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2. Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, and Benito, Yolanda A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Alzheimer Disease Genetics Consortium, European Alzheimer’s Disease Initiative, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology, Genetics
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

3. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author

Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, and Benito, Yolanda A

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Neurodegenerative, Dementia, Alzheimer's Disease, Aging, Prevention, Brain Disorders, Neurosciences, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Haplotypes, Humans, Immunity, Lipid Metabolism, Lipids, Male, tau Proteins, Alzheimer Disease Genetics Consortium (ADGC), European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.

Published
2019

5. Undetectable haptoglobin is associated with major adverse kidney events in critically ill burn patients.

Author

Dépret, François, Dunyach, Chloé, De Tymowski, Christian, Chaussard, Maïté, Bataille, Aurélien, Ferry, Axelle, Moreno, Nabila, Cupaciu, Alexandru, Soussi, Sabri, Benyamina, Mourad, Mebazaa, Alexandre, Serror, Kevin, Chaouat, Marc, Garnier, Jean-Pierre, Pirracchio, Romain, Legrand, Matthieu, and PRONOBURN group

Subjects
PRONOBURN group, Humans, Burns, Creatinine, Haptoglobins, Respiration, Artificial, Risk Factors, Statistics, Nonparametric, Retrospective Studies, Cohort Studies, Adult, Middle Aged, Intensive Care Units, Paris, Female, Male, Acute Kidney Injury, Acute kidney injury, Burn patients, Haptoglobin, Intravascular haemolysis, Major adverse kidney event, Kidney Disease, Clinical Research, Injury (total) Accidents/Adverse Effects, Renal and urogenital, Emergency & Critical Care Medicine, Medical and Health Sciences
Abstract

BackgroundIntravascular haemolysis has been associated with acute kidney injury (AKI) in different clinical settings (cardiac surgery, sickle cell disease). Haemolysis occurs frequently in critically ill burn patients. The aim of this study was to assess the predictive value of haptoglobin at admission to predict major adverse kidney events (MAKE) and AKI in critically ill burn patients.MethodsWe conducted a retrospective, single-centre cohort study in a burn critical care unit in a tertiary centre, including all consecutive severely burned patients (total burned body surface > 20% and/or shock and/or mechanical ventilation at admission) from January 2012 to April 2017 with a plasmatic haptoglobin dosage at admission.ResultsA total of 130 patients were included in the analysis. Their mean age was 49 (34-62) years, their median total body surface area burned was 29% (15-51%) and the intensive care unit (ICU) mortality was 25%. Early haemolysis was defined as an undetectable plasmatic haptoglobin at admission. We used logistic regression to identify MAKE and AKI risk factors. In multivariate analysis, undetectable haptoglobin was associated with MAKE and AKI (respectively, OR 6.33, 95% CI 2.34-16.45, p

Published
2017

9. Prediction of major adverse kidney events in critically ill burn patients

Author

Dépret, François, Boutin, Louis, Jarkovský, Jiří, Chaussard, Maité, Soussi, Sabri, Bataille, Aurélien, Oueslati, Haikel, Moreno, Nabila, de Tymowski, Christian, Parenica, Jiří, Benešová, Klára, Vauchel, Thomas, Ferry, Axelle, Benyamina, Mourad, Cupaciu, Alexandru, Coutrot, Maxime, Garnier, Jean-Pierre, Serror, Kevin, Chaouat, Marc, Mebazaa, Alexandre, and Legrand, Matthieu

Published
2018
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10. Coupling Component Systems towards Systems of Systems

Author

Autran, Frédéric, Auzelle, Jean-Philippe, Cattan, Denise, Garnier, Jean-Luc, Luzeaux, Dominique, Mayer, Frédérique, Peyrichon, Marc, and Ruault, Jean-René

Subjects
Computer Science - Distributed, Parallel, and Cluster Computing
Abstract

Systems of systems (SoS) are a hot topic in our "fully connected global world". Our aim is not to provide another definition of what SoS are, but rather to focus on the adequacy of reusing standard system architecting techniques within this approach in order to improve performance, fault detection and safety issues in large-scale coupled systems that definitely qualify as SoS, whatever the definition is. A key issue will be to secure the availability of the services provided by the SoS despite the evolution of the various systems composing the SoS. We will also tackle contracting issues and responsibility transfers, as they should be addressed to ensure the expected behavior of the SoS whilst the various independently contracted systems evolve asynchronously.

