication, Health survey, Health Surveys, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Older adults, Polypharmacy, Humans, Perceptions, Female, France, Self-medication, Geriatrics and Gerontology, Aged
Abstract

Background There are few studies reporting on self-medication, perceptions or difficulties older adults have with their medications. This study aimed to describe the uses and the perceptions of medications among older adults in France and to identify patient groups based on that information. Methods We used data from the 2020 ‘French Health Barometer’ – a nationally-representative cross-sectional survey. We assessed polypharmacy (five or more medications), self-medication, and patient perceptions of medications. Robust Poisson regression was used to investigate socio-demographic and health-related factors associated with the outcomes. Latent class analysis was used to identify patient groups classified by the use and the perceptions of medications. Factors associated with group assignment were investigated by multinomial logistic regression. All analyses were weighted. Results The study sample comprised 1,623 respondents aged 70–85 years. Polypharmacy and self-medication were reported in 23.5 and 48.7% of the older population, respectively. Polypharmacy was associated with increasing age, low education, and impaired health status. Self-medication was associated with female sex and high education. Among individuals taking at least 1 medication, 8.2% reported not to understand all their medications, and 9.7% having difficulty taking medications as prescribed. Among individuals taking at least 2 medications, 23.2% thought that they took too many medications. Three patient groups were identified: ‘Non-polypharmacy, positive perceptions’ (62.5%), ‘Polypharmacy, positive perceptions’ (28.0%), and ‘Negative perceptions’ (9.5%). Conclusions Polypharmacy and self-medication are common in French older adults. One segment of people reported negative perceptions of their medications regardless of their polypharmacy status. This underlines the difference between the objective and perceived measures of polypharmacy.

Published
2022

34. Association of food insecurity with suicidal ideation and suicide attempts in adults aged ≥50 years from low- and middle-income countries

Author

Lee Smith, Jae Il Shin, Christina Carmichael, Louis Jacob, Karel Kostev, Igor Grabovac, Yvonne Barnett, Laurie Butler, Rosie K. Lindsay, Damiano Pizzol, Nicola Veronese, Pinar Soysal, Ai Koyanagi, Smith, Lee, Shin, Jae Il, Carmichael, Christina, Jacob, Loui, Kostev, Karel, Grabovac, Igor, Barnett, Yvonne, Butler, Laurie, Lindsay, Rosie K, Pizzol, Damiano, Veronese, Nicola, Soysal, Pinar, Koyanagi, Ai, SOYSAL, PINAR, Anglia Ruskin University (ARU), Yonsei University, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), IQVIA, Medizinische Universität Wien = Medical University of Vienna, Università degli studi di Palermo - University of Palermo, ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), Universitat Pompeu Fabra [Barcelona] (UPF), National Institute on Aging, NIA: OGHA 04034785, R01-AG034479, R21-AG034263, Y1-AG-1005–01, YA1323–08-CN-0020, This paper uses data from WHO's Study on Global Aging 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 ., and European Project: 671500,H2020,H2020-FETHPC-2014,SAGE(2015)

Subjects
Male, Low- and middle-income countries, Suicide, Attempted, Suicidal Ideation, Psychiatry and Mental health, Clinical Psychology, Food Insecurity, Cross-Sectional Studies, Association of food insecurity with suicidal ideation and suicide attempts in adults aged ≥50 years from low- and middle-income countries.-, Journal of affective disorders, 2022, Risk Factors, Older adults, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Food insecurity, Low- and middle-income countries, Older adults, Suicidal ideation, Suicide attempts, Humans, Female, Developing Countries, Suicide attempts, Aged
Abstract

Background-\ud \ud The aim of the present study was to investigate associations between food insecurity with suicidal ideation and suicide attempts in adults aged ≥50 years from six low- and middle-income countries (LMICs).\ud \ud Methods-\ud \ud Cross-sectional, community-based data from the World Health Organisation's Study on Global Aging and Adult Health were analyzed. Self-reported information on past 12-month suicidal ideation and suicide attempts was collected. Past 12-month food insecurity was assessed with two questions on frequency of eating less and hunger due to lack of food. Multivariable logistic regression analysis was conducted to assess the association between food insecurity and suicidal ideation or suicide attempts.\ud \ud Results-\ud \ud The final analytical sample included 34,129 individuals aged ≥50 years [mean (SD) age 62.4 (16.0) years; 52.1% females]. Compared to no food insecurity, severe food insecurity was associated with a significant 2.78 (95%CI = 1.73–4.45) times higher odds for suicidal ideation, while moderate and severe food insecurity were associated with 2.59 (95%CI = 1.35–4.97) and 5.15 (95%CI = 2.52–10.53) times higher odds for suicide attempts, respectively.\ud \ud Limitations-\ud \ud The cross-sectional design, the use of self-reported wish to die as a measure of suicide ideation, and that suicidal ideation and suicide attempts were only assessed among those who had depressive symptoms, could be considered limitations of our study.\ud \ud Conclusions-\ud \ud Food insecurity was positively associated with suicidal ideation and suicide attempts. Targeting food insecurity among older adults in LMICs may lead to reduction in suicidal ideation and suicide attempts, although future longitudinal studies are warranted to confirm this.

