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101. Eigenvalue fluctuations for random elliptic operators in homogenization regime

Author: Mitia Duerinckx, Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: Mathematics - Spectral Theory, [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Mathematics - Analysis of PDEs, Probability (math.PR), FOS: Mathematics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Statistical and Nonlinear Physics, Mathematics::Spectral Theory, Spectral Theory (math.SP), Mathematical Physics, Mathematics - Probability, Analysis of PDEs (math.AP)
Abstract: This work is devoted to the asymptotic behavior of eigenvalues of an elliptic operator with rapidly oscillating random coefficients on a bounded domain with Dirichlet boundary conditions. A sharp convergence rate is obtained for isolated eigenvalues towards eigenvalues of the homogenized problem, as well as a quantitative two-scale expansion result for eigenfunctions. Next, a quantitative central limit theorem is established for eigenvalue fluctuations; more precisely, a pathwise characterization of eigenvalue fluctuations is obtained in terms of the so-called homogenization commutator, in parallel with the recent fluctuation theory for the solution operator., Comment: 19 pages
Published: 2021

102. Murlentamab, a Low Fucosylated Anti-Müllerian Hormone Type II Receptor (AMHRII) Antibody, Exhibits Anti-Tumor Activity through Tumor-Associated Macrophage Reprogrammation and T Cell Activation

Author: Mélissa Prat, Marie Salon, Thibault Allain, Olivier Dubreuil, Grégory Noël, Laurence Preisser, Bérangère Jean, Lydie Cassard, Fanny Lemée, Isabelle Tabah-Fish, Bernard Pipy, Pascale Jeannin, Jean-François Prost, Jean-Marc Barret, Agnès Coste, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Geroscience and rejuvenation research center (RESTORE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GamaMabs Pharma SA [Toulouse] ( Centre Pierre Potier), Oncopole de Toulouse-Centre Pierre Potier [Toulouse], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Gustave Roussy (IGR), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bernardo, Elizabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: glyco-engineered antibody, ovarian cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, tumor-associated macrophages, murlentamab, [SDV.CAN]Life Sciences [q-bio]/Cancer, adaptive immunity, immunotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article
Abstract: Simple Summary AMHRII, the anti-Müllerian hormone receptor, is selectively expressed in normal sexual organs in healthy adults but is also re-expressed in ovarian, colorectal and lung cancers. In this context, we developed murlentamab, a humanized glyco-engineered anti-AMHRII monoclonal antibody, currently in clinical trial. Preliminary data suggest that murlentamab anti-tumor activity involves immune response activation. Thus, in vitro experiments were performed to precisely characterize the murlentamab effect on the human immune system. We show that murlentamab treatment is associated with evidences of innate and adaptive immune cell activation in cancer patient samples. Moreover, we demonstrate that the murlentamab opsonization of AMHRII-expressing ovarian tumor cells promotes a polarization switch of both naïve and tumor-associated macrophages towards an anti-tumor M1-like phenotype. Our work also supports that, through macrophage reeducation, murlentamab activates an anti-tumor adaptive immune response. Finally, the combination of murlentamab with pembrolizumab confirmed novel clinical perspectives of murlentamab association with checkpoint inhibitors and other immuno-modulators. Abstract AMHRII, the anti-Müllerian hormone receptor, is selectively expressed in normal sexual organs but is also re-expressed in gynecologic cancers. Hence, we developed murlentamab, a humanized glyco-engineered anti-AMHRII monoclonal antibody currently in clinical trial. Low-fucosylated antibodies are known to increase the antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) potency of effector cells, but some preliminary results suggest a more global murlentamab-dependent activation of the immune system. In this context, we demonstrate here that the murlentamab opsonization of AMHRII-expressing ovarian tumor cells, in the presence of unstimulated- or tumor-associated macrophage (TAM)-like macrophages, significantly promotes macrophage-mediated ADCC and shifts the whole microenvironment towards a pro-inflammatory and anti-tumoral status, thus triggering anti-tumor activity. We also report that murlentamab orients both unstimulated- and TAM-like macrophages to an M1-like phenotype characterized by a strong expression of co-stimulation markers, pro-inflammatory cytokines and chemokines, favoring T cell recruitment and activation. Moreover, we show that murlentamab treatment shifts CD4+ Th1/Th2 balance towards a Th1 response and activates CD8+ T cells. Altogether, these results suggest that murlentamab, through naïve macrophage orientation and TAM reprogrammation, stimulates the anti-tumor adaptive immune response. Those mechanisms might contribute to the sustained clinical benefit observed in advanced cancer patients treated with murlentamab. Finally, the enhanced murlentamab activity in combination with pembrolizumab opens new therapeutic perspectives.
Published: 2021

103. Pattern mining‐based pruning strategies in stochastic local searches for scheduling problems

Author: Vincent Clerc, Damien Lamy, Arnaud Laurent, Benjamin Dalmas, Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT), Institut Henri Fayol (FAYOL-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratoire d'Informatique, de Modélisation et d'Optimisation des Systèmes (LIMOS), Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), FAYOL-ENSMSE - Département Génie mathématique et industriel, Centre Ingénierie et Santé (CIS-ENSMSE), Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Institut National de Recherche en Informatique et en Automatique (Inria), Département Génie mathématique et industriel (FAYOL-ENSMSE), Ecole Nationale Supérieure des Mines de St Etienne-Institut Henri Fayol, École des Mines, Centre Ingénierie Santé, Saint-Étienne (CIS - MINES), and Institut Henri Fayol-Ecole Nationale Supérieure des Mines de St Etienne
Subjects: Mathematical optimization, Speedup, Computer science, Job shop, Strategy and Management, 0211 other engineering and technologies, Scheduling (production processes), 02 engineering and technology, Management Science and Operations Research, Scheduling Problem, Machine Learning, Local optimum, Knowledge extraction, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Management of Technology and Innovation, 0202 electrical engineering, electronic engineering, information engineering, Local search (optimization), Resource Constrained Project Scheduling Problem, Pruning (decision trees), Business and International Management, 021103 operations research, Job shop scheduling, business.industry, Job-shop, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Pattern Mining, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Stochastic Local Search, Computer Science Applications, job‐shop, 020201 artificial intelligence & image processing, business
Abstract: International audience; Scheduling problems are a subclass of combinatorial problems consisting of a set of tasks/activities/jobs to be processed by a set of resources usually to minimize a time criterion. Some optimization methods used to solve these problems are hybridized with knowledge discovery techniques to extract information during the optimization process and enhance it. However, most of these hybrid techniques are custom‐designed and lack generalization. In this paper, a module for knowledge extraction in Stochastic Local Searches is designed, aiming to be problem independent and plugged into optimization methods that relies on multiple Stochastic Local Search replications. The objective is to prune parts of the search space for which the exploration is likely to lead to poor solutions. This is performed through the extraction of high‐quality patterns occurring in locally optimal solutions. Benchmarked on two well‐known scheduling problems, the Job‐shop Problem and the Resource Constrained Project Scheduling Problem, the results show both a speed up in the convergence and the reaching of better local optima solutions.
Published: 2021

104. Risk of relapse after anti-PD1 discontinuation in patients with Hodgkin lymphoma

Author: Marie Maerevoet, Jm Schiano, Bénédicte Deau, Mg Silva, Apasia Stamatoullas, Roch Houot, Guillaume Manson, Pauline Brice, Laurent Dercle, Herve Ghesquieres, Carmelo Carlo-Stella, Juliette Bouteloup, Kamal Bouabdallah, Charles Herbaux, Florence Poizeau, E. Nicolas-Virelizier, M. de Charette, Chloe Antier, CHU Pontchaillou [Rennes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instituto Português de Oncologia de Lisboa Francisco Gentil, CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre Hospitalier Chalon-sur-Saône William Morey, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hospices Civils de Lyon (HCL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre hospitalier universitaire de Nantes (CHU Nantes), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Humanitas University [Milan] (Hunimed), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut Gustave Roussy (IGR), Columbia University Medical Center (CUMC), Columbia University [New York], and Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: medicine.medical_specialty, Training set, business.industry, [SDV]Life Sciences [q-bio], Specific time, General Medicine, 3. Good health, 030218 nuclear medicine & medical imaging, Discontinuation, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Refractory Hodgkin Lymphoma, Medicine, Hodgkin lymphoma, Radiology, Nuclear Medicine and imaging, In patient, Immunotherapy, Relapse risk, business, Anti pd1, Biomarkers, Checkpoint inhibitors
Abstract: International audience; Introduction - Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. Methods - We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. Results - Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. Conclusion - In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.
Published: 2021

105. Patients’ real-world experience with inflammatory bowel disease: A cross-sectional survey in tertiary care centres from the GETAID group

Author: Maria Nachury, Yoram Bouhnik, Melanie Serrero, Jerome Filippi, Xavier Roblin, Julien Kirchgesner, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered Abitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Matthieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Sara Tadbiri, Matthieu Allez, Stephanie Viennot, Arnaud Bourreille, David Laharie, Aurelien Amiot, Charlotte Gagniere, Jenny Tannoury, Benjamin Pariente, Pauline Wils, Carmen Stefanescu, Xavier Treton, Xavier Hébuterne, Nadia Arab, Virginie Cluzeau, Emilie Del Tedesco, Laurent Beaugerie, Philippe Seksik, Anne Bourrier, Cecilia Landmann, Harry Sokol, Laurent Siproudhis, Marie DeWitte, Catherine Reenaers, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Olivier DeWitt, Nicolas Mathieu, Sandie Pestour, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Nina Dib, Hedi Brixi, Guillaume Cadiot, Medina Boualit, Claire Painchart, Laurianne Plastaras, Romain Altwegg, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Stephane Nahon, Noemie Tavernier, Marion Simon, Baya Coulibaly, Morgane Amil, Duveau Nicolas, Sherine Khater, Mehdi Kaassis, Felix Goutorbe, Driffa Moussata, Laurence Picon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pasteur [Nice] (CHU), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan), AbbVie, GETAID-patient experience study group: Aurelien Amiot , Sara Tadbiri , Charlotte Gagniere , Jenny Tannoury , Maria Nachury , Benjamin Pariente , Pauline Wils , Yoram Bouhnik , Carmen Stefanescu , Xavier Treton , Melanie Serrero , Jerome Filippi , Xavier Hébuterne , Nadia Arab , Virginie Cluzeau , Xavier Roblin , Emilie Del Tedesco , Laurent Beaugerie , Philippe Seksik , Anne Bourrier , Cecilia Landmann , Julien Kirchgesner , Harry Sokol , Guillaume Bouguen , Laurent Siproudhis , Marie DeWitte , Denis Franchimont , Guillaume Savoye , Anthony Buisson , Edouard Louis , Catherine Reenaers , Stephane Nancey , Gilles Boschetti , Claire Gay , Pauline Danion , Bernard Flourié , Vered Abitbol , Georgia Malamut , Jean-Marie Reimund , Benedicte Caron , Olivier DeWitt , Lucine Vuitton , Nicolas Mathieu , Sandie Pestour , Laurent Peyrin-Biroulet , Camille Zallot , Cyrielle Gilletta , Matthieu Allez , Jean-Marc Gornet , Clotilde Baudry , Stephanie Viennot , Arnaud Bourreille , Caroline Trang-Poisson , Nina Dib , Hedi Brixi , Guillaume Cadiot , Medina Boualit , Claire Painchart , Laurianne Plastaras , Romain Altwegg , Lucile Boivineau , Mathurin Fumery , Ludovic Caillo , David Laharie , Pauline Riviere , Florian Poullenot , Benoit Coffin , Henri Duboc , Stephane Nahon , Noemie Tavernier , Marion Simon , Baya Coulibaly , Morgane Amil , Duveau Nicolas , Sherine Khater , Mehdi Kaassis , Felix Goutorbe , Driffa Moussata , Laurence Picon, CHU Saint-Etienne, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Toulouse [Toulouse], CIC - Biotherapie - CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, 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)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Crohn’s disease, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Cross-sectional study, [SDV]Life Sciences [q-bio], Disease, Patients experience, Inflammatory bowel disease, Tertiary care, digestive system, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Belgium, Physicians, Outpatients, medicine, Quantitative assessment, Humans, Adverse effect, Crohn's disease, Physician-Patient Relations, Hepatology, business.industry, Gastroenterology, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 3. Good health, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Family medicine, 030211 gastroenterology & hepatology, Female, France, Self Report, business
Abstract: International audience; BACKGROUND: Patients’ experience with healthcare professionals could influence their clinical outcomes. AIMS: To assess inflammatory bowel disease (IBD) patients’ experience with their disease, their treatment and their relationship with their physician. METHODS: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD. RESULTS: A quantitative assessment of the doctor-patient relationship revealed that patients’ knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample. CONCLUSION: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals.
Published: 2021

106. Identification of three subtypes of triple-negative breast cancer with potential therapeutic implications

Author: Mario Campone, Wilfried Gouraud, Hubert Hondermarck, Hamza Lasla, Andrea Gombos, Florence Dalenc, Pascal Jézéquel, Olivier Kerdraon, Jean-Luc Canon, Suzette Delaloge, Catherine Guérin-Charbonnel, Véronique Verriele, Delphine Loussouarn, Jérôme Lemonnier, Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Unité Mixte de Génomique du Cancer [ICO, Saint Herblain] (Site René Gauducheau), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Hôpital Laennec, Unité de bioinfomique [ICO, Saint Herblain], UNICANCER-UNICANCER, Laboratoire d’Anatomie et Cytologie Pathologiques [ICO, Saint Herblain], School of Biomedical Sciences and Pharmacy [Callaghan, Australia], University of Newcastle [Australia] (UoN)-Hunter Medical Research Institute [Callaghan, Australia], Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Département Oncologie-Hématologie [Charleroi, Belgium], Grand Hôpital de Charleroi [Belgium], Département Oncologie Médicale [Bruxelles, Belgium], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Département d'Oncologie Médicale [CHU Toulouse] (IUCT Oncopole - Institut Universitaire du Cancer), Centre hospitalier universitaire de Toulouse - CHU Toulouse-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), French Breast Cancer Intergroup - UCBG [Paris] (R&D UNICANCER), R&D Unicancer [Paris], Laboratoire d'anatomie et cytologie pathologiques [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'oncologie médicale [Saint Herblain] (Centre René Gauducheau - ICO), Part of this study was funded by Comité Féminin 49., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bernardo, Elizabeth
Subjects: Molecular subtypes, Lymphocyte, Neurogenesis, Triple Negative Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Plasma cell, Biology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Immune system, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Cluster Analysis, Humans, Metabolomics, Transcriptomics, Immunome, B cell, Triple-negative breast cancer, Neoplasm Staging, Gene Expression Profiling, Computational Biology, Molecular Sequence Annotation, Acquired immune system, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Immune checkpoint, Tumor Burden, 3. Good health, Gene expression profiling, Cancérologie, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Triple-negative, Female, Neoplasm Grading, Transcriptome, Tertiary lymphoid structures, Research Article
Abstract: Background: Heterogeneity and lack of targeted therapies represent the two main impediments to precision treatment of triple-negative breast cancer (TNBC), and therefore, molecular subtyping and identification of therapeutic pathways are required to optimize medical care. The aim of the present study was to define robust TNBC subtypes with clinical relevance. Methods: Gene expression profiling by means of DNA chips was conducted in an internal TNBC cohort composed of 238 patients. In addition, external data (n = 257), obtained by using the same DNA chip, were used for validation. Fuzzy clustering was followed by functional annotation of the clusters. Immunohistochemistry was used to confirm transcriptomics results: CD138 and CD20 were used to test for plasma cell and B lymphocyte infiltrations, respectively; MECA79 and CD31 for tertiary lymphoid structures; and UCHL1/PGP9.5 and S100 for neurogenesis. Results: We identified three molecular clusters within TNBC: one molecular apocrine (C1) and two basal-like-enriched (C2 and C3). C2 presented pro-tumorigenic immune response (immune suppressive), high neurogenesis (nerve infiltration), and high biological aggressiveness. In contrast, C3 exhibited adaptive immune response associated with complete B cell differentiation that occurs in tertiary lymphoid structures, and immune checkpoint upregulation. External cohort subtyping by means of the same approach proved the robustness of these results. Furthermore, plasma cell and B lymphocyte infiltrates, tertiary lymphoid structures, and neurogenesis were validated at the protein levels by means of histological evaluation and immunohistochemistry. Conclusion: Our work showed that TNBC can be subcategorized in three different subtypes characterized by marked biological features, some of which could be targeted by specific therapies., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

107. Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes

Author: Richard Iggo, Jean-Michel Picquenot, Denis Larsimont, Véronique Becette, Jonas Bergh, Gaëtan MacGrogan, Jeremy Thomas, Olivier Kerdraon, Leen Slaets, David Cameron, Fanny Pommeret, C. Poncet, Jean-Christophe Tille, Frédéric Bibeau, Hervé Bonnefoi, Alexandre Bodmer, Jean-Pierre Ghnassia, Thomas Grellety, Donnat, Martin, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie, UNICANCER-UNICANCER, UNICANCER, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital René HUGUENIN (Saint-Cloud), Centre René Gauducheau, CRLCC René Gauducheau, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Paul Strauss, CRLCC Paul Strauss, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Cancer Research UK Edinburgh Centre [Edinburgh, UK], University of Edinburgh-MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council-Medical Research Council, Hôpitaux Universitaires de Genève (HUG), Department of Oncology-Pathology [Karolinska Institutet], Karolinska Institutet [Stockholm], Bordeaux PharmacoEpi, Inserm CIC1401, Université de Bordeaux, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], and Swiss Group for Clinical Cancer Research (SAKK)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Concordance, medicine.medical_treatment, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, ddc:616.07, Disease-Free Survival, Article, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Survival rate, Chemotherapy, business.industry, Gene Expression Profiling, Apocrine, medicine.disease, Immunohistochemistry, Subtyping, 3. Good health, Cancérologie, ErbB Receptors, Survival Rate, Clinical trial, Biological sciences, Treatment Outcome, Receptors, Estrogen, Chemotherapy, Adjuvant, Receptors, Androgen, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Receptors, Progesterone, business
Abstract: Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and “other”. The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4–43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2–68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

108. Unravelling the high-altitude Nansen blue ice field meteorite trap (East Antarctica) and implications for regional palaeo-conditions

Author: Jan T. M. Lenaerts, Steven Goderis, Philippe Huybrechts, Harry Zekollari, Philippe Claeys, Akira Yamaguchi, Jérôme Gattacceca, Matthias Van Ginneken, Vinciane Debaille, A. J. Timothy Jull, Université Libre de Bruxelles (ULB), Laboratoire G-Time, Université libre de Bruxelles (ULB), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Analytical, Environmental and Geo- Chemistry, Vrije Universiteit Brussel (VUB), Geography, Physical Geography, Earth System Sciences, Analytical, Environmental & Geo-Chemistry, Université Libre de Bruxelles [Bruxelles] (ULB), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Vrije Universiteit [Brussels] (VUB), and Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)
Subjects: Satellite derived velocities, 010504 meteorology & atmospheric sciences, Ice stream, Ice field, Blue ice, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Antarctic ice sheet, Palaeoclimate, 010502 geochemistry & geophysics, palaeoclimate, 01 natural sciences, Nansen ice field, Stable isotope geochemistry, Paleontology, Ice core, Geochemistry and Petrology, Nansen Ice field, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Antarctic meteorite trap, geography, geography.geographical_feature_category, European Project for Ice Coring in Antarctica, Géochimie, Pétrologie, Meteorite, 13. Climate action, Terrestrial age, Ice sheet, Geology
Abstract: Antarctic blue ice zones, the most productive locations for meteorite recovery on Earth, contain old ice that is easily accessible and available in large quantities. However, the mechanisms behind these meteorite traps remain a topic of ongoing debate. Here, we propose an interdisciplinary approach to improve our understanding of a meteorite trap in Dronning Maud Land (East Antarctica) on the Nansen blue ice field meteorite trap (2600–3100 m above sea level), where more than half of the Asuka meteorites have been collected. Based on 185 surface blue ice samples, one of the largest observed spatial patterns in oxygen isotopic variation to date is found. Relying on meteorites for which the terrestrial ages are determined using 14C and 36Cl, this surface ice is interpreted to date from the Last Interglacial up to the present-day. By combining state-of-the-art satellite derived surface velocities, surface mass balance modelling and ice flow modelling, we estimate that about 75–85% of the meteorites found on the ice field were supplied by ice flow after entering the ice sheet in an accumulation area of a few hundred square kilometres located south (upstream) of the ice field. Less than 0.4 new meteorites per year are supplied to the ice field through ice flow, suggesting that the hundreds of meteorites found 25 years after the first visit to this ice field mostly represent meteorites that were previously not found, rather than newly supplied meteorites. By combining these findings, the infall rate of meteorites from space is estimated, which is in line with values from the literature, but situated at the higher end of the range. A comparison of the oxygen isotopic variation of the surface blue ice to that of the European Project for Ice Coring in Antarctica (EPICA), Dronning Maud Land (EDML) ice core (located 750 km to the west, at the same elevation), suggests that the regional changes in topography have been relatively limited since the Last Interglacial, supporting theories of an overall stable East Antarctic Ice Sheet (EAIS) over this time period., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

109. An algorithm for cost optimization of PMU and communication infrastructure in WAMS

Author: Eglantine Camby, Marcia Helena Moreira Paiva, Helder Roberto de Oliveira Rocha, Marco António do Rosário Santos Cruz, Marcelo E. V. Segatto, Gilles Caporossi, Federal University of Espírito Santo, Graphes et Optimisation Mathématique [Bruxelles] (GOM), Université libre de Bruxelles (ULB), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Groupe d’études et de recherche en analyse des décisions (GERAD), Université du Québec à Montréal = University of Québec in Montréal (UQAM)-HEC Montréal (HEC Montréal)-McGill University = Université McGill [Montréal, Canada]-École Polytechnique de Montréal (EPM), and École Polytechnique de Montréal (EPM)-McGill University = Université McGill [Montréal, Canada]-HEC Montréal (HEC Montréal)-Université du Québec à Montréal = University of Québec in Montréal (UQAM)
Subjects: Flexibility (engineering), Heuristic (computer science), Computer science, 020209 energy, Variable Neighbourhood Search (VNS), 020208 electrical & electronic engineering, Energy Engineering and Power Technology, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], 02 engineering and technology, Transmission system, communication infrastructure, Phasor Measurement Unit (PMU), Variable (computer science), Electric power system, Transmission (telecommunications), Scalability, 0202 electrical engineering, electronic engineering, information engineering, optimal PMU placement, Transient (oscillation), Electrical and Electronic Engineering, Algorithm, power system observability
Abstract: International audience; Power system state estimation relies increasingly on PMU measurements to ef-fectively control and monitor growing and stressed transmission networks whichare also affected by transient and dynamic events. High PMU cost has moti-vated optimal PMU placement solutions but recent works have shown the effectof communication infrastructure cost in PMU configuration. In this paper,we present a new method for the design of Wide Area Measurement Systems.A topological analysis algorithm based on the Variable Neighbourhood Searchheuristic is proposed and tested in several networks, including the common IEEEtest networks and the 5804-bus Brazilian transmission system. Our results showthe flexibility, effectiveness, and scalability of the proposed methodology whencompared with recent research presented in the literature.
Published: 2019

110. The circular RNome of primary breast cancer

Author: Steven Van Laere, Colin A. Purdie, John A. Foekens, Gaëten MacGrogan, Marcel Smid, Andrew Futreal, Vanja de Weerd, Paul N. Span, Marc J. van de Vijver, Jorunn E. Eyfjord, Serena Nik-Zainal, F. Germán Rodríguez-González, Roberto Salgado, Peter T. Simpson, Christine Desmedt, Wendy J. C. Prager-van der Smissen, Fred C.G.J. Sweep, Tari A. King, Adam Butler, Michael R. Stratton, Carlos Caldas, Gert Van den Eynden, Sunil R. Lakhani, Saskia M. Wilting, Alastair M. Thompson, Angelo Paradiso, John W.M. Martens, Anne Vincent-Salomon, Johan Staaf, Anne van Galen, Sancha Martin, Hendrik G. Stunnenberg, Annegien Broeks, Andrea L. Richardson, Anne Lise Børresen-Dale, Helen Davies, Michelle van der Vlugt-Daane, Katharina Uhr, Stian Knappskog, Alain Viari, Anieta M. Sieuwerts, Medical Oncology, Smid, Marcel [0000-0003-0605-1901], Apollo - University of Cambridge Repository, Pathology, CCA - Cancer biology and immunology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), The Wellcome Trust Sanger Institute [Cambridge], Lund University [Lund], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Dana-Farber Cancer Institute [Boston], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Institut Bergonié [Bordeaux], UNICANCER, Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Translational Cancer Research Unit [Antwerp], Department of Pathology [Dundee], Ninewells Hospital and Medical School [Dundee], Radboud University Medical Center [Nijmegen], University of Southern Queensland (USQ), University of Antwerp (UA), Istituto Tumori 'Giovanni Paolo II' [Bari], University of Iceland [Reykjavik], Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), The University of Texas M.D. Anderson Cancer Center [Houston], University of Bergen (UiB), Haukeland University Hospital, Memorial Sloane Kettering Cancer Center [New York], Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institute for Cancer Research [Oslo], Oslo University Hospital [Oslo], Fondation Synergie Lyon Cancer [Lyon], Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
Subjects: Génétique clinique, Proliferation index, [SDV]Life Sciences [q-bio], Transcriptome, Exon, Breast cancer, 0302 clinical medicine, Brjóstakrabbamein, MUTATIONAL PROCESSES, Genetics (clinical), Genetics & Heredity, 0303 health sciences, Gene knockdown, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], ABUNDANT, CREB-Binding Protein, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, GENOME, Chemistry, Lymphatic Metastasis, RNA splicing, MCF-7 Cells, Female, Engineering sciences. Technology, Biologie, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Breast Neoplasms, Biology, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, REVEALS, Biomarkers, Tumor, Genetics, medicine, Erfðafræði, Humans, TAMOXIFEN, Molecular Biology, Gene, SIGNATURES, 030304 developmental biology, Science & Technology, LANDSCAPE, Research, MICRORNA, Cancer, RNA, Circular, medicine.disease, DNA-rannsóknir, GENE, RNAs, Repressor Proteins, Biotechnology & Applied Microbiology, Cancer research, RNA, Human medicine, Carrier Proteins, 030217 neurology & neurosurgery
Abstract: Publisher's version (útgefin grein), Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Of the circRNAs that match exon boundaries of the same gene, 668 showed a poor or even negative (R < 0.2) correlation with the expression level of the linear gene. In silico analysis showed only a minority (8.5%) of circRNAs could be explained by known splicing events. Both these observations suggest that specific regulatory processes for circRNAs exist. We confirmed the presence of circRNAs of CNOT2, CREBBP, and RERE in an independent pool of primary breast cancers. We identified circRNA profiles associated with subgroups of breast cancers and with biological and clinical features, such as amount of tumor lymphocytic infiltrate and proliferation index. siRNA-mediated knockdown of circCNOT2 was shown to significantly reduce viability of the breast cancer cell lines MCF-7 and BT-474, further underlining the biological relevance of circRNAs. Furthermore, we found that circular, and not linear, CNOT2 levels are predictive for progression-free survival time to aromatase inhibitor (AI) therapy in advanced breast cancer patients, and found that circCNOT2 is detectable in cell-free RNA from plasma. We showed that circRNAs are abundantly present, show characteristics of being specifically regulated, are associated with clinical and biological properties, and thus are relevant in breast cancer., We thank the Erasmus MC Cancer Computational Biology Center for giving access to their IT infrastructure and the software that was used for the computations and data analysis in this study. We thank Sandra Albassam for her help with the first versions of the script to identify circular regions. We thank Maurice P.H.M. Jansen, Jean C. Helmijr, Inge de Kruijff, and Manouk K. Bos for their help in evaluating plasma samples that were gathered in the EU-FP7 CareMore (nr 601760) project. We thank for technical support Miriam Ragle Aure and Anita Langerød of the Oslo University Hospital, Norway; Ewan Birney of the European Bioinformatics Institute, UK; and Stefania Tommasi of the IRCCS Istituto Tumori “Giovanni Paolo II,” Bari, Italy. We thank the Oslo Breast Cancer Research Consortium (OSBREAC), Norway (https://www.ous-research.no/home/kgjebsen/home/14105) for contributing patient samples and Sabine Linn and Marleen Kok of The Netherlands Cancer Institute for contributing samples for the AI cohort. Finally, we thank all members of the ICGC Breast Cancer Working Group. This work has been funded through the ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (a European research project funded by the European Community’s Seventh Framework Programme (FP7/2010-2014) under the grant agreement number 242006) and the Triple Negative project funded by the Wellcome Trust (grant reference 077012/Z/05/Z). F.G.R.-G. and S.M. were funded by BASIS. J.A.F. was funded through an ERC Advanced Grant (ERC-2012-AdG-322737) and ERC Proof-of-Concept Grant (ERC-2017-PoC-767854). K.U. was funded by the Daniel den Hoed Foundation. S.N.-Z. is a Wellcome Beit Fellow and personally funded by a Wellcome Trust Intermediate Fellowship (WT100183MA). A.L.R. is partially supported by the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer (NIH/NCI 5 P50 CA16 8504-02). A.M.S. was supported by Cancer Genomics Netherlands (CGC.nl) through a grant from the Netherlands Organization of Scientific research (NWO). M. Smid was supported by the EU-FP7-DDR response project. C.D. was supported by a grant from the Breast Cancer Research Foundation. J.E. was funded by The Icelandic Centre for Research (RANNIS).
Published: 2019

111. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma

Author: Philippe Moreau, Laurent Garderet, Bertrand Arnulf, Sabrina Maheo, Lotfi Benboubker, Mamoun Dib, Sabine Brechignac, Nelly Robillard, Mohamad Mohty, Margaret Macro, Brigitte Pegourie, Thierry Facon, Brigitte Kolb, Karim Belhadj, Nikhil C. Munshi, Bruno Royer, Olivier Decaux, Arnaud Jaccard, Valérie Lauwers-Cances, Marie-Lorraine Chretien, Anne-Marie Stoppa, Hervé Avet-Loiseau, Xavier Leleu, Kenneth C. Anderson, Jean-Richard Eveillard, Martin Moorhead, Chantal Doyen, Cecile Fohrer, Lionel Karlin, Jill Corre, Victoria Carlton, Paul G. Richardson, Malek Faham, Jean-Luc Harousseau, Michel Attal, Nathalie Meuleman, Thomas D. Willis, Aurore Perrot, Cyrille Hulin, Thomas Dejoie, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'épidémiologie [Toulouse], CHU Toulouse [Toulouse], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service d'Hématologie Biologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Biochimie [Nantes], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'hématologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d’Hématologie Clinique [Rennes], CHU Pontchaillou [Rennes], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Universitaire de Bobigny, Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Universitaire de Caen, Department of Energy / Joint Genome Institute (DOE), Los Alamos National Laboratory (LANL), Département d'Hématologie Clinique [CHU Nantes], Département d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département d'Hématologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département d'Hématologie [CHU Nantes], Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Hématologie [IUCT Oncopole, Toulouse], Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Département d'hématologie [CHU Saint-Antoine, AP-HP], AP-HP - Hôpital Saint-Antoine, Institut Jules Bordet, Service hématologie (CHU d'Amiens), Département d'Hématologie Clinique [CHU Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service d'Hématologie [CHU Toulouse]
Subjects: Male, 0301 basic medicine, Oncology, Neoplasm, Residual, Biochemistry, Dexamethasone, Bortezomib, Observations Lymphoid Neoplasia, 0302 clinical medicine, Maintenance therapy, Bone Marrow, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Lenalidomide, Multiple myeloma, Lymphoid Neoplasia, Hazard ratio, High-Throughput Nucleotide Sequencing, Hematology, Minimal Residual Disease Negativity, Middle Aged, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, medicine.drug, medicine.medical_specialty, Plasma Cells, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, medicine, Humans, Clinical Trials, Survival rate, Aged, business.industry, Cell Biology, medicine.disease, Minimal residual disease, Transplantation, 030104 developmental biology, business, Follow-Up Studies
Abstract: IF 15.132 (2017); International audience; The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (
Published: 2018