Published
2008

11. A new approach to highly reductive neutral organic molecules

Author

Garnier, Jean

Subjects
541.39
Abstract

Recently, our research group has been developing novel reactions involving powerful tetraazaalkene-based donors, reducing aryl halides into their corresponding aryl radicals or aryl anions. This thesis reports the development of new powerful donor D, a novel donor structure prepared by a novel route from precursor A. Oxdation of D into diction E provided suitable material for X-ray crystal analysis and electrochemical measurements of the redox potential for the D/E couple. Comparison with other neutral organic electron donors prepared in our group or published by others showed that the bispyridinylidene-based donors presented in this thesis are the isolated organic reagents with the most negative redox potentials recorded to date.

Published
2008

18. Table 2 from Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma

Author

Weeden, Clare E., primary, Holik, Aliaksei Z., primary, Young, Richard J., primary, Ma, Stephen B., primary, Garnier, Jean-Marc, primary, Fox, Stephen B., primary, Antippa, Phillip, primary, Irving, Louis B., primary, Steinfort, Daniel P., primary, Wright, Gavin M., primary, Russell, Prudence A., primary, Ritchie, Matthew E., primary, Burns, Christopher J., primary, Solomon, Benjamin, primary, and Asselin-Labat, Marie-Liesse, primary

Published
2023
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19. Data from Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma

Author

Weeden, Clare E., primary, Holik, Aliaksei Z., primary, Young, Richard J., primary, Ma, Stephen B., primary, Garnier, Jean-Marc, primary, Fox, Stephen B., primary, Antippa, Phillip, primary, Irving, Louis B., primary, Steinfort, Daniel P., primary, Wright, Gavin M., primary, Russell, Prudence A., primary, Ritchie, Matthew E., primary, Burns, Christopher J., primary, Solomon, Benjamin, primary, and Asselin-Labat, Marie-Liesse, primary

Published
2023
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20. Supplementary Tables S1, S3-S7, Supplementary Material and Methods, and Supplementary Figure Legends from Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma

Author

Weeden, Clare E., primary, Holik, Aliaksei Z., primary, Young, Richard J., primary, Ma, Stephen B., primary, Garnier, Jean-Marc, primary, Fox, Stephen B., primary, Antippa, Phillip, primary, Irving, Louis B., primary, Steinfort, Daniel P., primary, Wright, Gavin M., primary, Russell, Prudence A., primary, Ritchie, Matthew E., primary, Burns, Christopher J., primary, Solomon, Benjamin, primary, and Asselin-Labat, Marie-Liesse, primary

Published
2023
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21. Figure S1-S6 from Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma

Author

Weeden, Clare E., primary, Holik, Aliaksei Z., primary, Young, Richard J., primary, Ma, Stephen B., primary, Garnier, Jean-Marc, primary, Fox, Stephen B., primary, Antippa, Phillip, primary, Irving, Louis B., primary, Steinfort, Daniel P., primary, Wright, Gavin M., primary, Russell, Prudence A., primary, Ritchie, Matthew E., primary, Burns, Christopher J., primary, Solomon, Benjamin, primary, and Asselin-Labat, Marie-Liesse, primary

Published
2023
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22. Functional and structural characterization of the insertion region in the ligand binding domain of the vitamin D nuclear receptor

Author

Rochel, Natachu, Tocchini‐Valentini, Guiseppe, Egea, Pascal F, Juntunen, Kari, Garnier, Jean‐Marie, Vihko, Pirkko, and Moras, Dino