Published
2022

35. 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

36. Privacy-preserving mimic models for clinical named entity recognition in French

Author

Nesrine Bannour, Perceval Wajsbürt, Bastien Rance, Xavier Tannier, Aurélie Névéol, Information, Langue Ecrite et Signée (ILES), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Sciences et Technologies des Langues (STL), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), This work was supported by ITMO Cancer Aviesan. The funding organization had no role in the conceptualization, design, data collection and analysis, preparation of the paper, or the decision to publish it., Tannier, Xavier, École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE)

Subjects
Computer, Narration, Mimic learning, Privacy, [INFO.INFO-CL] Computer Science [cs]/Computation and Language [cs.CL], Natural language processing, Confidentiality Datasets as topic, Humans, Electronic health records, Health Informatics, Neural networks, [INFO.INFO-CL]Computer Science [cs]/Computation and Language [cs.CL], Computer Science Applications
Abstract

International audience; A vast amount of crucial information about patients resides solely in unstructured clinical narrative notes. There has been a growing interest in clinical Named Entity Recognition (NER) task using deep learning models. Such approaches require sufficient annotated data. However, there is little publicly available annotated corpora in the medical field due to the sensitive nature of the clinical text. In this paper, we tackle this problem by building privacy-preserving shareable models for French clinical Named Entity Recognition using the mimic learning approach to enable the knowledge transfer through a teacher model trained on a private corpus to a student model. This student model could be publicly shared without any access to the original sensitive data. We evaluated three privacy-preserving models using three medical corpora and compared the performance of our models to those of baseline models such as dictionary-based models. An overall macro F-measure of 70.6% could be achieved by a student model trained using silver annotations produced by the teacher model, compared to 85.7% for the original private teacher model. Our results revealed that these privacy-preserving mimic learning models offer a good compromise between performance and data privacy preservation.

Published
2022

37. 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

38. Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study

Author

Carmen Martinez, Petra H.M. Peeters, Merethe Kumle, Paolo Vineis, Armelle Munnia, Seymour Garte, Bas Bueno-de-Mesquita, Emmanuelle Gormally, Ole Raaschou-Nielsen, Antonio Agudo, Giuseppe Matullo, Bengt Järvholm, Françoise Clavel-Chapelon, José Ramón Quirós, Göran Berglund, Marco Peluso, Alison M. Dunning, Rosario Tumino, Alessandro Colombi, Salvatore Panico, Timothy J. Key, Luisa Airoldi, Elio Riboli, S Bingham, Fabrizio Veglia, Rudolf Kaaks, Antonia Trichopoulou, Aurelio Barricarte, Vittorio Krogh, Christian Malaveille, Nicholas E. Day, Kim Overvad, Rodolfo Saracci, Herman Autrup, María José Tormo, Domenico Palli, J. Linseisen, Heiner Boeing, Miren Dorronsoro, Faculteit Medische Wetenschappen/UMCG, Peluso, M, Airoldi, L, Munnia, A, Colombi, A, Veglia, F, Autrup, H, Dunning, A, Garte, S, Gormally, E, Malaveille, C, Matullo, G, Overvad, K, Raaschou Nielsen, O, Clavel Chapelon, F, Linseisen, J, Boeing, H, Trichopoulou, A, Palli, D, Krogh, V, Tumino, R, Panico, Salvatore, Bueno De Mesquita, Bh, Peeters, Ph, Kumle, M, Agudo, A, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, Mj, Quiros, Jr, Berglund, G, Jarvholm, B, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, Riboli, E, Bingham, S, Vineis, P., [Peluso,M, Munnia, A] Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy. [Airoldi,L, Colombi,A] Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. [Veglia, F, Matullo,G] ISI Foundation, Turin, Italy. [Autrup,H] Department of Environmental and Occupational Medicine, Aarhus, Denmark. [Dunning, A] Department of Oncology, University of Cambridge, Cambridge, UK. [Garte,S] Genetics Research Institute, Milan, Italy. [Gormally,E, Malaveille,C] International Agency for Research on Cancer, Lyon, France. [Overhad,K] Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Raaschou-Nielsen,O] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Clavel-Chapelon,F] INSERM (Institut National de la Sante´ et de la Recherche Me´dicale), ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, F-94805, France. [Linseisen,J] Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, German. [Boeing,H] German Institute of Human Nutrition, Potsdam-Rehbu¨cke, Germany. [Trichopoulou,A] Department of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Cancer Prevention Tuscany Region, Florence, Italy. [Krogh,V] Department of Epidemiology, National Cancer Institute, Milan, Italy. [Tumino,R] Cancer Registry, Azienda Ospedaliera ‘Civile MP Arezzo’, Ragusa, Ital. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Universita` Federico II, Naples, Italy. [Bueno-De-Mesquita,BH] Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherland. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Kumle,M] Institute of Community Medicine, University of Tromso, Tromso, Norway. [Agudo,A] Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain. [Martinez,C] Andalusian School of Public Health, Granada, Spain. [Dorronsoro,M] Department of Public Health of Guipuzkoa, San Sebastian, Spain. [Barricarte,A] Public Health Institute, Navarra, Spain. [Tormo,MJ] Epidemiology Department, Murcia Health Council, Murcia, Spain. Quiros, JR] Direccio´n General de Salud Pu´blica, Consejerı´a de Salud y Servicios Sanitarios Asturias, Oviedo, Spain. [Berglund,G] Malmo¨ Diet and Cancer Study, Lund University, Malmo¨, Sweden. [Jarvholm,G] Department of Nutritional Research, University of Umea˚, Umea˚ , Sweden. [Day,ND, Bingham,S] MRC Dunn Human Nutrition Unit, Cambridge University, UK. [Key,TJ].Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK. [Saracci,R] IFC National Research Council, Pisa, Italy. [Kaas,R] Division of Epidemiology, DKFZ Heidelberg, Germany. [Riboli,E] Imperial College London, London, UK. [Vineis,P] University of Turin, Turin, Italy. Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 1PG, UK, This paper was made possible by a grant of the European Community (5th Framework Programme) to P. V. (grant QLK4–CT–1999–00 927) and a grant of the Compagnia di San Paolo to the ISI Foundation. All authors are independent from funders. Mortality data for the Netherlands were obtained from Statistics Netherlands. Also, the work described in the paper was carried out with the financial support of: Europe Against Cancer Program of the European Commission (SANCO), ISCIII, Red de Centros RCESP, C03/09, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Dutch Ministry of Public Health, Welfare and Sports, World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Ska°ne, Sweden, Norwegian Cancer Society, and Research Council of Norway.