112. Visibly pushdown transducers

Author: Jean-Marc Talbot, Emmanuel Filiot, Frédéric Servais, Pierre-Alain Reynier, Jean-François Raskin, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratoire d'Informatique et Systèmes (LIS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Modélisation et Vérification (MOVE), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE40-0007,DELTA,DÉfis pour la Logique, les Transducteurs et les Automates(2016)
Subjects: Nested word, General Computer Science, Computer Networks and Communications, Computer science, media_common.quotation_subject, Transducers, Concatenation, 0102 computer and information sciences, 02 engineering and technology, Visbily Pushdown Automata, 01 natural sciences, Theoretical Computer Science, [INFO.INFO-FL]Computer Science [cs]/Formal Languages and Automata Theory [cs.FL], Reading (process), 0202 electrical engineering, electronic engineering, information engineering, Arithmetic, Functionality, media_common, Applied Mathematics, Pushdown automaton, Computer Science::Computation and Language (Computational Linguistics and Natural Language and Speech Processing), 16. Peace & justice, TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, Computational Theory and Mathematics, Closure (mathematics), 010201 computation theory & mathematics, Symbol (programming), 020201 artificial intelligence & image processing, Computer Science::Formal Languages and Automata Theory, Word (computer architecture), Stack (mathematics)
Abstract: Visibly pushdown transducers ( VPT ) extend visibly pushdown automata (VPA) with outputs. They read nested words, i.e. finite words on a structured alphabet partitioned into call, return and internal symbols, and produce output words, which are not necessarily nested. As for VPA , the behavior of the stack is synchronized with the types of input symbols: on reading a call symbol, exactly one stack symbol is pushed onto the stack; on reading a return symbol, exactly one stack symbol is popped from the stack; and the stack is untouched when reading internal symbols. Along their transitions VPT can append words on their output tape, whose concatenation define the resulting output word. Therefore VPT define transformations from nested words to words and can be seen as a subclass of pushdown transducers. In this paper, we study the algorithmic, closure and expressiveness properties of VPT .
Published: 2018

113. Disordered eating behaviors as a potential obesogenic factor in schizophrenia

Author: Rufin Louhou, Jean-Daniel Lalau, Brendon Stubbs, Ali Amad, Nathalie Renard, Gwenolé Loas, Momar Diouf, Youssef Kouidrat, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Biostatistiques [Amiens], CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: Adult, Male, [SDV]Life Sciences [q-bio], Disease, Affect (psychology), Body Mass Index, Feeding and Eating Disorders, Eating, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Cardiometabolic disorders, Antipsychotics, Humans, Medicine, Obesity, Metabolic disease, Disordered eating, Biological Psychiatry, Eating behaviors, business.industry, Cognition, Feeding Behavior, Middle Aged, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Eating disorders, Cross-Sectional Studies, Schizophrenia, Case-Control Studies, Female, Schizophrenic Psychology, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; Whilst people with schizophrenia have high levels of obesity and metabolic disease, our understanding of their eating behaviors is still limited. Our aim was to evaluate the relationships between eating behavior and clinical data in schizophrenia. A cross-sectional study including 66 schizophrenia outpatients compared to 81 healthy controls was undertaken. Eating behavior was assessed using the shortened 21-item version of the Three-Factor Eating Questionnaire (TFEQ-R21). The patients had a mean of 44 +/- 11 years; a mean BMI of 30.3 +/- 8 kg/m(2) (vs. 24 +/- 3.3 kg/m(2) for controls) and a mean duration of illness of 7.2 +/- 6 years. All mean TFEQ scores were significantly higher in patients (indicating poorer eating behaviors) compared to controls after adjustment for age and sex, BMI and smoking status. Among patients, mean TFEQ scores were not significantly different between men and women samples. The ``cognitive restraint'' factor was significantly higher in schizophrenia patients with a BMI < 25 than in the group of overweight patients with a BMI > 25. Our findings suggest that disordered eating behaviors affect schizophrenia patients regardless of gender or duration of disease compared to controls. More research is needed to help clarify the relationships between eating behaviors and weight-related outcomes in schizophrenia.
Published: 2018

114. Synthesis of Data Word Transducers

Author: Exibard, L��o, Filiot, Emmanuel, Reynier, Pierre-Alain, Laboratoire d'Informatique et Systèmes (LIS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Modélisation et Vérification (MOVE), Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: FOS: Computer and information sciences, 000 Computer science, knowledge, general works, TheoryofComputation_COMPUTATIONBYABSTRACTDEVICES, Formal Languages and Automata Theory (cs.FL), Register Automata, Transducers, Computer Science - Formal Languages and Automata Theory, Généralités, Data words, Synthesis, TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, [INFO.INFO-FL]Computer Science [cs]/Formal Languages and Automata Theory [cs.FL], Computer Science, Computer Science::Formal Languages and Automata Theory, Sciences exactes et naturelles
Abstract: In reactive synthesis, the goal is to automatically generate an implementation from a specification of the reactive and non-terminating input/output behaviours of a system. Specifications are usually modelled as logical formulae or automata over infinite sequences of signals (ω-words), while implementations are represented as transducers. In the classical setting, the set of signals is assumed to be finite. In this paper, we do not make such an assumption and consider data ω-words instead, i.e. words over an infinite alphabet. In this context, we study specifications and implementations respectively given as automata and transducers extended with a finite set of registers. We consider different instances, depending on whether the specification is nondeterministic, universal or deterministic, and depending on whether the number of registers of the implementation is given (bounded synthesis) or not.In the unbounded setting, we show undecidability for both universal and non-deterministic specifications, while decidability is recovered in the deterministic case. In the bounded setting, undecidability still holds for non-deterministic specifications, but can be recovered by disallowing tests over input data. The generic technique we use to show the latter result allows us to reprove some known result, namely decidability of bounded synthesis for universal specifications., CONCUR 2019, info:eu-repo/semantics/inPress
Published: 2021

115. Quantitative homogenization theory for random suspensions in steady Stokes flow

Author: Mitia Duerinckx, Antoine Gloria, Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Mathematics - Analysis of PDEs, 35R60, 76M50, 35Q35, 76D03, 76D07, General Mathematics, Probability (math.PR), FOS: Mathematics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Mathematics - Probability, Analysis of PDEs (math.AP)
Abstract: This work develops a quantitative homogenization theory for random suspensions of rigid particles in a steady Stokes flow, and completes recent qualitative results. More precisely, we establish a large-scale regularity theory for this Stokes problem, and we prove moment bounds for the associated correctors and optimal estimates on the homogenization error; the latter further requires a quantitative ergodicity assumption on the random suspension. Compared to the corresponding quantitative homogenization theory for divergence-form linear elliptic equations, substantial difficulties arise from the analysis of the fluid incompressibility and the particle rigidity constraints. Our analysis further applies to the problem of stiff inclusions in (compressible or incompressible) linear elasticity and in electrostatics; it is also new in those cases, even in the periodic setting., 57 pages
Published: 2021

116. Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features

Author: Jean-François Emile, Jean-Luc Van Laethem, Jérôme Torrisani, Pieter Demetter, Yuna Blum, Anne Couvelard, Pascal Hammel, Armelle Bardier-Dupas, Francesco Puleo, Miroslaw Radman, Jérôme Cros, Magali Svrcek, Rémy Nicolle, Jerome Raffenne, Valérie Paradis, Fernando Ariel Martin, Marina Konta, Jean-Baptiste Bachet, Vinciane Rebours, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Ambroise Paré [AP-HP], Hôpital Erasme [Bruxelles] (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Cancer Research, DNA repair, [SDV]Life Sciences [q-bio], Young patients, Biology, elderly patients, Multi‐omics, lcsh:RC254-282, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, medicine, Epigenomics, Two-dimensional gel electrophoresis, PDAC, Methylation, Sciences bio-médicales et agricoles, multi-omics, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV] Life Sciences [q-bio], Cancérologie, Elderly patients, young patients, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Proteome, Cancer research, Adenocarcinoma
Abstract: Pancreatic ducal adenocarcinoma is classically diagnosed in the 7th decade, but approximately 10% of patients are diagnosed under 55 years (y.o.). While the genomic and transcriptomic landscapes of late‐onset tumors (LOT) have been described, little is known about early‐onset tumors (EOT). Ageing is known to impact DNA methylation and proteome integrity through carbonylation‐related oxidative damages. We therefore aimed to assess the global molecular features of EOT. We compared 176 EOT (≤55 y.o.) and 316 LOT (≥70 y.o.) from three distinct surgical cohorts at the clinical/genomic/epigenomic/transcriptomic level. Furthermore, we assessed oxidative stress responses and oxidative proteome damages using 2D gel electrophoresis followed by mass spectrometry protein identification. There was no consistent clinical difference between EOT and LOT across the three cohorts. The mutational landscape of key driver genes and the global methylation profile were similar in the two groups. LOT did display age‐related features such as enriched DNA repair gene signatures and upregulation of oxidative stress defenses together with increased proteome carbonylation. However, these age‐related differences were more preeminent in non‐tumor tissues while tumor proteome and proteome damages were fairly comparable. In conclusion, this multiomics comparison showed that EOT harbor a comparable molecular profile to that of LOT., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021
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117. Neurological complications induced by immune checkpoint inhibitors: a comprehensive descriptive case-series unravelling high risk of long-term sequelae

Author: N. Noel, Amélie Deleporte, Anne-Laure Voisin, Jean-Marie Michot, Stéphane Champiat, Léo Plaçais, Capucine Baldini, Aurélien Marabelle, Céline Labeyrie, Stéphanie Dehette, Patricia Romano-Martin, Adeline Not, Olivier Lambotte, Maria Silva Joao, Andoni Echaniz-Laguna, Alexandre Thibault Jacques Maria, David H. Adams, Guillemette Beaudonnet, Agathe Masseau, Cécile Cauquil, A. Laparra, Christian Denier, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Service de neurologie [Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Compiègne-Noyon (CHCN), Centre Hospitalier Compiègne-Noyon, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and Salvy-Córdoba, Nathalie
Subjects: medicine.medical_specialty, Immune checkpoint inhibitors, medicine.medical_treatment, rechallenge, Corticosteroid treatment, paraneoplastic syndrome, immune checkpoint inhibitors, Internal medicine, medicine, neurological toxicity, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adverse effect, Adult patients, business.industry, AcademicSubjects/SCI01870, Mortality rate, General Engineering, Common Terminology Criteria for Adverse Events, Immunotherapy, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Cohort, immune-related adverse events, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Original Article, AcademicSubjects/MED00310, business
Abstract: Neurological immune-related adverse events are complications of programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies that can be life threatening and often lead to anticancer immunotherapy withdrawal. Scant clinical data are available that integrate the clinical presentation, therapeutic management and long-term outcome. All consecutive adult patients treated by programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies, given alone or in combination with other treatment, who experienced a neurological immune-related adverse event with a severity grade ≥2 in Paris Saclay-University hospitals were investigated from June 2014 to February 2019. The frequency of neurological immune-related adverse events was calculated from the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Forty patients presenting with 51 distinct neurological immune-related adverse events were included. The prevalence of grade ≥2 neurological immune-related adverse events was estimated to be 1.22% in the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Among 40 patients with neurological immune-related adverse events, 65% received programmed-cell death 1 or programmed-cell death 1 ligand monotherapy and 35% received a combination of programmed-cell death 1 plus anti-CTLA4 (Common Terminology Criteria for Adverse Events). Clinical neurological presentations were peripheral (48%), central (35%), or mixed (18%). The severity of neurological immune-related adverse events was grade 2 for 14 (35%) and ≥grade 3 for 26 patients (65%). The mortality rate related to neurological immune-related adverse events was 8%. Corticosteroid treatment led to neurological recovery in 74%. Long-term follow-up highlighted that 53% of patients experienced long-term neurological sequelae. Five patients were rechallenged by programmed-cell death 1 monotherapy without recurrence of their neurological immune-related adverse event(s). Neurological immune-related adverse events induced by programmed-cell death 1 or programmed-cell death 1 ligand are rare but are severe with a mortality rate of 8% and long-term sequelae for 53% of patients. Corticosteroids should be started when neurological immunological complications are identified to avoid long-term sequelae., Plaçais et al. report a large case-series of 40 patients presenting with 51 neurological adverse events of immune checkpoint inhibitors, wherein corticosteroid therapy was associated with a 74% rate of neurological recovery. Neurological adverse events were severe, as 7.5% of the included patients died and 53% kept long-term neurological sequelae., Graphical Abstract Graphical Abstract
Published: 2021

118. Reconstructing two millennia of copper and silver metallurgy in the Lake Titicaca region (Bolivia/Peru) using trace metals and lead isotopic composition

Author: Julien Barre, Stéphane Guédron, Christophe Delaere, Pierre Sabatier, Carlos Heredia, David Amouroux, Elodie Brisset, Sherilyn C. Fritz, Paul A. Baker, Sylvain Campillo, Julie Tolu, Richard Bindler, Institut des Sciences de la Terre (ISTerre), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel-Université Grenoble Alpes (UGA), Laboratorio de Hidroquímica - Instituto de Investigaciones Químicas, Universidad Mayor de San Andres, Campus Universitario de Cota Cota, Eawag, Swiss Federal Institute of Aquatic Science and Technology, CH-8600 Dübendorf, Switzerland and ETH Zürich, Universitätstrasse 16, CH-8092 Zürich, Switzerland, ETH Zurich, Universitatstrasse 16, 8092 Zurich, Switzerland, Oxford Centre for Maritime Archaeology (OCMA), University of Oxford (OCMA), Centre de Recherches en Archéologie et Patrimoine, Université libre de Bruxelles (ULB), Environnements, Dynamiques et Territoires de la Montagne (EDYTEM), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Umeå University, Department of Earth and Atmospheric Sciences, University of Nebraska-Lincoln, Division of Earth and Ocean Sciences [Durham], Duke University [Durham], ANR-10-LABX-0056,OSUG@2020,Innovative strategies for observing and modelling natural systems(2010), Université libre de Bruxelles (ULB), Environnements, Dynamiques et Territoires de Montagne (EDYTEM), and Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Global and Planetary Change, Silver, 010504 meteorology & atmospheric sciences, Ecology, Central Andes mining, Metallurgy, Lead (sea ice), chemistry.chemical_element, Sediment, 010501 environmental sciences, 01 natural sciences, Copper, Isotopic composition, Colonial period, Metal deposition, Lead isotopes, Lake Titicaca sediment, chemistry, Smelting, [SDE]Environmental Sciences, Earth and Planetary Sciences (miscellaneous), Period (geology), Geology, 0105 earth and related environmental sciences
Abstract: International audience; Copper, silver, and gold exploitation has been a foundation of economic and socio-cultural development of Andean societies, at least for the last three millennia. The main centers of pre-colonial metallurgy are well-known from archaeological artifacts, but temporal gaps inherent in this record handicap a finer understanding of the modalities of ore exploitation by succeeding civilizations. A continuous record over time of trace metals emitted during ore smelting operations make lake sediments excellent candidates to fill those gaps.Two millennia of metallurgy were reconstructed from atmospherically derived metals together with lead (Pb) isotope ratios in two dated sediment cores from Lake Titicaca. The first evidence for metallurgy is found during the apogee of the Tiwanaku state (AD 800 to 1150), with a higher copper (Cu) accumulation that can be attributed to the smelting of local Cu ores, based on Pb isotopic fingerprinting. During the Late Intermediate Period (AD 1150 to 1450), recorded peaks in metal deposition that persisted for ∼ twenty years show that mining activities were intensive but discontinuous. Pb isotope ratios suggest diversified extractive activities, mainly located in the southern part of the central Altiplano. Finally, the most intense mining epoch began during the Inca Empire (ca. AD 1500) and lasted until the end of the Colonial Period (AD 1830), with unprecedented metal deposition over this interval.Pb isotope fingerprinting shows that mining operations occurred mainly in the Lake Titicaca and Potosi areas and were responsible for metal emissions recorded in the entire Altiplano, as evidenced by other studies.
Published: 2021

119. Association between Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and Reduced Risk of Death in COVID-19 Patients: A Retrospective Cohort Study