Subjects
Nutrition, Genetics, Amino Acid Sequence, Animals, COS Cells, Calcitriol, Humans, Ligands, Models, Molecular, Molecular Sequence Data, Protein Structure, Tertiary, Receptors, Calcitriol, Sequence Deletion, Sequence Homology, Amino Acid, Transcriptional Activation, Transfection, X-Ray Diffraction, nuclear receptor, VDR LBD, ligand binding, conformation, transactivation, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology
Abstract

Vitamin D nuclear receptor mediates the genomic actions of the active form of vitamin D, 1,25(OH)2D3. This hormone is involved in calcium and phosphate metabolism and cell differentiation. Compared to other nuclear receptors, VDR presents a large insertion region at the N-terminal part of the ligand binding domain between helices H1 and H3, encoded by an additional exon. This region is poorly conserved in VDR in different species and is not well ordered as observed by secondary structure prediction. We engineered a VDR ligand binding domain mutant by removing this insertion region. Here we report its biochemical and biophysical characterization. The mutant protein exhibits the same ligand binding, dimerization with retinoid X receptor and transactivation properties as the wild-type VDR, suggesting that the insertion region does not affect these main functions. Solution studies by small angle X-ray scattering shows that the conformation in solution of the VDR mutant is similar to that observed in the crystal and that the insertion region in the VDR wild-type is not well ordered.

Published
2001

30. A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family

Author

Okutman, Ozlem, Muller, Jean, Skory, Valerie, Garnier, Jean Marie, Gaucherot, Angeline, Baert, Yoni, Lamour, Valérie, Serdarogullari, Munevver, Gultomruk, Meral, Röpke, Albrecht, Kliesch, Sabine, Herbepin, Viviana, Aknin, Isabelle, Benkhalifa, Moncef, Teletin, Marius, Bakircioglu, Emre, Goossens, Ellen, Charlet-Berguerand, Nicolas, Bahceci, Mustafa, Tüttelmann, Frank, and Viville, STéphane

Published
2017
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32. Hepatitis E infection in adults with primary immunodeficiency with or without immunoglobulin replacement therapy

Author

Gérard, Laurence, Garzaro, Margaux, Ferrer, Venicia, Malphettes, Marion, Fieschi, Claire, Garnier, Jean-Luc, Just, Nicolas, Masseau, Agathe, Delaugerre, Constance, Izopet, Jacques, Oksenhendler, Eric, and Abravanel, Florence

Subjects
Adult, Immunoglobulin M, Seroepidemiologic Studies, Immunoglobulin G, Hepatitis E virus, Other: Original article, Humans, RNA, Hepatitis Antibodies, Hepatitis E
Abstract

BACKGROUND: In a context of secondary immunodeficiency, hepatitis E virus (HEV) infection can be responsible for chronic liver disease. MATERIALS AND METHODS: We investigated HEV infection in patients with primary immunodeficiency treated (or not) with immunoglobulin (Ig) replacement therapy (IgRT) in France, a country with a high seroprevalence of HEV. In a nationwide study of individuals with primary immunodeficiency, 533 patients (349 and 184 receiving IgRT or not, respectively) were tested for HEV RNA and anti-HEV antibodies. In addition, 23 batches of five different commercially available immunoglobulin preparations were screened for anti-HEV IgG. RESULTS: Three of the 533 patients displayed markers of a recent HEV infection (HEV RNA in one case, and anti-HEV IgG and IgM in two) but no evidence of chronic liver disease. The overall seroprevalence of HEV was 50% (266 out of 533), with values of 68% and 16% in patients receiving IgRT or not, respectively (p

Published
2022

33. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death

Author

Hildebrand, Joanne M., Tanzer, Maria C., Lucet, Isabelle S., Young, Samuel N., Spall, Sukhdeep K., Sharma, Pooja, Pierotti, Catia, Garnier, Jean-Marc, Dobson, Renwick C.J., Webb, Andrew I., Tripaydonis, Anne, Babon, Jeffrey J., Mulcair, Mark D., Scanlon, Martin J., Alexander, Warren S., Wilks, Andrew F., Czabotar, Peter E., Lessene, Guillaume, Murphy, James M., and Silke, John