Subjects
Dietary Fiber, Male, Aflatoxin, Erythrocytes, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Hemoglobins [Medical Subject Headings], medicine.medical_treatment, air pollution, RESISTANT STARCH, Medicine (miscellaneous), GUIDELINES, Carcinógenos, Body Mass Index, COLORECTAL-CANCER, Food group, chemistry.chemical_compound, Hemoglobins, Vegetables, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants::Air Pollutants [Medical Subject Headings], Leukocytes, Aductos de ADN, Nutritional Physiological Phenomena, Food science, Prospective Studies, RISK, DNA adducts, Haemoglobin adducts, Non-smokers, Fibre intake, Air pollution, Publication Characteristics::Study Characteristics::Multicenter Study [Medical Subject Headings], Air Pollutants, Nutrition and Dietetics, Chemistry, Technology, Industry, Agriculture::Food and Beverages::Food::Dietary Fiber [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Noxae::Carcinogens [Medical Subject Headings], COLON-CANCER, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage::DNA Adducts [Medical Subject Headings], Fabaceae, Middle Aged, fibre intake, European Prospective Investigation into Cancer and Nutrition, Europe, Biochemistry, 4-Aminobiphenyl, Colonic Neoplasms, Hemoglobinas, Female, SMOKERS, Alcohol Drinking, BLADDER-CANCER, European Prospective Investigation into Cancer and Nutrition (EPIC), haemoglobin adducts, non-smokers, RATS, POLYCYCLIC AROMATIC-HYDROCARBONS, Ozone, LUNG-CANCER, DNA adduct, medicine, Humans, Contaminantes del aire, ddc:610, Carcinogen, Aged, Estudio multicéntrico, Vitamin E, Fruit, Multivariate Analysis, Fibras en la dieta, Carcinogens, Biomarkers, Food contaminant
Abstract

Udgivelsesdato: 2008-Feb-14 In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0.02), vitamin E (P = 0.04) and alcohol (P = 0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.

Published
2008

39. Sex Differences in Outcomes of Tetralogy of Fallot Patients With Implantable Cardioverter-Defibrillators

Author

Victor Waldmann, Abdeslam Bouzeman, Guillaume Duthoit, Linda Koutbi, Francis Bessière, Fabien Labombarda, Christelle Marquié, Jean-Baptiste Gourraud, Pierre Mondoly, Jean Marc Sellal, Pierre Bordachar, Alexis Hermida, Alain Al Arnaout, Frédéric Anselme, Caroline Audinet, Yvette Bernard, Serge Boveda, Sok Sithikun Bun, Morgane Chassignolle, Gaël Clerici, Antoine Da Costa, Maxime de Guillebon, Pascal Defaye, Nathalie Elbaz, Romain Eschalier, Rodrigue Garcia, Charles Guenancia, Benoit Guy-Moyat, Franck Halimi, Didier Irles, Laurence Iserin, François Jourda, Magalie Ladouceur, Philippe Lagrange, Mikael Laredo, Jacques Mansourati, Grégoire Massoulié, Amel Mathiron, Philippe Maury, Anne Messali, Kumar Narayanan, Cédric Nguyen, Sandro Ninni, Marie-Cécile Perier, Bertrand Pierre, Penelope Pujadas, Frédéric Sacher, Pascal Sagnol, Ardalan Sharifzadehgan, Camille Walton, Pierre Winum, Cyril Zakine, Laurent Fauchier, Raphaël Martins, Jean-Luc Pasquié, Jean-Benoit Thambo, Xavier Jouven, Nicolas Combes, Eloi Marijon, Chrystelle Akret, Jean-Paul Albenque, Vincent Algalarrondo, Christine Alonso, Denis Amet, Frédéric Ansselme, Anouk Asselin, Nicolas Badenco, Hugues Bader, Marc Badoz, Pierre Baudinaud, Nathalie Behar, Mouna Ben Kilani, Géraldine Bertaux, Cathy Bertrand, Francis Bessiere, Hughes Blangy, Damien Bonnet, Pierre Bordchar, Paul Bru, Adrien Carabelli, Christèle Cardin, Bruno Cauchemez, Tej Chalbia, Laure Champ-Rigot, Thomas Chastre, Philippe Chevallier, Nicolas Clementy, Stéphane Combes, Christian De Chillou, Maxime De Guillebon, Bruno Degand, Jean-Claude Deharo, Nicolas Derval, Sylvie Di Filippo, Guillaume Domain, Antoine Dompnier, Arnaud Dulac, Alexandre Duparc, D Cécile Duplantier, Rim El Bouazzaoui, Bogdan Enache, Fabrice Extramiana, Pierre Fiorello, Pierre Frey, Luc Freysz, Vincent Galand, Estelle Gandjbakhch, Kevin Gardey, Olivier Geoffroy, Bénédicte Godin, Samuel Goussot, Caroline Grimard, Jean-Baptiste Guichard, Michel Haissaguerre, David Hamon, Sébastien Hascoet, Karim Hasni, Jean-Sylvain Hermida, Françoise Hidden-Lucet, Mélèze Hocini, Jérome Hourdain, Peggy Jacon, Gaël Jauvert, Frédéric Jean, Nicolas Johnson, Pierre Khattar, Ziad Khoueiry, Rita Koutbi, Guillaume Laborie, Gabriel Lactu, Pierre-Marc Lallemand, Gabriel Laurent, Thomas Lavergne, Arnaud Lazarus, Laurianne Le Gloan, Christophe Leclercq, Antoine Leenhardt, Nicolas Lellouche, Christophe Loose, Philippe Mabo, Alice Maltret, Franck Mandel, Christelle Marquie, Carole Maupain, Antoine Milhelm, Paul Milliez, Adrian Mirolo, Ghassan Moubarak, Stéphane Mourot, Jacky Ollitrault, Pierre Ollitrault, Akli Otmani, Jean-Luc Pasquie, Dominique Pavin, Séverinne Philibert, Damien Poindron, Charlotte Potelle, Vincent Probst, Paul Puie, Anne Rollin, Cécile Romeyer-Bouchard, Nicolas Sadoul, Audrey Sagnard, Arnaud Savoure, Didier Scarlatti, Fabien Squara, Nikita Tanese, Jean Benoit Thambo, Olivier Thomas, Emie Varlet, Sandrine Venier, Quentin Voglimacci Stephanopoli, Xavier Waintraub, Françoise Wiart, Alexandre Zhao, Amir Zouaghi, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Clinique Pasteur, Clinique Pasteur [Toulouse], and This work was supported by the French Institute of Health and Medical Research, Fédération Française de Cardiologie, and Société Française de Cardiologie. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Subjects
Male, Adult, Heart Defects, Congenital, Sex Characteristics, sudden death, Middle Aged, congenital heart disease, Defibrillators, Implantable, Cohort Studies, implantable cardioverter-defibrillator, Death, Sudden, Cardiac, Tetralogy of Fallot, sex, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, women, ventricular arrhythmia
Abstract