Author: Olivier Le Moine, Pascal Le Corre, Gwenolé Loas, Gil Darquennes, Université libre de Bruxelles (ULB), 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 ), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Chard-Hutchinson, Xavier, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 )
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], functional inhibitors of acid sphingomyelinase (FIASMAs), COVID-19, lcsh:Medicine, lcsh:RS1-441, Pharmaceutical Science, Disease, amlodipine, Logistic regression, Article, lcsh:Pharmacy and materia medica, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Drug Discovery, Medicine, Amlodipine, Mortality, Medical prescription, 030304 developmental biology, 0303 health sciences, business.industry, SARS-CoV-2, lcsh:R, Biologie moléculaire, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Obesity, mortality, 3. Good health, [SDV] Life Sciences [q-bio], functional inhibitors of acid sphingomyelinase (FIASMAs), Functional inhibitors of acid sphingomyelinase (FIASMAs), COVID-19, Molecular Medicine, Sciences pharmaceutiques, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Given the current scarcity of curative treatment of COVID-19, the search for an effective treatment modality among all available medications has become a priority. This study aimed at investigating the role of functional inhibitors of acid sphingomyelinase (FIASMAs) on in-hospital COVID-19 mortality. In this retrospective cohort study, we included adult in-patients with laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged hospital or deceased) from Erasme Hospital (Brussels, Belgium). We used univariate and multivariate logistic regression models to explore the risk factors associated with in-hospital mortality. We included 350 patients (205 males, 145 females) with a mean age of 63.24 years (SD = 17.4, range: 21–96 years). Seventy-two patients died in the hospital and 278 were discharged. The four most common comorbidities were hypertension (184, 52.6%), chronic cardiac disease (110, 31.4%), obesity (96, 27.8%) and diabetes (95, 27.1%). Ninety-three participants (26.6%) received a long-term prescription for FIASMAs. Among these, 60 (64.5%) received amlodipine. For FIASMAs status, multivariable regression showed increasing odds ratio (OR) for in-hospital deaths associated with older age (OR 1.05, 95% CI: 1.02–1.07, p = 0.00015), and higher prevalence of malignant neoplasm (OR 2.09, 95% CI: 1.03–4.22, p = 0.039). Nonsignificant decreasing OR (0.53, 95% CI: 0.27–1.04, p = 0.064) was reported for FIASMA status. For amlodipine status, multivariable regression revealed increasing OR of in-hospital deaths associated with older age (OR 1.04, 95% CI: 1.02–1.07, p = 0.0009), higher prevalence of hypertension (OR 2.78, 95% CI: 1.33–5.79, p = 0.0062) and higher prevalence of malignant neoplasm (OR 2.71, 95% CI: 1.23–5.97, p = 0.013), then secondarily decreasing OR of in-hospital death associated with long-term treatment with amlodipine (OR 0.24, 95% CI: 0.09–0.62, p = 0.0031). Chronic treatment with amlodipine could be significantly associated with low mortality of COVID-19 in-patients.
Published: 2021

120. A Time-Expanded Network Reduction Matheuristic for the Logistics Service Network Design Problem

Author: Mike Hewitt, Simon Belieres, Nicolas Jozefowiez, Frédéric Semet, Équipe Recherche Opérationnelle, Optimisation Combinatoire et Contraintes (LAAS-ROC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Loyola University [Chicago], Laboratoire de Conception, Optimisation et Modélisation des Systèmes (LCOMS), Université de Lorraine (UL), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Service (systems architecture), Operations research, Computer science, Process (engineering), Supply chain, 0211 other engineering and technologies, Transportation, 02 engineering and technology, Logistics, [INFO.INFO-DM]Computer Science [cs]/Discrete Mathematics [cs.DM], 0502 economics and business, Heuristics, Service Network Design, Business and International Management, Civil and Structural Engineering, 050210 logistics & transportation, Transportation planning, 021103 operations research, Supply chain management, 05 social sciences, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Service provider, Network planning and design, Dynamic Discretization Discovery, Integer Programming
Abstract: Planning cost-effective logistics operations involve the integration of multiple decision-making levels. In thedomain of supply chain management, the last decades have seen the emergence of 3PL service providers thatspecialize in integrating warehousing and transportation services. In this paper, we study the operations performedby a 3PL in the supply chain management of a French restaurant chain. The transportation planning process isassisted by solving the Logistics Service Network Design Problem (LSNDP). As realistic instances are too largefor on-the-shelf optimization solvers to solve in acceptable run-times, we develop a network reduction heuristicinspired by the recent Dynamic Discretization Discovery algorithm. Through an extensive series of experimentscarried out on instances based on the operations of an industrial partner, we demonstrate the efficiency of theproposed approach. We also investigate the impact of the distribution strategy used in practice to determine thetransportation plan and how this distribution strategy can be modified to reduce the overall logistics costs.
Published: 2021

121. Repurposing functional inhibitors of acid sphingomyelinase (fiasmas): an opportunity against SARS-CoV-2 infection?

Author: Gwenolé Loas, Pascal Le Corre, 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 ), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), No funding, Chard-Hutchinson, Xavier, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 )
Subjects: in vitro and in silico, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, [SDV]Life Sciences [q-bio], repurposing, Bioinformatics, 030226 pharmacology & pharmacy, SARS‐CoV‐2, Virus, FIASMA, ABCB1 transporter, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, functional inhibitors of acid sphingomyelinase, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, acid sphingomyelinase, Repurposing, Pharmacology, business.industry, SARS-CoV-2, Drug Repositioning, COVID-19 Drug Treatment, 3. Good health, [SDV] Life Sciences [q-bio], Drug repositioning, Sphingomyelin Phosphodiesterase, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Commentary, antiviral activity, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Acid sphingomyelinase, business, medicine.drug
Abstract: What is known and objective Infection by SARS‐CoV‐2, the virus responsible of COVID‐19, is associated with limited treatment options. The purpose of this study was to evaluate the rationale for repurposing functional inhibitors of acid sphingomyelinase (FIASMAs), several of which are approved medicines, for the treatment of SAR‐CoV‐2 infections. Comment We propose and discuss the FIASMAs’ lysosomotropism as a possible explanation for their observed in vitro activities against viruses, and more specifically against infections caused by coronaviruses such as SARS‐CoV‐2. Successful in vitro‐to‐in vivo translation of FIASMAs requires that their pharmacokinetics (dosing regimen and drug‐drug interactions) are matched with viral kinetics. What is new and conclusion Drug repurposing to ensure rapid patient access to effective treatment has garnered much attention in this era of the COVID‐19 pandemic. The observed lysosomotropic activity of small‐molecule FIASMA compounds suggests that their repurposing as potential drugs against SARS‐CoV‐2 is promising., FIASMA are cationic drugs with lipophilic properties that diffuse in the lysosome by passive diffusion and potentially by using ABCB1 transporter located onto the lysosomal membrane. This diffusion increases the intra‐lysosomal pH so that acid sphingomyelinase (ASM) is detached from the inner leaflet of the lysosomal membrane, and is further degraded by proteolysis. Hence, ASM translocation is no longer effective and the formation of lipid rafts on the cell membrane is altered. These membrane modifications impair the different mechanisms of internalization (i.e., fusion and entry) used by viruses such as SARS‐CoV‐2 to penetrate in the cytosol of cells.
Published: 2021

122. Improving generalization in MR‐to‐CT synthesis in radiotherapy by using an augmented cycle generative adversarial network with unpaired data

Author: David Pasquier, Nick Reynaert, John Klein, Kévin Brou Boni, Akos Gulyban, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and Université de Lille-UNICANCER
Subjects: Computer science, Generalization, medicine.medical_treatment, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Text mining, Histogram, Hounsfield scale, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Unpaired Data, business.industry, Deep learning, Radiotherapy Planning, Computer-Assisted, Pattern recognition, Radiotherapy Dosage, General Medicine, Magnetic Resonance Imaging, Radiation therapy, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Artificial intelligence, Radiotherapy, Intensity-Modulated, business, Tomography, X-Ray Computed, Generative adversarial network, [PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis, Statistics and Probability [physics.data-an]
Abstract: PURPOSE MR-to-CT synthesis is one of the first steps in the establishment of an MRI-only workflow in radiotherapy. Current MR-to-CT synthesis methods in deep learning use unpaired MR and CT training images with a cycle generative adversarial network (CycleGAN) to minimize the effect of misalignment between paired images. However, this approach critically assumes that the underlying interdomain mapping is approximately deterministic and one-to-one. In the current study, we use an Augmented CycleGAN (AugCGAN) model to create a robust model that can be applied to different scanners and sequences using unpaired data. MATERIALS AND METHODS This study included T2-weighted MR and CT pelvic images of 38 patients in treatment position from five different centers. The AugCGAN was trained on 2D transverse slices of 19 patients from three different sites. The network was then used to generate synthetic CT (sCT) images of 19 patients from the two other sites. Mean absolute errors (MAEs) for each patient were evaluated between real and synthetic CT images. Original treatment plans of nine patients were recalculated using sCT images to assess the dose distribution in terms of voxel-wise dose difference, gamma, and dose-volume histogram analysis. RESULTS The mean MAEs were 59.8 Hounsfield units ( HU ) and 65.8 HU for the first and second test sites, respectively. The maximum dose difference to the target was 1.2% with a gamma pass rate using the 3%, 3 mm criteria above 99%. The average time required to generate a complete sCT image for a patient on our GPU was 8.5 s. CONCLUSION This study suggests that our unpaired approach achieves good performance in generalization with respect to sCT image generation.
Published: 2021

123. Naked mole rat TRF1 safeguards glycolytic capacity and telomere replication under low oxygen

Author: Marco Mariotti, Benjamin Beck, Eric Gilson, Vadim N. Gladyshev, Doria Filipponi, Mélanie Pousse, Adeline Augereau, Frédérick Libert, Vera Gorbunova, Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), University of Rochester [USA], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, I.R.I.B.H.M., Université libre de Bruxelles (ULB), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and augereau, adeline
Subjects: Rodent, [SDV]Life Sciences [q-bio], Mutant, 03 medical and health sciences, 0302 clinical medicine, Rates, biology.animal, medicine, Glycolysis, Càncer, Research Articles, Naked mole-rat, Cancer, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, biology, Chemistry, SciAdv r-articles, Life Sciences, Généralités, Cell Biology, Oxigen, Hypoxia (medical), biology.organism_classification, Rats, Cell biology, Amino acid, Telomere, [SDV] Life Sciences [q-bio], Oxygen, 030220 oncology & carcinogenesis, medicine.symptom, Nuclear localization sequence, Research Article
Abstract: The naked mole rat (NMR), a long-lived and cancer-resistant rodent, is highly resistant to hypoxia. Here, using robust cellular models wherein the mouse telomeric protein TRF1 is substituted by NMR TRF1 or its mutant forms, we show that TRF1 supports maximal glycolytic capacity under low oxygen, shows increased nuclear localization and association with telomeres, and protects telomeres from replicative stress. We pinpoint this evolutionary gain of metabolic function to specific amino acid changes in the homodimerization domain of this protein. We further find that NMR TRF1 accelerates telomere shortening. These findings reveal an evolutionary strategy to adapt telomere biology for metabolic control under an extreme environment., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

124. Limits of manifolds with a Kato bound on the Ricci curvature

Author: Carron, Gilles, Mondello, Ilaria, Tewodrose, David, Laboratoire de Mathématiques Jean Leray (LMJL), Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire Analyse et Mathématiques Appliquées (LAMA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), ANR-17-CE40-0034,CCEM,Contraintes de Courbure et Espace des Métriques(2017), ANR-18-CE40-0012,RAGE,Analyse Réelle et Géométrie(2018), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Carron, Gilles, Contraintes de Courbure et Espace des Métriques - - CCEM2017 - ANR-17-CE40-0034 - AAPG2017 - VALID, and Analyse Réelle et Géométrie - - RAGE2018 - ANR-18-CE40-0012 - AAPG2018 - VALID
Subjects: Mathematics - Differential Geometry, Differential Geometry (math.DG), [MATH.MATH-DG]Mathematics [math]/Differential Geometry [math.DG], FOS: Mathematics, Mathematics::Metric Geometry, Mathematics::Differential Geometry, [MATH.MATH-DG] Mathematics [math]/Differential Geometry [math.DG]
Abstract: We study the structure of Gromov-Hausdorff limits of sequences of Riemannian manifolds $\{(M_\alpha^n,g_\alpha)\}_{\alpha \in A}$ whose Ricci curvature satisfies a uniform Kato bound. We first obtain Mosco convergence of the Dirichlet energies to the Cheeger energy and show that tangent cones of such limits satisfy the $\mathrm{RCD}(0,n)$ condition. When assuming a non-collapsing assumption, we introduce a new family of monotone quantities, which allows us to prove that tangent cones are also metric cones. We then show the existence of a well-defined stratification in terms of splittings of tangent cones. We finally prove volume convergence to the Hausdorff $n$-measure.
Published: 2021

125. Non-perturbative approach to the Bourgain-Spencer conjecture in stochastic homogenization

Author: Duerinckx, Mitia, Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Mathematics - Analysis of PDEs, Probability (math.PR), FOS: Mathematics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], 35J15, 35B27, 60H25, 60H07, 60H30, 46F29, Mathematics - Probability, Analysis of PDEs (math.AP)
Abstract: In the context of stochastic homogenization, the Bourgain-Spencer conjecture states that the ensemble-averaged solution of a divergence-form linear elliptic equation with random coefficients admits an intrinsic description in terms of higher-order homogenized equations with an accuracy four times better than the almost sure solution itself. While previous rigorous results were restricted to a perturbative regime with small ellipticity ratio, we make the very first progress in a non-perturbative setting, establishing half of the conjectured optimal accuracy. The validity of the full conjecture remains an open question and might in fact fail in general. Our approach involves the construction of a new corrector theory in stochastic homogenization: while only a bounded number of correctors can be constructed as stationary random fields in a strong sense, we show that twice as many stationary correctors can be defined in a Schwartz-like distributional sense on the probability space. We focus on the Gaussian setting for the coefficient field, and the proof relies heavily on Malliavin calculus., Comment: 41 pages
Published: 2021

126. Selenocompounds and sepsis: redox bypass hypothesis for early diagnosis and treatment Part A: Early acute phase of sepsis: an extraordinary redox situation (leukocyte-endothelium interaction leading to endothelial damage)

Author: Pierre Van Antwerpen, Xavier Forceville, Jean-Charles Preiser, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier de Meaux, Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Endothelium, endothelium, Physiology, Neutrophils, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Ischemia, free radicals, Cell Communication, medicine.disease_cause, Biochemistry, Microcirculation, Sepsis, 03 medical and health sciences, chemistry.chemical_compound, leukocyte activation, Selenoprotein P, medicine, Leukocytes, Humans, oxidative stress, selenium, Molecular Biology, Cell damage, General Environmental Science, 030102 biochemistry & molecular biology, business.industry, Endothelial Cells, Cell Biology, medicine.disease, 3. Good health, Respiratory burst, 030104 developmental biology, medicine.anatomical_structure, Early Diagnosis, chemistry, redox state, Immunology, General Earth and Planetary Sciences, business, Oxidation-Reduction, Oxidative stress, Peroxynitrite
Abstract: International audience; SIGNIFICANCE: Sepsis is a health disaster. In sepsis, an initial, beneficial local immune response against infection evolves rapidly into a generalized, dysregulated response or a state of chaos, leading to multiple organ failure. Use of life-sustaining supportive therapies creates an unnatural condition, enabling the complex cascades of the sepsis response to develop in patients who would otherwise die. Multiple attempts to control sepsis at an early stage have been unsuccessful. Recent advances: Major events in early sepsis include activation and binding of leukocytes and endothelial cells in the microcirculation, damage of the endothelial surface layer and a decrease in the plasma concentration of the antioxidant enzyme, selenoprotein-P. These events induce an increase in intracellular redox potential and lymphocyte apoptosis, whereas apoptosis is delayed in monocytes and neutrophils. They also induce endothelial mitochondrial and cell damage. CRITICAL ISSUES: Neutrophil production increases dramatically and aggressive, immature forms are released. Leukocyte cross-talk with other leukocytes and with damaged endothelial cells amplifies the inflammatory response. The release of large quantities of reactive oxygen, halogen and nitrogen species as a result of the leukocyte respiratory burst, endothelial mitochondrial damage, and ischemia-reperfusion processes, along with the marked decrease in selenoprotein-P concentrations, leads to peroxynitrite damage of the endothelial surface layer, reducing flow and damaging the endothelial barrier. Future Direction: Endothelial barrier damage by activated leukocytes is a time-sensitive event in sepsis, occurring within hours and representing the first step towards organ failure and death. Reducing or stopping this event is necessary before irreversible damage occurs.
Published: 2021

127. Comparison of Cycle Reduction and Model Reduction Strategies for the Design Optimization of Hybrid Powertrains on Driving Cycles