Published
2014

34. Capital-labor substitution and indeterminacy in continuous-time two-sector models

Author

Garnier, Jean-Philippe, Nishimura, Kazuo, Venditti, Alain, Kusuoka, Shigeo, editor, Anderson, Robert, editor, Castaing, Charles, editor, Clarke, Frank H., editor, Dierker, Egbert, editor, Duffie, Darrell, editor, Evans, Lawrence C., editor, Fujimoto, Takao, editor, Grandmont, Jean-Michel, editor, Hirano, Norimichi, editor, Hurwicz, Leonid, editor, Ichiishi, Tatsuro, editor, Ioffe, Alexander, editor, Iwamoto, Seiichi, editor, Kamiya, Kazuya, editor, Kawamata, Kunio, editor, Kikuchi, Norio, editor, Maruyama, Toru, editor, Matano, Hiroshi, editor, Nishimura, Kazuo, editor, Richter, Marcel K., editor, Takahashi, Yoichiro, editor, Valadier, Michel, editor, Yano, Makoto, editor, and Yamazaki, Akira, editor

Published
2007
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38. The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study

Author

Johansson, Mattias, Carreras-Torres, Robert, Scelo, Ghislaine, Purdue, Mark P., Mariosa, Daniela, Muller, David C., Timpson, Nicolas J., Haycock, Philip C., Brown, Kevin M., Wang, Zhaoming, Ye, Yuanqing, Hofmann, Jonathan N., Foll, Matthieu, Gaborieau, Valerie, Machiela, Mitchell J., Colli, Leandro M., Li, Peng, Garnier, Jean-Guillaume, Blanche, Helene, Boland, Anne, Burdette, Laurie, Prokhortchouk, Egor, Skryabin, Konstantin G., Yeager, Meredith, Radojevic-Skodric, Sanja, Ognjanovic, Simona, Foretova, Lenka, Holcatova, Ivana, Janout, Vladimir, Mates, Dana, Mukeriya, Anush, Rascu, Stefan, Zaridze, David, Bencko, Vladimir, Cybulski, Cezary, Fabianova, Eleonora, Jinga, Viorel, Lissowska, Jolanta, Lubinski, Jan, Navratilova, Marie, Rudnai, Peter, Benhamou, Simone, Cancel-Tassin, Geraldine, Cussenot, Olivier, Weiderpass, Elisabete, Ljungberg, Börje, Tumkur Sitaram, Raviprakash, Häggström, Christel, Bruinsma, Fiona, Jordan, Susan J., Severi, Gianluca, Winship, Ingrid, Hveem, Kristian, Vatten, Lars J., Fletcher, Tony, Larsson, Susanna C., Wolk, Alicja, Banks, Rosamonde E., Selby, Peter J., Easton, Douglas F., Andreotti, Gabriella, Beane Freeman, Laura E., Koutros, Stella, Männistö, Satu, Weinstein, Stephanie, Clark, Peter E., Edwards, Todd L., Lipworth, Loren, Gapstur, Susan M., Stevens, Victoria L., Carol, Hallie, Freedman, Matthew L., Pomerantz, Mark M., Cho, Eunyoung, Wilson, Kathryn M., Gaziano, J. Michael, Sesso, Howard D., Freedman, Neal D., Parker, Alexander S., Eckel-Passow, Jeanette E., Huang, Wen-Yi, Kahnoski, Richard J., Lane, Brian R., Noyes, Sabrina L., Petillo, David, Teh, Bin Tean, Peters, Ulrike, White, Emily, Anderson, Garnet L., Johnson, Lisa, Luo, Juhua, Buring, Julie, Lee, I-Min, Chow, Wong-Ho, Moore, Lee E., Eisen, Timothy, Henrion, Marc, Larkin, James, Barman, Poulami, Leibovich, Bradley C., Choueiri, Toni K., Lathrop, G. Mark, Deleuze, Jean-Francois, Gunter, Marc, McKay, James D., Wu, Xifeng, Houlston, Richard S., Chanock, Stephen J., Relton, Caroline, Richards, J. Brent, Martin, Richard M., Davey Smith, George, and Brennan, Paul

