Author: "A, Toutain" / Topic: business - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"A, Toutain"' showing total 607 results

Start Over Author "A, Toutain" Topic business

607 results on '"A, Toutain"'

1. Medication control of flunixin in racing horses: Possible detection times using Monte Carlo simulations

Author: Kanichi Kusano, Fumio Sato, Masayuki Yamada, Kentaro Fukuda, Yohei Minamijima, Taisuke Kuroda, Pierre-Louis Toutain, Shun-ichi Nagata, Shozo Yamashita, Atsutoshi Kuwano, Norihisa Tamura, Hiroshi Mita, and Motoi Nomura
Subjects: Flunixin, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Monte Carlo method, Horse, Drug administration, General Medicine, Urine, Withdrawal time, Clonixin, Animal science, Tandem Mass Spectrometry, medicine, Animals, Female, Statistical analysis, Horses, Multiple administration, business, Monte Carlo Method, Chromatography, Liquid, medicine.drug
Abstract: Background For medication control in several jurisdictions, withdrawal time is the period of refrain from racing after drug administration. It is set by adding a safety period to an experimental detection time. However, there are no reports of statistical analyses of detection time for the determination of withdrawal time in flunixin meglumine-treated horses. Objective To analyse the population pharmacokinetics of flunixin in horses through the generation of a dataset for detection time statistical analysis and predictions via Monte Carlo simulation. Study design Experimental study. Methods Drug plasma and urine concentrations following single intravenous (i.v.) administration of flunixin 1.1 mg/kg bodyweight (BW) in 10 horses and multiple administration of q 24 h for 5 days in 10 horses were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Data were modelled using a nonlinear mixed effect model followed by Monte Carlo simulation. Irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were calculated using the Toutain approach. Detection times were obtained considering the time after the last administration for selected quantiles of 5000 hypothetical horses under the International Screening Limit (ISL) proposed by the International Federation of Horseracing Authorities (plasma: 1 ng/ml, urine; 100 ng/ml) RESULTS: For a regimen of 1.1 mg/kg BW q 24 h, the IPC and IUC values were 2.0 and 73.0 ng/ml, respectively. Detection times in plasma above the ISL for 90% of simulated horses were estimated as 74 h after a single 1.1 mg/kg dose administration, 149 h and 199 h after multiple doses over 5 days at either 24- or 12-h intervals, respectively. Corresponding detection times in urine were 46 h, 68 h and 104 h, respectively. Main limitation Only female horses were investigated. Conclusions Statistical detection times for different flunixin meglumine regimens indicated a delay of detection time in plasma after multiple administrations under ISL.
Published: 2021
Full Text: View/download PDF

2. Accelerated genome sequencing with controlled costs for infants in intensive care units: a feasibility study in a French hospital network

Author: Robert Olaso, Adeline Prost, Anne-Sophie Denommé-Pichon, Magali Gorce, Anne Boland, Mélanie Fradin, Magalie Barth, Mathilde Nizon, Antonio Vitobello, Dominique Bonneau, Bertrand Isidor, Christel Thauvin-Robinet, Frédéric Tran Mau-Them, Victor Couturier, Caroline Racine, Céline Besse, Marie Vincent, Bertrand Fin, Yline Capri, Alban Ziegler, Ange-Line Bruel, Yannis Duffourd, Christophe Philippe, P. Callier, Sébastien Moutton, Aurore Garde, Médéric Jeanne, Annick Toutain, Sophie Nambot, Delphine Bacq-Daian, Charlotte Poë, Emilie Tisserant, Aurélien Juven, Julien Van-Gils, Tiffany Busa, Laurent Pasquier, Sabine Sigaudy, Arthur Sorlin, Thibaud Jouan, Philippine Garret, Corinne Chantegret, Julian Delanne, Cyril Flamant, Alinoë Lavillaureix, Clement Prouteau, Paul Rollier, Laurence Faivre, and Jean-François Deleuze
Subjects: Protocol (science), Hospital network, medicine.medical_specialty, business.industry, Infant, Newborn, Infant, Pilot Projects, Context (language use), Disease, Hospitals, Article, Intensive Care Units, Intensive care, Genetics, medicine, Etiology, Feasibility Studies, Humans, Prospective Studies, Duration (project management), Child, Intensive care medicine, business, Genetics (clinical), Blood sampling
Abstract: Obtaining a rapid etiological diagnosis for infants with early-onset rare diseases remains a major challenge. These diseases often have a severe presentation and unknown prognosis, and the genetic causes are very heterogeneous. In a French hospital network, we assessed the feasibility of performing accelerated trio-genome sequencing (GS) with limited additional costs by integrating urgent requests into the routine workflow. In addition to evaluating our capacity for such an approach, this prospective multicentre pilot study was designed to identify pitfalls encountered during its implementation. Over 14 months, we included newborns and infants hospitalized in neonatal or paediatric intensive care units with probable genetic disease and in urgent need for etiological diagnosis to guide medical care. The duration of each step and the pitfalls were recorded. We analysed any deviation from the planned schedule and identified obstacles. Trio-GS was performed for 37 individuals, leading to a molecular diagnosis in 18/37 (49%), and 21/37 (57%) after reanalysis. Corrective measures and protocol adaptations resulted in a median duration of 42 days from blood sampling to report. Accelerated trio-GS is undeniably valuable for individuals in an urgent care context. Such a circuit should coexist with a rapid or ultra-rapid circuit, which, although more expensive, can be used in particularly urgent cases. The drop in GS costs should result in its generalized use for diagnostic purposes and lead to a reduction of the costs of rapid GS.
Published: 2021
Full Text: View/download PDF

3. Extracorporeal Membrane Oxygenation Induces Early Alterations in Coagulation and Fibrinolysis Profiles in COVID-19 Patients with Acute Respiratory Distress Syndrome

Author: Guillaume Lebreton, Ania Nieszkowska, Corinne Frere, Marc Pineton de Chambrun, Isabelle Martin-Toutain, Guillaume Hékimian, Manon Lejeune, Paul Masi, Juliette Chommeloux, Matthieu Schmidt, Charles-Edouard Luyt, Alain Combes, Nicolas Bréchot, Cyrielle Desnos, and Pascal Leprince
Subjects: Adult, Male, ARDS, medicine.medical_specialty, medicine.medical_treatment, Hemorrhage, 030204 cardiovascular system & hematology, Fibrinogen, law.invention, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Von Willebrand factor, law, Internal medicine, von Willebrand Factor, Fibrinolysis, medicine, Extracorporeal membrane oxygenation, Humans, Prospective Studies, Blood Coagulation, Respiratory Distress Syndrome, biology, business.industry, COVID-19, 030208 emergency & critical care medicine, Hematology, Middle Aged, medicine.disease, Intensive care unit, Coagulation, biology.protein, Cardiology, Female, Median body, business, medicine.drug
Abstract: Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35–56) years, with a median body mass index of 30 (27–35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8–16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin–antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p
Published: 2021
Full Text: View/download PDF

4. Clinical and neuroimaging findings in 33 patients with <scp>MCAP</scp> syndrome: A survey to evaluate relevant endpoints for future clinical trials

Author: Florence Petit, Fabienne Giuliano, Juliette Mazereeuw-Hautier, Marjolaine Willems, Christel Thauvin-Robinet, Patricia Blanchet, Laurence Faivre, Elodie Gautier, Anne-Claire Bursztejn, Renaud Touraine, Annick Toutain, Frederico Di Rocco, Maxime Luu, Patrick Edery, Arthur Sorlin, Jean-Luc Alessandri, Nicolas Chassaing, Alice Goldenberg, Christine Chiaverini, Fanny Morice-Picard, Aurore Garde, Stéphanie Arpin, Massimiliano Rossi, Marc Bardou, Claire Nicolas, Gilles Morin, Jenny Cornaton, Cyril Mignot, Christophe Philippe, V. Carmignac, Rodolphe Dard, Joelle Roume, Michèle Mathieu-Dramard, Philippe Khau Van Kien, Pierre Vabres, Didier Lacombe, Diane Doummar, Lucile Pinson, Christine Coubes, Laurent Guibaud, Olivia Boccara, Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), and Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Cutis marmorata, Adolescent, Class I Phosphatidylinositol 3-Kinases, Neuroimaging, Context (language use), Skin Diseases, Vascular, 030105 genetics & heredity, Cohort Studies, Young Adult, 03 medical and health sciences, Genetics, Polymicrogyria, medicine, Humans, PROS, Abnormalities, Multiple, Telangiectasis, Megalencephaly, Child, MCAP syndrome, Genetics (clinical), Chiari malformation, Clinical Trials as Topic, business.industry, Macrocephaly, PIK3CA, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Clinical trial, 030104 developmental biology, Child, Preschool, Postnatal macrocephaly, Female, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Forecasting, Ventriculomegaly
Abstract: Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.
Published: 2021
Full Text: View/download PDF

5. Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses

Author: Taisuke Kuroda, Pierre-Louis Toutain, Yuki Enoki, Kentaro Fukuda, Hiroshi Mita, Masahiro Kaimachi, Kazuaki Matsumoto, Norihisa Tamura, Yuto Suzuki, Kazuaki Taguchi, Hidekazu Niwa, Alain Bousquet-Mélou, Yohei Minamijima, Yoshinori Kasashima, Japan Racing Association, Laboratory of Racing Chemistry, Equine Research Institute, Faculty of Pharmacy Tokyo, Royal Veterinary College [London], University of London [London], Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Staphylococcus aureus, Dose, 040301 veterinary sciences, medicine.drug_class, [SDV]Life Sciences [q-bio], gram positive infection, Cephalosporin, Cefazolin, Microbial Sensitivity Tests, Pharmacology, 0403 veterinary science, Pharmacokinetics, Tandem Mass Spectrometry, Cephalothin, Medicine, Animals, Horses, ComputingMilieux_MISCELLANEOUS, biology, business.industry, 0402 animal and dairy science, Horse, 04 agricultural and veterinary sciences, General Medicine, biology.organism_classification, 040201 dairy & animal science, Blood proteins, Experimental and Basic Research Studies, 3. Good health, horse, Anti-Bacterial Agents, Regimen, Streptococcus zooepidemicus, General Article, business, medicine.drug, Chromatography, Liquid
Abstract: Background First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses. Objective To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts. Study design Experimental study with single administration. Methods Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six horses were measured using LC-MS/MS. Data were modelled using a nonlinear mixed effect modelling followed by Monte Carlo simulations. Minimum inhibitory concentrations (MICs) against Streptococcus zooepidemicus and Staphylococcus aureus isolated from horses were determined by the microbroth dilution method. Results The percentages of CET and CEZ binding to serum proteins were 19.9% ± 8.4% and 15.2% ± 8.5% respectively. For both CET and CEZ, the MIC90 against S. zooepidemicus was 0.12 mg/L and against S. aureus was 0.5 mg/L. For CET, to achieve a probability of target attainment (PTA) of 90% for a PK/PD target of a free serum plasma concentration exceeding the MIC90 for 40% of the dosing interval, an empirical CET dosage regimen of 22 mg/kg bwt q8h and 22 mg/kg bwt q4h i.v. administration were required for S. zooepidemicus and S. aureus respectively. For CEZ, the corresponding dosage regimens were 10 mg/kg bwt q12h and 10 mg/kg bwt q8h. Main limitations Small sample size only in healthy horses. Conclusions For CET, more frequent administration than that currently recommended (22 mg/kg bwt q6-12h) is required to empirically control S. aureus infection in horses. For CEZ, less frequent administration compared to the dosage regimen currently proposed (10-22 mg/kg bwt q6h) could control S. zooepidemicus and S. aureus infections in horses.
Published: 2021
Full Text: View/download PDF