Author: Mariam Ahmed, Stephane Brisset, Maxime Ogier, Adham Kaloun, Robin Vincent, Laboratoire d’Électrotechnique et d’Électronique de Puissance - ULR 2697 (L2EP), Centrale Lille-Haute Etude d'Ingénieurs-Université de Lille-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), VALEO, Integrated Optimization with Complex Structure (INOCS), Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Centrale Lille-Université de Lille-Arts et Métiers Sciences et Technologies, 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)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0209 industrial biotechnology, electric machines, Control and Optimization, Computer science, Powertrain, Energy Engineering and Power Technology, 02 engineering and technology, 7. Clean energy, lcsh:Technology, Reduction (complexity), optimal control, [SPI]Engineering Sciences [physics], 020901 industrial engineering & automation, 0203 mechanical engineering, Control theory, model reduction, Torque, Electrical and Electronic Engineering, optimal design, Hybrid vehicle, Hybrid powertrain, Engineering (miscellaneous), hybrid electric vehicle, Renewable Energy, Sustainability and the Environment, lcsh:T, cycle reduction, Plant/Controller optimization, [SPI.NRJ]Engineering Sciences [physics]/Electric power, 020302 automobile design & engineering, Optimal control, Cycle reduction, Fuel efficiency, Driving cycle, Energy (miscellaneous)
Abstract: International audience; Decision-making is a crucial and difficult step in the design process of complex systems such as the hybrid powertrain. Finding an optimal solution requires the system feedback. This can be, depending on the granularity of the models at the component level, highly time-consuming. This is even more true when the system’s performance is determined by its control. In fact, various possibilities can be selected to deliver the required torque to the wheels during a driving cycle. In this work, two different design strategies are proposed to minimize the fuel consumption and the cost of the hybrid powertrain. Both strategies adopt the iterative framework which allows for the separation of the powertrain design problem and its control while leading to system optimality. The first approach is based on model reduction, while the second approach relies on improved cycle reduction techniques. They are then applied to a parallel hybrid vehicle case study, leading to important cost reduction in reasonable delays and are compared using different metrics.
Published: 2021

128. From vertical to horizontal structures :New optimization challenges in electricity markets

Author: de Boeck, Jérôme, Fortz, Bernard, Goossens, Joël, Labbé, Martine, Brotcorne, Luce L.D., Van Vyve, M, Anjos, M, Graphes et Optimisation Mathématique [Bruxelles] (GOM), Université libre de Bruxelles (ULB), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Bernard Fortz
Subjects: Formulations étendues, Electricity markets, Marchés de l'électricité, Bilevel optimization, Mixed integer linear optimization, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Modèles mathématiques d'aide à la décision, Optimisation linéaire en nombres entiers mixtes, Recherche opérationnelle, Extended formulations, Unit commitment, Optimisation à deux niveaux
Abstract: La chaine d’approvisionnement énergétique a fortement évolué aux cours des 20 dernières années. La libéralisation des marchés de l’électricité et les nouvelles technologies ont fortement influencé la manière d’envisager la production et la transmission d’électricité. Les modèles mathématiques classiques utilisés dans les problèmes lié à l’énergie ont besoin d’être revus pour intégrer les contraintes pratiques modernes.Un problème classique pour un Compagnie Génératrice (CG) est le problème de Unit Commitment (UC) qui consiste à établir un plan de production pour une demande en électricité connue. Lorsque ce problème fut considéré, le prix de l’électricité et la demande étaient relativement simple à estimer comme une seule CG nationale avait le monopole du marché. Ce problème a été étudié de manière extensive en utilisant de la Programmation Mathématique (PM). Aujourd’hui, le prix de l’électricité est relativement volatile à cause de l’introduction de marchés dérégulés et la demande du marché est répartie entre plusieurs CGs en compétition sur divers marchés. Une CG ne peut se limiter à considérer un problème de UC seul pour envisager sa production. Il y a un besoin d’intégrer les incertitudes liées au marché de l’électricité et aux quantités à produire aux modèles utilisés pour qu’une CG puisse établir un plan de production rentable.La technologie a aussi permis d’envisager de nouveaux concept tel que les Micro-Grilles (MGs). Une MG est composée d’un ensemble de consommateurs reliés à travers un réseau de transmission, possédant des générateurs d’électricité et optimisant leur consommation interne. Ce concept est possible grâce à l’utilisation croissante d’énergies renouvelables locales ainsi que l’utilisant croissante d’appareils interconnectés. Cependant, étant donné que les énergies renouvelables ont un faible rendement, sont intermittentes et que les appareils de stockage d’énergie sont encore peu efficaces, les MGs ne peuvent pas envisager d’être pleinement autonome en électricité. Il y a donc une nécessité d’avoir un fournisseur d’électricité externe pour avoir suffisamment d’électricité disponible à tout moment. Une CG jouant le rôle de fournisseur auprès d’une MG fait face énormément d’incertitude concernant la demande à cause de la gestion interne de la MG sur laquelle elle n’a pas de contrôle.Dans cette thèse, des problèmes d’optimisation intégrant de nouvelles contraintes modernes liés à l’approvisionnement énergétique sont étudiés via la PM. Plusieurs problèmes considèrant des interactions entre plusieurs acteurs sont modélisés via des formulations bi-niveau. Nous illustrons comment les difficultés liées aux contraintes modernes peuvent être exploitées pour obtenir des propriétés permettant de reformuler les problèmes étudiés en formulation linéaire en nombre entiers. Des heuristiques performantes sont obtenus à partir des formulations exactes dont certaines sont applicables à des problèmes plus généraux. Une analyse extensive de la performance des méthodes de résolution ainsi que de l’influence des contraintes modernes sont présentées dans diverses expériences numériques., Doctorat en Sciences, info:eu-repo/semantics/nonPublished
Published: 2021

129. Subgame-perfect Equilibria in Mean-payoff Games

Author: Brice, Léonard, Raskin, Jean-François, van den Bogaard, Marie, Laboratoire d'Informatique Gaspard-Monge (LIGM), École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and ARC project Non-Zero Sum Game Graphs: Applications to Reactive Synthesis and Beyond (Fédération Wallonie-Bruxelles), EOS project Verifying Learning Artificial Intelligence Systems (F.R.S.-FNRS & FWO), COST Action 16228 GAMENET (European Cooperation in Science and Technology), PDR project Subgame perfection in graph games (F.R.S.- FNRS)
Subjects: FOS: Computer and information sciences, mean-payoff objectives, Computer Science::Computer Science and Game Theory, subgame-perfect equilibria, [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], Software and its engineering → Formal methods, Games on graphs, Computer Science - Computer Science and Game Theory, Theory of computation → Solution concepts in game theory, Theory of computation → Logic and verification, Computer Science and Game Theory (cs.GT)
Abstract: In this paper, we provide an effective characterization of all the subgame-perfect equilibria in infinite duration games played on finite graphs with mean-payoff objectives. To this end, we introduce the notion of requirement, and the notion of negotiation function. We establish that the plays that are supported by SPEs are exactly those that are consistent with the least fixed point of the negotiation function. Finally, we show that the negotiation function is piecewise linear, and can be analyzed using the linear algebraic tool box. As a corollary, we prove the decidability of the SPE constrained existence problem, whose status was left open in the literature., LIPIcs, Vol. 203, 32nd International Conference on Concurrency Theory (CONCUR 2021), pages 8:1-8:17
Published: 2021

130. NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female

Author: Bernard Robaye, Gilles Kauffenstein, Julie Pelletier, Jean Sévigny, Romuald Brice Babou Kammoe, Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Département de microbiologie-infectiologie et d’immunologie [Québec City, QC, Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and univOAK, Archive ouverte
Subjects: 0301 basic medicine, Male, Contraction (grammar), Thromboxane, Extracellular nucleotides, lcsh:QR1-502, Biochemistry, lcsh:Microbiology, chemistry.chemical_compound, Mice, 0302 clinical medicine, P2Y 6 receptor, Nucleotide, Receptor, bladder, chemistry.chemical_classification, Contraction, Chemistry, Nucleotides, Hydrolysis, Apyrase, NTPDase1, Smooth muscle contraction, extracellular nucleotides, smooth muscle cells, Smooth muscle cells, Nucleoside triphosphate, Sex, Female, P2Y6 receptor, Muscle Contraction, Bladder, Myocytes, Smooth Muscle, Urinary Bladder, Real-Time Polymerase Chain Reaction, Article, Uridine Diphosphate, 03 medical and health sciences, Antigens, CD, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, sex, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Gene Expression Profiling, Wild type, contraction, Généralités, Molecular biology, Uridine, 030104 developmental biology, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, 030217 neurology & neurosurgery
Abstract: Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1−/−) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6−/− bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1−/−, and P2ry6−/− female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021
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131. Alzheimer's Disease: Tau Pathology and Dysfunction of Endocytosis

Author: Jean Pierre Brion, Christophe Erneux, Marie-Ange De Fisenne, Marie-Claude Potier, Sarah Houben, Mégane Homa, Kunie Ando, Karelle Leroy, Laboratoire d'histologie générale, de neuroanatomie et de neuropathologie [Bruxelles], Université libre de Bruxelles (ULB), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5
Subjects: 0301 basic medicine, Opinion, Pathology, medicine.medical_specialty, Tau pathology, Amyloid s, Disease, Endocytosis, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, mental disorders, Amyloid precursor protein, Medicine, Dementia, endocytosis, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], tau, Molecular Biology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, genome-wide association study, biology, business.industry, Médecine pathologie humaine, Neuropathologie, phosphoinositides, Sciences bio-médicales et agricoles, Alzheimer's disease, medicine.disease, amyloid ß, 3. Good health, 030104 developmental biology, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; Alzheimer’s disease (AD) is the most common form of dementia. Its prevalence will significantlyincrease in the coming decades, whereas no efficient treatment is currently available. AD hastwo main neuropathological lesions: amyloid plaques and neurofibrillary tangles (NFTs). Amyloidplaques are composed of amyloid ß (Aß) peptides cleaved from the Amyloid Precursor Protein(APP) (Glenner and Wong, 1984). NFTs, present in the brain of AD and related neurodegenerativediseases, are constituted of tau proteins (Brion et al., 1985) in hyperphosphorylated and aggregatedform (Wang and Mandelkow, 2016).
Published: 2021

132. CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients

Author: Magalie Barth, Marie-Ange Nguyen-Morel, Marie Le Roux, Florence Renaldo, Nathalie Villeneuve, Florence Riant, Alec Aeby, Lionel Arnaud, Arnaud Biraben, Claude Cances, Catheline Vilain, Anne-Isabelle Vermersch, Patrick Van Bogaert, Edouard Hirsch, Chloé Angelini, Laurence Chaton, Gaetan Lesca, Julien Van Gils, Laurent Villard, Sophie Gueden, Patrick Desbordes de Cepoy, Vincent des Portes, Luc Valton, Cecilia Altuzarra, Audrey Riquet, Anne de Saint Martin, Gall, Valérie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Hôpital Erasme [Bruxelles], CHU Strasbourg, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Purpan (CHU Purpan), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de Bordeaux Pellegrin [Bordeaux], CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Pediatrics, medicine.medical_specialty, Early onset absence seizures, Stroke-like, [SDV]Life Sciences [q-bio], Status epilepticus, Lamotrigine, CACNA1A, Absence seizure, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Seizures, 030225 pediatrics, medicine, Humans, Spinocerebellar Ataxias, Familial hemiplegic migraine, Drug-resistance, Episodic ataxia, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Lennox-gastaut syndrome, General Medicine, medicine.disease, 3. Good health, Child, Preschool, Pediatrics, Perinatology and Child Health, Ataxia, Female, Neurology (clinical), Calcium Channels, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Lennox–Gastaut syndrome, medicine.drug
Abstract: International audience; CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.
Published: 2021

133. Copyful Streaming String Transducers

Author: Emmanuel Filiot, Pierre-Alain Reynier, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Modélisation et Vérification (MOVE), Laboratoire d'Informatique et Systèmes (LIS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), ANR-16-CE40-0007,DELTA,DÉfis pour la Logique, les Transducteurs et les Automates(2016), Laboratoire d'informatique Fondamentale de Marseille (LIF), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), and Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: TheoryofComputation_COMPUTATIONBYABSTRACTDEVICES, Computer science, 0102 computer and information sciences, 01 natural sciences, Theoretical Computer Science, Set (abstract data type), [INFO.INFO-FL]Computer Science [cs]/Formal Languages and Automata Theory [cs.FL], 0101 mathematics, Equivalence (formal languages), Physics::Atmospheric and Oceanic Physics, PSPACE, Variable (mathematics), Discrete mathematics, Algebra and Number Theory, Finite-state machine, 010102 general mathematics, String (computer science), [INFO.INFO-LO]Computer Science [cs]/Logic in Computer Science [cs.LO], Decidability, Automaton, TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, Computational Theory and Mathematics, 010201 computation theory & mathematics, Computer Science::Programming Languages, Computer Science::Formal Languages and Automata Theory, Information Systems
Abstract: International audience; Copyless streaming string transducers (copyless SST) have been introduced by R. Alur and P. ˇ Cern´yCern´y in 2010 as a one-way determin-istic automata model to define transductions of finite strings. Copyless SST extend deterministic finite state automata with a set of variables in which to store intermediate output strings, and those variables can be combined and updated all along the run, in a linear manner, i.e., no variable content can be copied on transitions. It is known that copyless SST capture exactly the class of MSO-definable string-to-string trans-ductions, and are as expressive as deterministic two-way transducers. They enjoy good algorithmic properties. Most notably, they have decid-able equivalence problem (in PSpace). On the other hand, HDT0L systems have been introduced for a while, the most prominent result being the decidability of the equivalence problem. In this paper, we propose a semantics of HDT0L systems in terms of transductions, and use it to study the class of deterministic copyful SST. Our contributions are as follows: (i) HDT0L systems and total deterministic copyful SST have the same expressive power, (ii) the equivalence problem for deterministic copyful SST and the equivalence problem for HDT0L systems are inter-reducible, in linear time. As a consequence, equivalence of deterministic SST is decid-able, (iii) the functionality of non-deterministic copyful SST is decidable, (iv) determining whether a deterministic copyful SST can be transformed into an equivalent deterministic copyless SST is decidable in polynomial time.
Published: 2021

134. A new model for Last-Mile Delivery and Satellite Depots management: The impact of the on-demand economy

Author: Maria Elena Bruni, Guido Perboli, Luce Brotcorne, Mariangela Rosano, Politecnico di Torino = Polytechnic of Turin (Polito), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Università della Calabria [Arcavacata di Rende] (Unical), Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Urban delivery, Last-mile delivery, 0211 other engineering and technologies, Transportation, 02 engineering and technology, Bin packing, On-demand economy, Consolidation (business), On demand, 0502 economics and business, Multiple delivery, Joint problem, Business and International Management, Integer programming, ComputingMilieux_MISCELLANEOUS, Civil and Structural Engineering, 050210 logistics & transportation, 021103 operations research, Urban consolidation, Bin packing problem, 05 social sciences, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Economy, Business, Heuristics
Abstract: Two-tier city logistics systems are playing a very important role nowadays in the management of urban freight activities. Although several city authorities have promoted different measures to foster the implementation of small urban consolidation centers in a two-tier system, only a few authors have addressed the joint problem of operating these facilities and providing services to customers. We show how the problem can be modeled as a new variant of the bin packing, for which we provide a mixed integer programming formulation and two heuristics that are shown to be quite effective in solving efficiently and to near optimality the problem. The application of our approach on real data from the city of Turin puts into highlight the superiority of the consolidation approach, including the bundle of goods from different providers, stockholding and other value-added logistics services, over the classical single-tier approach. In addition, the paper provides a thorough analysis of some emerging aspects of the on-demand economy, as the consideration of customers’ preferences and the integration of multiple delivery options. The managerial insights coming from this work will be part of the new Logistics and Mobility Plan to be activated in 2022 in the Piedmont region.
Published: 2021

135. The Stackelberg games of water extraction with myopic agents

Author: Alain Jean-Marie, Mabel Tidball, Víctor Bucarey López, Network Engineering and Operations (NEO ), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre d'Economie de l'Environnement - Montpellier - UMR 5211 (CEE-M), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad de O'Higgins (UOH), Centre d'Economie de l'Environnement - Montpellier (CEE-M), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), and ANR-16-CE03-0005,GREEN-Econ,Vers une économie plus verte : politiques environnementales et adaptation sociétale(2016)
Subjects: General Computer Science, Dynamic game, water resource management, 0502 economics and business, 05 social sciences, 050206 economic theory, Stackelberg game, 050207 economics, Statistics, Probability and Uncertainty, Business and International Management, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, [SHS]Humanities and Social Sciences
Abstract: We consider a discrete-time, infinite-horizon dynamic game of groundwater extraction. A Water Agency charges an extraction cost to water users and controls the marginal extraction cost so that it depends not only on the level of groundwater but also on total water extraction (through a parameter [Formula: see text] that represents the degree of strategic interactions between water users) and on rainfall (through parameter [Formula: see text]). The water users are selfish and myopic, and the goal of the agency is to give them incentives so as to improve their total discounted welfare. We look at this problem in several situations. In the first situation, the parameters [Formula: see text] and [Formula: see text] are considered to be fixed over time. The first result shows that when the Water Agency is patient (the discount factor tends to 1), the optimal marginal extraction cost asks for strategic interactions between agents. The contrary holds for a discount factor near 0. In a second situation, we look at the dynamic Stackelberg game where the Agency decides at each time what cost parameter they must announce. We study theoretically and numerically the solution to this problem. Simulations illustrate the possibility that threshold policies are good candidates for optimal policies.
Published: 2021