International audience; Background: Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far.Objectives: The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs).Methods: Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee.Results: A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95% CI: 0.8%-1.5%) vs 2.2% (95% CI: 1.8%-2.6%) in men (P < 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95% CI: 0.76-1.97; P = 0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95% CI: 0.81-2.19; P = 0.30), with 24 women (49.0%) experiencing at least 1 complication.Conclusions: Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574)

Published
2022

40. Impact of Coronavirus disease 2019 (COVID-19) on contraception use in 2020 and up until the end of April 2021 in France

Author

Noémie Roland, Jérôme Drouin, David Desplas, Lise Duranteau, François Cuenot, Rosemary Dray-Spira, Alain Weill, Mahmoud Zureik, HAL UVSQ, Équipe, 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, EPI-PHARE (EPI-PHARE), Caisse nationale d'assurance maladie des travailleurs salariés [CNAMTS]-Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM, Funding: This research was funded by EPI-PHARE, the French National Health Insurance Fund (CNAMTS) and the French National Agency for Medicines and Health Products Safety (ANSM). NR, DD, FC, RDS and MZ are employees of the French National Agency for Medicines and Health, JD and AW of the French National Health Insurance Fund., and Each author has confirmed compliance with the journal's requirements for authorship. We thank Anthony Saul for his help in correcting and clarifying the manuscript. Funding: This research was funded by EPI-PHARE, the French National Health Insurance Fund (CNAMTS) and the French National Agency for Medicines and Health Products Safety (ANSM). NR, DD, FC, RDS and MZ are employees of the French National Agency for Medicines and Health, JD and AW of the French National Health Insurance Fund. Declarations of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Subjects
Adult, Adolescent, Levonorgestrel, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Article, Young Adult, Pregnancy, Contraceptive Agents, Female, Humans, Pandemics, SARS-CoV-2, Infant, Obstetrics and Gynecology, Healthcare access, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Contraception, Reproductive Medicine, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Communicable Disease Control, Reproductive health, Contraceptive methods, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sexual Health, Contraception, Postcoital, Covid-19
Abstract

International audience; Objectives: To assess the impact of the COVID-19 pandemic on the use of reimbursed contraceptives in France after 15 months of the pandemic, according to age-group and updating previous data only pertaining to the first lockdown (2 months). Study design: We conducted a national register-based study by extracting all reimbursements of oral contraceptives (OC), emergency contraception (EC), intrauterine devices (IUD), and implants from the French National Health Insurance database (SNDS), which includes and covers 99.5% of the French population, in 2018, 2019, 2020 and from January 1, 2021 to April30, 2021. We calculated the expected use of contraceptives in 2020 and 2021 in the absence of the pandemic, based on 2018 and 2019 usage and taking annual trends into account. We assessed the difference between observed and expected dispensing rates by contraceptive type and by age-group (≤18 years old, 18< age ≤25, 25< age ≤35, >35). Results: Dispensing of all contraceptives decreased compared to expect dispensing numbers: −2.0% for OC, −5.3% for EC, −9.5% for LNG-IUS, −8.6% for C-IUD, and −16.4% for implant. This decrease in the dispensing of contraceptives was observed in all age-groups, but mainly concerned women under the age of 18 years (−22% for OC, −10% for EC, −37.2% for LNG-IUS, −36.4% for C-IUD, −26.4% for implant) and those aged 18 to 25 (−5.1% for OC, −11.9% for EC, −18.1% for LNG-IUS, −15.9% for C-IUD, −17.6% for implants). Conclusions: Our study showed that the dispensing of contraceptives in France was markedly impacted by the COVID-19 pandemic. Prescriptions for long-acting contraceptive use and women under the age of 25 years were the most substantially impacted. Ensuring access to contraceptive methods during health emergencies must be a public health policy priority. Implications: The COVID-19 pandemic strongly impacted the dispensing of contraceptives in France with varying degrees of decreased dispensing according to the type of contraceptive, the age-group and the level of pandemic-related restrictions. The impact of these restrictions on unintended pregnancy at the population level remains undetermined.

Published
2022

41. How much does prosody help word segmentation? A simulation study on infant-directed speech

Author

Emmanuel Dupoux, Reiko Mazuka, Alejandrina Cristia, Bogdan Ludusan, RIKEN Center for Brain Science [Wako] (RIKEN CBS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Department of Psychology and Neuroscience, Duke University [Durham], Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), 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), Apprentissage machine et développement cognitif (CoML), 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)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), École des hautes études en sciences sociales (EHESS), 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 RM. It was also supported by the European Research Council (ERC-2011-AdG-295810 BOOTPHON), the Agence Nationale pour la Recherche (ANR-17-CE28-0007 LangAge, ANR-16-DATA-0004 ACLEW, ANR-14-CE30-0003 MechELex, ANR-17-EURE-0017 Frontcog, ANR-10-IDEX-0001-02 PSL*, ANR-19-P3IA-0001 PRAIRIE 3IA Institute). ED is further grateful to the CIFAR (Learning in Machines and Brain), BL to the Canon Foundation in Europe, and AC to the JS McDonnell Foundation., ANR-17-CE28-0007,LangAge,Différences dans l'apprenabilité du langage selon l'âge(2017), ANR-16-DATA-0004,ACLEW,Analyzing Child Language Experiences Around the World(2016), ANR-14-CE30-0003,MechELex,Méchanismes d'acquisition lexicale précoce(2014), ANR-17-EURE-0017,FrontCog,Frontières en cognition(2017), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), European Project: 295810,EC:FP7:ERC,ERC-2011-ADG_20110406,BOOTPHON(2012), École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)

Subjects
Linguistics and Language, Cognitive Neuroscience, Speech recognition, Experimental and Cognitive Psychology, Prosody, Infant-directed speech, 050105 experimental psychology, Language and Linguistics, Speech Acoustics, Task (project management), Infant language acquisition, Developmental and Educational Psychology, Humans, Learning, Speech, 0501 psychology and cognitive sciences, Segmentation, Computer Simulation, ComputingMilieux_MISCELLANEOUS, Computational model, 05 social sciences, Text segmentation, Infant, acquisition, [SCCO.LING]Cognitive science/Linguistics, Word segmentation, [SCCO.PSYC]Cognitive science/Psychology, Speech Perception, Infant language, Cues, Heuristics, Psychology, Word (computer architecture), 050104 developmental & child psychology
Abstract

International audience; Infants come to learn several hundreds of word forms by two years of age, and it is possible this involves carving these forms out from continuous speech. It has been proposed that the task is facilitated by the presence of prosodic boundaries. We revisit this claim by running computational models of word segmentation, with and without prosodic information, on a corpus of infant-directed speech. We use five cognitively-based algorithms, which vary in whether they employ a sub-lexical or a lexical segmentation strategy and whether they are simple heuristics or embody an ideal learner. Results show that providing expert-annotated prosodic breaks does not uniformly help all segmentation models. The sub-lexical algorithms, which perform more poorly, benefit most, while the lexical ones show a very small gain. Moreover, when prosodic information is derived automatically from the acoustic cues infants are known to be sensitive to, errors in the detection of the boundaries lead to smaller positive effects, and even negative ones for some algorithms. This shows that even though infants could potentially use prosodic breaks, it does not necessarily follow that they should incorporate prosody into their segmentation strategies, when confronted with realistic signals.

Published
2022

42. 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

43. Cardiac Outcomes in Adults With Mitochondrial Diseases

Author

Konstantinos Savvatis, Christoffer Rasmus Vissing, Lori Klouvi, Anca Florian, Mehjabin Rahman, Anthony Béhin, Abdallah Fayssoil, Marion Masingue, Tanya Stojkovic, Henri Marc Bécane, Nawal Berber, Fanny Mochel, Denis Duboc, Bertrand Fontaine, Bjørg Krett, Caroline Stalens, Julie Lejeune, Robert D.S. Pitceathly, Luis Lopes, Malika Saadi, Thomas Gossios, Vincent Procaccio, Marco Spinazzi, Céline Tard, Pascal De Groote, Claire-Marie Dhaenens, Claire Douillard, Andoni Echaniz-Laguna, Ros Quinlivan, Michael G. Hanna, Ali Yilmaz, John Vissing, Pascal Laforêt, Perry Elliott, Karim Wahbi, Queen Mary University of London (QMUL), IT University of Copenhagen (ITU), Association française contre les myopathies (AFM-Téléthon), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University College of London [London] (UCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (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), Université Paris Cité (UPCité), Sorbonne Université (SU), Hôpital Cochin [AP-HP], Aristotle University of Thessaloniki, 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), Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Hôpital Claude Huriez [Lille], CHU Lille, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), MR/S005021/1, Association Française contre les Myopathies, AFM, Medical Research Council, MRC: MR/S002065/1, Department of Health and Social Care, DH, University College London Hospitals NHS Foundation Trust, UCLH, NIHR Cambridge Biomedical Research Centre, This study was funded by grants from the Association Française contre les Myopathies (French Alliance against Myopathies), which was not involved in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, the preparation, review or approval of the manuscript, and nor in the decision to submit the manuscript for publication. Dr Pitceathly is supported by a Medical Research Council (United Kingdom) Clinician Scientist Fellowship (MR/S002065/1). Drs Pitceathly and Hanna receive funding from a Medical Research Council (United Kingdom) strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) (MR/S005021/1). Dr Lopes is supported by a Medical Research Council (United Kingdom) clinical academic partnership (CARP) award. Dr Quinlivan was funded by National Institute for Health and Care Research Biomedical Research Centre, University College Hospitals Foundation Trust. The University College London Hospitals/University College London Queen Square Institute of Neurology sequencing facility receives a proportion of funding from the Department of Health's National Institute for Health and Care Research Biomedical Research Centre’s funding scheme. The clinical and diagnostic 'Rare Mitochondrial Disorders' Service in London is funded by the U.K. NHS Highly Specialised Commissioners. Dr Elliott has received consultancy fees from Pfizer, Sanofi, Sarepta, DinaQor, Freeline, Novo Nordisk, and Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Subjects
Adult, conduction disease, mitochondrial diseases, [SDV]Life Sciences [q-bio], heart failure, sudden death, Heart, Stroke Volume, Prognosis, DNA, Mitochondrial, Ventricular Function, Left, single large-scale deletions, Risk Factors, Humans, Hypertrophy, Left Ventricular, Cardiology and Cardiovascular Medicine, G%22">m3243A>G
Abstract