6. Determination of the pharmacokinetic‐pharmacodynamic cut‐off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing

Author: Alain Bousquet-Mélou, Pierre‐Louis Toutain, Elodie Lallemand, Marc Schneider, Cyrielle Triboulloy, Farid El Garch, Peter Damborg, Diane C. Broussou, Aude A. Ferran, Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Vétoquinol, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Copenhagen = Københavns Universitet (KU), and The Royal Veterinary College, Hawkshead Campus
Subjects: Streptococcus equi, PK/PD cut-off, medicine.drug_class, [SDV]Life Sciences [q-bio], Antibiotics, Population, Microbial Sensitivity Tests, Pharmacology, Gram-Positive Bacteria, medicine.disease_cause, monte carlo simulations, 03 medical and health sciences, 0302 clinical medicine, Anti-Infective Agents, Pharmacokinetics, Marbofloxacin, Gram-Negative Bacteria, medicine, Animals, Horses, 030212 general & internal medicine, education, antimicrobial susceptibility testing, 0303 health sciences, education.field_of_study, 030306 microbiology, business.industry, Broth microdilution, Horse, General Medicine, horse, Anti-Bacterial Agents, Staphylococcus aureus, population pharmacokinetic, business, Fluoroquinolones, medicine.drug
Abstract: Background Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses. Objectives To compute PK/PD cut-offs (PK/PDCO ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation. Study design A meta-analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings. Methods Horses (n = 131) received MBX intravenously at doses of either 2 or 10 mg/kg BW. They were richly sampled (five or six samples per horse). A population model was built to generate a virtual population of 5000 MBX disposition curves by Monte Carlo simulations (MCS) over 24 hours. The selected PK/PD index was the ratio of Area Under the free plasma concentration-time Curve divided by the MIC (fAUC/MIC). The PK/PDCO , which is the highest MIC for which 90% of horses can achieve an a priori selected critical value for the numerical value of the PK/PD index, was established for Gram-positive and Gram-negative bacteria for a dose of 2 mg/kg. Results The PK/PDCO of MBX in horses was 0.125 mg/L for Gram-positive pathogens and 0.0625 mg/L for Gram-negative pathogens. MBX MICs determined by broth microdilution for 54 Escherichia coli and 189 Streptococcus equi isolates are reported. Main limitation No clinical data are taken into account in the determination of a PK/PDco . Conclusion The computed PK/PDco predicts that MBX may be efficacious in horses to treat infections associated with Enterobacteriaceae but unlikely to those involving Staphylococcus aureus or Streptococcus equi.
Published: 2020
Full Text: View/download PDF

7. Entrepreneurial education: an entrepreneurial ecosystem approach

Author: Delwyn Clark, Valérie Ballereau, Sophie Reboud, Tim Mazzarol, and Olivier Toutain
Subjects: Organizational Behavior and Human Resource Management, Knowledge management, ComputingMilieux_THECOMPUTINGPROFESSION, business.industry, 05 social sciences, Public policy, New Ventures, 050905 science studies, Entrepreneurial education, Entrepreneurship education, Academic unit, 0502 economics and business, Portfolio, Business, 0509 other social sciences, Business and International Management, 050203 business & management, Entrepreneurial ecosystem
Abstract: How can an entrepreneurial education program simultaneously create entrepreneurial knowledge, skills and competencies, as well as new ventures and jobs? This is a particular challenge for universities that are keen to align with government policies and demonstrate impact. Our paper examines a novel approach to enterprise and entrepreneurship education that integrates training/learning with new venture creation by operating as an entrepreneurial ecosystem (EE). We outline a comprehensive EE framework and apply this model using an exploratory case study of an EE centred around an innovative academic unit called The Entrepreneurial Garden (TEG) at Burgundy School of Business in Dijon, France. TEG offers entrepreneurial education, research and new venture development as an integrated portfolio. This analysis shows how an academic unit can be developed as an EE building from local resources and expertise, aligning with macroeconomic policies and priorities, and leveraging partnerships to provide access to other entrepreneurial players, resources and networks.
Published: 2020
Full Text: View/download PDF

8. Heparin-induced thrombocytopenia in COVID-19 patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation: two case reports

Author: Guillaume Hékimian, Guillaume Lebreton, Corinne Frere, Alain Combes, Isabelle Martin-Toutain, Frank Bidar, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service d'Hématologie Biologique [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), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, ARDS, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 0206 medical engineering, Biomedical Engineering, Medicine (miscellaneous), 02 engineering and technology, 030204 cardiovascular system & hematology, Argatroban, law.invention, Biomaterials, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, law, Heparin-induced thrombocytopenia, Coagulopathy, Extracorporeal membrane oxygenation, Humans, Medicine, Intensive care medicine, Respiratory Distress Syndrome, Heparin, business.industry, Anticoagulants, COVID-19, Middle Aged, medicine.disease, Thrombocytopenia, 020601 biomedical engineering, Intensive care unit, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, surgical procedures, operative, Female, Cardiology and Cardiovascular Medicine, business, Complication, medicine.drug
Abstract: International audience; Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is increasingly used in Coronavirus disease-19 (COVID-19) patients with the most severe forms of acute respiratory distress syndrome (ARDS). Its use is associated with a significant hemostatic challenge, especially in COVID- 19 patients who have been demonstrated to otherwise present a COVID-19-associated coagulopathy. The systematic use of unfractionated heparin therapy to prevent circuit thrombosis is warranted during ECMO support. The clinical presentation and management of heparin-induced thrombocytopenia, which is a rare but life-threatening complication of heparin therapy, has not been described in those patients yet. We report herein two cases of laboratory-confirmed HIT in COVID-19 patients with severe ARDS admitted to our intensive care unit for VV-ECMO support and the successful use of argatroban as an alternative therapy. We also provide a brief literature review of best evidence for managing such patients. The diagnosis and management of HIT is particularly challenging in COVID-19 patients receiving ECMO support. An increased awareness is warranted in those patients who already present a procoagulant state leading to higher rates of thrombotic events which can confuse the issues. Argatroban seems to be an appropriate and safe therapeutic option in COVID-19 patients with HIT while on VV-ECMO.
Published: 2020
Full Text: View/download PDF

9. Systemic Inflammatory Response Syndrome Is a Major Contributor to COVID-19–Associated Coagulopathy

Author: Isabelle Martin-Toutain, Juliette Chommeloux, Alain Combes, Nicolas Bréchot, Charles Edouard Luyt, Ania Nieszkowska, Corinne Frere, Matthieu Schmidt, Guillaume Hékimian, Guillaume Lebreton, Marc Pineton de Chambrun, Cyrielle Desnos, Manon Lejeune, and Paul Masi
Subjects: medicine.medical_specialty, biology, Coronavirus disease 2019 (COVID-19), business.industry, 030204 cardiovascular system & hematology, biology.organism_classification, Single Center, medicine.disease, Systemic inflammatory response syndrome, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, Pandemic, medicine, Coagulopathy, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, Prospective cohort study, business, Betacoronavirus, Cohort study
Published: 2020
Full Text: View/download PDF

10. The Interest of Being Eligible

Author: Olivier Toutain, Charles O'Donnell, Jean-Stéphane Mésonnier, Centre de recherche de la Banque de France, Banque de France, Centre de recherche de la Banque Centrale européenne, Banque Centrale Européenne, Aix-Marseille Sciences Economiques (AMSE), and École des hautes études en sciences sociales (EHESS)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Economics and Econometrics, Ex-ante, Collateral, ACL-1, education, Monetary policy, monetary policy, Financial system, Collateral channel, Liquidity risk, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Market liquidity, Loan, Accounting, Economics, eurosystem, collateral frameworks, Business, eligibility discount, health care economics and organizations, Finance
Abstract: Major central banks often accept pooled individual corporate loans as collateral in their refinancing operations with credit institutions. Such ``eligible'' loans to firms therefore provide a liquidity advantage to the banks that originate them. Banks may in turn pass on this advantage to the borrowers in the form of a reduced liquidity risk premium: the eligibility discount. We exploit a temporary surprise extension of the Eurosystem's universe of eligible collateral to mediumquality corporate loans, the Additional Credit Claims (ACC) program of February 2012, to assess the eligibility discount to corporate loans spreads in France. We find that becoming eligible to the Eurosystem's collateral framework translates into a reduction in rates by 7bp for new loans issued to ACC-firms, controlling for loan-, firm- and bank-level characteristics. In line with the opportunity-cost view of collateral choice, we also find evidence that this collateral channel of monetary policy is only active for banks which ex ante pledged more credit claims as part of their collateral with the Eurosystem.
Published: 2022
Full Text: View/download PDF

11. Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility

Author: F. Dalin, M. Domberg, C Stenlund, Mikael Hedeland, Ulf Bondesson, Lena Ström, Carl Ekstrand, Pierre-Louis Toutain, Swedish University of Agricultural Sciences (SLU), National Veterinary Institute [Uppsala] (SVA), Department of Medicinal Chemistry, Uppsala University, Sweden, Uppsala University, Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The Royal Veterinary College, University of London, Hawkshead Campus, Hatfield AL9 7TA, UK., and Department of Biomedicine and Veterinary Public Health
Subjects: Atropine, Male, Colic, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 0403 veterinary science, ComputingMilieux_MISCELLANEOUS, Volume of distribution, Other Veterinary Science, education.field_of_study, lcsh:Veterinary medicine, 04 agricultural and veterinary sciences, General Medicine, Farmakologi och toxikologi, 3. Good health, Anesthesia, Injections, Intravenous, Female, Systemic exposure, Half-Life, Research Article, medicine.drug, Side effect, 040301 veterinary sciences, Population, Biological Availability, Pharmacology and Toxicology, Pharmacokinetics, medicine, Animals, Horses, education, Plasma disposition, General Veterinary, Equine, business.industry, 0402 animal and dairy science, Parasympatholytics, Eye drop, 040201 dairy & animal science, Bioavailability, Pharmacodynamics, lcsh:SF600-1100, Ophthalmic Solutions, Gastrointestinal Motility, business
Abstract: Background Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment. Results Atropine sulfate (1 mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and topically (manually as eye drops and through a subpalpebral lavage system) to six horses to document atropine disposition. Blood-samples were collected regularly and plasma was analyzed for atropine using UHPLC-MS/MS. Atropine plasma concentration was below lower limit of quantification (0.05 μg/L) within five hours, after both topical and IV administration. Atropine data were analyzed by means of population compartmental modeling and pharmacokinetic parameters estimated. The typical value was 1.7 L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9 L/h‧kg. The bioavailability after administration of an ophthalmic preparation as an eye drop or topical infusion were 69 and 68%, respectively. The terminal half-life was short (0.8 h). In part II, topical ophthalmic atropine sulfate and control treatment was administered to four horses in two dosing regimens to assess the effect on gastro-intestinal motility. Borborygmi-frequency monitored by auscultation was used for estimation of gut motility. A statistically significant decrease in intestinal motility was observed after administration of 1 mg topical ophthalmic atropine sulfate every three hours compared to control, but not after administration every six hours. Clinical signs of colic were not observed under any of the treatment protocols. Conclusions Taking the plasma exposure after topical administration into consideration, data and simulations indicate that eye drops administrated at a one and three hour interval will lead to atropine accumulation in plasma over 24 h but that a six hour interval allows total washout of atropine between two topical administrations. If constant corneal and conjunctival atropine exposure is required, a topical constant rate infusion at 5 μg/kg/24 h offers a safe alternative.
Published: 2021
Full Text: View/download PDF

12. [Assisted reproductive technology outcomes of infertile men carrying balanced chromosomal rearrangements or Y-chromosome microdeletions - Retrospective study]

Author: Hélène Lheureux, Julian Poquet, Lucie Chansel-Debordeaux, Bérénice Doray, Joffrey Mons, and Jérôme Toutain
Subjects: Male, medicine.medical_specialty, Reproductive Techniques, Assisted, Y chromosome microdeletion, medicine.medical_treatment, Clinical pregnancy, Sex Chromosome Disorders of Sex Development, Chromosomal rearrangement, Male infertility, Primary outcome, Pregnancy, Medicine, Humans, Infertility, Male, Sex Chromosome Aberrations, Azoospermia, Retrospective Studies, Gynecology, Assisted reproductive technology, Chromosomes, Human, Y, business.industry, Karyotype, Retrospective cohort study, General Medicine, medicine.disease, Case-Control Studies, Female, Chromosome Deletion, business
Abstract: The aim of this study was to evaluate the ART outcomes for infertile males carrying a balanced structural chromosomal rearrangement or a Y-chromosome microdeletion, and to compare the results with a control group. The primary outcome was the clinical pregnancy rate. A retrospective case-control study has been carried out in the ART departments of the university hospitals of Bordeaux and la Reunion. Results of karyotypes and Y-chromosome microdeletions analysis of infertile men with sperm concentration lower than 5 millions/mL have been extracted from the softwares Jfiv® (Bordeaux) and MediFirst® (la Reunion). The clinical pregnancy rate for carriers of balanced chromosomal rearrangements and Y-chromosome microdeletions was 28% and 43% respectively. The clinical pregnancy rate for the controls was 24% (non-significant difference). According to this study, balanced chromosomal rearrangements and Y-chromosome microdeletions are not found to affect the clinical pregnancy rate in conventional ART. Further larger scale studies are required to confirm these results.
Published: 2021

13. Response to Letter: ‘Reply to 'High frequency of antiphospholipid antibodies in critically ill COVID‐19 patients: a link with hypercoagulability?'’