136. Am I Cold? Investigating Ingroup Stereotype-Learning

Author: Annique Smeding, Julia Eberlen, Jean-Charles Quinton, Quinton, Jean-Charles, Laboratoire Inter-universitaire de Psychologie : Personnalité, Cognition, Changement Social (LIP-PC2S), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), Center for Social and Cultural Psychology (CeSCuP), Faculté des Sciences psychologiques et de l'éducation [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), 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 ), and Université Grenoble Alpes (UGA)
Subjects: [SCCO.PSYC]Cognitive science/Psychology, [SCCO.PSYC] Cognitive science/Psychology, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation
Abstract: International audience; Stereotypes, conceived as heuristics facilitating navigation of the social world, can be learned based on statistical contingencies between social group concepts and a stereotype-compatible characterization. However, a negative stereotype applied to an individual’s ingroup can conflict with the general tendency to see the self in a positive light, the self-positivity bias. Here, we used a modified minimal-group paradigm to create self-associations with members of an artificial social group (i.e., Fribble group) and test the impact of (counter-) stereotypical incidental learning on self- and group associations. Based on one pilot study (N = 43), a related simulation study, and two main experiments comprising human (N = 89 and N = 119) and simulated participant data, we tested whether minimally defined self- and group associations can be modified through incidental stereotype learning at the task temporal scale (i.e., duration of an experimental session rather than long-term socialization history). Results of the pilot and related simulation study established (i) that the pilot procedure for ingroup associations had to be strengthened; (ii) proof of concept of theoretical assumptions; (iii) feasibility of the experimental implementation of hypotheses; and (iv) optimal design for experimental studies to maximize statistical power. Findings of Experiment 1 subsequently showed that a stronger procedure was efficient to create self-ingroup associations and, by extension, ingroup stereotypes at the pre-learning phase. Furthermore, after incidental exposure to counter-stereotypical information, we observed changes in ingroup associations and self-related associations, even though the latter were never targeted by the counter-stereotypical information. Findings of Experiment 2 showed that the changes in self- and group associations observed in Experiment 1 were moderated by the proportion of positive/negative ingroup information to which participants were exposed during the learning phase. Experiment 2 also allowed discarding an alternative explanation of these changes in terms of memory loss. Together, findings provide an in-depth mechanistic account of the social-cognitive processes involved in stereotype learning and illustrate the benefits of mixed-methods (formal modelling, human and simulated participant data) to understand them.
Published: 2021

137. Coordinating resources in Stackelberg Security Games

Author: L Víctor Bucarey, Oscar Figueroa, Carlos Casorrán, Fernando Ordóñez, Martine Labbé, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Departamento de Ingenieria Industrial [Santiago] (DII), Carabineros de Chile, and Víctor Bucarey and Martine Labbé have been partially supported by the Fonds de la Recherche Scientifique - FNRS under Grant(s) no PDR T0098.18. Víctor was also partially funded by the CONICYT PFCHA/DOCTORADO NACIONAL/2013 - 21130556. Fernando Ordoñez acknowledges the support from Instituto Sistemas Complejos de Ingeniería (ISCI) through CONICYT - PIA/BASAL AFB180003 and from FONDECYT-Chile, grant No. 1171419.
Subjects: 050210 logistics & transportation, Matching (statistics), Mathematical optimization, 021103 operations research, Information Systems and Management, General Computer Science, Computer science, 05 social sciences, 0211 other engineering and technologies, 02 engineering and technology, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Management Science and Operations Research, 16. Peace & justice, OR in Defence, Industrial and Manufacturing Engineering, Set (abstract data type), Stackelberg Games, Bilevel Optimization, Modeling and Simulation, 0502 economics and business, Stackelberg competition, Probability distribution, Recherche opérationnelle, Integer (computer science)
Abstract: International audience; In this work we formulate a Stackelberg Security Game that coordinates resources in a border patrol problem. In this security domain, resources from different precincts have to be paired to conduct patrols in the border due to logistic constraints. Given this structure, models that enumerate the pure defender strategies scale poorly. We describe the set of mixed strategies using a polynomial number of variables but exponentially many constraints that come from the matching polytope. We then include this description in a mixed integer formulation to compute the Strong Stackelberg Equilibrium efficiently with a branch and cut scheme. Since the optimal patrol solution is a probability distribution over the set of exponential size, we also introduce an efficient sampling method that can be used to deploy the security resources every shift. Our computational results evaluate the efficiency of the branch and cut scheme developed and the accuracy of the sampling method.
Published: 2021

138. Radical collaboration during a global health emergency: Development of the RDA COVID-19 data sharing recommendations and guidelines

Author: Amy Pienta, Alejandra Gonzalez-Beltran, Zoe Cournia, Francis P. Crawley, Leyla Jael Castro, Sridhar Gutam, Daniel Mietchen, Timea Biro, Ingvill C. Mochmann, Marcos Roberto Tovani-Palone, Claire C. Austin, Geta Mitrea, Simon Parker, Katherine McNeill, Minglu Wang, Louise Bezuidenhout, Carlos Casorran, Anupama Gururaj, Natalie Harrower, Jitendra Jonnagaddala, Panayiota Polydoratou, Alexander Bernier, Claudia Engelhardt, Kheeran Dharmawardena, Ingrid Dillo, Mary O'Brien-Uhlmansiek, Romain David, Rajini Nagrani, Brian Pickering, Gayo Diallo, University of Oxford, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), European Research Infrastructure on Highly Pathogenic Agents (ERINHA-AISBL), Göttingen State and University Library (SUB Göttingen), Georg-August-University = Georg-August-Universität Göttingen, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Data Archiving and Networked Services (DANS-KNAW), Royal Netherlands Academy of Arts and Sciences (KNAW), and European Project: 824087,EOSC-Life
Subjects: medicine.medical_specialty, Knowledge management, Coronavirus disease 2019 (COVID-19), data sharing, global health, epidemic, pandemic, COVID-19, Research Data Alliance, public health, radical collaboration, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Collective identity, Political science, Global health, medicine, 030304 developmental biology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, business.industry, Public health, 05 social sciences, Articles, General Medicine, 3. Good health, Data sharing, Alliance, Work (electrical), [SHS.GESTION]Humanities and Social Sciences/Business administration, Survey data collection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0509 other social sciences, 050904 information & library sciences, business, Research Article
Abstract: Background: The coronavirus disease 2019 (COVID-19) global pandemic required a rapid and effective response. This included ethical and legally appropriate sharing of data. The European Commission (EC) called upon the Research Data Alliance (RDA) to recruit experts worldwide to quickly develop recommendations and guidelines for COVID-related data sharing. Purpose: The purpose of the present work was to explore how the RDA succeeded in engaging the participation of its community of scientists in a rapid response to the EC request. Methods: A survey questionnaire was developed and distributed among RDA COVID-19 work group members. A mixed-methods approach was used for analysis of the survey data. Results: The three constructs of radical collaboration (inclusiveness, distributed digital practices, productive and sustainable collaboration) were found to be well supported in both the quantitative and qualitative analyses of the survey data. Other social factors, such as motivation and group identity were also found to be important to the success of this extreme collaborative effort. Conclusions: Recommendations and suggestions for future work were formulated for consideration by the RDA to strengthen effective expert collaboration and interdisciplinary efforts.
Published: 2021

139. A Branch-Price-and-Cut Procedure for the Discrete Ordered Median Problem

Author: Martine Labbé, Diego Ponce, Justo Puerto, Samuel Deleplanque, Évaluation des Systèmes de Transports Automatisés et de leur Sécurité (IFSTTAR/COSYS/ESTAS), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-PRES Université Lille Nord de France, Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), Centre Interuniversitaire de Recherche sur les Réseaux d'Entreprise, la Logistique et le Transport (CIRRELT), École Polytechnique de Montréal (EPM)-Université de Montréal (UdeM)-HEC Montréal (HEC Montréal), Departamento de Matemática Aplicada I (IMUS), IMUS, This research was supported by Spanish/FEDER grants number MTM2016-74983-C02-01. The research of the second and third authors was supported by the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office. We thank the SCIP team (Gamrath et al. (2016)) for the helpful advices., IFFSTAR, Universidad de Sevilla. Departamento de Estadística e Investigación Operativa, and Universidad de Sevilla. FQM331: Metodos y Modelos de la Estadistica y la Investigacion Operativa
Subjects: 050210 logistics & transportation, 021103 operations research, Informatique générale, Branch and price, 05 social sciences, 0211 other engineering and technologies, General Engineering, Informatique appliquée logiciel, 02 engineering and technology, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Location theory, Set (abstract data type), location theory, branch and price, Variable (computer science), Discrete optimization, 0502 economics and business, Exponential number, ordered median problems, Applied mathematics, Théorie de la décision et des choix collectifs, discrete optimization, Mathematics
Abstract: The discrete ordered median problem (DOMP) is formulated as a set-partitioning problem using an exponential number of variables. Each variable corresponds to a set of demand points allocated to the same facility with the information of the sorting position of their corresponding costs. We develop a column generation approach to solve the continuous relaxation of this model. Then we apply a branch-price-and-cut algorithm to solve small- to large-sized instances of DOMP in competitive computational time., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

140. A column generation based heuristic for the generalized vehicle routing problem with time windows

Author: Diego Cattaruzza, Daniele Vigo, Frédéric Semet, Maxime Ogier, Yuan Yuan, Integrated Optimization with Complex Structure (INOCS), Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Alma Mater Studiorum University of Bologna (UNIBO), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Yuan Y., Cattaruzza D., Ogier M., Semet F., Vigo D., Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Operations Analytics, Amsterdam Business Research Institute, and Semet, Frédéric
Subjects: Mathematical optimization, time windows, [INFO.INFO-RO] Computer Science [cs]/Operations Research [cs.RO], Computer science, Heuristic (computer science), trunk/in-car delivery, Trunk/in-car delivery, 0211 other engineering and technologies, Transportation, 02 engineering and technology, [INFO] Computer Science [cs], Delivery options, generalized vehicle routing problem, last mile delivery, 0502 economics and business, Vehicle routing problem, [INFO]Computer Science [cs], Local search (optimization), Column generation, Generalized vehicle routing problem, Business and International Management, Time windows, ComputingMilieux_MISCELLANEOUS, Civil and Structural Engineering, 050210 logistics & transportation, 021103 operations research, Delivery option, business.industry, 05 social sciences, Directed graph, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Last mile delivery, Vertex (geometry), Time window, Routing (electronic design automation), business, Reduced cost, delivery options
Abstract: The generalized vehicle routing problem with time windows (GVRPTW) is defined on a directed graph G = ( V , A ) where the vertex set V is partitioned into clusters. One cluster contains only the depot, where is located a homogeneous fleet of vehicles, each with a limited capacity. The other clusters represent customers. A demand is associated with each cluster. Inside a cluster, the vertices represent the possible locations of the customer. A time window is associated with each vertex, during which the visit must take place if the vertex is visited. The objective is to find a set of routes such that the total traveling cost is minimized, exactly one vertex per cluster is visited, and all the capacity and time constraints are respected. This paper presents a set covering formulation for the GVRPTW which is used to provide a column generation based heuristic to solve it. The proposed solving method combines several components including a construction heuristic, a route optimization procedure, local search operators and the generation of negative reduced cost routes. Experimental results on benchmark instances show that the proposed algorithm is efficient and high-quality solutions for instances with up to 120 clusters are obtained within short computation times.
Published: 2021

141. Church Synthesis on Register Automata over Linearly Ordered Data Domains

Author: Exibard, Léo, Filiot, Emmanuel, Khalimov, Ayrat, Laboratoire d'Informatique et Systèmes (LIS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: FOS: Computer and information sciences, Ordered Data Words, Theory of computation → Automata over infinite objects, TheoryofComputation_COMPUTATIONBYABSTRACTDEVICES, Formal Languages and Automata Theory (cs.FL), Register Automata, Transducers, Généralités, Computer Science - Formal Languages and Automata Theory, Theory of computation → Transducers, 16. Peace & justice, Theory of computation → Logic and verification, Synthesis, TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, [INFO.INFO-FL]Computer Science [cs]/Formal Languages and Automata Theory [cs.FL], Informatique mathématique, Church Game, Computer Science::Formal Languages and Automata Theory
Abstract: Register automata are finite automata equipped with a finite set of registers in which they can store data, i.e. elements from an unbounded or infinite alphabet. They provide a simple formalism to specify the behaviour of reactive systems operating over data ω-words. We study the synthesis problem for specifications given as register automata over a linearly ordered data domain (e.g. (N, ≤) or (Q, ≤)), which allow for comparison of data with regards to the linear order. To that end, we extend the classical Church synthesis game to infinite alphabets: two players, Adam and Eve, alternately play some data, and Eve wins whenever their interaction complies with the specification, which is a language of ω-words over ordered data. Such games are however undecidable, even when the specification is recognised by a deterministic register automaton. This is in contrast with the equality case, where the problem is only undecidable for nondeterministic and universal specifications. Thus, we study one-sided Church games, where Eve instead operates over a finite alphabet, while Adam still manipulates data. We show they are determined, and deciding the existence of a winning strategy is in ExpTime, both for Q and N. This follows from a study of constraint sequences, which abstract the behaviour of register automata, and allow us to reduce Church games to ω-regular games. Lastly, we apply these results to the transducer synthesis problem for input-driven register automata, where each output data is restricted to be the content of some register, and show that if there exists an implementation, then there exists one which is a register transducer., SCOPUS: cp.p, info:eu-repo/semantics/published
Published: 2021
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142. Digestive involvement in a severe form of Snyder-Robinson syndrome: Possible expansion of the phenotype

Author: Ovidiu Balasel, Pauline Dontaine, Véronique Catros, Martine Dassonville, Julie Soblet, Elisa Kottos, Catheline Vilain, Pascale Perlot, Jonchère, Laurent, Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Université libre de Bruxelles (ULB), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)
Subjects: Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Hearing loss, Spermidine, [SDV]Life Sciences [q-bio], Spermine Synthase, Mutation, Missense, [SDV.GEN] Life Sciences [q-bio]/Genetics, New variant, Enteral administration, 03 medical and health sciences, Epilepsy, Cholestasis, Genetics, medicine, Humans, Exocrine pancreatic insufficiency, Main text, Genetics (clinical), 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Mendeliome, business.industry, 030305 genetics & heredity, Infant, General Medicine, Failure to thrive, Snyder-Robinson, medicine.disease, 3. Good health, Osteopenia, [SDV] Life Sciences [q-bio], Jejunum, Phenotype, SMS, Child, Preschool, Jejunal Stenosis, Mental Retardation, X-Linked, Spermine, medicine.symptom, business
Abstract: International audience; Snyder-Robinson syndrome (OMIM #309583) is a rare X-linked condition, caused by mutation in the SMS gene (MIM *300105), characterized by a wide spectrum of clinical signs including developmental delay, epilepsy, asthenic habitus, dysmorphism, osteopenia, and renal or genital anomalies. Here we describe two maternal half-brothers who both presented with severe neurodevelopmental delay, seizures, hearing loss, facial dysmorphism, renal and ophthalmologic anomalies, failure to thrive and premature death. A novel p.(Gly203Asp) variant was found at the hemizygous state in the two boys, and an elevated Spermidine/Spermine ratio confirmed the diagnosis of Snyder-Robinson syndrome. One of the brothers presented with gastrointestinal symptoms, with jejunal stenosis, enteral feeding intolerance, failure to thrive due to a dysfunctional gastrointestinal system, cholestasis and exocrine pancreatic insufficiency. Although more studies will be needed to understand its mechanisms, this observation lends further support to the possibility of severe digestive involvement in Snyder Robinson syndrome.
Published: 2021

143. El Problema de tarificación basado en preferencias : un enfoque desde la optimización lineal entera mixta

Author: Domínguez Sánchez, Concepción, Fortz, Bernard, Labbé, Martine, Marín, Alfredo, Escuela Internacional de Doctorado, Graphes et Optimisation Mathématique [Bruxelles] (GOM), Université libre de Bruxelles (ULB), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), research contract in Centrale Lille - Inria and by the 'Fonds de la Recheche Scientifique' undera FRIA grant, project MTM2015-65915-R (MINECO, Spain), project PID2019-110886RB-I00 (MICINN, Spain), Université libre de Bruxelles, Bernard Fortz, Alfredo Marin, and Martine Labbe
Subjects: Programación, 5 - Ciencias puras y naturales::51 - Matemáticas [CDU], Programmation en nombres entiers, optimisation combinatoire, Matemáticas, Bilevel Programming, Combinatorial Optimization, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Integer Programming, programmation à deux niveaux
Abstract: Esta tesis está dedicada a un estudio en profundidad del Problema de Tarificación basado en Preferencias (del inglés, Rank Pricing Problem (RPP)) y dos generalizaciones. El RPP es un problema de optimización combinatoria que tiene como objetivo fijar el precio de los productos de una compañía para maximizar su beneficio. En él, intervienen clientes unit-demand, es decir, clientes que están interesados en varios de los productos de la empresa, pero pretenden comprar como mucho uno de ellos. Los clientes tienen un presupuesto fijo y clasifican los productos que les interesan formando un ranking del “mejor” al “peor”. Cuando la compañía fije los precios, cada cliente comprará su producto preferido de entre los que se puede permitir. En el RPP, asumimos que los productos se ofertan en cantidad ilimitada, lo cual encaja si consideramos que la compañía tiene suficientes productos para satisfacer la demanda, o cuando los productos se pueden producir rápidamente con un coste despreciable (por ejemplo, los bienes digitales). Esta tesis doctoral consta de cuatro capítulos. El primero de ellos es un capítulo de introducción al problema y a los conceptos matemáticos presentes en la tesis, mientras que los tres siguientes se centran en cada uno de los problemas estudiados: el RPP y dos generalizaciones. Así, el tercer capítulo está dedicado al estudio del Problema de Tarificación basado en Preferencias con Empates (RPPT por sus siglas en inglés, Rank Pricing Problem with Ties). En esta extensión del problema, asumimos que los clientes pueden expresar su indiferencia entre productos de su interés mediante empates en su lista de preferencia. Y el último capítulo de la tesis comprende el estudio del Problema de Tarificación Capacitado basado en Preferencias o Capacitated Rank Pricing Problem (CRPP) con envidia. En esta extensión, hemos asumido precios de reserva en los clientes que reflejan lo que están dispuestos a pagar por cada producto, en vez de un solo presupuesto por consumidor. No obstante, la principal diferencia es que en el CRPP la compañía tiene un número limitado de productos y puede no ser capaz de satisfacer la demanda de todos los clientes. El objetivo de la tesis es obtener formulaciones lineales enteras mixtas para los tres problemas estudiados, y compararlas teórica y/o computacionalmente. Para ello, la metodología empleada se basa en la propuesta de variables de decisión y restricciones apropiadas que modelicen el problema. El siguiente objetivo es la mejora de estas formulaciones mediante desigualdades válidas que reducen la región factible de la relajación del problema y permiten obtener una mejor cota de la relajación lineal. Y finalmente, un tercer objetivo es la propuesta de algoritmos de resolución para cada uno de estos modelos, y su posterior comparativa mediante la realización de estudios computacionales y resolución mediante optimizadores comerciales. En el Capítulo 2 introducimos dos formulaciones no lineales para el RPP, una que surge de una formulación binivel y otra que está formulada directamente en un solo nivel. Las comparamos teóricamente, linealizamos su función objetivo (que es la misma en ambos casos) de dos formas distintas y proponemos técnicas de preprocesamiento que reducen el tamaño de las instancias fijando variables binarias a cero o a uno. También estudiamos el problema de empaquetamiento asociado a las variables binarias del mejor modelo, con lo que probamos que esta formulación es muy fuerte porque la mayoría de las restricciones que contiene definen facetas del subproblema asociado. Los resultados computacionales son consistentes con nuestra comparación teórica, ya que muestran la superioridad del modelo uninivel. También revelan que se obtienen mejores cotas y un mejor rendimiento en general con una de las linealizaciones propuestas, que se emplea en capítulos posteriores. En el Capítulo 3, proponemos la primera formulación con variables de tres índices para el RPPT. Luego incluimos un método de resolución basado en la introducción de un modelo más débil con un conjunto de variables y restricciones de menor tamaño (el modelo de dos índices), formulación que a continuación fortalecemos añadiendo desigualdades válidas. El segundo método de resolución propuesto está basado en la descomposición de Benders, un método ampliamente utilizado para problemas enteros mixtos. Así, proponemos un Modelo de Benders válido con un conjunto de variables y restricciones pequeño, que reforzamos mediante desigualdades válidas que surgen de la resolución de los subproblemas de Benders. En los experimentos computacionales, observamos que cada uno de los algoritmos de resolución propuestos destaca en una fase de la resolución del problema. En la fase de la relajación lineal, resulta más rápida la adición de cortes en el modelo de dos índices, ya que las desigualdades se pueden separar por productos (incluso si se incluyen más cortes). En la fase entera, sin embargo, el Modelo de Benders lleva a cabo la exploración de nodos más rápido que el otro modelo, probablemente debido a su reducido número de variables y restricciones. El Capítulo 4 comienza introduciendo una formulación con variables de tres índices para resolver el CRPP. Al contrario que en los capítulos precedentes, en este se incluyen varios conjuntos de desigualdades válidas para dicha formulación que utilizan las restricciones de capacidad y nuevas variables binarias. Estos conjuntos se utilizan después cuando se proyecta el modelo de tres índices en el modelo de dos índices, por lo que las desigualdades obtenidas son más difíciles de separar porque dependen de seis conjuntos de parámetros. Además de resolver el problema de separación con Xpress, también separamos teóricamente un conjunto de desigualdades que resulta muy efectivo en la práctica, y lo relacionamos con un conjunto de cortes propuesto para el RPP. La combinación de estas desigualdades con las últimas que proponemos da como resultado un algoritmo muy eficiente que reúne las ventajas de ambas: proporciona unas de las mejores cotas de la relajación lineal y las fases de inclusión de cortes en el nodo raíz y de ramificación son muy rápidas This doctorate is entirely devoted to an in-depth study of the Rank Pricing Problem (RPP) and two generalizations. The RPP is a combinatorial optimization problem which aims at setting the prices of a series of products of a company to maximize its revenue. This problem is specified by a set of unit-demand customers, that is, customers interested in a subset of the products offered by the company which intend to buy at most one of them. To do so, they count on a fixed budget, and they rank the products of their interest from the “best” to the “worst”. Once the prices are established by the company, they will purchase their highest-ranked product among the ones they can afford. In the RPP, it is assumed an unlimited supply of products, which is consistent with a company having enough copies of a product to satisfy the demand, or with a setting where the products can be produced quickly at negligible cost (e.g., digital goods). This dissertation consists of four chapters. The first chapter introduces the RPP problem and the mathematical concepts present in the work, whereas each of the next three chapters tackles the resolution of each of the problems of study: the RPP and two generalizations. Thus, Chapter 3 is dedicated to the Rank Pricing Problem with Ties (RPPT), an extension of the RPP where we consider that customers can express indifference among products in their preference list. And the last chapter of the thesis is devoted to a generalization of the problem that we have named the Capacitated Rank Pricing Problem (CRPP) with envy. For this generalization, we have considered reservation prices of customers for the different products that reflect their willingness to pay, instead of a single budget per customer. However, the main difference is that, in the CRPP, the company has a limited supply of products and might not be able to satisfy all the customers’ requests. This is a realistic assumption that we can find in many companies. The aim of this thesis is the proposal of mixed-integer linear formulations for the three problems of study, and their theoretical and/or computational comparison. The methodology used is based on the introduction of decision variables and adequate restrictions to model the problems. Another objective consists in strengthening the formulations by means of valid inequalities that reduce the feasible region of the relaxed problem and allow us to obtain better linear relaxation bounds. Finally, a third goal is to derive resolution algorithms for each of these models and compare them computationally, using commercial solvers. In Chapter 2, we give two nonlinear formulations for the RPP, one that comes from a bilevel formulation and another one that is directly formulated as a single-level one. We compare them theoretically, linearize their objective functions (which are the same) in two different ways and propose preprocessing techniques that effectively reduce the size of the instances by fixing variables to either zero or one. By studying the Set Packing Problem associated to the binary variables of the strongest model, we prove that this formulation is very tight, since most of its constraints are facet-defining in the corresponding subproblem. The computational results are consistent with our theoretical comparison, given that they show the superiority of the single-level model. They also disclose that one of the linearizations (used in following chapters) outperforms the other. In Chapter 3, we propose the first formulation with three-index variables for the RPPT. Next, we propose a resolution method based on the introduction of a weaker model with much less variables and constraints (the two-index model) and its strengthening by means of valid inequalities. The second resolution method is based on the Benders decomposition, a widely used approach for solving mixed-integer programs. Thus, we introduce a valid Benders Model with a small number of variables and constraints. Next, we reinforce the model dynamically adding valid inequalities obtained solving the Benders subproblems. In the computational testing, each of the resolution algorithms proposed excels in a specific phase. In the linear relaxation phase, the separation procedure designed to add valid inequalities is faster for the two-index model, since these inequalities can be separated by products. In the integer phase, however, the Benders Model outperforms the two-index model in the tree search because the node exploration is faster, probably due to the small number of variables and constraints it has. Chapter 4 begins with the introduction of a model with three-index variables for the CRPP. Unlike in the previous chapters, here the capacity constraints and the inclusion of new variables associated to the capacity allow to derive several sets of valid inequalities for the three-index formulation. These sets are then included in the projection of the three-index formulation into the two-index one, so the resultant inequalities are more difficult to separate because they depend on six sets of parameters. Besides solving the separation problem with Xpress, we theoretically separate a particular set of inequalities that proves to be very effective in practice, and link it with a family proposed for the RPP. The combination of these inequalities with the last set proposed results in a very efficient resolution method that combines the best linear relaxation gap with a rather quick inclusion of cuts in the root node and an effective node search.
Published: 2021

144. Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease

Author: Pierre Lefesvre, Katarina Coolens, Farzad Esni, Nelson Dusetti, Harry Heimberg, Luc Bouwens, Jean-Luc Van Laethem, Yves Heremans, Gunter Leuckx, Patrick Jacquemin, Angel Fernandez Ruiz, Tatjana Arsenijevic, Meritxell Rovira, Christelle Bouchart, Peter In't Veld, Wim Waelput, Ilse Rooman, Sandrina Martens, Nicky D'Haene, Abdessamad El Kaoutari, Jaime Martinez de Villareal, Diedert Luc De Paep, Francisco X. Real, Joan Casamitjana, Hediel Madhloum, Mathias Van Bulck, Vrije Universiteit Brussel (VUB), Université libre de Bruxelles (ULB), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-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), Spanish National Cancer Research Center (CNIO), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut Jules Bordet [Bruxelles], Centre de Recherche en Cancérologie de Marseille (CRCM), Basic (bio-) Medical Sciences, Experimental Pathology, Laboratory for Medical and Molecular Oncology, Faculty of Medicine and Pharmacy, Pathology/molecular and cellular medicine, Beta Cell Neogenesis, Cell Differentiation, Surgery, Diabetes Pathology & Therapy, Supporting clinical sciences, Pathology, 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)-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), UCL - SSS/DDUV - Institut de Duve, and UCL - SSS/DDUV/LPAD - Liver and pancreas differentiation
Subjects: 0301 basic medicine, Pancreatic disease, Cellular differentiation, Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, SOX9, Biology, Stem cell marker, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, development genes, stem cells, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Gastro-entérologie, cancer, pancreas, Gastroenterology, imaging, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Stem cell, Pancreas
Abstract: Objective: The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours, ΔNp63+ basal cells reportedly do not exist in the normal pancreas. Design: We evaluated ΔNp63 expression in human pancreas, chronic pancreatitis (CP) and PDAC. We further studied in depth the non-cancerous tissue and developed a three-dimensional (3D) imaging protocol (FLIP-IT, Fluorescence Light sheet microscopic Imaging of Paraffin-embedded or Intact Tissue) to study formalin-fixed paraffin-embedded samples at single cell resolution. Pertinent mouse models and HPDE cells were analysed. Results: In normal human pancreas, rare ΔNp63+ cells exist in ducts while their prevalence increases in CP and in a subset of PDAC. In non-cancer tissue, ΔNp63+ cells are atypical KRT19+ duct cells that overall lack SOX9 expression while they do express canonical basal markers and pertain to a niche of cells expressing gastrointestinal stem cell markers. 3D views show that the basal cells anchor on the basal membrane of normal medium to large ducts while in CP they exist in multilayer dome-like structures. In mice, ΔNp63 is not found in adult pancreas nor in selected models of CP or PDAC, but it is induced in organoids from larger Sox9low ducts. In HPDE, ΔNp63 supports a basal cell phenotype at the expense of a classical duct cell differentiation programme. Conclusion: In larger human pancreatic ducts, basal cells exist. ΔNp63 suppresses duct cell identity. These cells may play an important role in pancreatic disease, including PDAC ontogeny, but are not present in mouse models., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

145. Maintenance of wakefulness test: how does it predict accident risk in patients with sleep disorders?

Author: Kelly Guichard, Régis Lopez, Jean-Arthur Micoulaud-Franchi, Isabelle Arnulf, Yves Dauvilliers, Mélanie Strauss, Damien Leger, Emilie Pepin, Jacques Taillard, Patricia Sagaspe, Lucie Barateau, Pierre Philip, CCSD, Accord Elsevier, Sommeil, Addiction et Neuropsychiatrie [Bordeaux] (SANPSY), Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), Institut de Recherche Biomédicale des Armées (IRBA)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Sommeil, Attention et Neuropsychiatrie [Bordeaux] (SANPSY), Institut de Recherche Biomédicale des Armées (IRBA)-Université de Paris (UP), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Sleep Wake Disorders, medicine.medical_specialty, Automobile Driving, Maintenance of Wakefulness Test, Sleepiness, Accident risk, Disorders of Excessive Somnolence, Near miss, 03 medical and health sciences, 0302 clinical medicine, Sleep disorders, French drivers, medicine, Humans, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Wakefulness, Sleep disorder, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, MESH: Automobile Driving, business.industry, OSAS, General Medicine, medicine.disease, MESH: Case-Control Studies, MESH: Male, MESH: Sleep Wake Disorders, Test (assessment), Alertness, MESH: Wakefulness, 030228 respiratory system, Case-Control Studies, Physical therapy, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sleep (system call), business, human activities, MESH: Female, 030217 neurology & neurosurgery, MESH: Disorders of Excessive Somnolence, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Narcolepsy
Abstract: International audience; Study objective: To determine whether the objective level of alertness measured by the Maintenance of Wakefulness Test (MWT) is associated with the occurrence of self-reported sleepiness-related traffic near misses and accidents related to sleepiness in patients with sleep disorders.Methods: This case-control study was conducted over a three-year period in four French sleep centers during a 4∗40 min MWT in patients driving more than 5000 Km/year. Relationship between mean sleep latency on the MWT (MWT latency) and age, sex, driving, sleepiness-related near misses and accidents reported during the previous year, and sleep disorder characteristics was analyzed.Results: Of 377 patients suffering from OSAS, idiopathic hypersomnia, narcolepsy, restless leg syndrome or insufficient sleep syndrome, 176 were included. 74 cases reported an accident or near miss related to sleepiness at the wheel in the past year, and 102 reported no accident/near miss (control patients). Thirty-one (37.8 %) cases and 9 (8.8 %) controls reported being sleepy at the wheel more than once a week (p < 0.0001). After adjusted regression analyses, patients with MWT latency between 19 and 33 minutes had a 3.2- (CI 95%[1.5; 6.8], p < 0.0001) fold increase in risk of reporting a near miss/ accident and patients with MWT latency 33 min).Conclusions: MWT latency is associated with self-reported, sleepiness-related near misses and accidents related to sleepiness in the past year in patients routinely investigated in sleep clinics. The MWT could be used to assess driving risk together with clinical interviews assessing sleepiness at the wheel.
Published: 2021