Subjects
Obesity -- Genetic aspects -- Complications and side effects, Renal cell carcinoma -- Genetic aspects -- Development and progression -- Care and treatment, Genetic markers -- Health aspects, Etiology (Medicine), Genetics, Carcinoma, Cancer, Type 2 diabetes, Genomics, Insulin, Proxy, Lipids, Genomes, Fasting, Glucose, Biological sciences
Abstract

Background Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. Methods and findings Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (OR.sub.SD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (OR.sub.SD : 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (OR.sub.SD : 1.63, 95% CI 1.40-1.90) and body fat percentage (OR.sub.SD : 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (OR.sub.SD : 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; OR.sub.SD : 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (OR.sub.SD : 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. Conclusions This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk., Author(s): Mattias Johansson 1,*, Robert Carreras-Torres 1, Ghislaine Scelo 1, Mark P. Purdue 2, Daniela Mariosa 1, David C. Muller 3, Nicolas J. Timpson 4, Philip C. Haycock 4, Kevin [...]

Published
2019
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42. Summary of the Post-Long Shutdown 2 LHC Hardware Commissioning Campaign

Author

Apollonio, Andrea, Andreassen, Odd, Antoine, Alain, Argyropoulos, Theodoros, Bastos, Miguel, Bednarek, Mateusz, Bordini, Bernardo, Brodzinski, Krzysztof, Calia, Andrea, Charifoulline, Zinour, Coelingh, Gert-Jan, D'Angelo, Giorgio, Delikaris, Dimitri, Denz, Reiner, Fiscarelli, Lucio, Froidbise, Vincent, Galilée, Marc-Antoine, Garnier, Jean-Christophe, Gorbonosov, Roman, Hagen, Per, Hostettler, Michael, Jacquet, Delphine, Le Naour, Sandrine, Mirarchi, Daniele, Montabonnet, Valerie, Panev, Bozhidar Ivanov, Persson, Tobias, Podzorny, Tomasz, Pojer, Mirko, Ravaioli, Emmanuele, Rodriguez-Mateos, Felix, Siemko, Andrzej, Solfaroli, Matteo, Spasic, Jelena, Stanisz, Anita, Steckert, Jens, Steerenberg, Rende, Sudak, Slawomir, Thiesen, Hugues, Todesco, Ezio, Trad, Georges, Uythoven, Jan, Uznanski, Slawosz, Verweij, Arjan, Vizziello, Vito, Wenninger, Jorg, Willering, Gerard, Wollmann, Daniel, and Yammine, Samer

Subjects
Physics::Instrumentation and Detectors, MC4: Hadron Accelerators, Physics::Accelerator Physics, Accelerators and Storage Rings, Accelerator Physics
Abstract

In this contribution we provide a summary of the LHC hardware commissioning campaign following the second CERN Long Shutdown (LS2), initially targeting the nominal LHC energy of 7 TeV. A summary of the test procedures and tools used for testing the LHC superconducting circuits is given, together with statistics on the successful test execution. The paper then focuses on the experience and observations during the main dipole training campaign, describing the encountered problems, the related analysis and mitigation measures, ultimately leading to the decision to reduce the energy target to 6.8 TeV. The re-commissioning of two powering sectors, following the identified problems, is discussed in detail. The paper concludes with an outlook to the future hardware commissioning campaigns, discussing the lessons learnt and possible strategies moving forward., Proceedings of the 13th International Particle Accelerator Conference, IPAC2022, Bangkok, Thailand

Published
2022
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43. A Modernized Architecture for the Post Mortem System at CERN

Author

Barth, Jonas, Bogyai, Filip, Garnier, Jean-Christophe, Majewski, Marcin, Martins Ribeiro, Tiago, Mnich, Aleksandra, Pocwierz, Maciej, Selvek, Robert, Simpson, Robert, Stanisz, Anita, Wollmann, Daniel, and Zerlauth, Markus

Subjects
Accelerators and Storage Rings, Accelerator Physics, MC6: Beam Instrumentation, Controls, Feedback and Operational Aspects
Abstract

The control system of the accelerators at CERN stores and analyses more than 200 million dumps of high resolution data recordings every year in the Post Mortem (PM) system. A continuous increase in the complexity of the Large Hadron Collider’s (LHC) systems and the desire to collect more accurate data requires continuous improvement of the PM system. Recently, the PM system has been modernized ahead of the third operational Run of the LHC. The upgraded system implements well known data engineering principles such as horizontal scaling, stateless services and readiness for extensions. This paper recalls the purpose of the PM service and its current use cases. It presents its modernized architecture, reviews the current performance and limitations of the system, and draws perspectives for the next steps in its evolution., Proceedings of the 13th International Particle Accelerator Conference, IPAC2022, Bangkok, Thailand

Published
2022
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44. AFIS Report on Challenges for the Near Future

Author

Alix, Christophe, Garnier, Jean‐Luc, Le Mouëllic, Mikael, Alt, Laurent, Vingerhoed, Rob, and Bouyaud, Mickaël

Abstract

Systems engineering shall adapt itself with the changes of the world. System engineering communities like (AFIS 2022) and (INCOSE 2021) have been developing their visions with the identification of needs that systems engineering shall integrate to address new challenges. The systems engineering discipline shall be now considered at the enterprise level and be included in the governance of the project. Systems engineering and system thinking shall be deployed on all layers of the organization and horizontally to ensure the consistency the definition, production, and all phases of the lifecycle of the system within all involved organizations. The future is paved with unknowns. Systems engineering can integrate new methodologies, new posture to complete its analytical based tools to better face new kinds of complexity. These new challenges are often due to the reallocation of functions and responsibilities between human and machine in the context of autonomous systems. These collaborative socio‐technical systems induce new questions for systems engineering which needs to integrate new domain of skills and interacts with new disciplines from the soft sciences.

Published
2023
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47. Normal delivery: physiologic support and medical interventions. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF).

Author

Petitprez, Karine, Mattuizzi, Aurelien, Guillaume, Sophie, Arnal, Maud, Artzner, France, Bernard, Catherine, Caron, François-Marie, Chevalier, Isabelle, Daussy-Urvoy, Claude, DucloyBouthorsc, Anne-Sophie, Garnier, Jean-Michel, Keita-Meyer, Hawa, ere, Jacqueline Lavillonni, Lejeune-Sadaa, Valérie, Ray, Camille Le, Morandeau, Anne, Nadjafizade, Marjan, Pizzagalli, Franck, Schantz, Clemence, and Schmitz, Thomas

Subjects
UMBILICAL cord clamping, FIRST stage of labor (Obstetrics), UTERINE contraction, MIDWIVES, OBSTETRICIANS
Abstract

Objective: To define for women at low obstetric risk methods of management that respect the rhythm and the spontaneous course of giving birth as well as each woman’s preferences. Methods: These clinical practice guidelines were developed through professional consensus based on an analysis of the literature and of the French and international guidelines available on this topic. Results: Labor should be monitored with a partograph (professional consensus). Digital cervical examination should be offered every 4 h during the first stage of labor, hourly during the second. The choice between continuous (cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring should be left to the woman (professional consensus). In the active phase of the first stage of labor, dilation speed is considered abnormal if it is less than 1 cm/4 h between 5 and 7 cm or less than 1 cm/2 h after 7 cm. In those cases, an amniotomy is recommended if the membranes are intact, and the administration of oxytocin if the membranes are already broken and uterine contractions are judged insufficient (professional consensus). It is recommended that pushing not begin when full dilation has been reached; rather, the fetus should be allowed to descend (grade A). Umbilical cord clamping should be delayed beyond the first 30 s in newborns who do not require resuscitation (grade C). Conclusion: The establishment of these clinical practice guidelines should enable women at low obstetric risk to receive better care in conditions of optimal safety while supporting physiologic birth. [ABSTRACT FROM AUTHOR]

Published
2022
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