Author: Corinne Frere, A. Mathian, Guillaume Hékimian, Makoto Miyara, M. Pineton De Chambrun, Isabelle Martin-Toutain, Z. Amoura, and Alain Combes
Subjects: 0301 basic medicine, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Critical Illness, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, 030204 cardiovascular system & hematology, Virus diseases, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, Humans, Thrombophilia, Medicine, In patient, Intensive care medicine, biology, SARS-CoV-2, business.industry, Critically ill, COVID-19, 030104 developmental biology, Antibodies, Antiphospholipid, biology.protein, Antibody, business
Abstract: We read with great interest the comment by Suarez-Perez et al. on our article.[1] We share their concerns regarding the need for a cautious interpretation of antiphospholipid antibodies (aPLA) positivity in patients with coronary virus disease 2019 (COVID-19). Herein, we would like to add further insights in the discussion.
Published: 2020
Full Text: View/download PDF

14. High frequency of antiphospholipid antibodies in critically ill COVID‐19 patients: a link with hypercoagulability?

Author: Guillaume Hékimian, Z. Amoura, A. Mathian, Makoto Miyara, M. Pineton De Chambrun, Corinne Frere, Isabelle Martin-Toutain, and Alain Combes
Subjects: 0301 basic medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), macromolecular substances, 030204 cardiovascular system & hematology, Fibrinogen, Systemic inflammation, Gastroenterology, SARS‐CoV‐2, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, Internal medicine, antiphospholipid antibody, Internal Medicine, medicine, Letters to the Editor, Letter to the Editor, thrombosis, medicine.diagnostic_test, biology, business.industry, Retrospective cohort study, medicine.disease, Pulmonary embolism, Pneumonia, 030104 developmental biology, biology.protein, medicine.symptom, Antibody, business, medicine.drug, Partial thromboplastin time
Abstract: Coronavirus disease 2019 (COVID‐19) is associated with both severe systemic inflammation and a prothrombotic state, as reflected by significant increases in fibrinogen and D‐dimers levels that have been associated with poor prognosis and high rates of severe pulmonary embolism. A recent report suggested a role for antiphospholipid antibodies (aPLA) in the thrombotic manifestations associated with severe COVID‐19. As we also recently noticed unexplained lengthening of activated partial thromboplastin time (aPTT) in some critically ill COVID‐19 patients, we explored our patients for aPLA positivity.
Published: 2020
Full Text: View/download PDF

15. IPv6 over LPWANs: Connecting Low Power Wide Area Networks to the Internet (of Things)

Author: Juan Carlos Zuniga, Ana Minaburo, Laurent Toutain, Dominique Barthel, Carles Gomez, Universitat Politècnica de Catalunya. Departament d'Enginyeria Telemàtica, Universitat Politècnica de Catalunya. WNG - Grup de xarxes sense fils, Departament d'Arquitectura de Computadors - Universitat Politècnica de Catalunya (DAC), Universitat Politècnica de Catalunya [Barcelona] (UPC), Acklio, Objets communicants pour l'Internet du futur (OCIF), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-RÉSEAUX, TÉLÉCOMMUNICATION ET SERVICES (IRISA-D2), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Département Systèmes Réseaux, Cybersécurité et Droit du numérique (IMT Atlantique - SRCD), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Orange Labs [Belfort] (Orange Labs), France Télécom, and Sigfox
Subjects: Internet of things, LPWAN, Enginyeria de la telecomunicació::Telemàtica i xarxes d'ordinadors [Àrees temàtiques de la UPC], Wide area networks (Computer networks), Internet de les coses, Exploit, business.industry, Computer science, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, 020206 networking & telecommunications, Context (language use), 02 engineering and technology, Network topology, Computer Science Applications, IPv6, [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], 0202 electrical engineering, electronic engineering, information engineering, The Internet, Electrical and Electronic Engineering, business, 6LoWPAN, Adaptation (computer science), Xarxes d'àrea estesa (Xarxes d'ordinadors), Computer network
Abstract: © 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works. LPWANs have recently emerged as a promising solution for enabling industrial IoT applications. To fully exploit their potential, LPWANs need to be connected to the Internet. However, the severe capacity constraints of LPWAN technologies challenge IPv6 support, and even 6LoWPAN-based adaptations are not sufficient. In this paper, we present SCHC, an ultralightweight IPv6 adaptation layer designed for LPWANs, which is being standardized by the IETF.
Published: 2020
Full Text: View/download PDF

16. Immunopathological manifestations in Kabuki syndrome: a registry study of 177 individuals

Author: Margot, Henri, Boursier, Guilaine, Duflos, Claire, Sanchez, Elodie, Amiel, Jeanne, Andrau, Jean-Christophe, Arpin, Stéphanie, Brischoux-Boucher, Elise, Boute, Odile, Burglen, Lydie, Caille, Charlotte, Capri, Yline, Collignon, Patrick, Conrad, Solène, CORMIER-DAIRE, Valerie, Delplancq, Geoffroy, Dieterich, Klaus, Dollfus, Hélène, Fradin, Mélanie, Faivre, Laurence, Fernandes, Helder, Francannet, Christine, Gatinois, Vincent, Gérard, Marion, Goldenberg, Alice, Ghoumid, Jamal, Grotto, Sarah, Guerrot, Anne-Marie, Guichet, Agnès, Isidor, Bertrand, Jacquemont, Marie-Line, Julia, Sophie, Philip, K, Legendre, Marine, Le Quan Sang, K., Leheup, Bruno, Lyonnet, Stanislas, Magry, Virginie, Manouvrier, Sylvie, Martin, Dominique, Morel, Godelieve, Munnich, Arnold, Naudion, Sophie, Odent, Sylvie, Perrin, Laurence, Petit, Florence, Philip, Nicole, Rio, Marlène, Robbe, Julie, Rossi, Massimiliano, Sarrazin, Elisabeth, Toutain, Annick, Van Gils, Julien, Vera, Gabriella, Verloes, Alain, Weber, Sacha, Whalen, Sandra, Sanlaville, Damien, Lacombe, Didier, Aladjidi, Nathalie, Geneviève, David, Khau Van Kien, Philippe, Van Gils, Julie, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Paris Descartes - Paris 5 (UPD5), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de Génétique Médicale, Hôpital intercommunal de Font-Pré, Centre hospitalier universitaire de Nantes (CHU Nantes), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Muscle et Pathologies, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de génétique clinique, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux], Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des Maladies Rénales Héréditaires, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de génétique médicale et cytogénétique [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hydrosciences Montpellier (HSM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence car i b é en des maladies rares neuromusculaires et neurologiques adultes et enfant (CERCA), Hôpital Pierre Zobda Quitman-CHU Fort-de-France, U 1211 Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (MRGM), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire régional de télédétection, Institut de Recherche pour le Développement (IRD), Service de Génétique Cytogénétique et Embryologie [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), Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), AOM 07-090, Ministère de la Santé et des Services sociaux, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), gerard, marion, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, [SDV.GEN] Life Sciences [q-bio]/Genetics, Vitiligo, Severity of Illness Index, Hypogammaglobulinemia, 0302 clinical medicine, Prevalence, Medicine, KDM6A, Registries, Child, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Immunodeficiency, Histone Demethylases, 0303 health sciences, Genetic disorder, KMT2D, Middle Aged, Thrombocytopenic purpura, Neoplasm Proteins, 3. Good health, DNA-Binding Proteins, Vestibular Diseases, Child, Preschool, Female, Autoimmune hemolytic anemia, Adult, medicine.medical_specialty, Adolescent, Primary Immunodeficiency Diseases, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Autoimmune Diseases, Young Adult, 03 medical and health sciences, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Humans, Abnormalities, Multiple, Genetic Association Studies, Aged, 030304 developmental biology, Autoimmune disease, [SDV.GEN]Life Sciences [q-bio]/Genetics, Kabuki syndrome, business.industry, Infant, Newborn, Infant, medicine.disease, Hematologic Diseases, immunity, Dermatology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Face, Mutation, business, 030217 neurology & neurosurgery
Abstract: Kabuki syndrome (KS) (OMIM 147920 and 300867) is a rare genetic disorder characterized by specific facial features, intellectual disability, and various malformations. Immunopathological manifestations seem prevalent and increase the morbimortality. To assess the frequency and severity of the manifestations, we measured the prevalence of immunopathological manifestations as well as genotype–phenotype correlations in KS individuals from a registry. Data were for 177 KS individuals with KDM6A or KMT2D pathogenic variants. Questionnaires to clinicians were used to assess the presence of immunodeficiency and autoimmune diseases both on a clinical and biological basis. Overall, 44.1% (78/177) and 58.2% (46/79) of KS individuals exhibited infection susceptibility and hypogammaglobulinemia, respectively; 13.6% (24/177) had autoimmune disease (AID; 25.6% [11/43] in adults), 5.6% (10/177) with ≥2 AID manifestations. The most frequent AID manifestations were immune thrombocytopenic purpura (7.3% [13/177]) and autoimmune hemolytic anemia (4.0% [7/177]). Among nonhematological manifestations, vitiligo was frequent. Immune thrombocytopenic purpura was frequent with missense versus other types of variants (p = 0.027). The high prevalence of immunopathological manifestations in KS demonstrates the importance of systematic screening and efficient preventive management of these treatable and sometimes life-threatening conditions.
Published: 2020
Full Text: View/download PDF

17. Hereditary sensory autonomic neuropathy type II: Report of two novel mutations in the FAM134B gene

Author: de Becdelievre, Alix, Falcão de Campos, Catarina, Vidailhet, Marie, Toutain, Annick, Becdelièvre, Alix, Funalot, Benoît, Bonello‐Palot, Nathalie, Stojkovic, Tanya, Institut Mondor de Recherche Biomédicale (IMRB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Pathology, medicine.medical_specialty, Sensory axonal neuropathy, business.industry, General Neuroscience, Osteomyelitis, medicine.medical_treatment, Dysautonomia, Sensory system, medicine.disease, Phenotype, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Nociception, Amputation, 030220 oncology & carcinogenesis, Sensation, medicine, Neurology (clinical), medicine.symptom, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Hereditary sensory autonomic neuropathy (HSAN) type II is a rare, autosomal recessive, and early onset sensory neuropathy, characterized by severe and progressive sensation impairment, leading to ulcero-mutilating complications. FAM134B gene, also known as RETREG1 gene, mutations have been reported to be associated to HSAN-IIB. We report four patients from two unrelated families who developed during childhood a sensory axonal neuropathy with variable severity and pronounced nociception impairment. Complications such as recurrent ulcerations, osteomyelitis, and osteonecrosis leading to distal amputation were noticed. Dysautonomia was mild or even absent in our group of patients. Additionally, either clinical or neurophysiological motor impairment was not uncommon. Presence of upper motor neuron signs was also a distinctive feature in two related patients. After extensive workup, two novel homozygous mutations in the FAM134B gene were identified. This report expands the clinical and genetic spectrum of HSAN type II and emphasizes the phenotype variability even within the same family.
Published: 2019
Full Text: View/download PDF

18. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

Author: Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), 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 Régional Universitaire de Nancy (CHRU Nancy), Institut de cardiologie [CHU Pitié-Salpêtrière], 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 de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), 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)-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), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, 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], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, 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 Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Tachycardia, medicine.medical_specialty, implantable, Accurate estimation, Ventricular Tachyarrhythmias, Validation Studies as Topic, 030204 cardiovascular system & hematology, tachycardia, Sudden death, LMNA, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, death, Physiology (medical), Internal medicine, defibrillators, medicine, Humans, In patient, 030212 general & internal medicine, sudden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Prediction score, business.industry, Defibrillators, Implantable, ventricular, Tachycardia, Ventricular, Cardiology, Female, medicine.symptom, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract: Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.
Published: 2019
Full Text: View/download PDF

19. Brain Asymmetry in Pain Affective Modulation

Author: Raphael Silva do Rosário, Miguel A. Muñoz, Thaise Graziele L. de O. Toutain, José Garcia Vivas Miranda, Guzmán Alba, and Eduardo Pondé de Sena
Subjects: Male, medicine.medical_specialty, Brain Mapping, medicine.diagnostic_test, Brain activity and meditation, business.industry, Left Brain Hemisphere, Emotions, Brain, Pain, Electroencephalography, General Medicine, Audiology, Stimulus (physiology), Affective modulation, Homophily, Lateralization of brain function, Anesthesiology and Pain Medicine, medicine, Brain asymmetry, Humans, Female, Neurology (clinical), business
Abstract: Objective The aim of this study was to characterize the dynamic brain networks underlying the affective modulation of pleasant, unpleasant, and neutral image perception due to painful stimulations in healthy subjects. Methods Forty volunteers, 20 men and 20 women, participated in this study. Brain activity was recorded by 64-channel electroencephalography. After data cleaning, brain functional networks were built through the use of the motif synchronization method. Results We found that increased cerebral connectivity in the left hemisphere under the pain condition broke the connection symmetry. Both women and men showed homophilic connections (intrahemispheric), but women were more homophilic than men. The pain condition increased homophily in the left hemisphere, and emotions could modulate pain. The frontal, central, and left temporal regions showed homophilic variation, depending on the emotional stimulus. Conclusions Pain and emotions altered brain activity. There was increased connectivity and homophily in the left brain hemisphere for the painful experience. The emotions modulated brain activity in the pain condition. Overall, the brain presented homophilic characteristics; homophily changed, depending on emotion or pain. The left brain hemisphere seems to be related to pain processing.
Published: 2021