146. The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape

Author: Vandermeulen, Charlotte, O’grady, Tina, Wayet, Jerome, Galvan, Bartimee, Maseko, Sibusiso, Cherkaoui, Majid, Desbuleux, Alice, Coppin, Georges, Olivet, Julien, Ben Ameur, Lamya, Kataoka, Keisuke, Ogawa, Seishi, Hermine, Olivier, Marcais, Ambroise, Thiry, Marc, Mortreux, Franck, Calderwood, Michael, van Weyenbergh, Johan, Peloponese, Jean-Marie, Charloteaux, Benoit, van den Broeke, Anne, Hill, David E., Vidal, Marc, Dequiedt, Franck, Twizere, Jean-Claude, GIGA [Université Liège], Université de Liège, Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de 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), Kyoto University, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Liège (CHU-Liège), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and PELOPONESE, Jean-Marie
Subjects: RNA viruses, Interaction Networks, Retroviridae Proteins, LEUKEMIA-VIRUS TYPE-1, RNA-binding proteins, Virologie générale, Pathology and Laboratory Medicine, Biochemistry, ACTIVATION, Jurkat Cells, White Blood Cells, Animal Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunologie, BINDING, Medicine and Health Sciences, Leukemia-Lymphoma, Adult T-Cell, CD45, NETWORK, Biology (General), GENE-EXPRESSION, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Parasitologie, Human T-lymphotropic virus 1, T Cells, Gene Products, tax, Genomics, PROTEIN INTERACTS, Nucleic acids, TRANSCRIPTION FACTORS, Basic-Leucine Zipper Transcription Factors, Oncology, Medical Microbiology, Viral Pathogens, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pathogens, Cellular Types, Biologie, Life Sciences & Biomedicine, Transcriptome Analysis, Research Article, QH301-705.5, RNA Splicing, Immune Cells, Immunology, Microbiology, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Retroviruses, Genetics, Humans, RNA, Messenger, Microbial Pathogens, Molecular Biology, Science & Technology, Blood Cells, Biology and life sciences, Virologie médicale, RECOGNITION, Organisms, Biologie moléculaire, Cancers and Neoplasms, Proteins, Computational Biology, Htlv-1, Cell Biology, RC581-607, Splicing Factor U2AF, Genome Analysis, HTLV-I Infections, Alternative Splicing, HEK293 Cells, RNA processing, T-CELLS, RNA, Parasitology, Gene expression, Immunologic diseases. Allergy, Microbiologie et protistologie [bacteriol.virolog.mycolog.]
Abstract: Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

147. Le parcours de soins du patient dans le cadre des CAR T-cell : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Ibrahim Yakoub-Agha, Anne Wallart Brejaud, Isabelle Fournier, Christelle Andrianne, Corinne Courbon, Josiane Delorme, Sarah Bole, Clotilde Aubrun, Maxime Berquier, Damien Lacroix, Ghislaine François, David Beauvais, Marlene Vercasson, Marie-France Jaivenois, Isabelle Mussot, Alexis Caulier, Laetitia Le Bars, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Ambroise Paré [Mons, Belgium], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Amiens-Picardie, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôtel-Dieu de Nantes, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service d’Hématologie Clinique [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CCSD, Accord Elsevier, and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 0301 basic medicine, Cancer Research, Care process, Coordinating nurse, [SDV]Life Sciences [q-bio], Hematology, General Medicine, CAR T-cell, 3. Good health, Cell activity, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Nursing, 030220 oncology & carcinogenesis, Political science, Infirmier de coordination, Parcours de soins, Radiology, Nuclear Medicine and imaging
Abstract: International audience; In Europe, two CAR T-cell products, tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), were approved in 2018. While these treatments are available for use, allogeneic hematopoietic stem cell transplantation centers still need to set up a dedicated care process inspired by established procedures in the field. In order to determine necessary resources and actors, each step of the CAR T-cell care process must be planned in advance. This process, implemented by the center's coordinating nurse, should be able to be adapted to each center's needs. The purpose of this workshop is to provide the organizational basis for such a process so that each center wishing to set up CAR-T cell activity can do so effectively. After detailing the coordinating nurse's role, we explain each step of the care process and specify essential additional tests.
Published: 2020

148. Mutualisation des outils de qualité pour les cellules CAR-T : recommandations de la Société francophone de greffe de moelle et thérapie cellulaire (SFGM-TC)

Author: Remy Dulery, Jean-Louis Beaumont, Agnes Perrin, Sylvie Carnoy, Cécile Gibault-Joffe, Virginie Ader, Nathalie Contentin, Sophie Plaza-Milhe, Nathalie Fegueux, Philippe Lewalle, Christine Giraud, Marie-Noëlle Lacassagne, Thi Ngoc Phuong Huynh, Alexandre Carpentier, Agnès Bonnin, Marie-Agnès Guerout-Verite, Ibrahim Yakoub-Agha, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Amiens-Picardie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement Français du Sang Nouvelle Aquitaine [Bordeaux] (EFS Bordeaux Nouvelle Aquitaine), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang [Occitanie] (EFS Occitanie), CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Universitaire de Genève, Etablissement français du sang [Rennes] (EFS Bretagne), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Service Gestion du Risque Infectieux, des Vigilances et Infectiologie (SGRIVI), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Service d'hématologie [CRLCC Henri Becquerel], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), CCSD, Accord Elsevier, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Activité électrique du coeur, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, JACIE, Cancer Research, medicine.medical_specialty, CAR T-cells, Lymphoma, [SDV]Life Sciences [q-bio], Cellular therapy, Pharmacy, Acute lymphoblastic leukemia, CAR T-cell, Lymphome, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Therapeutic apheresis, Hematopoietic cell, Quality assessment, business.industry, Leucémie aiguë lymphoblastique, Hematology, General Medicine, Chimeric antigen receptor, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Car t cells, business, Outils de qualité, Thérapie cellulaire
Abstract: International audience; CAR T-cells are anti-cancer immunocellular therapy drugs that involve reprogramming the patient's T-cells using a transgene encoding a chimeric antigen receptor (CAR). Although CAR T-cells are cellular therapies, the organization for manufacturing and delivering these medicinal products is in many ways different from the one for hematopoietic cell grafts or donor lymphocyte infusions. The implementation of this innovative therapy is recent and requires close coordination between clinical teams, the therapeutic apheresis unit, the cell therapy unit, the pharmaceutical laboratory, and pharmacy. Apart from the regulatory texts, which are regularly modified, and the specific requirements of each pharmaceutical laboratory, there is currently no guide to help the centers initiating their activity and there is no specific indicator to assess the quality of the CAR T-cell activity in each center. The purpose of the current harmonization workshop is to clarify the regulatory prerequisites warranted for a center to have a CAR T-cell activity and to propose recommendations for implementing quality tools, in particular indicators, and allowing their sharing.
Published: 2020

149. A study of predictable execution models implementation for industrial data-flow applications on a multi-core platform with shared banked memory

Author: Benoit Dupont de Dinechin, Joël Goossens, Pascal Raymond, Matheus Schuh, Claire Maiza, Kalray, VERIMAG (VERIMAG - IMAG), 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), Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: 010302 applied physics, Multi-core processor, Informatique générale, Computer science, business.industry, Suite, 02 engineering and technology, 01 natural sciences, Toolchain, 020202 computer hardware & architecture, Scheduling (computing), Data flow diagram, Embedded system, 0103 physical sciences, 0202 electrical engineering, electronic engineering, information engineering, Task analysis, [INFO.INFO-ES]Computer Science [cs]/Embedded Systems, System on a chip, [INFO.INFO-OS]Computer Science [cs]/Operating Systems [cs.OS], Isolation (database systems), [INFO.INFO-DC]Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC], business
Abstract: We study the implementation of data- flow applications on multi-core processor with on-chip shared multi-banked memory. Specifically, we consider the Kalray MPPA2 processor and three applications coded using the industrial toolchain SCADE Suite. We focus on the runtime environment assuming global static scheduling, time-triggered and non-preemptive execution of tasks. Our contributions include (i) a technique to implement SCADE applications compli- ant with execution models inspired by PREMs (PRe- dictable Execution Models), (ii) an exhaustive com- parison of three execution models with and without isolation, and finally (iii) guidelines for predictable implementation of a data-flow application on multi-core processors with shared on-chip memory., info:eu-repo/semantics/published
Published: 2020

150. European Multicenter Study of ET-COVID-19

Author: Federico Cagnazzo, Michel Piotin, Simon Escalard, Benjamin Maier, Marc Ribo, Manuel Requena, Raoul Pop, Anca Hasiu, Roberto Gasparotti, Dikran Mardighian, Mariangela Piano, Amedeo Cervo, Omer Faruk Eker, Vincent Durous, Nader-Antoine Sourour, Mahmoud Elhorany, Andrea Zini, Luigi Simonetti, Simona Marcheselli, Nuzzi Nunzio Paolo, Emmanuel Houdart, Alexis Guédon, Noémie Ligot, Benjamin Mine, Arturo Consoli, Bertrand Lapergue, Pere Cordona Portela, Xabier Urra, Alejandro Rodriguez, Federico Bolognini, Pablo Ariel Lebedinsky, Anne Pasco-Papon, Sophie Godard, Gaultier Marnat, Igor Sibon, Nicola Limbucci, Patrizia Nencini, Sergio Nappini, Valentina Saia, Valentina Caldiera, Daniele Romano, Giulia Frauenfelder, Ivan Gallesio, Giuliano Gola, Roberto Menozzi, Antonio Genovese, Alberto Terrana, Andrea Giorgianni, Manuel Cappellari, Raffaele Augelli, Paolo Invernizzi, Marco Pavia, Elvis Lafe, Anna Cavallini, Alessia Giossi, Michele Besana, Luca Valvassori, Antonio Macera, Lucio Castellan, Giancarlo Salsano, Fortunato Di Caterino, Alessandra Biondi, Caroline Arquizan, Julien Lebreuche, Gianluca Galvano, Alfio Cannella, Mirco Cosottini, Guido Lazzarotti, Giuseppe Guizzardi, Alessandro Stecco, Rossana Tassi, Sandra Bracco, Elena Bianchini, Camilla Micieli, Rosario Pascarella, Manuela Napoli, Francesco Causin, Hubert Desal, François Cotton, Vincent Costalat, François Delvoye, Gabriele Ciccio, Stanislas Smajda, Hocine Redjem, Solène Hébert, Raphaël Blanc, Mikael Mazighi, Jean-Philippes Desilles, Dan Mihoc, Monica Manisor, Rémy Beaujeux, Véronique Quenardelle, Roxana Gheoca, Valérie Wolff, Guiglielmo Pero, Giussani Giuditta, Ceresa Chiara, Roberto Riva, Matteo Cappucci, Morgane Laubacher, Celia Tuttle, Lorenzo Piergallini, Francis Turjman, Frédéric Clarençon, Eimad Shotar, Stéphanie Lenck, Kevin Premat, Vincent Degos, Yves Samson, Charlotte Rosso, Sonia Alamowitch, Luigi Cirillo, Mauro Gentile, Ludovica Migliaccio, Salvatore Isceri, Simone Rossi, Tommaso Baldini, Massimo Dall’Olio, Martino Cellerini, Jean-Pierre Saint-Maurice, Vittorio Civelli, Matteo Fantoni, Naeije Gilles, Jodaïtis Lise, Lubicz Boris, Stephanie Elens, Bonnet Thomas, Guenego Adrien, Sadeghi Niloufar, Van Nuffelen Marc, Federico Di Maria, Oguzhan Coskun, Georges Rodesch, Sergio Zimatore, Gariel Florent, Jérôme Berge, Patrice Menegon, Xavier Barreau, Thomas Tourdias, Stéphane Olindo, Ludovic Lucas, Jean-Sebastien Liegey, Sharmila Sagnier, Pauline Renou, Marie Couture, Sabrina Debruxelles, Mathilde Poli, Mariano Musacchio, Mariette Delaitre, Riccardo Padolecchia, Giuseppe Ganci, Annalisa Sugo, Barbero Stefano, Taverna Giacomo Giovanni, Umberto Scoditti, Paola Castellini, Lilia Latte, Ilaria Grisendi, Enrico Epifani, Francesco Vizzari, Stefano Molinaro, Luca Nativo, Gabriele Vinacci, Bruno Bonetti, Nicola Micheletti, Giampaolo Tomelleri, Piergiuseppe Zampieri, Mauro Plebani, Andrea Grazioli, Giuseppe Kenneth Ricciardi, Alessandra Polistena, Sgreccia Alessando, Giuseppina Sanfilippo, Alessandra Persico, William Boadu, Maria Giovanna Cuzzoni, Serena Magno, Gianpaolo Toscano, Maria Federica Denaro, Piera Tosi, Bruno Censori, Valentina Puglisi, Luisa Vinciguerra, Valeria De Giuli, Nicola Mavillo, Leonardo Renieri, Enrico Fainardi, Giovanni Vitale, Primikiris Panagiotis, Guillaume Charbonnier, Moratti Claudio, Fabrizio Sallustio, Andrea Wlderk, Riccardo Russo, Mauro Bergui, Chiara Comelli, Andrea Boghi, Marinette Moynier, Elisa Francesca Maria Ciceri, Danilo Toni, Julien Frandon, Isabelle Mourand, Nicolas Gaillard, Salvatore Mangiafico, Imad Derraz, Cyril Dargazanli, Pierre-Henri Lefevre, Carlos Riquelme, Gregory Gascou, Alain Bonafe, Cagnazzo F., Piotin M., Escalard S., Maier B., Ribo M., Requena M., Pop R., Hasiu A., Gasparotti R., Mardighian D., Piano M., Cervo A., Eker O.F., Durous V., Sourour N.-A., Elhorany M., Zini A., Simonetti L., Marcheselli S., Paolo N.N., Houdart E., Guedon A., Ligot N., Mine B., Consoli A., Lapergue B., Cordona Portela P., Urra X., Rodriguez A., Bolognini F., Lebedinsky P.A., Pasco-Papon A., Godard S., Marnat G., Sibon I., Limbucci N., Nencini P., Nappini S., Saia V., Caldiera V., Romano D., Frauenfelder G., Gallesio I., Gola G., Menozzi R., Genovese A., Terrana A., Giorgianni A., Cappellari M., Augelli R., Invernizzi P., Pavia M., Lafe E., Cavallini A., Giossi A., Besana M., Valvassori L., MacEra A., Castellan L., Salsano G., Di Caterino F., Biondi A., Arquizan C., Lebreuche J., Galvano G., Cannella A., Cosottini M., Lazzarotti G., Guizzardi G., Stecco A., Tassi R., Bracco S., Bianchini E., Micieli C., Pascarella R., Napoli M., Causin F., Desal H., Cotton F., Costalat V., Luigi Cirillo, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Strasbourg, Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CH Colmar, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], CHU Lille, Université de Lille, and Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Registrie, Male, MESH: Registries, [SDV]Life Sciences [q-bio], Brain ischemia, Cohort Studies, MESH: Aged, 80 and over, MESH: Risk Factors, Risk Factors, Epidemiology, Medicine, MESH: Thrombectomy, MESH: COVID-19, Registries, MESH: Cohort Studies, MESH: Treatment Outcome, Thrombectomy, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, Cerebral infarction, Endovascular Procedures, Middle Aged, cerebral infarction, COVID-19, intracranial hemorrhage, lymphocyte count, thrombectomy, Europe, Treatment Outcome, Cardiology, Female, Cardiology and Cardiovascular Medicine, COVID-19/*complications/epidemiology Cohort Studies *Endovascular Procedures/mortality Europe Female Humans Ischemic Stroke/*complications/mortality/*surgery Male Middle Aged Registries Risk Factors SARS-CoV-2 *Thrombectomy/mortality Treatment Outcome Covid-19 cerebral infarction intracranial hemorrhage lymphocyte count thrombectomy, Cohort study, MESH: Ischemic Stroke, Human, medicine.medical_specialty, MESH: Endovascular Procedures, Coronavirus disease 2019 (COVID-19), Internal medicine, Humans, MESH: SARS-CoV-2, Risk factor, Aged, Ischemic Stroke, Advanced and Specialized Nursing, Endovascular Procedure, MESH: Humans, business.industry, SARS-CoV-2, Risk Factor, medicine.disease, MESH: Male, Clinical trial, Neurology (clinical), MESH: Europe, Cohort Studie, business, Complication, MESH: Female
Abstract: Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090.
Published: 2020

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