International audience; Background: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE). Objectives: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population. Methods: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases. Results: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction

Published
2022

44. A new SARS-CoV-2 variant poorly detected by RT-PCR on nasopharyngeal samples, with high lethality: an observational study

Author

Fillâtre, Pierre, Dufour, Marie-José, Behillil, Sylvie, Vatan, Remi, Reusse, Pascale, Gabellec, Alice, Velmans, Nicolas, Montagne, Catherine, Du Coudret, Sophie Geffroy, Droumaguet, Edith, Merour, Véronique, Enouf, Vincent, Buzele, Rodolphe, Valence, Marion, Guillotel, Elena, Gagniere, Bertrand, Baidaliuk, Artem, Zhukova, Anna, Tourdjman, Mathieu, Thibault, V., Grolhier, Claire, Pronier, Charlotte, Lescure, François-Xavier, Simon-Loriere, Etienne, Costagliola, Dominique, Van Der Werf, Sylvie, Tattevin, Pierre, Massart, Nicolas, CHU de Saint-Brieuc, Centre hospitalier Pierre Le Damany - Lannion, Centre hospitalier de Lannion, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Pasteur International Bioresources network (PIBNet), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, CHU Pontchaillou [Rennes], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ARN régulateurs bactériens et médecine (BRM), 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 ), None, We thank Olivia Da Conceicao and Cylia Imekhlaf for their help in collecting data from patients' charts. We would like to thank all the healthcare workers, public health employees, and scientists involved in the COVID-19 response to this outbreak. We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID (Supplementary Material Table S2). We avoided any direct analysis of genomic data not submitted as part of this paper and used this genomic data only as background. This work used the computational and storage services (Maestro cluster) provided by the IT department at Institut Pasteur, Paris., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Jonchère, Laurent, Virus et Interférence ARN - Viruses and RNA Interference, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Morphogenèse du cœur - Heart morphogenesis (Imagine - Institut Pasteur U1163), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and 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 )

Subjects
SARS-CoV-2 variants, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, [SDV]Life Sciences [q-bio], COVID-19, Coronavirus infections, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Humans, Original Article, Severity of illness index / Virology, France, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, COVID-19 / Epidemiology, Retrospective Studies
Abstract

Objectives In early January 2021, an outbreak of nosocomial cases of COVID-19 emerged in Western France, with RT-PCR tests repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole genome sequencing (WGS) revealed a new variant, currently defining a novel SARS-CoV-2 lineage: B.1.616. In March, WHO classified this variant as ‘under investigation’ (VUI). We analyzed the characteristics and outcomes of COVID-19 cases related to this new variant. Methods Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled inpatients with either: i) positive SARS-CoV-2 RT-PCR on a respiratory sample; ii) seroconversion with anti-SARS-CoV-2 IgG/IgM; iii) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as either: i) B.1.616; ii) variant of concern (VOC); iii) unknown. Results From January 1st to March 24th, 2021, 114 patients fulfilled inclusion criteria: B.1.616 (n=39), VOC (n=32), and unknown (n=43). B.1.616-related cases were older than VOC-related cases (81 years interquartile range [IQR] [73-88], vs 73 years IQR [67-82], P, Graphical abstract Image 1

Published
2022

45. Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition

Author

Marie Breeur, Pietro Ferrari, Laure Dossus, Mazda Jenab, Mattias Johansson, Sabina Rinaldi, Ruth C. Travis, Mathilde His, Tim J. Key, Julie A. Schmidt, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Joseph A. Rothwell, Nasser Laouali, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Fabian Eichelmann, Domenico Palli, Sara Grioni, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Bas Bueno-de-Mesquita, Karina Standahl Olsen, Torkjel Manning Sandanger, Therese Haugdahl Nøst, J. Ramón Quirós, Catalina Bonet, Miguel Rodríguez Barranco, María-Dolores Chirlaque, Eva Ardanaz, Malte Sandsveden, Jonas Manjer, Linda Vidman, Matilda Rentoft, David Muller, Kostas Tsilidis, Alicia K. Heath, Hector Keun, Jerzy Adamski, Pekka Keski-Rahkonen, Augustin Scalbert, Marc J. Gunter, Vivian Viallon, Cancer Research UK, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), 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, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC: 2014/1183, C8221/A19170, Seventh Framework Programme, FP7: 2014/1193, 313010, C19335/A21351, National Research Council, NRC, World Cancer Research Fund International, WCRF, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, European Commission, EC, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Generalitat de Catalunya, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2009-139, 2013/1002, 2014-1-RT-02-CIRC-1, 2015-166, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Consejería de Salud y Familias, Junta de Andalucía, NIHR Imperial Biomedical Research Centre, BRC, The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., This paper is dedicated to the memory our of colleague Dr. Bas Bueno-de-Mesquita. 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., The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). IDIBELL acknowledges support from the Generalitat de Catalunya through the CERCA Program. The breast cancer study was funded by the French National Cancer Institute (grant number 2015-166). The colorectal cancer studies were funded by World Cancer Research Fund (reference: 2013/1002, reference: 313010, reference: 2014/1193, INCa, grant numbers 2009-139 and 2014-1-RT-02-CIRC-1) and by internal funds of the IARC. For the participants in the prostate cancer study, sample retrieval and preparation, and assays of metabolites were supported by Cancer Research UK (C8221/A19170), and funding for grant 2014/1183 was obtained from the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme. Mathilde His’ work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC. The funders were not involved in designing the study, collecting, analysing, and interpreting results, or writing and submitting the manuscript for publication., and HAL UVSQ, Équipe

Subjects
Male, Carcinoma, Hepatocellular, Proline, Glutamine, Kidney, Risk Factors, General & Internal Medicine, Humans, Metabolomics, Histidine, Prospective Studies, Breast, Càncer, 11 Medical and Health Sciences, Colorectal, Cancer, Cancer och onkologi, Liver Neoplasms, Prostate, Lysophosphatidylcholines, General Medicine, Sphingomyelins, Metabolòmica, Liver, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Cancer and Oncology, Carcinoma, Hepatocellular/diagnosis, Phosphatidylcholines, Epic, Endometrial, Lasso, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, EPIC
Abstract

Background Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. Results Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. Conclusions These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.

Published
2022

46. 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

47. 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

48. Hygrometric Performances of Different High-Flow Nasal Cannula Devices: Bench Evaluation and Clinical Tolerance

Author

Pierre-Alexandre Bouchard, Serge Simard, François Lellouche, Mathieu Delorme, Equipe de Recherche Paramédicale sur le Handicap NeuroMoteur (ERPHAN), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, American Thoracic Society, ATS, Dr Lellouche presented a version of this paper at the European Society of Intensive Care Medicine Congress, held in Berlin, Germany, in 2015, and at the American Thoracic Society Congress, held in San Francisco, California, in 2016.Devices and consumables were provided by Fisher & Paykel Healthcare, Vapotherm, and Hydrate, who had no other involvement in the study. The study was supported by the Groupe de Recherche en Sant? Respiratoire de l?Universit? Laval (GESER).The authors would like to thank all participants who accepted being enrolled as healthy subjects in this study., and Devices and consumables were provided by Fisher & Paykel Healthcare, Vapotherm, and Hydrate, who had no other involvement in the study. The study was supported by the Groupe de Recherche en Santé Respiratoire de l’Université Laval (GESER).

Subjects
Pulmonary and Respiratory Medicine, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, medicine.disease_cause, Psychrometry, Healthy volunteers, Medicine, Cannula, Humans, Absolute humidity, Original Research, Noninvasive Ventilation, business.industry, Breathing comfort, Respiration, Healthy subjects, Oxygen Inhalation Therapy, Temperature, General Medicine, Compensation algorithm, Humidification performances, Anesthesia, High-flow nasal cannula, Breathing, Noninvasive ventilation, High flow, business, Respiratory Insufficiency, Nasal cannula
Abstract

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly used for the management of respiratory failure. Settings include [Formula: see text] , total gas flow, and temperature target. Resulting absolute humidity (AH) at the nasal cannula may affect clinical tolerance, and optimal settings with respect to hygrometry remain poorly documented. METHODS: A bench study was designed to assess AH delivered by 4 HFNC devices (Optiflow, Airvo 2, Precision Flow, and Hydrate) according to flow, ambient temperature, and other available settings. Clinical tolerance of different levels of hygrometry (20, 30, and 40 mg H(2)O/L) was evaluated in 15 healthy volunteers. RESULTS: With [Formula: see text] set at 1.0, normal ambient temperature, and settings made accordingly to the manufacturers’ recommendations, mean ± SD AH was 42.2 ± 3.1, 39.5 ± 1.8, 35.7 ± 2.0, and 32.9 ± 2.7 mg H(2)O/L for the Airvo 2, Optiflow, Hydrate, and Precision Flow, respectively, (P < .001). AH dropped from −3.5 to −10.7 mg H(2)O/L (P

Published
2021

49. Agent-based modelling of reactive vaccination of workplaces and schools against COVID-19

Author

Benjamin Faucher, Rania Assab, Jonathan Roux, Daniel Levy-Bruhl, Cécile Tran Kiem, Simon Cauchemez, Laura Zanetti, Vittoria Colizza, Pierre-Yves Boëlle, Chiara Poletto, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), École des Hautes Études en Santé Publique [EHESP] (EHESP), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Tokyo Institute of Technology [Tokyo] (TITECH), We acknowledge financial support from Haute Autorité de Santé, the ANR and Fondation de France through the project NoCOV (00105995), the Municipality of Paris (https://www.paris.fr/) through the programme Emergence(s), EU H2020 grants MOOD(H2020-874850, paper MOOD 035) and RECOVER (H2020-101003589) (the contents of this publication do not necessarily reflect the views of the European Commission), the ANRS through the project EMERGEN (ANRS0151), and the Institut des Sciences duCalcul et de la Donnée., ANR-20-COVI-0070,NoCOV,Prévisions au court et moyen terme de la diffusion de COVID-19 dans la population générale française(2020), European Project: 874850,H2020-SC1-2019-Single-Stage-RTD,MOOD(2020), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), EHESP, SCD, Prévisions au court et moyen terme de la diffusion de COVID-19 dans la population générale française - - NoCOV2020 - ANR-20-COVI-0070 - COVID-19 - VALID, MOnitoring Outbreak events for Disease surveillance in a data science context - MOOD - 874850 - INCOMING, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, and European Project: 874850,MOOD