20. A Large Impact of Obesity on the Disposition of Ivermectin, Moxidectin and Eprinomectin in a Canine Model: Relevance for COVID-19 Patients

Author: Alain Bousquet-Mélou, Isabelle Bargues, Jean-François Sutra, Pierre-Louis Toutain, Anne Lespine, Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and The Royal Veterinary College, Hawkshead Campus
Subjects: 0301 basic medicine, obesity, Calorie, [SDV]Life Sciences [q-bio], 030231 tropical medicine, 030106 microbiology, RM1-950, Pharmacology, Loading dose, ivermectin, 03 medical and health sciences, chemistry.chemical_compound, canine model, 0302 clinical medicine, Ivermectin, Pharmacokinetics, Medicine, Pharmacology (medical), Original Research, Volume of distribution, business.industry, urogenital system, COVID-19, dosage regimen, medicine.disease, Obesity, 3. Good health, Moxidectin, chemistry, embryonic structures, Lean body mass, moxidectin, Therapeutics. Pharmacology, business, pharmacokinetics, medicine.drug
Abstract: Ivermectin (IVM) and moxidectin (MOX) are used extensively as parasiticides in veterinary medicine. Based on in vitro data, IVM has recently been proposed for the prevention and treatment of COVID-19 infection, a condition for which obesity is a major risk factor. In patients, IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM, MOX, and a third analog, eprinomectin (EPR). An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX, and EPR were administered intravenously, in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX but was reduced for IVM and EPR, compared to the initial control state. However, when scaled by body weight (L/day/kg), plasma clearance was reduced by 55, 42, and 63%, for IVM, MOX and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased, in absolute values (L), by obesity. For IVM and MOX, this obese dog model suggests that the maintenance doses in the obese subject should be based on lean body weight rather than total weight. On the other hand, the loading dose, when required, should be based on the total body weight of the obese subject.
Published: 2021
Full Text: View/download PDF

21. Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy

Author: Aurélien Corroyer-Dulmont, Cécile Perrio, Didier Divoux, Guénaëlle Levallet, Méziane Ibazizène, Stéphane Guillouet, Jérôme Levallet, Samuel Valable, Jade Fantin, Jérôme Toutain, Louisa Barré, Elise Letissier, Sylvain Teulier, Françoise Chapon, Nicola R. Sibson, Sébastien Serres, Céline Bazille, Laurent Chatre, Myriam Bernaudin, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de pneumologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Département de Pathologie [CHU Caen], School of Life Sciences, University of Nottingham, UK (UON), Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford [Oxford], Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Oncology [Oxford, UK] (CRUK/MRC), and University of Oxford
Subjects: Cancer microenvironment, medicine.medical_specialty, Lung Neoplasms, Cancer therapy, [SDV]Life Sciences [q-bio], Science, medicine.medical_treatment, Article, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, medicine, Pimonidazole, Animals, Humans, Registries, Lung cancer, 030304 developmental biology, Aged, 0303 health sciences, Multidisciplinary, Tumor hypoxia, Radiotherapy, business.industry, Brain Neoplasms, Hypoxia (medical), Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Rats, Radiation therapy, CNS cancer, 030220 oncology & carcinogenesis, Cancer research, Medicine, Tumor Hypoxia, Neurosurgery, medicine.symptom, business, Immunostaining, Radiotherapy, Image-Guided
Abstract: Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated in 28 biopsies from patients with non‑small cell lung cancer (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, CA-IX and HIF-1α) was also performed in different preclinical NSCLC BM models induced either by intracerebral injection of tumor cells (H2030-Br3M, H1915) into the cortex and striatum, or intracardial injection of tumor cells (H2030-Br3M). Additionally, [18F]-FMISO-PET and oxygen-saturation-mapping-MRI (SatO2-MRI) were carried out in the intracerebral BM models to further characterize tumor hypoxia and evaluate the potential of Hypoxia-image-guided-RT (HIGRT). The effect of RT on proliferation of BM ([18F]-FLT-PET), tumor volume and overall survival was determined. We showed that hypoxia is a major yet heterogeneous feature of BM from lung cancer both preclinically and clinically. HIGRT, based on hypoxia heterogeneity observed between cortical and striatal metastases in the intracerebrally induced models, showed significant potential for tumor control and animal survival. These results collectively highlight hypoxia as a hallmark of BM from lung cancer and the value of HIGRT in better controlling tumor growth.
Published: 2021
Full Text: View/download PDF

22. A Combined Study with 18F-FDG and 11C-Methionine Dynamic PET for the Grading of Brain Gliomas

Author: N Vikhrova, D Kalaeva, Toutain J, Valable S, A Postnov, Derlon J, Konakova T, Clerck Nd, Usachev D, I Pronin, NN Burdenko Neurosurgical Institute (NNBNI), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Republican Research and Practical Center of Neurology and Neurosurgery, and University of Antwerp (UA)
Subjects: 18 F-FDG, Pathology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], PET-CT, 11c methionine, Brain gliomas, Text mining, Glioma grading, Medicine, 11C-Methionine, business, Grading (tumors), metabolism
Abstract: Purpose: Conventional MRI based on contrast enhancement and T2/FLAIR is often not sufficient in differentiating grade II from grade III and grade III from grade IV diffuse gliomas. Here we assessed advanced metabolic imaging using two well characterized PET tracers, namely 18F-FDG and 11C-Methionine.Methods: In this prospective study, 39 patients were enrolled with diffuse gliomas of grades II, III or IV underwent dynamic [18F]-FDF-PET and [11C]-Methionine. The first minutes were taken into accountResults: The use of 11C- Methionine provided significant differences between the different histologic subgroups with a higher number of parameters than did the use of 18 F-FDG. The most informative parameter is T/Np (T/N at the peak of the first maximum) with 11C- Methionine.Conclusion: The study of the first minute passage of 18F-FDG and/or 11C- Methionine through the tumor and healthy tissues in brain gliomas could not only allow improving the identification of the different glioma grades, but also to shorten the time spent by the patients under the camera. In case of using one tracer, methionine still would be the best choice. Otherwise, the use of 18F-FDG and SUVр (SUV at the peak of the first maximum) would provide results likely comparable to methionine T/N index.
Published: 2021

23. Collocated microstrip antennas for MIMO systems with a low mutual coupling using mode confinement

Author: Sarrazin, J., Mahe, Y., Avrillon, S., and Toutain, S.
Subjects: Antennas (Electronics) -- Design and construction, Correlation (Statistics) -- Usage, MIMO communications -- Analysis, Business, Computers, Electronics, Electronics and electrical industries
Published: 2010

24. Pattern reconfigurable cubic antenna

Author: Sarrazin, Julien, Mahe, Yann, Avrillon, Stephane, and Toutain, Serge
Subjects: Antennas (Electronics) -- Analysis, Electromagnetic waves -- Polarization, Electromagnetic waves -- Analysis, Business, Computers, Electronics, Electronics and electrical industries
Abstract: A new single-feed reconfigurable antenna for pattern diversity is presented in this paper. The proposed structure is based on a metallic cubic cavity which radiates through rectangular slots. The pattern reconfiguration is achieved with PIN diode switches by short-circuiting slots in their center. The designed antenna can switch between three different radiation patterns which radiate in a 4[pi] steradian range and can receive any incident field polarizations. A prototype of the antenna, including PIN diodes and operating in the 5 GHz band, has been built to demonstrate the feasibility of the concept. Measurements have been conducted and three-dimensional radiation patterns are provided. Diversity performances are evaluated by calculating the envelope correlation coefficient. Index Terms--Envelope correlation coefficient, pattern diversity, PIN diode switches, reconfigurable antennas, slots and cavity.
Published: 2009

25. Critical role of Aquaporin-1 and telocytes in infantile hemangioma response to propranolol beta blockade

Author: Sandra Oucherif, Marie-Laure Jullie, Benoit Rousseau, Sabrina Lacomme, Alain Taieb, Hamid Reza Rezvani, François Moisan, Christine Léauté-Labrèze, Marc Bonneu, Stéphane Claverol, Jerome Toutain, Maya Loot, P. Kaulanjan-Checkmodine, Thierry Couffinhal, Sorilla Prey, Léa Dousset, Etienne Gontier, and Muriel Cario-André
Subjects: 0301 basic medicine, Stromal cell, Proteome, Angiogenesis, Adrenergic beta-Antagonists, Propranolol, Hemangioma, Mice, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Neoplastic Syndromes, Hereditary, Cell Line, Tumor, medicine, Animals, Humans, Hemangioma, Capillary, Telocytes, Receptor, Tube formation, Matrigel, Multidisciplinary, Aquaporin 1, Neovascularization, Pathologic, business.industry, Biological Sciences, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Receptors, Adrenergic, beta-2, business, medicine.drug
Abstract: Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is the first-line therapy for severe infantile hemangiomas (IH). Since the incidental discovery of propranolol efficacy in IH, preclinical and clinical investigations have shown evidence of adjuvant propranolol response in some malignant tumors. However, the mechanism for propranolol antitumor effect is still largely unknown, owing to the absence of a tumor model responsive to propranolol at nontoxic concentrations. Immunodeficient mice engrafted with different human tumor cell lines were treated with anti-VEGF bevacizumab to create a model sensitive to propranolol. Proteomics analysis was used to reveal propranolol-mediated protein alteration correlating with tumor growth inhibition, and Aquaporin-1 (AQP1), a water channel modulated in tumor cell migration and invasion, was identified. IH tissues and cells were then functionally investigated. Our functional protein association networks analysis and knockdown of ADRB2 and AQP1 indicated that propranolol treatment and AQP1 down-regulation trigger the same pathway, suggesting that AQP1 is a major driver of beta-blocker antitumor response. Examining AQP1 in human hemangioma samples, we found it exclusively in a perivascular layer, so far unrecognized in IH, made of telocytes (TCs). Functional in vitro studies showed that AQP1-positive TCs play a critical role in IH response to propranolol and that modulation of AQP1 in IH-TC by propranolol or shAQP1 decreases capillary-like tube formation in a Matrigel-based angiogenesis assay. We conclude that IH sensitivity to propranolol may rely, at least in part, on a cross talk between lesional vascular cells and stromal TCs.
Published: 2021
Full Text: View/download PDF

26. Pediatric Acute B-Cell Lymphoblastic Leukemia Developing Following Recent SARS-CoV-2 Infection

Author: Noémie Wagner, Frederic Baleydier, Fabienne Toutain, Arnaud G L'Huillier, Anne-Marie Calza, Charlotte Leclercq, Céline Lironi, Marc Ansari, and Geraldine Blanchard-Rohner
Subjects: Male, Pancytopenia, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), B-Cell Lymphoblastic Leukemia, medicine.disease_cause, Virus, EBV, Acute lymphocytic leukemia, hemic and lymphatic diseases, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, medicine, Humans, Pediatrics, Perinatology, and Child Health, Child, Coronavirus, Pediatric, Leukemi, ddc:618, business.industry, SARS-CoV-2, COVID-19, Hematology, Exanthema, medicine.disease, Prognosis, Rash, Cutaneous, Oncology, Pediatrics, Perinatology and Child Health, Immunology, Etiology, medicine.symptom, business
Abstract: Coronavirus disease-2019 in children has been linked to various clinical presentation, from paucisymptomatic cutaneous eruptions, to multisystemic inflammatory syndrome. We report the case of an 8-year-old boy who presented with persistent fever and pancytopenia, associated to a skin rash. An extensive etiological workup showed a positive serology for severe acute respiratory syndrome coronavirus 2 and Epstein-Barr virus. A few weeks later, type B acute lymphocytic leukemia was diagnosed. This case underlines the polymorphic appearance of coronavirus disease-2019 and the need for critical appraisal.
Published: 2021
Full Text: View/download PDF

27. Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients

Author: Isabelle Bargues, Anne Lespine, Jean-François Sutra, Alain Bousquet-Melou, and Pierre-Louis Toutain
Subjects: Volume of distribution, Calorie, urogenital system, business.industry, Maintenance dose, Pharmacology, medicine.disease, Loading dose, Obesity, Moxidectin, chemistry.chemical_compound, Ivermectin, chemistry, Lean body mass, Medicine, business, medicine.drug
Abstract: Background and Purpose: Based on in vitro data, ivermectin (IVM) has been proposed for the prevention and treatment of COVID-19, a condition for which obesity is a major risk factor. IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM and two analog compounds, moxidectin (MOX) and eprinomectin (EPR). Experimental Approach: An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX and EPR were administered intravenously, simultaneously in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. Key Results: In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX and reduced for IVM and EPR, compared to the initial control state. When scaled by body weight (L/day/kg), plasma clearance was reduced by 42, 55 and 63%, for MOX, IVM and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased in absolute values (L) by obesity. Conclusion and Implications: For IVM and MOX, the obese dog model suggests that the maintenance dose should not be adjusted by total body weight in the obese subject but should be based on lean body weight. On the other hand, the loading dose should be computed based on the total body weight of the obese subject.
Published: 2021
Full Text: View/download PDF

28. Population pharmacokinetics of intravenous amoxicillin combined with clavulanic acid in healthy and critically ill dogs

Author: Maria D. Vegas Cómitre, Stefano Cortellini, Marc Cherlet, Mathias Devreese, Beatrice B. Roques, Alain Bousquet-Melou, Pierre-Louis Toutain, and Ludovic Pelligand
Subjects: medicine.medical_specialty, PK, BIOAVAILABILITY, Veterinary medicine, Population, Gastroenterology, clinical breakpoint, law.invention, Augmentin, Pharmacokinetics, law, Internal medicine, Clavulanic acid, SF600-1100, medicine, Dosing, Veterinary Sciences, MIC, education, PK/PD models, Original Research, education.field_of_study, Amoxicillin/clavulanic acid, General Veterinary, SEPSIS, business.industry, PK/PD, NLME, Amoxicillin, QUANTIFICATION, Intensive care unit, PROTEIN-BINDING, ICU, antimicrobial, PD, Veterinary Science, business, VetCast, medicine.drug
Abstract: Background: Data regarding antimicrobial pharmacokinetics (PK) in critically ill dogs are lacking and likely differ from those of healthy dogs. The aim of this work is to describe a population PK model for intravenous (IV) amoxicillin–clavulanic acid (AMC) in both healthy and sick dogs and to simulate a range of clinical dosing scenarios to compute PK/PD cutoffs for both populations.Methods: This study used a prospective clinical trial in normal and critically ill dogs. Twelve client-owned dogs hospitalized in the intensive care unit (ICU) received IV AMC 20 mg/kg every 8 h (0.5-h infusion) during at least 48 h. Eight blood samples were collected at predetermined times, including four trough samples before the next administration. Clinical covariates and outcome were recorded, including survival to discharge and bacteriologic clinical failure. Satellite PK data were obtained de novo from a group of 12 healthy research dogs that were dosed with a single AMC 20 mg/kg IV. Non-linear mixed-effects model was used to estimate the PK parameters (and the effect of health upon them) together with variability within and between subjects. Monte Carlo simulations were performed with seven dosage regimens (standard and increased doses). The correlation between model-derived drug exposure and clinical covariates was tested with Spearman's non-parametric correlation analysis. Outcome was recorded including survival to discharge and bacteriologic clinical failure.Results: A total of 218 amoxicillin concentrations in plasma were available for healthy and sick dogs. A tricompartmental model best described the data. Amoxicillin clearance was reduced by 56% in sick dogs (0.147 L/kg/h) compared with healthy dogs (0.336 L/kg/h); intercompartmental clearance was also decreased (p Conclusions: The PK of AMC is profoundly different in critically ill dogs compared with normal dogs, with much higher interindividual variability and a lower systemic clearance. Our study allows to generate hypotheses with regard to higher AMC exposure in clinical dogs and provides supporting data to revise current AMC clinical breakpoint for IV administration.
Published: 2021

29. Physical resilience to insider attacks in IoT networks: Independent cryptographically secure sequences for DSSS anti-jamming

Author: Georgios Z. Papadopoulos, Laurent Toutain, Frédéric Cuppens, Renzo E. Navas, Nora Cuppens, Département Systèmes Réseaux, Cybersécurité et Droit du numérique (IMT Atlantique - SRCD), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Lab-STICC_IMTA_CID_IRIS, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), Université de Brest (UBO)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Université Bretagne Loire (UBL)-Centre National de la Recherche Scientifique (CNRS)-Université de Bretagne Sud (UBS)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Brest (UBO)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Université Bretagne Loire (UBL)-Centre National de la Recherche Scientifique (CNRS)-Université de Bretagne Sud (UBS)-École Nationale d'Ingénieurs de Brest (ENIB), Institut Mines-Télécom [Paris] (IMT)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), École Polytechnique de Montréal (EPM), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), IMT Atlantique (IMT Atlantique), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique)
Subjects: Computer Networks and Communications, Computer science, Internet of Things, Sequence Sets, Jamming, 02 engineering and technology, Direct-sequence spread spectrum, DSSS, Computer security, computer.software_genre, [INFO.INFO-CR]Computer Science [cs]/Cryptography and Security [cs.CR], [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], 0202 electrical engineering, electronic engineering, information engineering, Wireless, Cross-Correlation, Resilience (network), business.industry, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, Physical layer, 020206 networking & telecommunications, Adversary, Direct-Sequence Spread-Spectrum, Anti-Jamming, Moving Target Defense, Stream Cipher, Key (cryptography), 020201 artificial intelligence & image processing, business, computer, Cryptographically Secure Pseudo-Random
Abstract: International audience; Wireless communication is a key technology for the Internet of Things (IoT).Due to its open nature, the physical layer of wireless systems is a high-priority target for an adversary whose goal is to disrupt the normal behavior of the system. In particular, jamming attacks are one of the most straightforward and effective types of attacks: information flow of the system is stopped or severely disturbed.In this paper, we propose a method to improve the jamming resilience of IoT systems based on Direct-Sequence Spread-Spectrum (DSSS) techniques. Our proposal is inspired by the Moving Target Defense (MTD) paradigm. MTD strategies randomize components of a system, increasing the effort an attacker needs to compromise the system. We use state-of-the-art Cryptographically Secure Pseudo-Random Number Generators outputs as spreading sequences for DSSS. The sequences of the proposed system are generated in an ad-hoc, independent, and distributed way. We show probabilistically that the generated sequences have robust cross-correlation properties.We define a multi-user system model to evaluate the Bit-Error-Rate of our proposal in the presence of two types of jammers: a classical band-limited Gaussian noise jammer, and an insider smart jammer with knowledge of one spreading sequence used in the system. Our proposal proactively mitigates the insider jammer attack. We quantify the insider smart jammer resilience of a system implementing our proposal, as a function of the length of the spreading sequences and the jammer power.
Published: 2021
Full Text: View/download PDF

30. Using deep-neural-network-driven facial recognition to identify distinct Kabuki syndrome 1 and 2 gestalt

Author: Didier Lacombe, Claire Duflos, David Geneviève, Jeanne Amiel, Elodie Sanchez, Yline Capri, Damien Sanlaville, Marlène Rio, Alexandra Afenjar, Fabienne Giuliano, Elise Brischoux-Boucher, Mathilde Nizon, Stanislas Lyonnet, Sébastien Moutton, Vincent Gatinois, Stéphanie Arpin, Annick Toutain, Mouna Barat-Houari, Guilaine Boursier, Flavien Rouxel, Sophie Julia, Klaus Dieterich, Aurélia Jacquette, Boris Keren, Kevin Yauy, Patricia Blanchet, Marie-Line Jacquemont, Damien Haye, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Lausanne (UNIL), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), CHU Necker - Enfants Malades [AP-HP], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Centre de génétique humaine [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Toulouse [Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes), GRC ConCer-LD, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maison de Santé Protestante Bagatelle, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), and Hospices Civils de Lyon (HCL)
Subjects: Image Series, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biology, [INFO.INFO-NE]Computer Science [cs]/Neural and Evolutionary Computing [cs.NE], Facial recognition system, Article, Genetics, medicine, Humans, Abnormalities, Multiple, Genetics (clinical), [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Artificial neural network, Receiver operating characteristic, business.industry, Significant difference, Genetic disorder, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Pattern recognition, medicine.disease, Hematologic Diseases, Vestibular Diseases, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Face, Mutation, Gestalt psychology, Artificial intelligence, business, Kabuki syndrome, Facial Recognition
Abstract: International audience; Kabuki syndrome (KS) is a rare genetic disorder caused by mutations in two major genes, KMT2D and KDM6A, that are responsible for Kabuki syndrome 1 (KS1, OMIM147920) and Kabuki syndrome 2 (KS2, OMIM300867), respectively. We lack a description of clinical signs to distinguish KS1 and KS2. We used facial morphology analysis to detect any facial morphological differences between the two KS types. We used a facial-recognition algorithm to explore any facial morphologic differences between the two types of KS. We compared several image series of KS1 and KS2 individuals, then compared images of those of Caucasian origin only (12 individuals for each gene) because this was the main ethnicity in this series. We also collected 32 images from the literature to amass a large series. We externally validated results obtained by the algorithm with evaluations by trained clinical geneticists using the same set of pictures. Use of the algorithm revealed a statistically significant difference between each group for our series of images, demonstrating a different facial morphotype between KS1 and KS2 individuals (mean area under the receiver operating characteristic curve = 0.85 [p = 0.027] between KS1 and KS2). The algorithm was better at discriminating between the two types of KS with images from our series than those from the literature (p = 0.0007). Clinical geneticists trained to distinguished KS1 and KS2 significantly recognised a unique facial morphotype, which validated algorithm findings (p = 1.6e-11). Our deep-neural-network-driven facial-recognition algorithm can reveal specific composite gestalt images for KS1 and KS2 individuals.
Published: 2021
Full Text: View/download PDF

31. Validating an empiric sulfadiazine–trimethoprim dosage regimen for treatment of Escherichia coli and Staphylococcus delphini infections in mink ( Neovison vison )

Author: Peter Damborg, Nanett Kvist Nikolaisen, Helle Harding Poulsen, Tina Struve, Stine Green Hansen, Henrik Lauritz Frandsen, Amir Atabak Ronaghinia, Pierre-Louis Toutain, University of Copenhagen = Københavns Universitet (KU), Technical University of Denmark, Kopenhagen Amba, Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Royal Veterinary College [London], University of London [London], Department of Veterinary and Animal Sciences, University of Massachusetts System (UMASS), Innovationsfonden, Grant/Award Number: 5189-00060B, and Danish fur breeder association
Subjects: 0301 basic medicine, 040301 veterinary sciences, Staphylococcus, Staphylococcus delphini, [SDV]Life Sciences [q-bio], 030106 microbiology, Anti-Infective Agents, Urinary, Pharmacology, urologic and male genital diseases, 0403 veterinary science, 03 medical and health sciences, Sulfadiazine, Pharmacokinetics, biology.animal, medicine, Escherichia coli, Animals, heterocyclic compounds, trimethoprim, Mink, Escherichia coli Infections, General Veterinary, biology, business.industry, sulfadiazine, mink, 04 agricultural and veterinary sciences, Staphylococcal Infections, Antimicrobial, biology.organism_classification, bacterial infections and mycoses, Trimethoprim, female genital diseases and pregnancy complications, 3. Good health, Neovison vison, Regimen, Drug Combinations, Pharmacodynamics, Area Under Curve, business, human activities, medicine.drug, Half-Life
Abstract: International audience; Antimicrobial agents are used extensively off-label in mink, as almost no agents are registered for this animal species. Pharmacokinetic (PK) and pharmacodynamic (PD) data are required to determine antimicrobial dosages specifically targeting mink bacterial pathogens. The aims of this study were to assess, in a PKPD framework, the empirical dosage regimen for a combination of trimethoprim (TMP) and sulfadiazine (SDZ) in mink, and secondarily to produce data for future setting of clinical breakpoints. TMP and SDZ PK parameters were obtained experimentally in 22 minks following IV or oral administration of TMP/SDZ (30 mg/kg, i.e. 5 mg/kg TMP and 25 mg/kg SDZ). fAUC/MIC with a target value of 24 hr was selected as the PKPD index predictive of TMP/SDZ efficacy. Using a modeling approach, PKPD cutoffs for TMP and SDZ were determined as 0.062 and 16 mg/L, respectively. By incorporating an anticipated potentiation effect of SDZ on TMP against Escherichia coli and Staphylococcus delphini, the PKPD cutoff of TMP was revised to 0.312 mg/L, which is above the tentative epidemiological cutoffs (TECOFF) for these species. The current empirical TMP/SDZ dosage regimen (30 mg/kg, PO, once daily) therefore appears adequate for treatment of wild-type E. coli and S. delphini infections in mink.
Published: 2021
Full Text: View/download PDF

32. The pharmacokinetic/pharmacodynamic paradigm for antimicrobial drugs in veterinary medicine: Recent advances and critical appraisal