Subjects
Multidisciplinary, Schools, Systems Analysis, Vaccination, General Physics and Astronomy, COVID-19, General Chemistry, General Biochemistry, Genetics and Molecular Biology, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Workplace, COVID 19
Abstract

With vaccination against COVID-19 stalled in some countries, increasing vaccine accessibility and distribution could help keep transmission under control. Here, we study the impact of reactive vaccination targeting schools and workplaces where cases are detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, demographics, behavioural changes and social distancing. In most scenarios, reactive vaccination leads to a higher reduction in cases compared with non-reactive strategies using the same number of doses. The reactive strategy could however be less effective than a moderate/high pace mass vaccination program if initial vaccination coverage is high or disease incidence is low, because few people would be vaccinated around each case. In case of flare-ups, reactive vaccination could better mitigate spread if it is implemented quickly, is supported by enhanced test-trace-isolate and triggers an increased vaccine uptake. These results provide key information to plan an adaptive vaccination rollout.

Published
2021

50. Halving food-related greenhouse gas emissions can be achieved by redistributing meat consumption: progressive optimization Results of the NutriNet-Santé cohort

Author

Julia Baudry, Denis Lairon, Alison Dussiot, Philippe Pointereau, Brigitte Langevin, Benjamin Allès, Pauline Rebouillat, Emmanuelle Kesse-Guyot, Mathilde Touvier, Joséphine Brunin, Serge Hercberg, François Mariotti, Hélène Fouillet, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914)), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SOLAGRO, Solagro, Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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)-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), Association Solagro (Solagro), The NutriNet-Sante study is funded by FrenchMinistry of Health and Social Affairs, Sante Publique France, Institut National de la Sante et de la Recherche Medicale, Institut National de la Recherche Agronomique, Conservatoire National des Arts et Metiers, and Sorbonne Paris Nord University. The BioNutriNet project was supported by the French National Research Agency (Agence Nationale de la Recherche) in the context of the 2013 Programme de Recherche Systemes Alimentaires Durables (ANR-13-ALID-0001). The funders had no role in the study design, data collection, analysis, interpretation of data, preparation of the manuscript, and decision to submit the paper., ANR-13-ALID-0001,BioNutriNet,Consommation d'aliments issus de l'agriculture biologique: déterminants et motivation vis-à-vis de la durabilité, impact nutritionnel, économique, environnemental et toxicologique(2013), Kesse-guyot, Emmanuelle, and Systèmes Alimentaires Durables - Consommation d'aliments issus de l'agriculture biologique: déterminants et motivation vis-à-vis de la durabilité, impact nutritionnel, économique, environnemental et toxicologique - - BioNutriNet2013 - ANR-13-ALID-0001 - ALID - VALID

Subjects
Adult, Male, Meat, Environmental Engineering, 010504 meteorology & atmospheric sciences, Animal food, 010501 environmental sciences, 01 natural sciences, Food Supply, Nutrition Policy, Greenhouse Gases, Nutrient, Animal science, Ruminant, Animals, Humans, Environmental Chemistry, Waste Management and Disposal, Aged, 0105 earth and related environmental sciences, 2. Zero hunger, Consumption (economics), [SDV.EE]Life Sciences [q-bio]/Ecology, environment, biology, business.industry, Intensive farming, greenhouse gas emissions, Middle Aged, biology.organism_classification, co-product tradeoffs, Pollution, Diet, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.EE] Life Sciences [q-bio]/Ecology, environment, diet sustainability, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 13. Climate action, Greenhouse gas, Cohort, Food processing, Environmental science, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, optimization modelling, Energy Intake, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Background Diet-related greenhouse gas emissions (GHGe) mainly comes from animal-sourced foods. As progressive changes are more acceptable for a sustainable food transition, we aimed to identify nutritionally adequate and culturally acceptable optimized diets ensuring a gradual reduction in GHGe, using observed diet from a large sample of French adults, while considering the mode of food production (organic vs conventional farming) and the co-production link between milk and beef. Material and method Based on the consumption of 257 organic and conventional foods among 29,413 participants (75% women, age: 53.5 ± 14.0y) of the NutriNet-Sante study, we modelled optimal diets according to GHGe reduction scenarios in 5% steps, from 0 to 50% with nutritional, acceptability, and coproduct constraints, for men, premenopausal and menopausal women separately. Results Gradual GHGe decrease under these constraints led to optimal diets with an overall decrease in animal foods, with marked reductions in dairy products (up to −83%), together with a stable but largely redistributed meat consumption in favor of poultry (up to +182%) and pork (up to +46%) and at the expense of ruminant meat (down to −92%). Amounts of legumes increases dramatically (up to +238%). The greater the reduction in diet-related GHGe, the lower the cumulative energy demand (about −25%) and land use (about −43%). The proportion of organic food increased from ~30% in the observed diets to ~70% in the optimized diets. Conclusion Our results suggest that meeting both nutrient reference value and environmental objectives of up to 50% GHGe reduction requires the reduction of animal foods together with important substitutions between animal food groups, which result in drastic reductions in beef and dairy products. Further research is required to explore alignment with long-term health value and conflict with acceptability, in particular for even greater GHGe reductions.

Published
2021