Author: Ludovic Pelligand, Peter Lees, Pierre-Louis Toutain, Alain Bousquet-Mélou, John D. Turnidge, Aude A. Ferran, Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Royal Veterinary College - University of London, University of Adelaide, and UK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC)BB/S011269/1
Subjects: 0301 basic medicine, Veterinary medicine, [SDV]Life Sciences [q-bio], 030106 microbiology, Population, Microbial Sensitivity Tests, antimicrobials, PKPD, 03 medical and health sciences, Anti-Infective Agents, Pharmacokinetics, Animals, Medicine, education, PK/PD models, Pharmacology, education.field_of_study, General Veterinary, Pharmacokinetic pharmacodynamic, business.industry, Area under the curve, dosage regimen, Antimicrobial, Anti-Bacterial Agents, 3. Good health, Critical appraisal, 030104 developmental biology, veterinary medicine, Pharmaceutical Preparations, Area Under Curve, Pharmacodynamics, business
Abstract: International audience; Pharmacokinetic/pharmacodynamic (PK/PD) modelling is the initial step in the semi-mechanistic approach for optimizing dosage regimens for systemically acting antimicrobial drugs (AMDs). Numerical values of PK/PD indices are used to predict dose and dosing interval on a rational basis followed by confirmation in clinical trials. The value of PK/PD indices lies in their universal applicability amongst animal species. Two PK/PD indices are routinely used in veterinary medicine, the ratio of the area under the curve of the free drug plasma concentration to the minimum inhibitory concentration (MIC) (fAUC/MIC) and the time that free plasma concentration exceeds the MIC over the dosing interval (fT > MIC). The basic concepts of PK/PD modelling of AMDs were established some 20 years ago. Earlier studies have been reviewed previously and are not reconsidered in this review. This review describes and provides a critical appraisal of more recent, advanced PK/PD approaches, with particular reference to their application in veterinary medicine. Also discussed are some hypotheses and new areas for future developments.First,a brief overview of PK/PD principles is presented as the basis for then reviewing more advanced mechanistic considerations on the precise nature of selected indices. Then, several new approaches to selecting PK/PD indices and establishing their numerical values are reviewed, including (a) the modelling of time-kill curves and (b) the use of population PK investigations. PK/PD indices can be used for dose determination, and they are required to establish clinical breakpoints for antimicrobial susceptibility testing. A particular consideration is given to the precise nature of MIC, because it is pivotal in establishing PK/PD indices, explaining that it is not a "pharmacodynamic parameter" in the usual sense of this term.
Published: 2021
Full Text: View/download PDF

33. [Computerized method for calculating cervical vertebral maturation]

Author: Emmanuelle Bocquet, Gaspard Toutain, Philippe Decocq, Jacques Honoré, and Max Crocquet
Subjects: Orthodontics, Male, business.industry, Cephalometry, Radiography, Bone age, General Medicine, Skeletal maturity, Age Determination by Skeleton, Child, Preschool, Cervical Vertebrae, Medicine, Humans, Female, Stage (cooking), business
Abstract: For Helm, "the rhythm of facial growth often governs the course of orthodontic treatment". The moment of treatment is an important dimension for our therapy to last a minimum of time with a greatest chance of success and stability. This notion of processing time is a daily requirement in our practices. The radiographs of the wrists will gradually disappear according to the ALARA principle, since we can in a single irradiation, via the profile radiography, have sufficient information to situate the patient on its growth curve. The vertebral stages are good biological indicators of individual skeletal maturity but their interpretation remains difficult. In this work, a computerized method was used to determine the stage of vertebral maturation in a reliable and reproducible manner. In this study, 15 young boys and 15 young girls (total 30 patients) were included, 12,2 years old on average with a standard deviation of 2,6 years. To determine the skeletal age of these patients, the practitioner made an hand-wrist x-ray and, for diagnostic reasons, he also made a profile radiography the same day. The patients who didn't made an hand-wrist x-ray were excluded. The vertebral computerized method seems to be a reliable method to be used in orthodontic practices. Other studies would allow to use this method for average ages, gender-appropriate.
Published: 2020

34. Author response for 'Clinical and neuroimaging findings in 33 patients with MCAP syndrome: a survey to evaluate relevant endpoints for future clinical trials'

Author: Florence Petit, Juliette Mazereeuw-Hautier, Christine Coubes, Patricia Blanchet, Jenny Cornaton, Frederico Di Rocco, Fabienne Giuliano, Arthur Sorlin, Elodie Gautier, Laurent Guibaud, Renaud Touraine, Massimiliano Rossi, Christophe Philippe, Jean-Luc Alessandri, Joelle Roume, Patrick Edery, Gilles Morin, Christine Chiaverini, Diane Doummar, Michèle Mathieu-Dramard, Olivia Boccara, Philippe Khau Van Kien, Aurore Garde, Claire Nicolas, Maxime Luu, Lucile Pinson, Nicolas Chassaing, Fanny Morice-Picard, Christel Thauvin-Robinet, Rodolphe Dard, Cyril Mignot, Marc Bardou, V. Carmignac, Pierre Vabres, Alice Goldenberg, Laurence Faivre, Didier Lacombe, Annick Toutain, Stéphanie Arpin, Marjolaine Willems, and Anne-Claire Bursztejn
Subjects: Clinical trial, medicine.medical_specialty, Neuroimaging, business.industry, medicine, Intensive care medicine, business
Published: 2020
Full Text: View/download PDF

35. Neuropsychological study in 19 French patients with White‐Sutton syndrome and POGZ mutations

Author: Anne Miret, Lola Lemasson, Benjamin Cogné, Laurence Perrin, Frédéric Tran Mau-Them, Rémi Mathevet, Marion Boucon, Elise Schaefer, Christel Thauvin-Robinet, Christine Juif, Juliette Piard, Solène Bourgouin, Jenny Cornaton, Bertrand Isidor, Catherine Sarret, Fabienne Prieur, Coralie Gonin-Olympiade, Alexandra Afenjar, Christine Coubes, Boris Keren, Bénédicte Gérard, Catherine Vincent-Delorme, Kim Giraudat, Laurence Faivre, Amélie Piton, Antonio Vitobello, Thomas Smol, Annick Toutain, Arthur Sorlin, Sylvie Odent, Yann Trousselet, Fanny Tessier, Martin Chevarin, David Geneviève, Sébastien Moutton, Anne-Claire Gelineau, Ange-Line Bruel, Claire Nicolas, Aurore Garde, Philippe Khau-Van-Kien, Christophe Philippe, Solveig Heide, Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Les Hôpitaux Universitaires de Strasbourg (HUS), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Centre de génétique humaine [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Etienne, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, and SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Adolescent, Autism Spectrum Disorder, Developmental Disabilities, [SDV]Life Sciences [q-bio], Neurocognitive Disorders, Transposases, Neuropsychological Tests, 030105 genetics & heredity, Cohort Studies, Young Adult, 03 medical and health sciences, [SCCO]Cognitive science, Intellectual Disability, Intellectual disability, Genetics, medicine, Humans, Genetic Predisposition to Disease, Global developmental delay, Child, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Dysexecutive syndrome, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Neuropsychology, Genetic Variation, medicine.disease, 3. Good health, Developmental disorder, Phenotype, 030104 developmental biology, Autism spectrum disorder, Child, Preschool, Mutation, Autism, Female, France, business, Neurocognitive
Abstract: White-Sutton syndrome is a rare developmental disorder characterized by global developmental delay, intellectual disabilities (ID), and neurobehavioral abnormalities secondary to pathogenic pogo transposable element-derived protein with zinc finger domain (POGZ) variants. The purpose of our study was to describe the neurocognitive phenotype of an unbiased national cohort of patients with identified POGZ pathogenic variants. This study is based on a French collaboration through the AnDDI-Rares network, and includes 19 patients from 18 families with POGZ pathogenic variants. All clinical data and neuropsychological tests were collected from medical files. Among the 19 patients, 14 patients exhibited ID (six mild, five moderate and three severe). The five remaining patients had learning disabilities and shared a similar neurocognitive profile, including language difficulties, dysexecutive syndrome, attention disorders, slowness, and social difficulties. One patient evaluated for autism was found to have moderate autism spectrum disorder. This study reveals that the cognitive phenotype of patients with POGZ pathogenic variants can range from learning disabilities to severe ID. It highlights that pathogenic variations in the same genes can be reported in a large spectrum of neurocognitive profiles, and that children with learning disabilities could benefit from next generation sequencing techniques.
Published: 2020
Full Text: View/download PDF

36. Performance Analysis and Optimal Tuning of IETF LPWAN SCHC ACK-on-Error Mode

Author: Carles Gomez, Nicolas Montavont, Patrick Maillé, Sergio Aguilar, Georgios Z. Papadopoulos, Laurent Toutain, Rafael Vidal, Universitat Politècnica de Catalunya [Barcelona] (UPC), Dependability Interoperability and perfOrmance aNalYsiS Of networkS (DIONYSOS), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-RÉSEAUX, TÉLÉCOMMUNICATION ET SERVICES (IRISA-D2), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Département Systèmes Réseaux, Cybersécurité et Droit du numérique (IMT Atlantique - SRCD), IMT Atlantique (IMT Atlantique), Objets communicants pour l'Internet du futur (OCIF), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-RÉSEAUX, TÉLÉCOMMUNICATION ET SERVICES (IRISA-D2), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), This work was supported in part by the Spanish Government through project TEC2016-79988-P, AEI/FEDER, EU., Universitat Politècnica de Catalunya. Doctorat en Enginyeria Telemàtica, Universitat Politècnica de Catalunya. Departament d'Enginyeria Telemàtica, and Universitat Politècnica de Catalunya. WNG - Grup de xarxes sense fils
Subjects: Internet of things, LPWAN, IoT, Enginyeria de la telecomunicació::Telemàtica i xarxes d'ordinadors [Àrees temàtiques de la UPC], Wide area networks (Computer networks), Internet de les coses, Computer science, ACK-on-Error, 01 natural sciences, LoRa, fragmentation, Telecommunications link, Electrical and Electronic Engineering, Instrumentation, Computer networks, IETF, [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], business.industry, Network packet, 010401 analytical chemistry, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], SCHC, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, 0104 chemical sciences, IPv6, LoRaWAN, Wide area network, Sigfox, The Internet, business, Optimal tuning, Ordinadors, Xarxes d', mathematical model, Computer network
Abstract: © 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes,creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works. The Internet Engineering Task Force (IETF) Low Power Wide Area Network (LPWAN) Working Group has developed the Static Context Header Compression (SCHC) framework to enable IPv6 over LPWAN. In order to support 1280-byte packets, as required for IPv6, SCHC includes a fragmentation functionality, since relevant LPWAN technologies offer very short data unit sizes and do not provide native fragmentation mechanisms. SCHC offers 3 fragmentation modes: No-ACK, ACK-Always, and ACK-on-Error, the latter being especially promising due to its reliability and high efficiency. In this article, we develop a mathematical model to compute the most critical performance parameters for the SCHC ACK-on-Error mode, namely, the acknowledgment traffic incurred by a fragment receiver for the successful delivery of a fragmented packet. The model is used to evaluate the SCHC ACK-on-Error mode performance, as well as to optimally tune its main parameters when used over LoRaWAN and Sigfox, for different packet sizes. Additionally, we illustrate how our derived optimal settings allow to reduce the acknowledgment traffic in a number of scenarios.
Published: 2020
Full Text: View/download PDF

37. MTD, Where Art Thou? A Systematic Review of Moving Target Defense Techniques for IoT

Author: Renzo E. Navas, Nora Cuppens, Laurent Toutain, Frédéric Cuppens, Georgios Z. Papadopoulos, Département Systèmes Réseaux, Cybersécurité et Droit du numérique (IMT Atlantique - SRCD), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Lab-STICC_IMTA_CID_IRIS, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)
Subjects: Computer Networks and Communications, Computer science, Entropy, Internet of Things, Cyber Security, Context (language use), 02 engineering and technology, Computer security, computer.software_genre, [INFO.INFO-CR]Computer Science [cs]/Cryptography and Security [cs.CR], [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], Systematics, 0202 electrical engineering, electronic engineering, information engineering, Moving target defense, Systematic Literature Review, Taxonomy, Measurement, business.industry, 020206 networking & telecommunications, 020207 software engineering, Computer Science Applications, Variety (cybernetics), Bibliographies, Moving Target Defense, Hardware and Architecture, Software deployment, Signal Processing, Metrics, Metric (unit), business, computer, Information Systems
Abstract: International audience; Context: Internet of Things (IoT) systems are increasingly deployed in the real world, but their security lags behind the state of the art of non-IoT systems. Moving Target Defense (MTD) is a cyberdefense paradigm, successfully implemented in conventional systems, that could improve IoT security.Objective: Identify and synthesize existing MTD techniques for IoT and validate the feasibility of MTD as a cybersecurity paradigm suitable for IoT systems.Method: We use a systematic literature review method to search and analyze existing MTD for IoT techniques up to July 2020. We evaluated the existing techniques in terms of security foundations and real-world deployability using the evidence they provide. We define and use entropy-related metrics to categorize them. This is the first MTD survey to use Shannon’s entropy metric empirically.Results: Thirty-two distinct MTD for IoT techniques exist: 54% are Network-layer-based, 50% present strong evidence about their real-world deployment, and 64% have weak security foundations.Conclusion: MTD for IoT is a feasible cyberdefense approach. A variety of proposals exist, with evidence about their implementation and evaluation. Nevertheless, the MTD for IoT state of the art is still immature: the security foundations of most existing proposals are weak. Novel techniques should prioritize providing convincing security foundations and real-world deployment evidence.
Published: 2020
Full Text: View/download PDF

38. Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis

Author: Jean M. Connors, Dominique Farge, Corinne Frere, Guillaume Hékimian, M. Sakka, I. Colmegna, B. Crichi, D. Bonnefont-Rousselot, I. Martin-Toutain, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), McGill University = Université McGill [Montréal, Canada], Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and CCSD, Accord Elsevier
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Pneumonia, Viral, 030204 cardiovascular system & hematology, Risk Assessment, Severity of Illness Index, Article, Fibrin Fibrinogen Degradation Products, D-Dimer, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Internal medicine, Severity of illness, Risk of mortality, medicine, Humans, 030212 general & internal medicine, Mortality, Pandemics, Survival analysis, IQR, interquartile range, Retrospective Studies, Coronavirus disease 2019, business.industry, SARS-CoV-2, ADRS, acute detress respiratory syndrome, COVID-19, Retrospective cohort study, Middle Aged, Survival Analysis, Confidence interval, 3. Good health, NR, not reported, Hospitalization, [SDV] Life Sciences [q-bio], Strictly standardized mean difference, COVID-19, Coronavirus Disease 2019, biomarker, Observational study, Female, Risk assessment, business, Coronavirus Infections, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract: International audience; Background: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts.Objectives: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19.Methods: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI).Results: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59μg/L (95% CI 2.79-4.40μg/L), and the Z-score for overall effect was 8.74 (P
Published: 2020
Full Text: View/download PDF

39. Author response for 'Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses'

Author: Pierre-Louis Toutain, Alain Bousquet-Mélou, Yuki Enoki, Masahiro Kaimachi, Yuto Suzuki, Yoshinori Kasashima, Yohei Minamijima, Hidekazu Niwa, Kazuaki Taguchi, Taisuke Kuroda, Kentaro Fukuda, Norihisa Tamura, Hiroshi Mita, and Kazuaki Matsumoto
Subjects: Pharmacokinetics, business.industry, Cefazolin, medicine, Pharmacology, business, medicine.drug
Published: 2020
Full Text: View/download PDF

40. Reduced Rivaroxaban Dose Versus Dual Antiplatelet Therapy After Left Atrial Appendage Closure: ADRIFT a Randomized Pilot Study

Author: Nicolas Lellouche, Marie Hauguel-Moreau, Didier Klug, Hui Wang, Jean-Michel Juliard, Guillaume Duthoit, Isabelle Martin-Toutain, Eric Vicaut, N. Zannad, Delphine Brugier, Corinne Frere, Jacques Mansourati, Sandrine Deltour, Gregory Ducrocq, Solohaja-Faniaha Dimby, Eric Brochet, Eloi Marijon, Nassim Braik, Luc Lorgis, Nadjib Hammoudi, Johanne Silvain, Christian Spaulding, Batric Popovic, Antoine Lepillier, David Attias, Gilles Montalescot, and Alexandre Ceccaldi
Subjects: Male, medicine.medical_specialty, Cardiac Catheterization, Percutaneous, Time Factors, Antithrombin III, Atrial Appendage, Pilot Projects, 030204 cardiovascular system & hematology, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Rivaroxaban, Left atrial, Heart Rate, Internal medicine, Atrial Fibrillation, Medicine, Humans, 030212 general & internal medicine, Contraindication, Blood Coagulation, Aged, Appendage, Aged, 80 and over, business.industry, Dual Anti-Platelet Therapy, Atrial fibrillation, Thrombosis, Clopidogrel, medicine.disease, Peptide Fragments, 3. Good health, Treatment Outcome, Cardiology, Atrial Function, Left, Female, Prothrombin, France, Cardiology and Cardiovascular Medicine, business, Biomarkers, Platelet Aggregation Inhibitors, medicine.drug, Factor Xa Inhibitors, Peptide Hydrolases
Abstract: Background: Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC. Methods: ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to either rivaroxaban 10 mg (R 10 , n=37), rivaroxaban 15 mg (R 15 , n=35), or DAPT with aspirin 75 mg and clopidogrel 75 mg (n=33). The primary end point was thrombin generation (prothrombin fragments 1+2) measured 2 to 4 hours after drug intake, 10 days after treatment initiation. Thrombin-antithrombin complex, D-dimers, rivaroxaban concentrations were also measured at 10 days and 3 months. Clinical end points were evaluated at 3-month follow-up. Results: The primary end point was reduced with R 10 (179 pmol/L [interquartile range (IQR), 129–273], P 15 (163 pmol/L [IQR, 112–231], P 10 and R 15 while rivaroxaban concentrations increased significantly from 184 ng/mL (IQR, 127–290) with R 10 to 274 ng/mL (IQR, 192–377) with R 15 , P Conclusions: Thrombin generation measured after LAAC was lower in patients treated by reduced rivaroxaban doses than DAPT, supporting an alternative to the antithrombotic regimens currently used after LAAC and deserves further evaluation in larger studies. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03273322.
Published: 2020

41. IANVS: A Moving Target Defense Framework for a Resilient Internet of Things

Author: Frédéric Cuppens, Renzo E. Navas, Georgios Z. Papadopoulos, Nora Cuppens, Laurent Toutain, Hakon Sandaker, Département Systèmes Réseaux, Cybersécurité et Droit du numérique (IMT Atlantique - SRCD), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Lab-STICC_IMTA_CID_IRIS, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)
Subjects: IoT, Computer science, design, 0507 social and economic geography, hping3, ChaCha20, 02 engineering and technology, Computer security, computer.software_genre, [INFO.INFO-CR]Computer Science [cs]/Cryptography and Security [cs.CR], [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], stream-cipher, Resource (project management), framework, 0202 electrical engineering, electronic engineering, information engineering, User Datagram Protocol, Moving target defense, business.industry, reconnaissance, 05 social sciences, attack, port-hopping, 020207 software engineering, LoPy4, Variety (cybernetics), MTD, Moving Target Defense, Software deployment, CoAP, Security, The Internet, Internet of Things, business, 050703 geography, computer
Abstract: International audience; The Internet of Things (IoT) is more and more present in fundamental aspects of our societies and personal life. Billions of objects now have access to the Internet. This networking capability allows for new beneficial services and applications. However, it is also the entry-point for a wide variety of cyber-attacks that target these devices. The security measures present in real IoT systems lag behind those of the standard Internet. Security is sometimes completely absent. Moving Target Defense (MTD) is a 10-year-old cyber-defense paradigm. It proposes to randomize components of a system. Reasonably, an attacker will have a higher cost attacking an MTD-version of a system compared with a static-version of it. Even if MTD has been successfully applied to standard systems, its deployment for IoT is still lacking. In this paper, we propose a generic MTD framework suitable for IoT systems: IANVS (pronounced Janus). Our framework has a modular design. Its components can be adapted according to the specific constraints and requirements of a particular IoT system. We use it to instantiate two concrete MTD strategies. One that targets the UDP port numbers (port-hopping), and another a CoAP resource URI. We implement our proposal on real hardware using Pycom LoPy4 nodes. We expose the nodes to a remote Denial-of-Service attack and evaluate the effectiveness of the IANVS-based port-hopping MTD proposal.
Published: 2020
Full Text: View/download PDF

42. A New Drug–Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study

Author: Jean Louis Montastruc, Pierre-Louis Toutain, Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and The Royal Veterinary College
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), endocrine system diseases, Pneumonia, Viral, Toxicology, 030226 pharmacology & pharmacy, 03 medical and health sciences, Betacoronavirus, Pharmacovigilance, 0302 clinical medicine, Pharmacotherapy, Internal medicine, Medicine, Adverse Drug Reaction Reporting Systems, Humans, Hypoglycemic Agents, Pharmacology (medical), Drug Interactions, 030212 general & internal medicine, Original Research Article, Pandemics, ComputingMilieux_MISCELLANEOUS, Pharmacology, business.industry, SARS-CoV-2, nutritional and metabolic diseases, COVID-19, Hydroxychloroquine, Odds ratio, Middle Aged, Confidence interval, Metformin, 3. Good health, Toxicity, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Drug Therapy, Combination, Female, business, Coronavirus Infections, medicine.drug
Abstract: Introduction Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. Objective The present study was undertaken to investigate the reality of this putative drug–drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. Methods Using VigiBase®, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. Results Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as ‘fatal outcomes’. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9–139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6–13.8). Conclusion Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.
Published: 2020
Full Text: View/download PDF

43. Psychosocial Impact of Predictive Genetic Testing in Hereditary Heart Diseases: The PREDICT Study

Author: Elise Schaefer, Delphine Dupin Deguine, C. Rouzier, Estelle Gandjbakhch, Krystelle Séné, Claire Cécile Michon, Marie Lise Babonneau, Philippe Charron, Caroline Sawka, Bertrand Isidor, Jean François Pruny, Mélanie Hebert, Stéphanie Staraci, Isabelle Denjoy, Caroline Rooryck-Thambo, Ibticem Raji, Rafik Mansouri, Aurélien Palmyre, Linda Akloul, Sandrine Brice, Annick Toutain, Sophie Tezenas du Montcel, Angelique Curjol, Carole Maupain, Gipsy Billy, Céline Bordet, Alexandre Moerman, Pascale Richard, Marcela Gargiulo, Véronique Fressart, Elsa Le Boette, Flavie Ader, Bruno Leheup, Marc Planes, Karine Nguyen, A.C. Brehin, Jean Michael Mazzella, Amine Bekhechi, Service de Génétique Cytogénétique et Embryologie [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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Ambroise Paré [AP-HP], Service de Génétique Médicale [Lille], Institut de génétique médicale-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, CHU Pontchaillou [Rennes], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), CHU Rouen, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux], CHU Strasbourg, 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), CHU Toulouse [Toulouse], 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), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Pointe-à-Pitre/Abymes [Guadeloupe], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU de Saint-Brieuc, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Paris - UFR Pharmacie [Santé] (UP UFR Pharmacie), Université de Paris (UP), Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Nice Sophia Antipolis (1965 - 2019) (UNS), UFR Pharmacie [Santé] - Université Paris Cité (UFR Pharmacie UPCité), and Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, cardiomyopathies, medicine.medical_specialty, lcsh:Medicine, 030204 cardiovascular system & hematology, 030105 genetics & heredity, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, History of depression, Medicine, Prospective cohort study, predictive genetic testing, Genetic testing, hereditary heart diseases, medicine.diagnostic_test, business.industry, lcsh:R, distress, Retrospective cohort study, social, General Medicine, anxiety, Family life, 3. Good health, Distress, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Anxiety, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, psychological, medicine.symptom, business, Psychosocial
Abstract: Predictive genetic testing (PGT) is offered to asymptomatic relatives at risk of hereditary heart disease, but the impact of result disclosure has been little studied. We evaluated the psychosocial impacts of PGT in hereditary heart disease, using self-report questionnaires (including the State-Trait Anxiety Inventory) in 517 adults, administered three times to the prospective cohort (PCo: n = 264) and once to the retrospective cohort (RCo: n = 253). The main motivations for undergoing PGT were &ldquo, to remove doubt&rdquo, and &ldquo, for their children&rdquo, The level of anxiety increased between pre-test and result appointments (p &lt, 0.0001), returned to baseline after the result (PCo), and was moderately elevated at 4.4 years (RCo). Subjects with a history of depression or with high baseline anxiety were more likely to develop anxiety after PGT result (p = 0.004 and p &lt, 0.0001, respectively), whatever it was. Unfavourable changes in professional and/or family life were observed in 12.4% (PCo) and 18.7% (RCo) of subjects. Few regrets about PGT were expressed (0.8% RCo, 2.3% PCo). Medical benefit was not the main motivation, which emphasises the role of pre/post-test counselling. When PGT was performed by expert teams, the negative impact was modest, but careful management is required in specific categories of subjects, whatever the genetic test result.
Published: 2020
Full Text: View/download PDF

44. CytoProcessorTM: A New Cervical Cancer Screening System for Remote Diagnosis

Author: Matthieu Toutain, Joëlle Depardon, Arnaud Renouf, Incarnation Garcia, Romain Brixtel, Carole Ferreri, Yann Caillot, Cyril Bazin, François Saunier, Marie-Claire Mathieu, Elizabeth Faris Crowell, Jérôme Vaussanvin, and Boris Lesner
Subjects: medicine.medical_specialty, education.field_of_study, Histology, Cervical screening, business.industry, Population, Digital pathology, Papanicolaou stain, General Medicine, Papanicolaou Test, 030224 pathology, medicine.disease, Pathology and Forensic Medicine, 03 medical and health sciences, Squamous intraepithelial lesion, 0302 clinical medicine, 030220 oncology & carcinogenesis, Medicine, Radiology, Medical diagnosis, business, education, Virtual slide
Abstract: Background: Current automated cervical cytology screening systems still heavily depend on manipulation of glass slides. We developed a new system called CytoProcessorTM (DATEXIM, Caen, France), which increases sensitivity and takes advantage of virtual slide technology to simplify the workflow and save worker time. We used an approach based on artificial intelligence to identify abnormal cells among the tens of thousands in a cervical preparation. Objectives: We set out to compare the diagnostic sensitivity and specificity of CytoProcessorTM and the ThinPrep Imaging System (HOLOGIC, Marlborough, MA, USA). Methods: A representative population of 1,352 cases was selected from the routine workflow in a private laboratory. Diagnoses were established using the ThinPrep Imaging System and CytoProcessorTM. All discordances were resolved by a consensus committee. Results: Compared to the ThinPrep Imaging System, CytoProcessorTM significantly improves diagnostic sensitivity without compromising specificity. The sensitivity of detection of “atypical squamous cells of undetermined significance (ASC-US) and more severe” and “low-grade squamous intraepithelial lesion and more severe” was significantly higher using CytoProcessorTM. Considering that cases with a truth diagnosis of ASC-US or more severe required clinical follow-up, 1.5% of the cases (21/1,360) would have been missed if the CytoProcessorTM diagnosis had been used for clinical decision-making. In contrast, 4% of the cases (54/1,360) were missed when the ThinPrep Imaging System diagnosis was used for clinical decision-making. There were 2.6 times fewer false negatives using CytoProcessorTM. The CytoProcessorTM workflow was 1.5 times faster in terms of worker time. Conclusions: CytoProcessorTM is the first of a new generation of automated screening systems, demonstrating improved sensitivity and yielding significant gains in processing time. In addition, the fully digital nature of slide presentation in CytoProcessorTM allows the remote diagnosis of Papanicolaou tests for the first time.
Published: 2019
Full Text: View/download PDF

45. [Adenoviral respiratory diseases in healthy children: a study of 116 hospital cases]

Author: N Bach, J. Brouard, A. Vabret, Duhamel Jf, F. Freymuth, and F. Toutain
Subjects: medicine.medical_specialty, Article, Internal medicine, medicine, pneumonia, Pharmacology (medical), enfant, child, Bacterial disease, business.industry, Viral culture, Respiratory infection, Common cold, adenovirus, medicine.disease, infant, nourrisson, Pneumonia, bronchiolite, Infectious Diseases, Bronchiolitis, pneumopathie, Croup, bronchiolitis, adénovirus, Infection, business, Meningitis
Abstract: Résumé Les adénovirus sont une cause commune d’atteinte respiratoire ; bien que dépendant du sérotype, ils peuvent également être la cause d’atteintes extrarespiratoires. Le diagnostic positif peut en être difficile. Les résultats cliniques chez 116 enfants hospitalisés en raison d’une infection adénovirale ont été repris rétrospectivement. Chez 71 enfants, le diagnostic virologique a été obtenu par immunofluorescence directe sur les aspirations nasales, 71 par culture virale de ces mêmes prélèvements. Le tableau clinique de l’infection adénovirale est caractérisé par une fièvre élevée (moyenne 39°1C) et prolongée (durée moyenne 4,3 jours). L’atteinte des voies aériennes supérieures (rhinopharyngite, angine, otite) et des voies aériennes inférieures (bronchite, bronchiolite, pneumopathie) sont les plus fréquentes. Douze enfants ont présenté des convulsions hyperpyrétiques, 6 avaient une méningite lymphocytaire. Les examens complémentaires ont objectivé des valeurs allant de la normalité à celles évocatrices d’infection bactérienne. Cinquante-neuf enfants furent adressés pour fièvre résistante à une antibiothérapie. Les symptômes de l’atteinte respiratoire dues aux infections adénovirales s’étendent de la rhinite à la pneumopathie et la bronchiolite. Les adénovirus peuvent entraîner des séquelles graves même chez l’enfant sain. Les recherches sur les mécanismes moléculaires de l’infection virale sur les voies aériennes amèneront d’importantes voies de réflexion sur la nature des processus inflammatoires participant à l’asthme et à la bronchite chronique obstructive. La plupart des infections sont modérées et ne nécessitent qu’un traitement symptomatique. Il n’existe pas actuellement de traitement antiviral efficace pour les infections adénovirales graves. Le diagnostic virologique rapide par l’étude des sécrétions nasopharyngées est d’une grande utilité clinique.
Published: 2020

46. SCHC: Generic Framework for Static Context Header Compression and Fragmentation

Author: Carles Gomez, Laurent Toutain, Juan Carlos Zuniga, Dominique Barthel, and Ana Minaburo
Subjects: LPWAN, Wide area, Computer science, business.industry, Datagram, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, Fragmentation (computing), Data_CODINGANDINFORMATIONTHEORY, business, IPv6, Computer network, Data modeling, Header compression
Abstract: This document defines the Static Context Header Compression (SCHC) framework, which provides both a header compression mechanism and an optional fragmentation mechanism. SCHC has been designed for Low Power Wide Area Networks (LPWAN). SCHC compression is based on a common static context stored both in the LPWAN device and in the network infrastructure side. This document defines a generic header compression mechanism and its application to compress IPv6/UDP headers. This document also specifies an optional fragmentation and reassembly mechanism. It can be used to support the IPv6 MTU requirement over the LPWAN technologies. Fragmentation is needed for IPv6 datagrams that, after SCHC compression or when such compression was not possible, still exceed the layer-2 maximum payload size. The SCHC header compression and fragmentation mechanisms are independent of the specific LPWAN technology over which they are used. This document defines generic functionalities and offers flexibility with regard to parameter settings and mechanism choices. This document standardizes the exchange over the LPWAN between two SCHC entities. Settings and choices specific to a technology or a product are expected to be grouped into profiles, which are specified in other documents. Data models for the context and profiles are out of scope.
Published: 2020
Full Text: View/download PDF

47. Interest of chromosomal microarray analysis in the prenatal diagnosis of fetal intrauterine growth restriction

Author: Frederic Coatleven, Didier Lacombe, Caroline Rooryck, Stephanie Brun, Jérôme Toutain, Benoit Arveiler, Perrine Pennamen, Marie Laure Vuillaume, and Aurelien Mattuizzi
Subjects: Adult, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, DNA Copy Number Variations, Karyotype, Population, Intrauterine growth restriction, Prenatal diagnosis, 030105 genetics & heredity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Prenatal Diagnosis, medicine, Humans, Copy-number variation, education, In Situ Hybridization, Fluorescence, reproductive and urinary physiology, Genetics (clinical), Retrospective Studies, Gynecology, Comparative Genomic Hybridization, Fetus, education.field_of_study, Fetal Growth Retardation, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, Obstetrics and Gynecology, Microarray Analysis, medicine.disease, female genital diseases and pregnancy complications, Confidence interval, Karyotyping, embryonic structures, Female, business, Fluorescence in situ hybridization
Abstract: Objective The aim of this study is to evaluate the diagnostic utility of prenatal diagnosis using the chromosomal microarray analysis (CMA) for fetuses presenting with isolated or associated intrauterine growth restriction (IUGR). Method We retrospectively included all fetuses with IUGR referred for prenatal testing and studied by rapid fluorescence in situ hybridization (FISH), karyotype, and CMA. Results Among the 162 IUGR fetuses (78 associated and 84 isolated IUGR) included, 15 had an abnormal FISH result: 10 associated and five isolated fetal IUGRs. Among the 143 fetuses studied by CMA, 10 (7%) presented pathogenic copy number variations (CNVs). All 10 were in the associated fetal IUGR group (10/65 or 15.4%; 95% confidence interval [CI]: 8.4%-26.2%) versus 0/78 in the isolated fetal IUGR group (95% CI: 0%-5.6%). Six fetuses (4.2%) carried variants of unknown significance (VOUS) (three associated and three isolated fetal IUGRs). Conclusion Our study highlights the added value of CMA in the case of associated fetal IUGR with an incremental yield of 6.1% (4/65) over karyotyping. No pathogenic CNVs were reported in the isolated fetal IUGR group. More studies must be conducted to determine when and whether CMA would be wisely indicated in this population.
Published: 2018
Full Text: View/download PDF

48. Bisphenol S instead of Bisphenol A: Toxicokinetic investigations in the ovine materno-feto-placental unit

Author: Hanna Mila, Nicole Picard-Hagen, Marlène Z. Lacroix, Pierre-Louis Toutain, Glenn Gauderat, Véronique Gayrard, Flore C. Grandin, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Innovations Thérapeutiques et Résistances (InTheRes), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: 0301 basic medicine, Male, Bisphenol A, Bisphenol S, [SDV]Life Sciences [q-bio], Placenta, Urine, 010501 environmental sciences, Endocrine Disruptors, Fetal exposure, urologic and male genital diseases, 01 natural sciences, chemistry.chemical_compound, Bisphenol S Glucuronide, Pregnancy, Bisphenol A analogue, Sulfones, Maternal-Fetal Exchange, lcsh:Environmental sciences, General Environmental Science, lcsh:GE1-350, Compartment (chemistry), Toxicokinetic, 3. Good health, Toxicokinetics, embryonic structures, Female, hormones, hormone substitutes, and hormone antagonists, endocrine system, Andrology, 03 medical and health sciences, Fetus, Glucuronides, Phenols, medicine, Animals, Humans, Benzhydryl Compounds, 0105 earth and related environmental sciences, Sheep, business.industry, medicine.disease, 030104 developmental biology, chemistry, business
Abstract: Bisphenol S (BPS) is widely used as a substitute for Bisphenol A in consumer products. Despite its potential endocrine-disrupting effects and widespread exposure, toxicokinetic data, particularly during the critical period of pregnancy, are not available for BPS. The objectives of our study were to evaluate the mechanisms determining fetal exposure to BPS and to BPS glucuronide (BPSG) and to compare them with those prevailing for BPA.The disposition of BPS and BPSG was evaluated in the materno-fetal unit of the catheterized pregnant ewe model, following intravenous administrations of BPS and BPSG to mothers and their fetuses. In a second experiment, the rate of BPS accumulation in the fetal compartment was determined under steady-state conditions after repeated intravenous BPS administrations to the mother.In the maternal compartment, BPS was mainly metabolized into BPSG and totally eliminated in urine. Only 0.40% of the maternal dose was transferred to the fetus. However, once in the fetal compartment, 26% of the fetal dose was rapidly eliminated through placental transfer, while 46% of BPS was metabolized into BPSG which remained trapped in the fetal compartment. Thus, the elimination of BPSG from the fetal compartment required its back-conversion into bioactive BPS, leading to an 87% enhancement of the fetal BPS exposure.Our findings demonstrate that, despite the low materno-fetal placental transfer of BPS, this substitute for BPA is able to accumulate in the fetal compartment after repeated maternal exposure, leading to chronic fetal exposure to BPS in a range of concentrations similar to those of BPA. Keywords: Bisphenol S, Bisphenol S Glucuronide, Toxicokinetic, Fetal exposure, Bisphenol A analogue
Published: 2018
Full Text: View/download PDF

49. Scabies in an obese patient: How should the ivermectin dosing be adapted?

Author: Guillaume Mellon, A Lespine, P L Toutain, Anne Dulioust, L. Hermet, Etablissement Public de Santé National de Fresnes, Partenaires INRAE, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Innovations Thérapeutiques et Résistances (InTheRes), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: medicine.medical_specialty, Ivermectin, Ivermectine, business.industry, [SDV]Life Sciences [q-bio], medicine.disease, 030226 pharmacology & pharmacy, Dermatology, Gale, Patients obèses, Scabies, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, medicine, 030212 general & internal medicine, Dosing, Obese patients, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience
Published: 2019
Full Text: View/download PDF

50. Hybrid rectenna and monolithic integrated zero-bias microwave rectifier

Author: Zbitou, Jamal, Latrach, Mohamed, and Toutain, Serge
Subjects: Microwave antennas -- Design and construction, Diodes, Schottky-barrier -- Design and construction, Microwave integrated circuits -- Design and construction, Business, Computers, Electronics, Electronics and electrical industries
Abstract: In this study, we have developed a hybrid sensitive rectenna (rectifier + antenna) system at 2.45 GHz. To achieve this system, we have first optimized and validated a zero-bias microwave sensitive rectifier using commercial Schottky diodes. We have then optimized and achieved a 2 x 2 patch antenna array, which is associated to the microwave rectifier in order to validate the rectenna system, where an RF-dc conversion efficiency of 56% has been observed experimentally. In order to minimize the rectenna dimensions, we have conducted a study using the OMMIC ED02AH 0.20-[micro]m GaAs pseudomorphic high electron-mobility transistor process to develop and achieve a monolithic rectifier at 2.45 GHz with RF-dc conversion efficiency of 65%. Index Terms--Monolithic microwave rectifier, rectenna, rectifier, Schottky diode, wireless power transmission.
Published: 2006

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

607 results on '"A, Toutain"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources