Search

Your search keyword '"Universität Ulm - Ulm University [Ulm, Allemagne]"' showing total 115 results
Start Over Author "Universität Ulm - Ulm University [Ulm, Allemagne]" Topic business.industry
115 results on '"Universität Ulm - Ulm University [Ulm, Allemagne]"'

1. Cardiac and metabolic effects of hypothermia and inhaled hydrogen sulfide in anesthetized and ventilated mice*

Author

Csaba Szabó, Michael Gröger, Pierre Asfar, Sandra Weber, Gerd Albuszies, Eberhard Barth, Vladislava Simkova, Josef Vogt, Michael K. Georgieff, Katja Baumgart, Florian Wagner, Markus W. Knöferl, Enrico Calzia, Peter Radermacher, Markus Huber-Lang, Ulrich Wachter, Universitätsklinikum Ulm - University Hospital of Ulm, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinikum, Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery [Ulm, Germany], Universität Ulm - Ulm University [Ulm, Allemagne]-Center of Surgery [Ulm, Germany], Departement of Anaesthesiology [Ulm, Germany], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Lithosphere Fluid Research Lab, Eötvös Loránd University (ELTE), and Universität Ulm - Ulm University [Ulm, Allemagne]

Subjects
Male, Resuscitation, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Hydrogen sulfide, Cell Respiration, Blood Pressure, Critical Care and Intensive Care Medicine, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Heart Rate, Hypothermia, Induced, Intensive care, Administration, Inhalation, medicine, Animals, Anesthesia, Hydrogen Sulfide, Cardiac Output, 030304 developmental biology, Mechanical ventilation, 0303 health sciences, Inhalation, business.industry, Heart, Stroke Volume, 030208 emergency & critical care medicine, Hypothermia, Respiration, Artificial, 3. Good health, Cardiovascular physiology, Mice, Inbred C57BL, Oxidative Stress, Glucose, chemistry, Circulatory system, medicine.symptom, business, Oxidation-Reduction
Abstract

International audience; Objective: To test the hypothesis whether inhaled hydrogen sulfide amplifies the effects of deliberate hypothermia during anesthesia and mechanical ventilation as hypothermia is used to provide organ protection after brain trauma or circulatory arrest. Awake mice inhaling hydrogen sulfide exhibit reduced energy expenditure, hypothermia, and bradycardia despite unchanged systolic heart function. In rodents, anesthesia alone causes decreased metabolic rate and thus hypothermia and bradycardia.Design: Prospective, controlled, randomized study. Setting: University animal research laboratory. Subjects: Male C57/B6 mice. Interventions: After surgical instrumentation (central venous, left ventricular pressure-conductance catheters, ultrasound flow probes on the portal vein and superior mesenteric artery), normo- or hypothermic animals (core temperature = 38°C and 27°C) received either 100 ppm hydrogen sulfide or vehicle over 5 hrs (3 hrs hydrogen sulfide during normothermia). Measurements and Main Results: During normothermia, hydrogen sulfide had no hemodynamic or metabolic effect. With or without hydrogen sulfide, hypothermia decreased blood pressure, heart rate, and cardiac output, whereas stroke volume, ejection fraction, and end-diastolic pressure remained unaffected. Myocardial and hepatic oxidative deoxyribonucleic acid damage (comet assay) and endogenous glucose production (rate of appearance of 1,2,3,4,5,6-13C6-glucose) were similar in all groups. Hypothermia comparably decreased CO2 production with or without inhaled hydrogen sulfide. During hypothermia, inhaled hydrogen sulfide increased the glucose oxidation rate (derived from the expiratory 13CO2/12CO2 ratio). This shift toward preferential carbohydrate utilization coincided with a significantly attenuated responsiveness of hepatic mitochondrial respiration to stimulation with exogenous cytochrome-c-oxidase (high-resolution respirometry). Conclusions: In anesthetized and mechanically ventilated mice, inhaled hydrogen sulfide did not amplify the systemic hemodynamic and cardiac effects of hypothermia alone. The increased aerobic glucose oxidation together with the reduced responsiveness of cellular respiration to exogenous cytochrome-c stimulation suggest that, during hypothermia, inhaled hydrogen sulfide improved the yield of mitochondrial respiration, possibly via the maintenance of mitochondrial integrity. Hence, inhaled hydrogen sulfide may offer metabolic benefit during therapeutic hypothermia.

Published
2010

2. Hyperoxia During Septic Shock—Dr. Jekyll or Mr. Hyde?

Author

Markus Huber-Lang, Enrico Calzia, Anita Ignatius, Peter Radermacher, Pierre Asfar, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Universität Ulm - Ulm University [Ulm, Allemagne], Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery [Ulm, Germany], Universität Ulm - Ulm University [Ulm, Allemagne]-Center of Surgery [Ulm, Germany], Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, and Universitatsklinikum

Subjects
Hyperoxia, Male, business.industry, Septic shock, [SDV]Life Sciences [q-bio], Ischemia, 030208 emergency & critical care medicine, Pneumonia, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, Sepsis, Oxygen, 03 medical and health sciences, 0302 clinical medicine, Anesthesia, Emergency Medicine, medicine, Animals, medicine.symptom, business, Lung, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2012

3. Cardiopulmonary, Histologic, and Inflammatory Effects of Intravenous Na2S After Blunt Chest Trauma-Induced Lung Contusion in Mice

Author

Bettina Stahl, Daniel H. Seitz, Peter Radermacher, Florian Gebhard, Csaba Szabó, Angelika Scheuerle, Sandra Weber, Markus W. Knöferl, Peter Möller, Michael Georgieff, Katja Wagner, Jörg Thomas, Pierre Asfar, Markus Huber-Lang, Enrico Calzia, Oscar McCook, Florian Wagner, Universitätsklinikum Ulm - University Hospital of Ulm, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinikum, Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery [Ulm, Germany], Universität Ulm - Ulm University [Ulm, Allemagne]-Center of Surgery [Ulm, Germany], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Department of Algebra and Number Theory [Budapest], Eötvös Loránd University (ELTE), Universität Ulm - Ulm University [Ulm, Allemagne], and Departement of Anaesthesiology [Ulm, Germany]

Subjects
Male, medicine.medical_specialty, Pathology, Sulfide, [SDV]Life Sciences [q-bio], Blotting, Western, Inflammation, Sulfides, Lung injury, Wounds, Nonpenetrating, Critical Care and Intensive Care Medicine, medicine.disease_cause, Sensitivity and Specificity, Mice, Random Allocation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Infusions, Intravenous, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Lung, biology, Pulmonary Gas Exchange, business.industry, Hemodynamics, 030208 emergency & critical care medicine, Metabolic acidosis, Lung Injury, Hypothermia, medicine.disease, Immunohistochemistry, Cystathionine beta synthase, Mice, Inbred C57BL, Disease Models, Animal, Oxidative Stress, Endocrinology, medicine.anatomical_structure, chemistry, Respiratory Mechanics, biology.protein, Cytokines, Surgery, medicine.symptom, business, Oxidative stress
Abstract

International audience; Background: When used as a pretreatment, hydrogen sulfide (H2S) either attenuated or aggravated lung injury. Therefore, we tested the hypothesis whether posttreatment intravenous Na2S (sulfide) may attenuate lung injury.Methods: After blast wave blunt chest trauma or sham procedure, anesthetized and instrumented mice received continuous intravenous sulfide or vehicle while being kept at 37°C or 32°C core temperature. After 4 hours of pressure-controlled, thoracopulmonary compliance-titrated, lung-protective mechanical ventilation, blood and tissue were harvested for cytokine concentrations, heme oxygenase-1, IκBα, Bcl-Xl, and pBad expression (western blotting), nuclear factor-κB activation (electrophoretic mobility shift assay), and activated caspase-3, cystathionine-β synthase and cystathionine-γ lyase (immunohistochemistry). Results: Hypothermia caused marked bradycardia and metabolic acidosis unaltered by sulfide. Chest trauma impaired thoracopulmonary compliance and arterial Po2, again without sulfide effect. Cytokine levels showed inconsistent response. Sulfide increased nuclear factor-κB activation during normothermia, but this effect was blunted during hypothermia. While histologic lung injury was variable, both sulfide and hypothermia attenuated the trauma-related increase in heme oxygenase-1 expression and activated caspase-3 staining, which coincided with increased Bad phosphorylation and Bcl-Xl expression. Sulfide and hypothermia also attenuated the trauma-induced cystathionine-β synthase and cystathionine-γ lyase expression. Conclusions: Posttreatment sulfide infusion after blunt chest trauma did not affect the impaired lung mechanics and gas exchange but attenuated stress protein expression and apoptotic cell death. This protective effect was amplified by moderate hypothermia. The simultaneous reduction in cystathionine-β synthase and cystathionine-γ lyase expression supports the role of H2S-generating enzymes as an adaptive response during stress states.

Published
2011

4. Inflammatory Effects of Hypothermia and Inhaled H2S During Resuscitated, Hyperdynamic Murine Septic Shock

Author

Florian Wagner, Michael K. Georgieff, Markus Huber-Lang, Pierre Asfar, Sandra Weber, Markus W. Knöferl, Florian Gebhard, Katja Wagner, Vladislava Hysa, Enrico Calzia, Daniel H. Seitz, Peter Radermacher, Bettina Stahl, Uwe Senftleben, Universitätsklinikum Ulm - University Hospital of Ulm, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinikum, Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery [Ulm, Germany], Universität Ulm - Ulm University [Ulm, Allemagne]-Center of Surgery [Ulm, Germany], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Universität Ulm - Ulm University [Ulm, Allemagne], and Departement of Anaesthesiology [Ulm, Germany]

Subjects
Male, Chemokine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Electrophoretic Mobility Shift Assay, Hypothermia, Critical Care and Intensive Care Medicine, Sepsis, Mice, 03 medical and health sciences, 0302 clinical medicine, Animals, Chemokine CCL8, Medicine, Hydrogen Sulfide, Chemokine CCL2, 030304 developmental biology, Inflammation, Mechanical ventilation, 0303 health sciences, biology, Interleukin-6, Tumor Necrosis Factor-alpha, business.industry, Septic shock, Hemodynamics, NF-kappa B, 030208 emergency & critical care medicine, medicine.disease, equipment and supplies, Shock, Septic, 3. Good health, Mice, Inbred C57BL, Heme oxygenase, Cytokine, Anesthesia, Shock (circulatory), Emergency Medicine, biology.protein, Chemokines, medicine.symptom, business, Heme Oxygenase-1
Abstract

International audience; Inhaling hydrogen sulfide (H2S) reduced energy expenditure resulting in hypothermia. Because the inflammatory effects of either hypothermia alone or H2S per se still are a matter of debate, we tested the hypothesis whether inhaled H2S amplifies the hypothermia-related modulation of the inflammatory response. Fifteen hours after cecal ligation and puncture or sham laparotomy, anesthetized and mechanically ventilated normothermic and hypothermic mice (core temperature kept at 38°C and 27°C, respectively) received either 100 ppm H2S or vehicle. In the sham-operated animals, inhaled H2S and hypothermia alone comparably reduced the plasma chemokine and IL-6 levels, but combining hypothermia and inhaled H2S had no additional effect. The lung tissue cytokine and chemokine patterns revealed a similar response. During sepsis, inhaled H2S reduced the blood cytokine concentrations only, without effects on the plasma chemokine or the lung tissue levels. Again, inhaled H2S had no major additional effect during hypothermia. With or without sepsis, inhaled H2S and hypothermia alone comparably reduced the lung tissue heme oxygenase 1 expression, whereas inhaled H2S had no additional effect during hypothermia. Lung tissue nuclear transcription factor κB activation was reduced by combining H2S with hypothermia in the sham-operated animals, whereas it was increased by inhaled H2S during sepsis. Hypothermia amplified this response. Hence, during anesthesia and mechanical ventilation, inhaled H2S exerted anti-inflammatory effects, which were, however, not amplified by adding deliberate hypothermia. Sepsis attenuated these anti-inflammatory effects of inhaled H2S, which were at least in part independent of the nuclear transcription factor κB pathway.

Published
2011

5. What Is the Future of Modeling?

Author

Massimo Tisi, Matthias Tichy, Leen Lambers, Antonio Bucchiarone, Alfonso Pierantonio, Federico Ciccozzi, Andreas Wortmann, Vadim Zaytsev, Formal Methods and Tools, Fondazione Bruno Kessler [Trento, Italy] (FBK), Mälardalen University (MDH), University of Potsdam = Universität Potsdam, Università degli Studi dell'Aquila = University of L'Aquila (UNIVAQ), Universität Ulm - Ulm University [Ulm, Allemagne], Département Automatique, Productique et Informatique (IMT Atlantique - DAPI), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), NaoMod - Nantes Software Modeling Group (LS2N - équipe NaoMod), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), and University of Twente

Subjects
Research Roadmap, [INFO.INFO-PL]Computer Science [cs]/Programming Languages [cs.PL], Modeling language, business.industry, Computer science, 020207 software engineering, [INFO.INFO-SE]Computer Science [cs]/Software Engineering [cs.SE], 02 engineering and technology, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Software Modelling, [INFO.INFO-FL]Computer Science [cs]/Formal Languages and Automata Theory [cs.FL], 0202 electrical engineering, electronic engineering, information engineering, Key (cryptography), Success Stories, Model-driven architecture, Software engineering, business, computer, Software, computer.programming_language
Abstract

International audience; Modelling languages and frameworks have been the key technology for advancing Model-Driven Engineering (MDE) methods and tools. Many industrial and research tools have been realised and are used across many domains. Hence, we think it is the right time to define what should be the future of modelling technologies, especially the requirements for the next generation of modelling frameworks and languages. In January 2020, the Second Winter Modelling Meeting (WMM2020) was held in San Vigilio di Marebbe (Italy), focusing on the analysis of the state of research, state of practice, and state of the art in MDE. The event brought together experts from industry, academia, and the open-source community to assess (i) what had changed in research on modelling in the last ten years, (ii) which problems are still unsolved, and (iii) which new challenges have arisen. This article presents a set of success stories and driving success factors of modelling and MDE, as well as a set of challenges and corresponding research directions that emerged from the synthesis of the results of our analysis.

Published
2021

6. Clinical activity of abemaciclib in patients with relapsed or refractory mantle cell lymphoma - a phase II study

Author

Sophie de Guibert, P. Kellie Turner, Kamal Bouabdallah, Catherine Thieblemont, Florian Zettl, Siva Rama Prasad Kambhampati, Franck Morschhauser, Li Li, Sean Buchanan, Stephan Stilgenbauer, Lily Q. Li, Susana Barriga, Lawrence M. Gelbert, Martin Wilhelm, Georg Hess, Melissa M. Bear, Hôpital Claude Huriez [Lille], CHU Lille, CHU Bordeaux [Bordeaux], Universität Ulm - Ulm University [Ulm, Allemagne], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Georg-August-University [Göttingen], LMG PharmaTech, Eli Lilly and Company [Indianapolis], Klinikum Nürnberg Nord, Johannes Gutenberg - Universität Mainz (JGU), Georg-August-University = Georg-August-Universität Göttingen, and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)

Subjects
Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Treatment outcome, Phases of clinical research, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Text mining, Internal medicine, medicine, In patient, Letters to the Editor, Abemaciclib, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Mantle cell lymphoma, business.industry, non-Hodgkin lymphoma, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, 3. Good health, Lymphoma, Clinical trial, chemistry, 030220 oncology & carcinogenesis, Refractory Mantle Cell Lymphoma, CDK4 and 6 inhibitor, business
Abstract

International audience

Published
2020

7. Magnetic resonance spectroscopy in the rodent brain: Experts' consensus recommendations

Author

Bernard Lanz, Firat Kara, Volker Rasche, Cristina Cudalbu, Phil Lee, In-Young Choi, Lijing Xin, Pierre Gilles Henry, Vladimir Mlynarik, Małgorzata Marjańska, Norbert W. Lutz, Kejal Kantarci, Rolf Gruetter, Julien Valette, Olivier Braissant, Alireza Abaei, Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), University of Kansas Medical Center [Kansas City, KS, USA], Mayo Clinic, Aix Marseille Université (AMU), Medizinische Universität Wien = Medical University of Vienna, Universität Ulm - Ulm University [Ulm, Allemagne], University of Minnesota Medical School, University of Minnesota System, and Université Paris-Sud - Paris 11 (UP11)

Subjects
[SDV]Life Sciences [q-bio], vivo h-1-nmr spectroscopy, anesthesia, consensus review, neurochemical profile, in-vivo, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, rat-brain, dynamic mrs, Medicine, Radiology, Nuclear Medicine and imaging, preclinical mrs, Spectroscopy, pentobarbital sleeping time, relaxation-times, c-13 nmr-spectroscopy, single-shot localization, business.industry, Rat brain, Proton mr spectroscopy, brain metabolism, proton mr spectroscopy, Molecular Medicine, central-nervous-system, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

In vivo MRS is a non-invasive measurement technique used not only in humans, but also in animal models using high-field magnets. MRS enables the measurement of metabolite concentrations as well as metabolic rates and their modifications in healthy animals and disease models. Such data open the way to a deeper understanding of the underlying biochemistry, related disturbances and mechanisms taking place during or prior to symptoms and tissue changes. In this work, we focus on the main preclinical (1)H, (31)P and (13)C MRS approaches to study brain metabolism in rodent models, with the aim of providing general experts’ consensus recommendations (animal models, anesthesia, data acquisition protocols). An overview of the main practical differences in preclinical compared with clinical MRS studies is presented, as well as the additional biochemical information that can be obtained in animal models in terms of metabolite concentrations and metabolic flux measurements. The properties of high-field preclinical MRS and the technical limitations are also described.

Published
2021

8. Visual pursuit biases tactile velocity perception

Author

Thies Pfeiffer, Alessandro Moscatelli, Marc O. Ernst, Cécile R Scotto, Centre de Recherches sur la Cognition et l'Apprentissage (CeRCA), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université de Poitiers, University of Roma Tor Vegata, Cognitive Interaction Technology [Bielefeld] (CITEC), Universität Bielefeld = Bielefeld University, Institute of Communications Engineering [Ulm] (INT - University of Ulm.), Universität Ulm - Ulm University [Ulm, Allemagne], and Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Physiology, media_common.quotation_subject, Illusion, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, Motion Perception, Settore BIO/09, 050105 experimental psychology, Smooth pursuit, Motion (physics), Fingers, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Perception, Humans, 0501 psychology and cognitive sciences, Computer vision, Motion perception, Reliability (statistics), Haptic technology, media_common, Movement (music), business.industry, General Neuroscience, 05 social sciences, Pursuit, Smooth, Touch Perception, Touch, Female, Artificial intelligence, Psychology, business, 030217 neurology & neurosurgery, Psychomotor Performance
Abstract

International audience; The study showed that smooth pursuit eye movement produces a bias in tactile motion perception. This phenomenon is modulated by the reliability of the tactile estimate and by the presence of a visual background, in line with the predictions of the Bayesian framework of motion perception. Overall, these results support the hypothesis of shared representations for motion perception.

Published
2021

9. Arithmetic, Geometry, Cryptography and Coding Theory

Author

Stéphane Ballet, Gaetan Bisson, Irene I. Bouw, Laboratoire de Géométrie Algébrique et Applications à la Théorie de l'Information (GAATI), Université de la Polynésie Française (UPF), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Universität Ulm - Ulm University [Ulm, Allemagne], and Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)

Subjects
Algorithmic complexity, Computer science, business.industry, Geometry, Cryptography, Field (mathematics), Coding theory, Algebraic geometry, [MATH.MATH-AG]Mathematics [math]/Algebraic Geometry [math.AG], Arithmetic, business
Abstract

International audience; This volume contains the proceedings of the 17th International Conference on Arithmetic, Geometry, Cryptography and Coding Theory (AGC2T-17), held from June 10–14, 2019, at the Centre International de Rencontres Mathématiques in Marseille, France. The conference was dedicated to the memory of Gilles Lachaud, one of the founding fathers of the AGC2T series.Since the first meeting in 1987 the biennial AGC2T meetings have brought together the leading experts on arithmetic and algebraic geometry, and the connections to coding theory, cryptography, and algorithmic complexity. This volume highlights important new developments in the field.

Published
2021

10. Foreword to the Special Issue on Configurable Systems

Author

Laurence Duchien, Thomas Thüm, Paul Grünbacher, Self-adaptation for distributed services and large software systems (SPIRALS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institute of Software Systems Engineering, Johannes Kepler University Linz [Linz] (JKU), Institute of Software Engineering and Programming Languages, Universität Ulm - Ulm University [Ulm, Allemagne], and Johannes Kepler Universität Linz - Johannes Kepler University Linz [Autriche] (JKU)

Subjects
Knowledge representation and reasoning, business.industry, Computer science, Context (language use), Artifact (software development), [INFO.INFO-SE]Computer Science [cs]/Software Engineering [cs.SE], Personalization, Software, Empirical research, Software deployment, Component (UML), [INFO]Computer Science [cs], Software engineering, business
Abstract

International audience; Welcome to this special issue that includes empirical studies on configurable systems. This special issue in the Empirical Software Engineering journal is intended to provide the systems and software product lines community with a valuable collection of high-quality research articles that explore configurable systems with empirical studies. Particular attention was paid to research and industrial work carrying out experiments on configuration steps in the life cycle of system and software product lines. A configurable system is an artifact composed from instances of a set of predefined component types that can be composed and parameterized. The configuration step requires knowledge representation formalisms to capture variety and complexity of configurable products, but also acquisition methods and efficient reasoning algorithms for supporting solution search, to represent, and integrate user settings, personalization, and optimization. The configuration ends with the deployment and launches execution steps. This configuration can also change over time, because of a change of context. This is called reconfiguration. The majority of articles extend research presented at SPLC, the 23rd International Systems and Software Product Lines Conference. The conference was held from September 9 to 13, 2019 in Paris, France [1]. We received seventeen articles for this special issue. The call was open, but the SPLC 2019 authors were encouraged to prepare a revised and substantially extended version, and to consider as possible extensions additional practical applications determined by case studies or experiences, empirical validations, systematic comparisons with other approaches, or sound theoretical foundations. The submitted manuscripts were each peer reviewed by three reviewers. Finally, ten papers were accepted for inclusion in this special issue and six of them were extended versions of the SPLC 2019 research papers.

Published
2021

11. Shared-Dining: Broadcasting Secret Shares Using Dining-Cryptographers Groups

Author

Juri Dispan, David Mödinger, Franz J. Hauck, Institute of Distributed Systems, Universität Ulm - Ulm University [Ulm, Allemagne], Miguel Matos, Fabíola Greve, TC 6, and WG 6.1

Subjects
FOS: Computer and information sciences, 050101 languages & linguistics, Security analysis, Dining cryptographers problem, Computer Science - Cryptography and Security, Computer science, Throughput, 02 engineering and technology, Broadcasting, Computer security, computer.software_genre, Secret sharing, Computer Science - Networking and Internet Architecture, [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], Privacy protocol, 0202 electrical engineering, electronic engineering, information engineering, 0501 psychology and cognitive sciences, [INFO]Computer Science [cs], Communication source, Network protocol, Peer-to-Peer networking, Networking and Internet Architecture (cs.NI), business.industry, 05 social sciences, Flooding (computer networking), Dining cryptographers, 020201 artificial intelligence & image processing, business, computer, Cryptography and Security (cs.CR), Anonymity
Abstract

A k-anonymous broadcast can be implemented using a small group of dining cryptographers to first share the message, followed by a flooding phase started by group members. Members have little incentive to forward the message in a timely manner, as forwarding incurs costs, or they may even profit from keeping the message. In worst case, this leaves the true originator as the only sender, rendering the dining-cryptographers phase useless and compromising their privacy. We present a novel approach using a modified dining-cryptographers protocol to distributed shares of an (n,k)-Shamir's secret sharing scheme. Finally, all group members broadcast their received share through the network, allowing any recipient of k shares to reconstruct the message, enforcing anonymity. If less than k group members broadcast their shares, the message cannot be decoded thus preventing privacy breaches for the originator. Our system provides (n-|attackers|)-anonymity for up to k-1 attackers and has little performance impact on dissemination. We show these results in a security analysis and performance evaluation based on a proof-of-concept prototype. Throughput rates between 10 and 100 kB/s are enough for many real applications with high privacy requirements, e.g., financial blockchain system., 16 pages, 5 figures

Published
2021

12. Prevalence of malnutrition using harmonized definitions in older adults from different settings – A MaNuEL study

Author

Wolters, Maike, Volkert, Dorothee, Streicher, Melanie, Kiesswetter, Eva, Torbahn, Gabriel, O’Connor, Eibhlís M., O’keeffe, Mary, Kelly, Mary, O’herlihy, Eileen, O’Toole, Paul W., Timmons, Suzanne, O’Shea, Emma, Kearney, Patricia, van Zwienen-Pot, Judith, Visser, Marjolein, Maître, Isabelle, Van Wymelbeke, Virginie, Sulmont-Rossé, Claire, Nagel, Gabriele, Flechtner Mors, Marion, Goisser, Sabine, Teh, Ruth, Hebestreit, Antje, on behalf of the MaNuEL consortium, ., Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University of Limerick (UL), University College Cork (UCC), VU University Medical Center [Amsterdam], VU University Amsterdam, Groupe de Recherche en Agroalimentaire sur les Produits et les Procédés (GRAPPE), Institut National de la Recherche Agronomique (INRA)-Ecole supérieure d'Agricultures d'Angers (ESA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Universität Ulm - Ulm University [Ulm, Allemagne], Heidelberg University, University of Auckland [Auckland], The European Federation of the Associations of Dietitians, Partenaires INRAE, University Hospital, European Union, University of Parma = Università degli studi di Parma [Parme, Italie], The European Nutrition for Health Alliance, Optimal Nutrition Care for All, The European Society for Clinical Nutrition and Metabolism, Projet MalNutrition in the ELderly (MANUEL), Agence Nationale de la Recherche (ANR), German Federal Ministry of Food and Agriculture (BMEL), Department of Agriculture, Food and the Marine, HRB, Nutrition and Health, APH - Aging & Later Life, APH - Societal Participation & Health, APH - Health Behaviors & Chronic Diseases, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Internal medicine, and AGEM - Endocrinology, metabolism and nutrition

Subjects
0301 basic medicine, Male, Mini nutritional assessment, Hospitalized patients, Nutritional Status, Prevalence, Older adults, Elderly, Older people, Malnutrition, 030209 endocrinology & metabolism, Critical Care and Intensive Care Medicine, Affect (psychology), Residential Facilities, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Environmental health, medicine, Humans, SDG 2 - Zero Hunger, Geriatric Assessment, Aged, 2. Zero hunger, Aged, 80 and over, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Mean age, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 16. Peace & justice, medicine.disease, 3. Good health, Cross-Sectional Studies, Nutrition Assessment, Functional status, Female, Nursing homes, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Background & aims: Malnutrition is widespread among older people and related to poor outcome. Reported prevalences vary widely, also because of different diagnostic criteria used. This study aimed to describe prevalences in several populations of older persons in different settings using harmonized definitions. Methods: Available studies within the Joint Programming Initiative (JPI) Knowledge Hub ‘Malnutrition in the Elderly’ (MaNuEL) were used to calculate and compare prevalences of malnutrition indicators: low BMI (2 ; age-specific BMI 2 if age ≥70 years), previous weight loss (WL), moderate and severe decrease in food intake, and combined BMI 2 and/or WL in participants aged ≥65 years. Results: Fifteen samples with in total 5956 participants (59.3% women) were included: 7 consisting of community-dwelling persons, 2 studies in geriatric day hospitals, 3 studies in hospitalized patients and 3 in nursing homes. Mean age of participants ranged between 67 and 87 years. Up to 4.2% of community-dwelling persons had a BMI 2 , 1.6 and 9% of geriatric day hospital patients, 4.5–9.4% of hospital patients and 3.8–18.2% of nursing home residents. Using age-specific cut-offs doubled these prevalences. WL was reported in 2.3–10.5% of community-dwelling persons, 6% and 12.6% of geriatric day hospital patients, 5–14% of hospitalized patients and 4.5–7.7% of nursing home residents. Severe decrease in food intake was recorded in up to 9.6% of community-dwelling persons, 1.5% and 12% of geriatric day hospital patients, 3.4–34.2% of hospitalized patients and 1.5–8.2% of nursing home residents. The criteria age-specific BMI and WL showed opposing prevalences across all settings. Compared to women, low BMI and moderate decrease in food intake showed low prevalences in men but similar prevalences were observed for weight loss and severe decrease in food intake. In half of the study samples, participants in a younger age group had a higher prevalence of WL compared to those of an older age group. Prevalence of BMI 2 and WL at the same time did not exceed 2.6% in all samples. The highest prevalences were observed based on combined definitions when only one of the three criteria had to be present. Conclusions: Prevalences for different criteria vary between and within the settings which might be explained by varying functional status. The criteria used strongly affect prevalence and it may be preferable to look at each criterion separately as each may indicate a nutritional problem.

Published
2019

13. A Model of Spatial Directness in Interactive Visualization

Author

Stefan Bruckner, Alexander Wiebel, Tobias Isenberg, Timo Ropinski, University of Bergen (UiB), Analysis and Visualization (AVIZ), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Universität Ulm - Ulm University [Ulm, Allemagne], and Hochschule Worms University of Applied Sciences

Subjects
business.industry, Computer science, direct interaction, [SCCO.COMP]Cognitive science/Computer science, 020207 software engineering, Usability, Context (language use), 02 engineering and technology, Space (commercial competition), Computer Graphics and Computer-Aided Design, Visualization, human-computer interaction (HCI), Data visualization, Human–computer interaction, Signal Processing, 0202 electrical engineering, electronic engineering, information engineering, Computer Vision and Pattern Recognition, business, Interactive visualization, visualization, Software
Abstract

International audience; We discuss the concept of directness in the context of spatial interaction with visualization. In particular, we propose a model that allows practitioners to analyze and describe the spatial directness of interaction techniques, ultimately to be able to better understand interaction issues that may affect usability. To reach these goals, we distinguish between different types of directness. Each type of directness depends on a particular mapping between different spaces, for which we consider the data space, the visualization space, the output space, the user space, the manipulation space, and the interaction space. In addition to the introduction of the model itself, we also show how to apply it to several real-world interaction scenarios in visualization, and thus discuss the resulting types of spatial directness, without recommending either more direct or more indirect interaction techniques. In particular, we will demonstrate descriptive and evaluative usage of the proposed model, and also briefly discuss its generative usage.

Published
2019

14. Clinical, biological, and molecular genetic features of Richter syndrome and prognostic significance: a study of the French Innovative Leukemia Organization

Author

Reiner Siebert, Anne Quinquenel, Romain Guieze, Catherine Thieblemont, Frederic Davi, Caroline Dartigeas, Sébastien Hergalant, Mathilde Hunault, Florence Cymbalista, Christof Schneider, Marie-Christine Béné, Cécile Tomowiak, Thomas Remen, Kamel Laribi, Damien Roos-Weil, Julien Broséus, Gregory Lazarian, Francis Guillemin, Odile Blanchet, Florian Bouclet, Elise Chapiro, Eugen Tausch, Stephan Stilgenbauer, Sandra Lomazzi, Florence Nguyen-Khac, Pierre Feugier, Charline Moulin, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Reims (CHU Reims), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Ulm - Ulm University [Ulm, Allemagne], Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre de Ressources Biologiques - [Nancy] (CRB Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hergalant, Sébastien, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Richter syndrome, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hematology, medicine.disease, Prognosis, Survival Analysis, 3. Good health, [STAT] Statistics [stat], [STAT]Statistics [stat], Leukemia, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Mutation, Disease Progression, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Lymphoma, Large B-Cell, Diffuse, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business
Abstract

International audience

Published
2021

15. Validating automated segmentation tools in the assessment of caudate atrophy in Huntington's disease

Author

Nicola Z. Hobbs, Alexandra Durr, Bernhard Landwehrmeyer, Raymund A.C. Roos, Nina M. Mansoor, Sarah J. Tabrizi, Eileanoir B. Johnson, Tishok Vanniyasingam, Elin M. Rees, Rachael I. Scahill, Ian B. Malone, University College of London [London] (UCL), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Leiden University Medical Center (LUMC), Universität Ulm - Ulm University [Ulm, Allemagne], Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, medicine.medical_specialty, Jaccard index, Huntington (disease), MALP-EM, [SDV]Life Sciences [q-bio], FreeSurfer, Automated segmentation, Huntington-Chorea, FIRST, lcsh:RC346-429, Hirnstamm, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Physical medicine and rehabilitation, Bildgebendes Verfahren, Huntington's disease, Neuroimaging, medicine, Segmentation, ddc:610, automated segmentation, caudate, lcsh:Neurology. Diseases of the nervous system, Original Research, Brain, Diagnostic imaging, business.industry, Gold standard (test), Huntington disease, medicine.disease, [SDV] Life Sciences [q-bio], 030104 developmental biology, Caudate atrophy, Neurology, Methods, STEPS, Neurology (clinical), Gehirn, business, 030217 neurology & neurosurgery, Software
Abstract

Background: Neuroimaging shows considerable promise in generating sensitive and objective outcome measures for therapeutic trials across a range of neurodegenerative conditions. For volumetric measures the current gold standard is manual delineation, which is unfeasible for samples sizes required for large clinical trials.Methods: Using a cohort of early Huntington’s disease (HD) patients (n = 46) and controls (n = 35), we compared the performance of four automated segmentation tools (FIRST, FreeSurfer, STEPS, MALP-EM) with manual delineation for generating cross-sectional caudate volume, a region known to be vulnerable in HD. We then examined the effect of each of these baseline regions on the ability to detect change over 15 months using the established longitudinal Caudate Boundary Shift Integral (cBSI) method, an automated longitudinal pipeline requiring a baseline caudate region as an input.Results: All tools, except Freesurfer, generated significantly smaller caudate volumes than the manually derived regions. Jaccard indices showed poorer levels of overlap between each automated segmentation and manual delineation in the HD patients compared with controls. Nevertheless, each method was able to demonstrate significant group differences in volume (p < 0.001). STEPS performed best qualitatively as well as quantitively in the baseline analysis. Caudate atrophy measures generated by the cBSI using automated baseline regions were largely consistent with those derived from a manually segmented baseline, with STEPS providing the most robust cBSI values across both control and HD groups.Conclusions: Atrophy measures from the cBSI were relatively robust to differences in baseline segmentation technique, suggesting that fully automated pipelines could be used to generate outcome measures for clinical trials.

Published
2021

16. Cost-effectiveness of low-dose colchicine after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)

Author

François Roubille, Simon Kouz, Jean-Claude Tardif, Marie-Pierre Dubé, Rafael Diaz, Aldo P. Maggioni, Wolfgang Koenig, Marie-Claude Guertin, Fausto J. Pinto, Dominic Mitchell, Michelle Samuel, Lucie Blondeau, Nadia Bouabdallaoui, Habib Gamra, Jean Grégoire, Petr Ostadal, Philippe L. L’Allier, Colin Berry, Ghassan S. Kiwan, Andreas Orfanos, Reda Ibrahim, David D. Waters, Jacques LeLorier, Jose Lopez-Sendon, Mylène Provencher, Paul Khairy, Repositório da Universidade de Lisboa, Montreal Heart Institute - Institut de Cardiologie de Montréal, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Division of Cardiology, Zuckerberg San Francisco General Hospital, Department of Medicine, University of California, San Francisco, USA., Cardiology Department, CHULN, Centro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal, Research Center [Associazione Nazionale Medici Cardiologi Ospedalieri] (ANMCO Research Center), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), Department of General Surgery. Surgical Oncology Unit, Reina Sofía University Hospital, Estudios Clinicos Latinoamerica, Rosario, Argentina, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Department of Internal Medicine II – Cardiology, Universität Ulm - Ulm University [Ulm, Allemagne], University of Ulm (UUlm), Department of Cardiology Cardiovascular Center, NaHomolce Hospital, Prague, Czech Republic, Na Homolce Hospital, Prague, Czech Republic., Cardiology department Hospital Universitario La Paz. UAM. IdiPaz. CIBER-CV, Madrid, Spain, CHU Fattouma Bourguiba [Monastir] (HFB), Bellevue Medical Center, Beirut, Lebanon, Montreal Health Innovations Coordinating Center [Montreal Heart Institute] (MHICC), Institut de Cardiologie et Pneumologie de Québec, Quebec City, Université Laval [Québec] (ULaval), Centre Hospitalier Régional de Lanaudière, Joliette, Canada, Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours, Logimetrix Inc, Canada, Montreal Health Innovation Coordination Center, Montreal Heart Institute Coordinating Centre (MHICC), Université de Montréal (UdeM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT), MORNET, Dominique, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Canada, medicine.medical_specialty, Heart disease, Cost effectiveness, Cost-Benefit Analysis, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Placebo, Angina, 03 medical and health sciences, 0302 clinical medicine, Myocardial infarction, Internal medicine, medicine, Humans, AcademicSubjects/MED00200, 030212 general & internal medicine, Stroke, health care economics and organizations, ComputingMilieux_MISCELLANEOUS, business.industry, Health Policy, Clopidogrel, medicine.disease, 3. Good health, Quality-adjusted life year, [SDV] Life Sciences [q-bio], Original Article, Quality-Adjusted Life Years, Cardiology and Cardiovascular Medicine, business, Colchicine, medicine.drug
Abstract

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com, Aims: In the randomized, placebo-controlled Colchicine Cardiovascular Outcomes Trial (COLCOT) of 4745 patients enrolled within 30 days after myocardial infarction (MI), low-dose colchicine (0.5 mg once daily) reduced the incidence of the primary composite endpoint of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. To assess the in-trial period and lifetime cost-effectiveness of low-dose colchicine therapy compared to placebo in post-MI patients on standard-of-care therapy. Methods and results: A multistate Markov model was developed incorporating the primary efficacy and safety results from COLCOT, as well as healthcare costs and utilities from the Canadian healthcare system perspective. All components of the primary outcome, non-cardiovascular deaths, and pneumonia were included as health states in the model as both primary and recurrent events. In the main analysis, a deterministic approach was used to estimate the incremental cost-effectiveness ratio (ICER) for the trial period (24 months) and lifetime (20 years). Over the in-trial period, the addition of colchicine to post-MI standard-of-care treatment decreased the mean overall per-patient costs by 47%, from $502 to $265 Canadian dollar (CAD), and increased the quality-adjusted life years (QALYs) from 1.30 to 1.34. The lifetime per-patient costs were further reduced (69%) and QALYs increased with colchicine therapy (from 8.82 to 11.68). As a result, both in-trial and lifetime ICERs indicated colchicine therapy was a dominant strategy. Conclusion: Cost-effectiveness analyses indicate that the addition of colchicine to standard-of-care therapy after MI is economically dominant and therefore generates cost savings.

Published
2021

17. RENEB/EURADOS Field Exercise 2019: Robust Dose Estimation under outdoor Conditions based on the Dicentric Chromosome Assay

Author

Octávia Monteiro Gil, Ursula Oestreicher, Rositsa Histova, Olga Sevriukova, Laure Bobyk, Yoann Ristic, Antonella Testa, Juan S. Martinez, Clemens Woda, Alfredo Hernandez, Ulrike Kulka, Lovisa Waldner, Eric Gregoire, Georgia I. Terzoudi, Elizabeth A. Ainsbury, Sotiria Triantopoulou, Alegría Montoro, Mirta Milić, Joan Francesc Barquinero, Andrzej Wojcik, Anne Vral, Katalin Lumniczky, David Endesfelder, Sylwester Sommer, Laure Sabatier, François Trompier, Clarice Patrono, M. Valente, Rita Hargitai, Stephen Barnard, Christina Beinke, Mercedes Moreno Domene, Jayne Moquet, María Jesús Prieto, Bundesamt für Strahlenschutz (BfS), Federal Office for Radiation Protection (BfS), Public Health England (PHE), Public Health England, Centre for Radiation Chemical and Environmental Hazards (PHE), PSE-SANTE/SERAMED/LRAcc, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SDOS/LDRI, Institute of Radiation Medicine, Helmholtz Zentrum München, Lund University and Lund University Hospital, Bundeswehr Institute of Radiobiology affiliated to the University of Ulm (BIR), Universiteit Gent, Universitat Autonoma de Barcelona, Institute of Nuclear Chemistry and Technology (INCT), National Research Institute for Radiobiology & Radiohygiene, National Public Health Centre, Fundación para la Investigación del Hospital Universitario LA FE de la Comunidad Valenciana (LA FE), IMROH, Instituto Superior Técnico, IRBA, Radiation Protection Centre, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hospital General Universitario Gregorio Marañon, Servicio Madrileño de Salud - Hospital General Universitario Gregorio Marañón (SERMAS), Agenzia Nazionale per le Nuove Tecnologie, L’energia e lo Sviluppo Economico Sostenibile, National Center for Scientific Research 'Demokritos' (NCSRD), National Centre for Scientific Research ‘Demokritos’, National Centre of Radiobiology and Radiation Protection, Stockolm University (SU), Bundesamt für Strahlenschutz - Federal Office for Radiation Protection (BfS), Laboratoire de Radiobiologie des expositions accidentelles (IRSN/PSE-SANTE/SERAMED/LRAcc), Service de recherche en radiobiologie et en médecine régénérative (IRSN/PSE-SANTE/SERAMED), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de dosimétrie des rayonnements ionisants (IRSN/PSE-SANTE/SDOS/LDRI), Service de dosimétrie (IRSN/PSE-SANTE/SDOS), Lund University [Lund], Universität Ulm - Ulm University [Ulm, Allemagne], Universiteit Gent = Ghent University (UGENT), Universitat Autònoma de Barcelona (UAB), and Stockholm University

Subjects
Chromosome Aberrations, Dosimeter, Radiological and Ultrasound Technology, business.industry, [SDV]Life Sciences [q-bio], Radiation Exposure, Medical decision making, Dicentric chromosome, EURADOS, RENEB, biological dosimetry, inter-laboratory comparison, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Dicentric chromosome, dicentric chromosome, RENEB, EURADOS, inter-laboratory comparison, biological dosimetry, 0302 clinical medicine, Homogeneous, 030220 oncology & carcinogenesis, Dose estimation, Chromosomes, Human, Humans, Dosimetry, Medicine, Radiology, Nuclear Medicine and imaging, Radiometry, business, Nuclear medicine, Retrospective Studies
Abstract

Purpose: Depending on the exposure scenario, different biological and/or physical assays will be required to recover the exposure situation and to obtain reliable dose estimates to aid medical decision making. Inter-laboratory comparisons (ILCs) are a central tool to validate and improve the performance of methods and laboratories. In most cases such ILCs are performed under laboratory conditions where the influence of parameters contributing to uncertainties can be minimized. In a reallife scenario, the situation is much more complicated, and it is therefore crucial to validate methods and laboratories’ abilities to carry out these methods under more realistic conditions. In 2019, EURADOS (The European Radiation Dosimetry Group) Working Group 10 (Retrospective Dosimetry) and RENEB (Running the European Network of Biological and retrospective Physical dosimetry) organized a field exercise in Lund, Sweden, to validate different methods for biological and physical retrospective dosimetry in parallel by simulating real- life exposure scenarios. Materials and methods: For the dicentric chromosome assay (DCA), 18 blood tubes were distributed across 8 thermos flasks filled with heated water and positioned at the hips and shoulders of anthropomorphic phantoms in different geometries. Two irradiations were performed with a 1.36 TBq 192Ir-source, each with two phantoms, to simulate close, distant, lateral or partially shielded exposures. For each of the blood tubes DCA dose estimates were provided by at least one laboratory and for tubes from four thermos flasks by 17 participating RENEB laboratories. In addition, blood from the different thermos flasks on each phantom was mixed to simulate heterogeneous exposures. Three radio-photoluminescence (RPL) glass dosimeters (GD) were placed at each tube to assess reference doses and the inter- and intra-tube variability. Results: The results from the DCA were homogeneous between participants and matched well with RPL GD reference doses (≥95% of estimates within ±0.5 Gy of the reference). For samples close to the source, exposed to doses >1 Gy, systematic underestimation could be corrected by accounting for exposure time. Heterogeneity within and between tubes was detected for RPL GD reference doses as well as for doses estimates from the DCA. The sample simulating a heterogeneous exposure with two different doses was detected by ~50% of the participants. Conclusions: The participants were able to successfully estimate the doses and to provide important information on the exposure scenarios under conditions closely resembling a real-life situation. The reliability of the results emphasizes the value of the DCA for retrospective dosimetry under field conditions.

Published
2021

18. Clinico-Biological, Molecular and Prognostic Features of Patients with Diffuse Large B-Cell Lymphoma-Variant of Richter Syndrome: A Multicenter Retrospective Study of the French Innovative Leukemia Organization

Author

Romain Guieze, Thomas Remen, Julien Broséus, Catherine Thieblemont, Stephan Stilgenbauer, Sandra Lomazzi, Eugen Tausch, Florian Bouclet, Hélène Busby, Kamel Laribi, Veronique Leblond, Marie C. Béné, Florence Cymbalista, Caroline Dartigeas, Sébastien Hergalant, Cécile Tomowiak, Romain Morizot, Hélène Augé, Charline Moulin, Francis Guillemin, Anne Quinquenel, Pierre Feugier, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d'Hématologie [CHRU Nancy], Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Pathologie [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universität Ulm - Ulm University [Ulm, Allemagne], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Oncology, medicine.medical_specialty, Richter syndrome, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], business.industry, Retrospective cohort study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, [STAT]Statistics [stat], Leukemia, business, Diffuse large B-cell lymphoma, 030215 immunology
Abstract

Richter Syndrome (RS) corresponds to the transformation of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) into an aggressive lymphoma, in most cases a Diffuse Large B-Cell Lymphoma (DLBCL). RS outcome is variable and still poorly understood. The aim of our study was to analyze the clinical, biological and molecular features liable to predict survival in a retrospective series of newly diagnosed RS from the French Innovative Leukemia Organization (FILO). From 10 French centers, 103 biopsy-confirmed DLBCL subtype RS, diagnosed from 2001 to 2019, were identified. Fresh-frozen biopsies (FB) were available in 58 cases. All biopsies were centrally reviewed. Clinical and biological characteristics at CLL and RS diagnoses including cytogenetics, clonal relationship with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) according to the Hans algorithm, RS prognostic scores (Tsimberidou et al. J Clin Oncol. 2006, Rossi et al. Blood 2011) as well as treatment and outcomes were collected. Targeted next generation sequencing was used on RS FB for the following gene set: TP53, ATM, SF3B1, NOTCH1, BIRC3, FBXW7, RPS15, EGR2, MYD88, XPO1, POT1, BRAF, and NFKBIE. Overall Survival (OS) was defined as time from RS diagnosis until the date of death or end of follow-up and analyzed using Kaplan-Meier method. Multivariable analysis was performed using Cox regression model for variables with a p-value Clinical and biological characteristics and outcomes were broadly similar between the full 103-patient cohort and the subset of 58 patients with available gene mutation data. The latter only was considered for the subsequent analyses. The median age at CLL/SLL diagnosis was 60 (range 34-81) and 39 patients (67.2%) were male. Prior to RS, 24 (41.38%) received more than 1 line of treatment for CLL. The median time to transformation was 5 years (range 0-22). The median OS from RS diagnosis was 8 months (Figure 1a). The median age at RS diagnosis was 65.5 years (range 42-87). ECOG Performance Status (PS) was >1 in 29/53 patients (54.8%) and 32/56 (57.1%) had a Bulky disease. Elevated Lactate DeHydrogenase (LDH) levels (≥ 1.5N) were found in 38/49 patients (77.6%). Unmutated IGHV was observed in 45/58 (77.6%) RS samples. CLL and RS were clonally related for 29/33 (87.9%) RS with available IGHV sequence at CLL diagnosis. TP53 disruption was detected in 34/56 (60.7%) RS cases including TP53 mutations in 23/58 (39.7%). According to Tsimberidou et al., 10/46 (21.7%) RS were in the low-risk group, 10 in the low-intermediate risk group, 11 (23.9%) in the high-intermediate risk group and the other 15 in the high-risk group. According to the Rossi score, only 4/51 RS (7.8%) were low risk, and 19 (37.3%) and 28 (54.9%) intermediate and high-risk, respectively. The most frequent treatment for RS was R-CHOP-like regimen [38/56 (67.9%)], 5 and 2 patients received autologous or allogeneic stem cell transplantation respectively. Most patients, 40/56 (71.4%) failed to reach complete remission after the first line. By bivariate analysis (Figure 1b-e), ECOG PS, platelet count and TP53 disruption worsened OS (p1, platelet count RS outcome is poor. Here, we focused specifically on Richter cells on diagnostic biopsies for genetic analyses. Unmutated IGHV status was identified as prognostic factor for RS, in addition to the previously described: ECOG PS, platelet count and TP53 disruption. More molecular studies are necessary to increase knowledge about RS and improve the survival of patients with DLBCL-type RS. Disclosures Dartigeas: Janssen: Honoraria; Roche: Honoraria; Gilead: Other: non-financial support. Tausch:Roche: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding. Leblond:Roche: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Amgen: Honoraria; AstraZeneca: Consultancy, Honoraria; Lilly: Consultancy. Thieblemont:Incyte: Honoraria; Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Hospira: Research Funding; Bayer: Honoraria. Laribi:abbvie: Honoraria, Research Funding; amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding. Stilgenbauer:F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; Genzyme: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Mundipharma: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding. Guieze:abbvie: Honoraria, Other: advisory board, travel funds; janssen cilag: Honoraria, Other: advisory board, travel funds; roche: Other: travle funds; gilead: Honoraria, Other: travel funds; astrazanecka: Honoraria, Other: advisory board. Feugier:gilead: Consultancy, Honoraria, Research Funding; janssen: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; astrazeneca: Consultancy, Honoraria, Research Funding. Broséus:Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Gilead: Honoraria.

Published
2020

19. Approximating Maximum Acyclic Matchings by Greedy and Local Search Strategies

Author

Dieter Rautenbach, Julien Baste, Maximilian Fürst, and Universität Ulm - Ulm University [Ulm, Allemagne]

Subjects
021103 operations research, Matching (graph theory), business.industry, [INFO.INFO-DS]Computer Science [cs]/Data Structures and Algorithms [cs.DS], 0211 other engineering and technologies, Approximation algorithm, 0102 computer and information sciences, 02 engineering and technology, Edge (geometry), [INFO.INFO-DM]Computer Science [cs]/Discrete Mathematics [cs.DM], 01 natural sciences, Graph, Combinatorics, 010201 computation theory & mathematics, Bounded function, Local search (optimization), business, Greedy algorithm, ComputingMilieux_MISCELLANEOUS, MathematicsofComputing_DISCRETEMATHEMATICS, Mathematics
Abstract

A matching M in a graph G is acyclic if the subgraph of G induced by the vertices that are incident to an edge in M is a forest. Even restricted to graphs of bounded maximum degree, the maximum acyclic matching problem is hard. We contribute efficient approximation algorithms for this problem, based on greedy and local search strategies, that have performance guarantees involving the maximum degree of the input graphs.

Published
2020

20. Variants of uncertain clinical significance in hereditary breast and ovarian cancer genes: best practices in functional analysis for clinical annotation

Author

Gaël A. Millot, Diana Eccles, Lisa Wiesmüller, Jean-Yves Masson, Fergus J. Couch, Arne Nedergaard Kousholt, Ralph Scully, Maaike P.G. Vreeswijk, Marjanka K. Schmidt, Peter Bouwman, Shyam K. Sharan, Alvaro N.A. Monteiro, H. Lee Moffitt Cancer Center and Research Institute, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, University of Southampton, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Cancer Research Center - Centre de recherche sur le cancer [Québec] (CRC), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), National Cancer Institute Frederick, Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Universität Ulm - Ulm University [Ulm, Allemagne], Mayo Clinic [Rochester], Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, The meeting was supported by funds from the Cancer Genomics Center Netherlands through the Netherlands Organization for Scientific Research (NWO), the Royal Netherlands Academy of Arts and Sciences (KNAW), the Danish Counsil for Independent Research (DFF), the Netherlands Cancer Institute and from IDT and BIOKÉ., The authors would like to thank Amanda Spurdle for helpful discussions, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, medicine.medical_specialty, Population, 030105 genetics & heredity, Bioinformatics, Article, Germline, cancer: breast, 03 medical and health sciences, Germline mutation, Molecular genetics, Genetics, medicine, Humans, cancer, Genetic Predisposition to Disease, Clinical significance, Allele, skin and connective tissue diseases, education, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, breast, BRCA2 Protein, education.field_of_study, BRCA1 Protein, business.industry, Cancer, genetic screening/counselling, genetic screening, medicine.disease, 3. Good health, counselling, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, molecular genetics, Hereditary Breast and Ovarian Cancer Syndrome, Medical genetics, Female, getting research into practice, business, clinical genetics
Abstract

Since the identification and cloning of BRCA1 in 1994,1 and shortly thereafter of BRCA2 ,2 genetic tests of germline DNA to identify pathogenic variants in genes linked to hereditary breast and ovarian cancer (HBOC) have become mainstream.3 These tests are critical to identify women at increased risk relative to the general population. Women at moderate risk (2≤relative risk (RR) 4), including those with BRCA1 and BRCA2 pathogenic variants, may also benefit from preventive surgery. Germline mutation testing is also becoming increasingly relevant in the cancer treatment setting because carriers of pathogenic variants in BRCA1/2 may benefit from poly-ADP ribose polymerase (PARP) inhibitors.4 5 Importantly, genetic tests can identify individuals in HBOC families who do not carry the relevant predisposing allele and are not at elevated risk of cancer.6 A significant fraction of documented variants in BRCA1 and BRCA2 are considered variants of uncertain clinical significance (VUS), for which cancer association has not been assessed or could not be determined due to insufficient information (table 1). In ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), a clinically oriented database, currently ~37% of BRCA1 and ~45% of BRCA2 unique variants recorded are VUS. Thus, there is a critical need to classify variants according to their pathogenicity. View this table: Table 1 Fraction of VUS in BRCA1 and BRCA2 Over the past decade, functional assays have emerged that can be included as a source of evidence to classify variants according to their pathogenicity, with the potential to greatly accelerate classification.7 Here, we discuss several technical and conceptual aspects relevant for the use of functional assays in the classification of variants. We present best practice recommendations to improve annotation quality and accuracy, and to provide a basis for the comparison and integration of functional data …

Published
2020

21. VRSketchIn:Exploring the Design Space of Pen and Tablet Interaction for 3D Sketching in Virtual Reality

Author

Julian Karlbauer, Enrico Rukzio, Maximilian Milo, Jan Gugenheimer, Tobias Drey, Universität Ulm - Ulm University [Ulm, Allemagne], Télécom ParisTech, Institut Polytechnique de Paris (IP Paris), Design, Interaction, Visualization & Applications (DIVA), Laboratoire Traitement et Communication de l'Information (LTCI), and Institut Mines-Télécom [Paris] (IMT)-Télécom Paris-Institut Mines-Télécom [Paris] (IMT)-Télécom Paris

Subjects
InformationSystems_INFORMATIONINTERFACESANDPRESENTATION(e.g.,HCI), Computer science, business.industry, media_common.quotation_subject, 05 social sciences, 020207 software engineering, Input device, Usability, 02 engineering and technology, Virtual reality, Task (project management), Categorization, Human–computer interaction, Perception, 0202 electrical engineering, electronic engineering, information engineering, 0501 psychology and cognitive sciences, [INFO.INFO-HC]Computer Science [cs]/Human-Computer Interaction [cs.HC], Set (psychology), business, Design space, 050107 human factors, ComputingMilieux_MISCELLANEOUS, ComputingMethodologies_COMPUTERGRAPHICS, media_common
Abstract

Sketching in virtual reality (VR) enhances perception and understanding of 3D volumes, but is currently a challenging task, as spatial input devices (e.g., tracked controllers) do not provide any scaffolding or constraints for mid-air interaction. We present VRSketchIn, a VR sketching application using a 6DoF-tracked pen and a 6DoF-tracked tablet as input devices, combining unconstrained 3D mid-air with constrained 2D surface-based sketching. To explore what possibilities arise from this combination of 2D (pen on tablet) and 3D input (6DoF pen), we present a set of design dimensions and define the design space for 2D and 3D sketching interaction metaphors in VR. We categorize prior art inside our design space and implemented a subset of metaphors for pen and tablet sketching in our prototype. To gain a deeper understanding which specific sketching operations users perform with 2D and which with 3D metaphors, we present findings of usability walkthroughs with six participants.

Published
2020

22. Association of Insulin-like Growth Factor 1 Concentrations with Risk for and Prognosis of Amyotrophic Lateral Sclerosis - Results from the ALS Registry Swabia

Author

Dietrich Rothenbacher, Angela Rosenbohm, Wolfgang Koenig, Albert C. Ludolph, Gabriele Nagel, Raphael Simon Peter, Luc Dupuis, Institute of Epidemiology and Medical Biometry [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Department of Neurology [Ulm, Allemagne], Deutsches Herzzentrum München [Munich, Allemagne] (DHM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Munich Heart Alliance [Munich, Allemagne] (MHA), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), The ALS registry Swabia and this study have been supported by the German Research Council (DFG)., and Bodescot, Myriam

Subjects
Male, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, lcsh:Medicine, Cohort Studies, Prognostic markers, Insulin-like growth factor, 0302 clinical medicine, Germany, Registries, Insulin-Like Growth Factor I, Amyotrophic lateral sclerosis, lcsh:Science, 0303 health sciences, Multidisciplinary, Middle Aged, Prognosis, Survival Rate, Quartile, Female, Cohort study, Risk, medicine.medical_specialty, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Survival rate, Aged, Proportional Hazards Models, 030304 developmental biology, business.industry, Proportional hazards model, Amyotrophic Lateral Sclerosis, lcsh:R, Case-control study, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Serum samples, Logistic Models, Risk factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

We investigated the associations of serum concentration of insulin-like growth factor 1 (IGF1) with risk and prognosis of ALS in the ALS registry (October 2010–June 2014, median follow-up 67.6 months) in a case-control and cohort study, respectively. Serum samples were measured for IGF-1. Information on covariates was collected by standardized questionnaire. We applied conditional logistic regression to appraise the risk and Cox proportional hazards models to appraise the prognostic value of IGF-1. Data of 294 ALS patients (mean age 65.4 (SD 11.0) years, 60.2% men) and 504 controls were included in the case-control study. Median serum IGF-1 concentrations were slightly higher in ALS cases than in controls (101 vs. 99.5 ng/ml). IGF-1 concentrations were not associated with ALS risk in the fully adjusted model (top vs. bottom quartile: OR 1.16; 95%-CI 0.73–1.84, p for trend = 0.44). Among 293 ALS cases (mean age 65.5 (SD 10.5) years, 56.8% men) 243 died during follow-up. We found a statistically significant inverse association between continuous IGF-1 concentrations and survival (p = 0.01). Very high values IGF-1 were associated with a better prognosis of ALS suggesting that functions related to IGF-1 could be involved in survival.

Published
2020

23. Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia: a subgroup analysis of the GREEN study

Author

Andrey Zaritskey, Jean Louis Merot, Ekaterina Gresko, Stephan Stilgenbauer, Francesc Bosch, Mehmet Turgut, Kerstin Trunzer, Veronique Leblond, Agostino Cortelezzi, Eugen Tausch, Sebastian Böttcher, Mourad Tiab, Susan Robson, Wolfgang Knauf, Robin Foà, Guy Cantin, OMÜ, Institut Català de la Salut, [Bosch F] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Cantin G] Hopital De L’Enfant—Jesus, Quebec City, QC, Canada. [Cortelezzi A] Hematology Unit, Policlinico Hospital and University of Milan, Milan, Italy. [Knauf W] Onkologische Gemeinschaftspraxis, Agaplesion Bethanien Krankenhaus, Frankfurt, Germany. [Tiab M] University Hospital, La Roche Sur Yon, France. [Turgut M] Ondokuz Mayis University, Samsun, Turkey, Vall d'Hebron Barcelona Hospital Campus, Gestionnaire, Hal Sorbonne Université, Vall d'Hebron University Hospital [Barcelona], Università degli Studi di Milano = University of Milan (UNIMI), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), IQVIA, Universität des Saarlandes [Saarbrücken], Universität Ulm - Ulm University [Ulm, Allemagne], F. Hoffmann-La Roche [Basel], University of Rostock, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Milano [Milano] (UNIMI), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], CIC Pitié BT, 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, Male, Cancer Research, Chronic lymphocytic leukemia, medicine.medical_treatment, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Obinutuzumab, Antineoplastic Combined Chemotherapy Protocols, Medicine, Other subheadings::/therapeutic use [Other subheadings], Leucèmia limfocítica crònica - Quimioteràpia, Remission Induction, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Prognosis, Progression-Free Survival, 3. Good health, Fludarabine, Leukemia, Oncology, Tolerability, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Vidarabine, medicine.drug, neoplasias::neoplasias por tipo histológico::leucemia::leucemia linfoide::leucemia de células B::leucemia linfocítica crónica de células B [ENFERMEDADES], Adult, medicine.medical_specialty, Cyclophosphamide, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Antibodies, Monoclonal, Humanized, Article, Quimioteràpia combinada, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Humans, Aged, Chemotherapy, Haematological cancer, business.industry, Otros calificadores::/uso terapéutico [Otros calificadores], [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 030104 developmental biology, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Leukemia, B-Cell::Leukemia, Lymphocytic, Chronic, B-Cell [DISEASES], chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract

Bosch, Francesc/0000-0001-9241-2886 WOS: 000523481800012 PubMed: 31455851 GREEN (NCT01905943) is a nonrandomized, open-label, single-arm, phase 3b study investigating the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in chronic lymphocytic leukemia (CLL). We report the preplanned subgroup analysis of 140 previously untreated, fit CLL patients who received obinutuzumab plus fludarabine and cyclophosphamide (G-FC). The primary endpoint was safety and tolerability. Efficacy was the secondary endpoint. Obinutuzumab 1000 mg was administered intravenously on Day (D)1 (dose split D1.2), D8 and D15 of Cycle (C)1, and D1 of C2-6 (28-day cycles). Standard intravenous/oral doses of fludarabine and cyclophosphamide were administered on D1-3 of C1-6. Overall, 87.1% of patients experienced grade >= 3 adverse events (AEs), including neutropenia (67.1%) and thrombocytopenia (17.1%). Serious AEs were experienced by 42.1% of patients. Rates of grade >= 3 infusion-related reactions and infections were 19.3% and 15.7%, respectively. Overall response rate was observed in 90.0%, with 46.4% of patients achieving complete response (CR; including CR with incomplete marrow recovery). Minimal residual disease negativity rates were 64.3% in peripheral blood and 35.7% in bone marrow (intent-to-treat analysis). After a median observation time of 25.6 months, 2 year progression-free survival was 91%. Frontline G-FC represents a promising treatment option for fit patients with CLL. F. Hoffmann-La Roche Ltd.Hoffmann-La Roche This study was sponsored by F. Hoffmann-La Roche Ltd.

Published
2020

24. Efficacy and safety of low-dose colchicine after myocardial infarction

Author

Lucie Blondeau, Mylène Provencher, Olivier F. Bertrand, Aldo P. Maggioni, José López-Sendón, Jean-Claude Tardif, François Roubille, Simon Kouz, Wolfgang Koenig, Marie-Pierre Dubé, Rafael Diaz, Andreas Orfanos, Reda Ibrahim, Denis Angoulvant, Petr Ostadal, Fausto J. Pinto, Jean Grégoire, Ghassan S. Kiwan, Marie-Claude Guertin, David D. Waters, Marc-André Lavoie, David Rhainds, Colin Berry, Habib Gamra, Philippe L. L’Allier, Montreal Heart Institute Coordinating Centre (MHICC), Université de Montréal (UdeM), Montreal Heart Institute, Montreal, Canada, Université Laval [Québec] (ULaval), Division of Cardiology, Zuckerberg San Francisco General Hospital, Department of Medicine, University of California, San Francisco, USA., Institut de Cardiologie et Pneumologie de Québec, Quebec City, ECLAEstudios Clínicos Latino América & Instituto Cardiovascular de Rosario), Rosario, Argentina, Research Center [Associazione Nazionale Medici Cardiologi Ospedalieri] (ANMCO Research Center), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), Cardiology Department, CHULN, Centro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal, Montrea l Heart Institute, Université de Montréal, Montreal, Canada, CHU Fattouma Bourguiba [Monastir] (HFB), Bellevue Medical Center, Beirut, Lebanon, Institute of Cardiovascular and Medical Sciences, University of Glasgow, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Cardiology department Hospital Universitario La Paz. UAM. IdiPaz. CIBER-CV, Madrid, Spain, Department of Cardiology Cardiovascular Center, NaHomolce Hospital, Prague, Czech Republic, Department of Internal Medicine II – Cardiology, Universität Ulm - Ulm University [Ulm, Allemagne], München, Technische Universität München, German Research Center for Cardiovascular Disease (DZHK), Partner site Munich Heart Alliance, Institute of Epidemiology and Medical Biometry, University of Ulm, Munich, Germany, Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT), Centre Hospitalier Universitaire (CHU) de Tours and Équipe d'Accueil 4245 Transplantation Immunité Inflammation Loire Valley Cardiovascular Collaboration, Tours University, Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Montreal Heart Institute - Institut de Cardiologie de Montréal, Montreal Health Innovations Coordinating Center [Montreal Heart Institute] (MHICC), Montreal Health Innovation Coordination Center, 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), MORNET, Dominique, Repositório da Universidade de Lisboa, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Myocardial Infarction, Anti-Inflammatory Agents, Inflammation, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Pharmacology, Medical and Health Sciences, law.invention, Angina Pectoris, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Percutaneous Coronary Intervention, Randomized controlled trial, Double-Blind Method, law, Recurrence, General & Internal Medicine, medicine, Colchicine, Humans, 030212 general & internal medicine, Myocardial infarction, Proportional Hazards Models, Aged, Intention-to-treat analysis, business.industry, Incidence, Low dose, Percutaneous coronary intervention, General Medicine, Middle Aged, medicine.disease, 3. Good health, Intention to Treat Analysis, Stroke, [SDV] Life Sciences [q-bio], C-Reactive Protein, chemistry, Clinical evidence, Cardiovascular Diseases, Female, medicine.symptom, business, Biomarkers
Abstract

Copyright © 2019 Massachusetts Medical Society. All rights reserved., Background: Experimental and clinical evidence support the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis. Methods: We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed. Results: A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03). Conclusions: Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.).

Published
2019

25. Potentially modifiable determinants of malnutrition in older adults:A systematic review

Author

E. O'Herlihy, Paul W. O'Toole, Isabelle Maître, M. Streicher, Isabelle Papet, Emma O'Shea, Mary Hickson, Karin Schindler, O. van de Rest, Gabriel Torbahn, Dominique Dardevet, Sulmont Rosse, Suzanne Timmons, Mary O'Keeffe, Antje Hebestreit, Marjolein Visser, Eva Kiesswetter, Marie-Agnès Peyron, Catherine Stanton, Maike Wolters, Mary Kelly, Ruth Teh, Sylvie Issanchou, Eibhlís M. O'Connor, Patricia M. Kearney, Marion Flechtner-Mors, Gabriele Nagel, Marta Stelmach-Mardas, L. C. P. G. M. De Groot, Dorothee Volkert, Yves Rolland, Department of Biological Sciences, Dartmouth College [Hanover], University College Cork (UCC), Teagasc Agriculture and Food Development Authority (Teagasc), University of Plymouth, Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Ecole Supérieure d'Agricultures d'Angers (ESA d'Angers), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Poznan University of Medical Sciences, Universität Ulm - Ulm University [Ulm, Allemagne], Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Wageningen University and Research Centre (WUR), University of Auckland [Auckland], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Medizinische Universität Wien = Medical University of Vienna, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), University of Limerick (UL), Austria, Federal Ministry of Science, Research and Economy (BMWFW), France, Ecole Supérieure d’Agricultires (ESA), Germany, Federal Ministry of Food and Agriculture (BMEL) represented by Federal Office forAgriculture and Food (BLE), Ireland, Department of Agriculture, Food and the Marine (DAFM) and the Health Research Board (HRB), Spain, Instituto de Salud Carlos III, and the SENATOR trial (FP7-HEALTH-2012-305930), The Netherlands, The Netherlands Organisation for Health Research and Development (ZonMw)., Austrian Federal Ministry of Education, Science and Research, Ecole Supérieure d’Agricultires, Federal Ministry of Food and Agriculture (BMEL), Institut National de la Recherche Agronomique, Federal Ministry of Food and Agriculture, Department of Agriculture, Food and the Marine, Health Research Board, Instituto de Salud Carlos III, Spain, The Netherlands Organisation for Health Research and Development, MaNuEL Knowledge Hub, BMWFW-10.420/0003-WF/V/3C/2016, FAU: 2815ERA10E, BIPS: 815ERA09E, 15HDHL2, Nutrition and Health, APH - Aging & Later Life, APH - Societal Participation & Health, APH - Health Behaviors & Chronic Diseases, O’connor, Eibhlís M., HRB, Plymouth University, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Vrije Universiteit Amsterdam [Amsterdam] (VU), ProdInra, Migration, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), and VU University Amsterdam

Subjects
Male, 0301 basic medicine, prospective cohort studies, Critical Care and Intensive Care Medicine, Cognition, 0302 clinical medicine, systematic review, Risk Factors, déterminant, Medicine, Prospective cohort study, older adults, Determinants, Aged, 80 and over, 2. Zero hunger, education.field_of_study, Nutrition and Dietetics, determinants, Nutritional Biology, 3. Good health, Hospitalization, Systematic review, Meta-analysis, Older adults, Alimentation et Nutrition, Female, étude de cohorte, Psychosocial, Cohort study, Environmental Risk Assessment, Population, 030209 endocrinology & metabolism, malnutrition, personne âgée, Prospective cohort studies, 03 medical and health sciences, Malnutrition, BU Authenticity & Bioassays, Environmental health, Humans, Food and Nutrition, education, SDG 2 - Zero Hunger, Exercise, Aged, VLAG, Polypharmacy, 030109 nutrition & dietetics, business.industry, étude prospective, medicine.disease, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, BU Authenticiteit & Bioassays, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

open access article; International audience; [u]Background & Aims[/u] Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. [u]Methods[/u] A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. [u]Results[/u] Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. [u]Conclusion[/u] There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly aging population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

Published
2019

26. When a duck is not a duck; a new interdisciplinary synthesis for environmental radiation protection

Author

Eline Saenen, Michael Abend, Gibin G. Powathil, Munira Kadhim, Deborah Oughton, Anders Pape Møller, Paul N. Schofield, Carmel Mothersill, George Iliakis, François Bréchignac, Fen Ru Tang, Jill Sutcliffe, Nathalie Impens, Colin Seymour, Schofield, Paul [0000-0002-5111-7263], Apollo - University of Cambridge Repository, McMaster University [Hamilton, Ontario], Bundeswehr Institute of Radiobiology, Universität Ulm - Ulm University [Ulm, Allemagne], Institut de Radioprotection et de Sûreté Nucléaire (IRSN), University of Duisburg-Essen, Oxford Brookes University, Centre National de la Recherche Scientifique (CNRS), Norwegian University of Life Sciences (NMBU), Swansea University, National University of Singapore (NUS), and University of Cambridge [UK] (CAM)

Subjects
0301 basic medicine, Conservation of Natural Resources, Reference animals and plants, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Medizin, Environment, 010501 environmental sciences, Radiation Dosage, Radioecology, 01 natural sciences, Biochemistry, 03 medical and health sciences, Germany, Political science, medicine, Humans, Environmental planning, 0105 earth and related environmental sciences, General Environmental Science, Radiation protection, business.industry, Low dose, Radiobiology, 030104 developmental biology, 13. Climate action, business
Abstract

International audience; This consensus paper presents the results of a workshop held in Essen, Germany in September 2017, called to examine critically the current approach to radiological environmental protection. The meeting brought together participants from the field of low dose radiobiology and those working in radioecology. Both groups have a common aim of identifying radiation exposures and protecting populations and individuals from harmful effects of ionising radiation exposure, but rarely work closely together. A key question in radiobiology is to understand mechanisms triggered by low doses or dose rates, leading to adverse outcomes of individuals while in radioecology a key objective is to recognise when harm is occurring at the level of the ecosystem. The discussion provided a total of six strategic recommendations which would help to address these questions. © 2018 The Authors

Published
2018

27. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition

Author

Christine Prell, Dominique Darmaun, Walter A. Mihatsch, Anne A.M.W. van Kempen, Venetia Simchowitz, Corina Hartman, Silvia Iacobelli, Krisztina Mihalyi, Berthold Koletzko, Mary Fewtrell, Sanja Kolaček, Arieh Riskin, Antonia Nomayo, Johannes B. van Goudoever, Dieter Mesotten, Nicholas D. Embleton, Virgilio P. Carnielli, Christian Braegger, Francis B. Mimouni, Frank Jochum, Jiri Bronsky, Chris H. B. van den Akker, Sissel J. Moltu, Olivier Goulet, Weihui Yan, Koen F. M. Joosten, Janusz Ksiazyk, John W L Puntis, Jean-Charles Picaud, Szimonetta Lohner, Alexandre Lapillonne, Ranaan Shamir, Tamas Desci, Hill Susan, Cristina Campoy, Merit M. Tabbers, Magnus Domellöf, Miguel Saenz de Pipaon, Jiang Wu, Thibault Senterre, Iva Hojsak, Axel Franz, Peter Szitanyi, Christian Mølgaard, Nataša Fidler Mis, Sascha Verbruggen, Wei Cai, Universität Ulm - Ulm University [Ulm, Allemagne], University Children’s Hospital Zurich, University Hospital Motol [Prague], Shanghai Jiao Tong University [Shanghai], Universidad de Granada = University of Granada (UGR), Polytechnic University of Marche, Université de Nantes (UN), University of Pecs, Umeå University, University of Newcastle upon Tyne, NHS Foundation Trust, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), University Children's Hospital, Université Paris Descartes - Paris 5 (UPD5), Schneider Children's Medical Center of Israel, Children's Hospital Zagreb, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Evangelisches Waldkrankenhaus Spandau, Partenaires INRAE, Eramus MC-Sophia Children’s Hospital, Ludwig-Maximilians University [Munich] (LMU), The Children’s Memorial Health Institute, Katholieke Universiteit Leuven, Department of Pediatrics-Division of Neonatology, University of Alberta, University of Copenhagen = Københavns Universitet (UCPH), Oslo University Hospital [Oslo], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), The General Infirmary at Leeds, Bnai Zion Medical Center, Hospital Universitario La Paz, Centre Hospitalier Universitaire de Liège (CHU-Liège), General University Hospital in Prague, Emma Children’s Hospital Academic Medical Centre, OLVG Hospital, Xinhua Hospital, ProdInra, Migration, Pediatrics, Pediatric surgery, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, Amsterdam Reproduction & Development (AR&D), University of Granada, Ludwig Maximilians University of Munich, University of Copenhagen = Københavns Universitet (KU), Paediatric Gastroenterology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, ARD - Amsterdam Reproduction and Development, and Neonatology

Subjects
0301 basic medicine, medicine.medical_specialty, Adolescent, MEDLINE, parenteral nutrition, Clinical nutrition, Critical Care and Intensive Care Medicine, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, 030225 pediatrics, medicine, Humans, Guideline development, Child, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Infant, Newborn, Consensus conference, Infant, Guideline, Chinese society, Evidence level, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Parenteral nutrition, Child, Preschool, Family medicine, Practice Guidelines as Topic, Child Nutritional Physiological Phenomena, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Background: Previous guidelines on Paediatric Parenteral Nutrition (PN) were published in 2010, by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR) were published. The aim of the present paper was to provide up-to-date evidence for health professionals working with infants, children and adolescents receiving PN. Methods: The current document is a revision of the 2005 guidelines produced by the same 3 organizations (ESPEN, ESPGHAN, ESPR) together with the Chinese Society of Parenteral and Enteral Nutrition (CSPEN). Experts participating in the guideline updating process were all professionals with extensive experience in managing PN from a wide range of European countries, Israel and China. The guideline development process was coordinated by a guideline steering committee. Each chapter of the guideline was prepared by a separate author group. These author groups were responsible for screening titles and abstracts identified by a systematic literature search for inclusion, for conducting additional expert searches (including secondary sources such as other published valid guidelines), for evaluating the quality of studies included in the given chapter and assigning evidence levels to the literature. Based on the evidence level of included studies experts formulated and graded recommendations. A consensus conference was held in February 2015. All chapter manuscripts were revised following the recommendations of the consensus conference and then reviewed and edited by the project steering committee. Final consensus on each individual guideline and its individual recommendations was achieved and assessed by online voting. This process lasted until January 2018. Funding for the consensus conference (including travel expenses for participants) was provided by all participating societies. No other funding was received for the guideline updating process and participants received no payment. Support was provided by the Hungarian Cochrane organization. Results/conclusions: The present document provides guideline for the use of PN across the wide range of pediatric patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg [1]. It covers their individual macro- and micronutrient needs [2], [3], [4], [5], [6], [7], [8], fluid requirements [9], venous access [10], organizational aspects [11], home parenteral nutrition [12], standardized vs. individualized PN [13], and last but not least a wide range of safety considerations for prevention and management of complications such central line associated bloodstream infections (CLABSI)

Published
2018

28. A step towards precision medicine in management of severe transient polyhydramnios: MAGED2 variant

Author

Tiphaine Bihouée, Norbert Winer, Mathilde Nizon, Nadir Benbrik, Martin Kömhoff, Vera Riehmer, Bodo B. Beck, Alexandra Bruel, Chloé Arthuis, Bertrand Isidor, Service de Gynécologie Obstétrique (NANTES - Gynéco Obstétrique), Centre hospitalier universitaire de Nantes (CHU Nantes), Philipps University of Marburg, Institute of Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], University of Cologne, Service de Pédiatrie, Physiopathologie des Adaptations Nutritionnelles (PhAN), and Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
Male, Polyhydramnios, medicine.medical_specialty, 030232 urology & nephrology, Excessive amniotic fluid, Infant, Premature, Diseases, génétique, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Antigens, Neoplasm, Pregnancy, Internal medicine, medicine, Humans, 030212 general & internal medicine, gynécologie, ComputingMilieux_MISCELLANEOUS, perinatal, Adaptor Proteins, Signal Transducing, business.industry, fungi, Infant, Newborn, Bartter Syndrome, food and beverages, Obstetrics and Gynecology, fluide, medicine.disease, Precision medicine, Pedigree, 3. Good health, Increased risk, Mutation, Cardiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Polyhydramnios is a recurrent clinical concern. Excessive amniotic fluid can be caused by an imbalance between its production and its removal, and is associated with an increased risk of an adverse...

Published
2018

29. 3D Electron Diffraction: The Nanocrystallography Revolution

Author

Philippe Boullay, Sven Hovmöller, Jan Pieter Abrahams, Enrico Mugnaioli, Ute Kolb, Lukáš Palatinus, Mauro Gemmi, Tatiana E. Gorelik, Laboratoire de cristallographie et sciences des matériaux (CRISMAT), École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC), Istituto Italiano di Tecnologia (IIT), Universität Ulm - Ulm University [Ulm, Allemagne], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Technische Universität Darmstadt - Technical University of Darmstadt (TU Darmstadt), Institute of Physics of the Czech Academy of Sciences (FZU / CAS), Czech Academy of Sciences [Prague] (CAS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Stockholm University, University of Basel (Unibas), Paul Scherrer Institute (PSI), Institute Biology Leiden (IBL), and Universiteit Leiden

Subjects
Diffraction, Materials science, Cryo-electron microscopy, Physical and chemical processes, General Chemical Engineering, 010402 general chemistry, 01 natural sciences, Crystals, Crystal, Optics, QD1-999, Structure determination, Materials, 010405 organic chemistry, business.industry, Crystal structure, General Chemistry, Nanocrystalline material, 0104 chemical sciences, Chemistry, Electron diffraction, Transmission electron microscopy, Goniometer, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], business, Protein crystallization, Outlook
Abstract

Crystallography of nanocrystalline materials has witnessed a true revolution in the past 10 years, thanks to the introduction of protocols for 3D acquisition and analysis of electron diffraction data. This method provides single-crystal data of structure solution and refinement quality, allowing the atomic structure determination of those materials that remained hitherto unknown because of their limited crystallinity. Several experimental protocols exist, which share the common idea of sampling a sequence of diffraction patterns while the crystal is tilted around a noncrystallographic axis, namely, the goniometer axis of the transmission electron microscope sample stage. This Outlook reviews most important 3D electron diffraction applications for different kinds of samples and problematics, related with both materials and life sciences. Structure refinement including dynamical scattering is also briefly discussed., 3D electron diffraction allows the atomic structure determination of inorganic, organic, and macromolecular materials that remained hitherto unknown because of their limited crystal size.

Published
2019

30. Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease

Author

Markus Otto, Henrik Zetterberg, Piotr Lewczuk, Oskar Hansson, Sylvain Lehmann, Clinical Memory Research Unit [Malmö, Suède], Department of Clinical Sciences [Malmö, Suède], Lund University [Malmö, Suède]-Lund University [Malmö, Suède], Memory Clinic [Malmö, Suède], Skåne University Hospital [Malmö, Suède], 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), Department of Neurology [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Clinical Neurochemistry Laboratory [Göteborg, Suède], Department of Psychiatry and Neurochemistry [Goteborg], Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg]-Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Neurodegenerative Disease [Londres, Royaume-Uni], Institute of Neurology [London], University College of London [London] (UCL)-University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), Department of Psychiatry and Psychotherapy [Erlangen, Allemagne], Universitätsklinikum Erlangen [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of Neurodegeneration Diagnostics [Bialystok, Pologne], Medical University of Bialystok [Bialystok, Pologne], Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Universitätsklinikum Erlangen [Erlangen, Allemagne], Fujirebio Europe sponsored this paper, however, it had no influence on its factual content. PL was supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. OH has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio and Euroimmun. HZ’s research is supported by the Swedish Research Council, the European Research Council, the Knut and Alice Wallenberg Foundation, the Olav Thon Foundation, the UK Dementia Research Institute at UCL and Swedish State Support for Clinical Research (ALFGBG)., Lund University [Lund]-Lund University [Lund], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Medical University of Białystok (MUB), and Bodescot, Myriam

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Neurology, Amyloid β, Cognitive Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Diagnostic accuracy, Disease, Review, Aβ 42/40 ratio, Alzheimer's Disease, lcsh:RC346-429, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Medizinische Fakultät, Alzheimer Disease, Internal medicine, medicine, Dementia, Humans, ddc:610, Alzheimer’s Disease, Cognitive impairment, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biochemical markers, lcsh:Neurology. Diseases of the nervous system, Cerebrospinal Fluid, Amyloid beta-Peptides, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Peptide Fragments, 030104 developmental biology, Aβ42/40 ratio, Neurology (clinical), business, 030217 neurology & neurosurgery, Amyloidβ Peptides, Biomarkers
Abstract

International audience; The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer's Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it is important to be able to distinguish between AD and other types of dementia (non-AD). The concentration ratio of Aβ42 to Aβ40 (Aβ42/40 Ratio) has been suggested to be superior to the concentration of Aβ42 alone when identifying patients with AD. This article reviews the available evidence on the use of the CSF Aβ42/40 ratio in the diagnosis of AD. Based on the body of evidence presented herein, it is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSF Aβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.

Published
2019

31. Editorial: Towards an Understanding of Tinnitus Heterogeneity

Author

Christopher R. Cederroth, Silvano Gallus, Deborah A. Hall, Tobias Kleinjung, Berthold Langguth, Antonello Maruotti, Martin Meyer, Arnaud Norena, Thomas Probst, Rüdiger Pryss, Grant Searchfield, Giriraj Shekhawat, Myra Spiliopoulou, Sven Vanneste, Winfried Schlee, Karolinska Institutet [Stockholm], Istituto di Ricerche Farmacologiche 'Mario Negri', 20156 Milan, University of Nottingham, UK (UON), Universität Zürich [Zürich] = University of Zurich (UZH), University of Regensburg, University of Southampton, SPRU, Neurosciences sensorielles et cognitives (NSC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Danube University Krems, Universität Ulm - Ulm University [Ulm, Allemagne], University of Auckland [Auckland], Auckland University of Technology (AUT), Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Brain Research centre Antwerp for Innovative and Interdisciplinary Neuromodulation (BRAI²N), Antwerp University Hospital [Edegem] (UZA), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Otto-von-Guericke University [Magdeburg] (OVGU), University of Zurich, and Cederroth, Christopher R

Subjects
2805 Cognitive Neuroscience, Aging, Cognitive Neuroscience, 610 Medicine & health, 10045 Clinic for Otorhinolaryngology, Cognitive neuroscience, lcsh:RC321-571, neuroscience, 03 medical and health sciences, 0302 clinical medicine, Animal model, 1302 Aging, Medicine, tinnitus, 030223 otorhinolaryngology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, ComputingMilieux_MISCELLANEOUS, business.industry, 10093 Institute of Psychology, [SCCO.NEUR]Cognitive science/Neuroscience, animal model, Ageing, Editorial, hearing, medicine.symptom, heterogeneity, genetic, business, Neuroscience, 030217 neurology & neurosurgery, Tinnitus
Abstract

International audience

Published
2019

32. Control of TLR7-mediated type I IFN signaling in pDCs through CXCR4 engagement—A new target for lupus treatment

Author

Smith, Nikaïa, Rodéro, Mathieu, Bekaddour, Nassima, Bondet, Vincent, Ruiz-Blanco, Yasser, Harms, Mirja, Mayer, Benjamin, Bader-Meunier, Brigitte, Quartier, Pierre, Bodemer, Christine, Baudouin, Véronique, Dieudonné, Yannick, Kirchhoff, Frank, Sanchez Garcia, Elsa, Charbit, Bruno, Leboulanger, Nicolas, Jahrsdörfer, Bernd, Korganow, Anne-sophie, Münch, Jan, Nisole, Sébastien, Duffy, Darragh, Herbeuval, Jean-Philippe, Audemard-Verger, Alexandra, Pillebout, Evangeline, Jamin, Agnès, Berthelot, Laureline, Aufray, Cédric, Martin, Bruno, Sannier, Aurélie, Daugas, Eric, Déchanet-Merville, Julie, Monteiro, Renato, Lucas, Bruno, Ramspott, Jan Philipp, Bekkat, Fériel, Bod, Lloyd, Favier, Maryline, Terris, Benoît, Salomon, Anne, Djerroudi, Lounes, Zaenker, Kurt, Richard, Yolande, Molinier-Frenkel, Valérie, Castellano, Flavia, Avril, Marie-Françoise, Prévost-Blondel, Armelle, Vougny, Marie-Christine, Universitätsklinikum Ulm - University Hospital of Ulm, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Duisburg-Essen [Essen], Universität Ulm - Ulm University [Ulm, Allemagne], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, CHU Strasbourg, Université de Strasbourg (UNISTRA), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Institute of Transfusion Medicine and Immunogenetics, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Agence National de la Recherche sur le SIDA et les Hépatites ANRS (to J.-P.H.) for the experiments and N.B. Fellowship (AAP 2017-166). N.S. acknowledges support from the ANRS for Fellowship (AAP 2016-1), the European Molecular Biology Organization (EMBO) for Fellowship (LT-834-2017), the start-up funding program 'Baustein' of the Medical Faculty of Ulm University (LSBN.0147), and the Deutsche Forschungsgemeinschaft (DFG, SM 544/1-1). This work was also supported by SATT IDF Innov (www.idfinnov.com) through the project under grant no. 303. D.D. acknowledges support from the Agence National de Recherche ANR (CE17001002) and ImmunoQure for provision of mAbs for Simoa assays. J.M. acknowledges support from DFG (MU3115-8/1 and CRC1279). A.-S.K and Y.D. acknowledge support from the Société Nationale Française de Médecine Interne (SNFMI), from Hôpitaux Universitaires de Strasbourg (HUS), and from EU-funded (ERDF) project Interreg V 'RARENET'. A.-S.K. also acknowledges support from the French Ministry of Health (PHRC IR 2011). S.N. has benefited from support by the LABEX EpiGenMed, an 'Investissements d’avenir' program (reference, ANR-10-LABX-12-01). B.J. acknowledges the BSD grant (Budgetantrag, 11225783). E.S.G. acknowledges the support of the German Research Foundation (DFG) under Germany’s Excellence Strategy—EXC-2033—Projektnummer 390677874, the CRC1279, and the Boehringer-Ingelheim Foundation (Plus-3 Grant). These experiments used reagents provided by the AIDS and Cancer Virus Program, Biological Products Core Laboratory, Frederick National Laboratory for Cancer Research, supported with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E, We thank S. Dupuy from the Common Service of Flux Cytometry (S2C) of Paris Descartes University. We also thank N. Pietrancosta for providing us with some IT1t for the mice study. Furthermore, we thank J. Bess and J. Lifson for providing us with the inactivated purified HIV-1 viruses., Universität Duisburg-Essen = University of Duisburg-Essen [Essen], ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), ANR-16-CE17-0010,IFNX,Investigation des interferonopathies type I humaine(2016), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Modélisation et Immunologie pour la Thérapie (CBMIT), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Immunologie et Hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence national des Maladies Génétiques à Expression Cutanée (MAGEC), CHU Necker - Enfants Malades [AP-HP]-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratory of neurogenetics and neuroinflammation (Equipe Inserm U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Institute of Molecular Virology [Ulm, Allemagne], Centre de Recherche Translationnelle (CRT), Institut Pasteur [Paris], INSERM U955, équipe 13, VNI et pathologie ORL, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP]-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institute of Molecular Virology, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Centre d'Immunologie Humaine (CIH), CHU Cochin [AP-HP], Service de rhumatologie, CHU Bordeaux [Bordeaux], Alimentation Adaptations Digestives, Nerveuse et Comportementales (ADNC), Institut National de la Recherche Agronomique (INRA)-centre de rennes, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Centre de recherche sur l'Inflammation (CRI), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), INSERM U25, Hôpital Necker, Paris, France, MINACOM, XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et de cytologie pathologiques [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Immunologie et Oncogenese des Tumeurs Lymphoides, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Equipe 09, Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
[SDV]Life Sciences [q-bio], Aucun, Systemic inflammation, Ligands, Mice, 0302 clinical medicine, Interferon, Lupus Erythematosus, Systemic, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Research Articles, 0303 health sciences, Multidisciplinary, Systemic lupus erythematosus, SciAdv r-articles, hemic and immune systems, 3. Good health, 030220 oncology & carcinogenesis, Interferon Type I, Disease Progression, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Disease Susceptibility, medicine.symptom, Signal transduction, Biologie, medicine.drug, Protein Binding, Signal Transduction, Research Article, Receptors, CXCR4, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Inflammation, 03 medical and health sciences, Chorea, medicine, Animals, Humans, 030304 developmental biology, Lupus erythematosus, business.industry, Gene Expression Profiling, Autoantibody, TLR7, Dendritic Cells, medicine.disease, Disease Models, Animal, Toll-Like Receptor 7, business
Abstract

CXCR4 engagement by amines leads to the control of IFN signaling in pDCs and opens new therapeutic perspectives in Lupus patients., Type I interferons are highly potent cytokines essential for self-protection against tumors and infections. Deregulations of type I interferon signaling are associated with multiple diseases that require novel therapeutic options. Here, we identified the small molecule, IT1t, a previously described CXCR4 ligand, as a highly potent inhibitor of Toll-like receptor 7 (TLR7)–mediated inflammation. IT1t inhibits chemical (R848) and natural (HIV) TLR7-mediated inflammation in purified human plasmacytoid dendritic cells from blood and human tonsils. In a TLR7-dependent lupus-like model, in vivo treatment of mice with IT1t drives drastic reduction of both systemic inflammation and anti–double-stranded DNA autoantibodies and prevents glomerulonephritis. Furthermore, IT1t controls inflammation, including interferon α secretion, in resting and stimulated cells from patients with systemic lupus erythematosus. Our findings highlight a groundbreaking immunoregulatory property of CXCR4 signaling that opens new therapeutic perspectives in inflammatory settings and autoimmune diseases.

Published
2019

33. Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MS

Author

Valérie Jolivel, Florian C. Kurschus, Ari Waisman, Morad Zayoud, Hayrettin Tumani, Felix Luessi, Stefan H.P. Kraus, Sinah Engel, Karolina Rosenfeld, Roberto Furlan, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaim Sheba Medical Center, Universität Ulm - Ulm University [Ulm, Allemagne], San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, and univOAK, Archive ouverte

Subjects
Adult, Male, Lipopolysaccharide, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, CD14, medicine.medical_treatment, Interleukin-1beta, Quinolones, Lymphocyte Activation, Monocytes, Article, Flow cytometry, chemistry.chemical_compound, Multiple Sclerosis, Relapsing-Remitting, Downregulation and upregulation, medicine, Humans, CD86, medicine.diagnostic_test, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Interleukin, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Middle Aged, Molecular biology, Cross-Sectional Studies, Cytokine, Neurology, chemistry, Th17 Cells, Female, Neurology (clinical), [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, Laquinimod, Signal Transduction
Abstract

ObjectiveTo assess the impact of laquinimod treatment on monocytes and to investigate the underlying immunomodulatory mechanisms in MS.MethodsIn this cross-sectional study, we performed in vivo and in vitro analyses of cluster of differentiation (CD14+) monocytes isolated from healthy donors (n = 15), untreated (n = 13), and laquinimod-treated patients with MS (n = 14). Their frequency and the expression of surface activation markers were assessed by flow cytometry and the viability by calcein staining. Cytokine concentrations in the supernatants of lipopolysaccharide (LPS)-stimulated monocytes were determined by flow cytometry. The messenger ribonucleic acid (mRNA) expression level of genes involved in cytokine expression was measured by quantitative PCR. The LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activation was determined by the quantification of the phosphorylation level of the p65 subunit. Laquinimod-treated monocytes were cocultured with CD4+ T cells, and the resulting cytokine production was analyzed by flow cytometry after intracellular cytokine staining. The interleukin (IL)-17A concentration of the supernatant was assessed by ELISA.ResultsLaquinimod did not alter the frequency or viability of circulating monocytes, but led to an upregulation of CD86 expression. LPS-stimulated monocytes of laquinimod-treated patients with MS secreted less IL-1β following a downregulation of IL-1β gene expression. Phosphorylation levels of the NF-κB p65 subunit were reduced after laquinimod treatment, indicating a laquinimod-associated inhibition of the NF-κB pathway. T cells primed with laquinimod-treated monocytes differentiated significantly less into IL-17A–producing T helper (Th)-17 cells.ConclusionsOur findings suggest that inhibited NF-κB signaling and downregulation of IL-1β expression in monocytes contributes to the immunomodulatory effects of laquinimod and that the impairment of Th17 polarization might mediate its disease-modifying activity in MS.

Published
2020

34. Cardiac Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine

Author

Michael Gröger, Clair Hartmann, Thomas Datzmann, Martin Wepler, Ulrich Wachter, Tamara Merz, Peter Radermacher, Benedikt L. Nussbaum, Josef Vogt, Oscar McCook, Enrico Calzia, Pierre Asfar, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitatsklinikum, Universität Ulm - Ulm University [Ulm, Allemagne], Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Anesthesia, and Universitätsklinikum Ulm - University Hospital of Ulm

Subjects
medicine.medical_specialty, Resuscitation, Swine, [SDV]Life Sciences [q-bio], Nitric Oxide Synthase Type II, 030204 cardiovascular system & hematology, Hyperoxia, Shock, Hemorrhagic, Critical Care and Intensive Care Medicine, Gene Expression Regulation, Enzymologic, Ventricular Function, Left, Cardiac dysfunction, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Animals, Tyrosine Metabolism, Ventricular function, business.industry, Myocardium, 030208 emergency & critical care medicine, respiratory system, respiratory tract diseases, Shock (circulatory), Hemorrhagic shock, Emergency Medicine, Breathing, Cardiology, cardiovascular system, Tyrosine, medicine.symptom, business, circulatory and respiratory physiology
Abstract

International audience; Hyperoxia (ventilation with FIO2 = 1.0) has vasoconstrictor properties, in particular in the coronary vascular bed, and, hence, may promote cardiac dysfunction. However, we previously showed that hyperoxia attenuated myocardial injury during resuscitation from hemorrhage in swine with coronary artery disease. Therefore, we tested the hypothesis whether hyperoxia would also mitigate myocardial injury and improve heart function in the absence of chronic cardiovascular co-morbidity.After 3 hours of hemorrhage (removal of 30% of the calculated blood volume and subsequent titration of mean arterial pressure to 40mmHg) 19 anesthetized, mechanically ventilated and instrumented pigs received FIO2 = 0.3(control) or hyperoxia(FIO2 = 1.0) during the first 24 hours. Before, at the end of and every 12 hours after shock, hemodynamics, blood gases, metabolism, cytokines and cardiac function (pulmonary artery thermodilution, left ventricular pressure-conductance catheterization) were recorded. At 48 hours, cardiac tissue was harvested for western blotting, immunohistochemistry and mitochondrial respiration.Except for higher left ventricular end-diastolic pressures at 24 hours (hyperoxia 21(17;24),control 17(15;18)mmHg;p = 0.046), hyperoxia affected neither left ventricular function cardiac injury (max. Troponin I at 12 hours: hyperoxia:9(6;23),control:17(11;24)ng mL;p = 0.395), nor plasma cytokines (except for interleukin-1β: hyperoxia 10(10;10) and 10(10;10)/control 14(10;22), 12(10;15)pg mL, p = 0.023 and 0.021 at 12 and 24 hours, respectively), oxidation and nitrosative stress, and mitochondrial respiration. However, hyperoxia decreased cardiac tissue 3-nitrotyrosine formation (p

Published
2018

35. Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Author

Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Olama, Ali Amin Al, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Géraldine, Sorensen, Karina D., Maehle, Lovise, Grindedal, Eli M., Strom, Sara S., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Bensen, Jeanette T., Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A., Pandha, Hardev, Thibodeau, Stephen N., Schaid, Daniel J., Henderson, Brian E., Stern, Mariana C., Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Cook, Margaret, Fachal, Laura, Weinstein, Stephanie, Beane Freeman, Laura E., Hoover, Robert N., Machiela, Mitchell J., Lophatananon, Artitaya, Carter, Brian D., Goodman, Phyllis J., Moya, Leire, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Yeadon, Trina, Eckert, Allison, Eklund, Martin, Cavalli-Bjoerkman, Carin, Dunning, Alison M., Sipeky, Csilla, Hakansson, Niclas, Elliott, Rebecca, Ranu, Hardeep, Giovannucci, Edward, Turman, Constance, Hunter, David J., Cussenot, Olivier, Orntoft, Torben Falck, Lane, Athene, Lewis, Sarah J., Davis, Michael, Key, Tim J., Brown, Paul, Kulkarni, Girish S., Zlotta, Alexandre R., Fleshner, Neil E., Finelli, Antonio, Mao, Xueying, Marzec, Jacek, MacInnis, Robert J., Milne, Roger, Hopper, John L., Aguado, Miguel, Bustamante, Mariona, Castaño-Vinyals, Gemma, Gracia-Lavedan, Esther, Cecchini, Lluís, Stampfer, Meir, Ma, Jing, Sellers, Thomas A., Geybels, Milan S., Park, Hyun, Zachariah, Babu, Kolb, Suzanne, Wokolorczyk, Dominika, Lubinski, Jan, Kluzniak, Wojciech, Nielsen, Sune F., Weisher, Maren, Cuk, Katarina, Vogel, Walther, Luedeke, Manuel, Logothetis, Christopher J. J., Paulo, Paula, Cardoso, Marta, Maia, Sofia, Silva, Maria P., Steele, Linda, Ding, Yuan Chun, De Meerleer, Gert, De Langhe, Sofie, Thierens, Hubert, Lim, Jasmine, Tan, Meng H., Ong, Aik T., Lin, Daniel W., Kachakova, Darina, Mitkova, Atanaska, Mitev, Vanio, Parliament, Matthew, Jenster, Guido, Bangma, Christopher, Schroder, F. H., Truong, Thérèse, Koudou, Yves Akoli, Michael, Agnieszka, Kierzek, Andrzej, Karlsson, Ami, Broms, Michael, Wu, Huihai, Aukim-Hastie, Claire, Tillmans, Lori, Riska, Shaun, McDonnell, Shannon K., Dearnaley, David, Spurdle, Amanda, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Papargiris, Melissa, Saunders, Pamela, Kujala, Paula, Talala, Kirsi, Taari, Kimmo, Bentzen, Søren, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, George, Anne, Toi, Ants, Evans, Andrew, van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Zhao, Shan-Chao, Ren, Guoping, Zhang, Yangling, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Pedersen, John, Lobato-Busto, Ramón, Ruiz-Dominguez, José Manuel, Mengual, Lourdes, Alcaraz, Antonio, Pow-Sang, Julio, Herkommer, Kathleen, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Adolfsson, Jan, Stattin, Par, Johansson, Jan-Erik, Martin, Richard M., Thompson, Ian M., Chambers, Suzanne, Aitken, Joanne, Horvath, Lisa, Haynes, Anne-Maree, Tilley, Wayne, Risbridger, Gail, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Tammela, Teuvo L. J., Murtola, Teemu, Auvinen, Anssi, Burnet, Neil, Barnett, Gill, Andriole, Gerald, Klim, Aleksandra, Drake, Bettina F., Borre, Michael, Kerns, Sarah, Ostrer, Harry, Zhang, Hong-Wei, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Feng, Ninghan, Li, Jie, He, Weiyang, Guo, Xin, Sun, Zan, Wang, Guomin, Guo, Jianming, Southey, Melissa C., Fitzgerald, Liesel M., Marsden, Gemma, Gómez-Caamaño, Antonio, Carballo, Ana, Peleteiro, Paula, Calvo, Patricia, Szulkin, Robert, Llorca, Javier, Dierssen-Sotos, Trinidad, Gómez Acebo, Inés, Lin, Hui-Yi, Ostrander, Elaine A., Bisbjerg, Rasmus, Klarskov, Peter, Røder, Martin Andreas, Iversen, Peter, Holleczek, Bernd, Stegmaier, Christa, Schnoeller, Thomas, Bohnert, Philipp, John, Esther M., Ost, Piet, Teo, Soo-Hwang, Gamulin, Marija, Kulis, Tomislav, Kastelan, Zeljko, Slavov, Chavdar, Popov, Elenko, Van den Broeck, Thomas, Joniau, Steven, Larkin, Samantha, Castelao, Jose Esteban, Martinez, Maria Elena, van Schaik, Ron H. N., Xu, Jianfeng, Lindström, Sara, Riboli, Elio, Berry, Clare, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Freedman, Matthew, Cenee, Sylvie, Sanchez, Marie, Wiklund, Fredrik, Chanock, Stephen J., Easton, Douglas F., Eeles, Rosalind A., Kote-Jarai, Zsofia, Conti, David V., Haiman, Christopher A., Universidad de Cantabria, De Meerleer, Gert, Keck School of Medicine [Los Angeles], University of Southern California (USC), The institute of cancer research [London], Department of Clinical Neurosciences [Cambridge], University of Cambridge [UK] (CAM), Centre for Cancer Genetic Epidemiology [Cambridge], Department of Oncology-University of Cambridge [UK] (CAM), Case Western Reserve University [Cleveland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Warwick Medical School, University of Warwick [Coventry], University of Manchester [Manchester], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University College of London [London] (UCL), University of Turku, University of Tampere [Finland], The Institute of Environmental Medicine [Stockholm] (IMM), Manchester Academic Health Science Centre (MAHSC), Harvard School of Public Health, Harvard T.H. Chan School of Public Health, Université Pierre et Marie Curie - Paris 6 (UPMC), Aarhus University Hospital, Aarhus University [Aarhus], Oslo University Hospital [Oslo], The University of Texas M.D. Anderson Cancer Center [Houston], Addenbrooke's Hospital, Cambridge University NHS Trust, University of Oxford [Oxford], School of Social and Community Medicine [Bristol], University of Bristol [Bristol], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Centre for Molecular Oncology and Imaging, Centre for Molecular Oncology and Imaging, Barts Cancer Institute, Queen Mary University of London (QMUL), University of Melbourne, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), CIBER de Enfermedades Raras (CIBERER), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), University of Washington [Seattle], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), National Center for Tumor Diseases [Dresden] (NCT), Technische Universität Dresden = Dresden University of Technology (TU Dresden)-German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Universität Ulm - Ulm University [Ulm, Allemagne], Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Universiteit Gent = Ghent University [Belgium] (UGENT), University of Malaya [Kuala Lumpur, Malaisie], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University of Alberta, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of California [San Diego] (UC San Diego), University of California, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, University of Utah School of Medicine [Salt Lake City], University of Surrey (UNIS), Mayo Clinic [Rochester], Royal Marsden NHS Foundation Trust, Dadaev, Tokhir [0000-0002-8268-0438], Brook, Mark N [0000-0002-8969-2378], Wang, Kan [0000-0002-0640-6058], Olama, Ali Amin Al [0000-0002-7178-3431], Schumacher, Fredrick R [0000-0002-3073-7463], Muir, Kenneth [0000-0001-6429-988X], Batra, Jyotsna [0000-0003-4646-6247], Pashayan, Nora [0000-0003-0843-2468], Schleutker, Johanna [0000-0002-1863-0305], Wolk, Alicja [0000-0001-7387-6845], Cancel-Tassin, Géraldine [0000-0002-9583-6382], Sorensen, Karina D [0000-0002-4902-5490], Lessel, Davor [0000-0003-4496-244X], Roobol, Monique J [0000-0001-6967-1708], Chanock, Stephen J [0000-0002-2324-3393], Easton, Douglas F [0000-0003-2444-3247], Eeles, Rosalind A [0000-0002-3698-6241], Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM)-Department of Oncology, University of Oxford, Universidade do Porto = University of Porto, Universiteit Gent = Ghent University (UGENT), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), University of California (UC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Gestionnaire, Hal Sorbonne Université, Urology, University Management, Clinicum, and HUS Abdominal Center

Subjects
0301 basic medicine, Oncology, Male, [SDV]Life Sciences [q-bio], LOCI, General Physics and Astronomy, Genome-wide association study, PROGRESSION, [SDV.GEN] Life Sciences [q-bio]/Genetics, MYC, SUSCEPTIBILITY, UP-REGULATION, Prostate cancer, Risk Factors, Genotype, Urologi och njurmedicin, Medicine, lcsh:Science, Pròstata -- Càncer, education.field_of_study, RARE VARIANT, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Manchester Cancer Research Centre, LONG NONCODING RNA, Chromosome Mapping, Men, 3. Good health, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, Science & Technology - Other Topics, Disease Susceptibility, Risk assessment, Chromosomes, Human, Pair 8, Genetic Markers, medicine.medical_specialty, Science, 3122 Cancers, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Article, General Biochemistry, Genetics and Molecular Biology, White People, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, Genetics, Urology and Nephrology, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, Author Correction, METAANALYSIS, [SDV.GEN]Life Sciences [q-bio]/Genetics, Cancer och onkologi, Science & Technology, Càncer de pròstata, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Case-control study, Cancer, Prostatic Neoplasms, General Chemistry, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, 030104 developmental biology, Homes, Haplotypes, Cancer and Oncology, Case-Control Studies, lcsh:Q, Population Risk, business, Genètica, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p, Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Published
2018

36. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial

Author

Björn Steffen, Eunice S. Wang, Elihu H. Estey, Philippe Rousselot, Hartmut Döhner, Stephen A. Strickland, Claudia D. Baldus, Alexander E. Perl, Neil P. Shah, Catherine C. Smith, Norbert Ifrah, Denise Trone, Hagop M. Kantarjian, Jorge E. Cortes, Alan Kenneth Burnett, Deborah Lazzaretto, Giovanni Martinelli, Guy Gammon, Jessica K. Altman, Hervé Dombret, Tibor Kovacsovics, Alwin Krämer, Mark J. Levis, Nigel H. Russell, MD Anderson Cancer Center, The University of Texas Health Science Center at Houston (UTHealth), Internal Medicine III, Universität Ulm - Ulm University [Ulm, Allemagne], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universität Heidelberg [Heidelberg], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
0301 basic medicine, Male, Myeloid, Internationality, [SDV]Life Sciences [q-bio], Administration, Oral, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, Cancer, Pediatric, education.field_of_study, Leukemia, Hematology, Middle Aged, Prognosis, 3. Good health, Survival Rate, Europe, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Treatment Outcome, Oncology, Local, 030220 oncology & carcinogenesis, 6.1 Pharmaceuticals, Administration, Female, Drug, Oral, Adult, medicine.medical_specialty, Canada, Maximum Tolerated Dose, Pediatric Cancer, Population, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, Neutropenia, Acute, Article, Disease-Free Survival, Drug Administration Schedule, Dose-Response Relationship, 03 medical and health sciences, Young Adult, Clinical Research, Internal medicine, medicine, Humans, Benzothiazoles, Oncology & Carcinogenesis, education, Survival rate, Quizartinib, Aged, Performance status, Dose-Response Relationship, Drug, business.industry, Phenylurea Compounds, Evaluation of treatments and therapeutic interventions, medicine.disease, United States, Transplantation, 030104 developmental biology, Neoplasm Recurrence, chemistry, fms-Like Tyrosine Kinase 3, Neoplasm Recurrence, Local, business, Febrile neutropenia
Abstract

International audience; BACKGROUND: Old age and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations in patients with acute myeloid leukaemia are associated with early relapse and poor survival. Quizartinib is an oral, highly potent, and selective next-generation FLT3 inhibitor with clinical antileukaemic activity in relapsed or refractory acute myeloid leukaemia. We aimed to assess the efficacy and safety of single-agent quizartinib in patients with relapsed or refractory acute myeloid leukaemia.METHODS: We did an open-label, multicentre, single-arm, phase 2 trial at 76 hospitals and cancer centres in the USA, Europe, and Canada. We enrolled patients with morphologically documented primary acute myeloid leukaemia or acute myeloid leukaemia secondary to myelodysplastic syndromes and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 into two predefined, independent cohorts: patients who were aged 60 years or older with relapsed or refractory acute myeloid leukaemia within 1 year after first-line therapy (cohort 1), and those who were 18 years or older with relapsed or refractory disease following salvage chemotherapy or haemopoietic stem cell transplantation (cohort 2). Patients with an FLT3-ITD allelic frequency of more than 10% were considered as FLT3-ITD positive, whereas all other patients were considered as FLT3-ITD negative. Patients received quizartinib once daily as an oral solution; the initial 17 patients received 200 mg per day but the QTcF interval was prolonged for more than 60 ms above baseline in some of these patients. Subsequently, doses were amended for all patients to 135 mg per day for men and 90 mg per day for women. The co-primary endpoints were the proportion of patients who achieved a composite complete remission (defined as complete remission + complete remission with incomplete platelet recovery + complete remission with incomplete haematological recovery) and the proportion of patients who achieved a complete remission. Efficacy and safety analyses included all patients who received at least one dose of quizartinib (ie, the intention-to-treat population). Patients with a locally assessed post-treatment bone marrow aspirate or biopsy were included in efficacy analyses by response; all other patients were considered to have an unknown response. This study is registered with ClinicalTrials.gov, number NCT00989261, and with the European Clinical Trials Database, EudraCT 2009-013093-41, and is completed.FINDINGS: Between Nov 19, 2009, and Oct 31, 2011, a total of 333 patients were enrolled (157 in cohort 1 and 176 in cohort 2). In cohort 1, 63 (56%) of 112 FLT3-ITD-positive patients and 16 (36%) of 44 FLT3-ITD-negative patients achieved composite complete remission, with three (3%) FLT3-ITD-positive patients and two (5%) FLT3-ITD-negative patients achieving complete remission. In cohort 2, 62 (46%) of 136 FLT3-ITD-positive patients achieved composite complete remission with five (4%) achieving complete remission, whereas 12 (30%) of 40 FLT3-ITD-negative patients achieved composite complete remission with one (3%) achieving complete remission. Across both cohorts (ie, the intention-to-treat population of 333 patients), grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients were febrile neutropenia (76 [23%] of 333), anaemia (75 [23%]), thrombocytopenia (39 [12%]), QT interval corrected using Fridericia's formula (QTcF) prolongation (33 [10%]), neutropenia (31 [9%]), leucopenia (22 [7%]), decreased platelet count (20 [6%]), and pneumonia (17 [5%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (126 [38%] of 333; 76 treatment related), acute myeloid leukaemia progression (73 [22%]), pneumonia (40 [12%]; 14 treatment related), QTcF prolongation (33 [10%]; 32 treatment related), sepsis (25 [8%]; eight treatment related), and pyrexia (18 [5%]; nine treatment related). Notable serious adverse events occurring in less than 5% of patients were torsades de pointes (one [INTERPRETATION: Single-agent quizartinib was shown to be highly active and generally well tolerated in patients with relapsed or refractory acute myeloid leukaemia, particularly those with FLT3-ITD mutations. These findings confirm that targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor is a promising clinical strategy to help improve clinical outcomes in patients with very few options. Phase 3 studies (NCT02039726; NCT02668653) will examine quizartinib at lower starting doses.FUNDING: Ambit Biosciences/Daiichi Sankyo.

Published
2018

37. Prognosis for patients with amyotrophic lateral sclerosis : development and validation of a personalised prediction model

Author

Christopher J McDermott, Philip Van Damme, Beatrice Stubendorff, Markus Weber, Sonja Körner, Andrea Calvo, Christopher Shaw, Martin R Turner, Mark Heverin, Annelien L. Bredenoord, Orla Hardiman, Susanne Petri, Karel G.M. Moons, Bas M. Middelkoop, Philippe Couratier, Angela Rosenbohm, Mamede de Carvalho, Albert C. Ludolph, Wouter van Rheenen, Ruben P A van Eijk, Hannah Hollinger, Leonard H. van den Berg, Alexander G. Thompson, Mbombe Kazoka, Adriano Chiò, Anne E. Visser, A. Rödiger, A. Gunkel, Sarah Martin, Philippe Corcia, Joke van Vugt, Xenia Kobeleva, Thomas P. A. Debray, James Rooney, Pamela J. Shaw, Annelot M. Dekker, Ammar Al-Chalabi, Marta Gromicho, Alice Vajda, Kevin Talbot, Thomas M. Ringer, Helma Sommer, Julian Grosskreutz, Susana Pinto, Michael A van Es, Henk Jan Westeneng, Jan H. Veldink, Università degli studi di Torino ( UNITO ), Universidade de Lisboa, Faculdade de Ciências, Departamento de Geologia e Instituto Dom Luiz (IDL), Campo Grande, C6-4º, 1749-016 Lisboa (Portugal)., Universidade de Lisboa ( ULISBOA ), University Medical Center Utrecht, Service de Neurologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale ( NET ), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ) -CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ), German Research Center for Artificial Intelligence ( DFKI ), DFKI, Service de Neurologie, Universität Ulm, Hannover Medical School [Hannover] ( MHH ), Department of Neurology, Hospital de Santa Maria, Catholic University of Leuven ( KU Leuven ), Institute of Psychiatry, Institute of psychiatry, Trinity College Dublin, Università degli studi di Torino (UNITO), Centro de Geologia [Lisboa], Universidade de Lisboa (ULISBOA), University Medical Center [Utrecht], Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Deutsches Forschungszentrum für Künstliche Intelligenz GmbH (DFKI), Universität Ulm - Ulm University [Ulm, Allemagne], Hannover Medical School [Hannover] (MHH), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Deutsches Forschungszentrum für Künstliche Intelligenz GmbH = German Research Center for Artificial Intelligence (DFKI)

Subjects
Male, medicine.medical_specialty, Concordance, Models, Neurological, Population, Clinical Neurology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, Humans, Medicine, 030212 general & internal medicine, Precision Medicine, Amyotrophic lateral sclerosis, 10. No inequality, education, Survival analysis, Aged, education.field_of_study, Receiver operating characteristic, business.industry, Amyotrophic Lateral Sclerosis, Hazard ratio, Reproducibility of Results, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Europe, Cohort, Disease Progression, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Summary\ud Background\ud Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive, fatal motor neuron disease with a variable natural history. There are no accurate models that predict the disease course and outcomes, which complicates risk assessment and counselling for individual patients, stratification of patients for trials, and timing of interventions. We therefore aimed to develop and validate a model for predicting a composite survival endpoint for individual patients with ALS.\ud \ud Methods\ud We obtained data for patients from 14 specialised ALS centres (each one designated as a cohort) in Belgium, France, the Netherlands, Germany, Ireland, Italy, Portugal, Switzerland, and the UK. All patients were diagnosed in the centres after excluding other diagnoses and classified according to revised El Escorial criteria. We assessed 16 patient characteristics as potential predictors of a composite survival outcome (time between onset of symptoms and non-invasive ventilation for more than 23 h per day, tracheostomy, or death) and applied backward elimination with bootstrapping in the largest population-based dataset for predictor selection. Data were gathered on the day of diagnosis or as soon as possible thereafter. Predictors that were selected in more than 70% of the bootstrap resamples were used to develop a multivariable Royston-Parmar model for predicting the composite survival outcome in individual patients. We assessed the generalisability of the model by estimating heterogeneity of predictive accuracy across external populations (ie, populations not used to develop the model) using internal–external cross-validation, and quantified the discrimination using the concordance (c) statistic (area under the receiver operator characteristic curve) and calibration using a calibration slope.\ud \ud Findings\ud Data were collected between Jan 1, 1992, and Sept 22, 2016 (the largest data-set included data from 1936 patients). The median follow-up time was 97·5 months (IQR 52·9–168·5). Eight candidate predictors entered the prediction model: bulbar versus non-bulbar onset (univariable hazard ratio [HR] 1·71, 95% CI 1·63–1·79), age at onset (1·03, 1·03–1·03), definite versus probable or possible ALS (1·47, 1·39–1·55), diagnostic delay (0·52, 0·51–0·53), forced vital capacity (HR 0·99, 0·99–0·99), progression rate (6·33, 5·92–6·76), frontotemporal dementia (1·34, 1·20–1·50), and presence of a C9orf72 repeat expansion (1·45, 1·31–1·61), all p

Published
2018

38. Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial

Author

Hubert Schrezenmeier, Pierre Layrolle, Harald Gjengedal, Annika Rosén, Xie-Qi Shi, Kamal Mustafa, Xin Feng, Siren Skaale, Sølve Hellem, Bjørn Tore Gjertsen, Trond Inge Berge, Markus Rojewski, Mohammed A. Yassin, Cecilie Gudveig Gjerde, Aymen Bushra Ahmed, Institute of Clinical Dentistry [Bergen, Norway], University of Bergen (UiB), Institute for Clinical Transfusion Medicine and Immunogenetics [Ulm, Germany], German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, Institute of Transfusion Medicine [Ulm, Germany], Universität Ulm - Ulm University [Ulm, Allemagne], Department of Fibre and Polymer Technology [Stockholm, Sweden], Royal Institute of Technology [Stockholm] (KTH ), Department of Clinical Science [Bergen, Norway] (Section for Hematology ), Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB), Department of Clinical Science [Bergen, Norway] (Precision Oncology Research Group), Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), The financial support of the European Union’s Seventh Framework Programme under grant agreement number 241879—REBORNE is acknowledged. The authors also acknowledge the significant contribution by Institut Straumann AG (Basel, Switzerland) for providing the dental implants, Osteogenics Biomedical (Lubbock, TX, USA for the Cytoplast polytetrafluoroethylene membranes, an Ostell (Gothenburg, Sweden) for the Ostell device., maurice, sandrine, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
0301 basic medicine, Male, Bone Regeneration, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Alveolar Bone Loss, Cell- and Tissue-Based Therapy, Medicine (miscellaneous), Dentistry, Biphasic calcium phosphate, Bone tissue engineering, 0302 clinical medicine, lcsh:QD415-436, Alveolar ridge augmentation, Dental implant, Aged, 80 and over, lcsh:R5-920, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Bone Transplantation, Alveolar Ridge Augmentation, Middle Aged, 3. Good health, Resorption, medicine.anatomical_structure, Molecular Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, Hydroxyapatites, lcsh:Medicine (General), Adult, Adolescent, Bone Marrow Cells, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Biochemistry, Genetics and Molecular Biology (miscellaneous), lcsh:Biochemistry, 03 medical and health sciences, Young Adult, Alveolar ridge, medicine, Humans, Bone regeneration, Aged, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Dental Implants, Wound Healing, Tissue Engineering, business.industry, Research, Mesenchymal stem cell, Mesenchymal Stem Cells, 030206 dentistry, Cell Biology, 030104 developmental biology, Implant, Bone marrow, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Autologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autologous bone grafting. This comprehensive clinical trial included subjects with severe mandibular ridge resorption. Methods The study included 11 subjects aged 52–79 years with severe mandibular ridge resorption. Bone marrow cells were aspirated from the posterior iliac crest and plastic adherent cells were expanded in culture medium containing human platelet lysate. The MSCs and biphasic calcium phosphate granules as scaffolds were inserted subperiosteally onto the resorbed alveolar ridge. After 4–6 months of healing, new bone formation was assessed clinically and radiographically, as were safety and feasibility. Bone at the implant site was biopsied for micro-computed topography and histological analyses and dental implants were placed in the newly regenerated bone. Functional outcomes and patient satisfaction were assessed after 12 months. Results The bone marrow cells, expanded in vitro and inserted into the defect together with biphasic calcium phosphate granules, induced significant new bone formation. The regenerated bone volume was adequate for dental implant installation. Healing was uneventful, without adverse events. The patients were satisfied with the esthetic and functional outcomes. No side effects were observed. Conclusions The results of this comprehensive clinical trial in human subjects confirm that MSCs can successfully induce significant formation of new bone, with no untoward sequelae. Hence, this novel augmentation procedure warrants further investigation and may form the basis of a valid treatment protocol, challenging the current gold standard. Trial registration EudraCT, 2012-003139-50. Registered on 21 August 2013. ClinicalTrials.gov, NCT 02751125. Registered on 26 April 2016.

Published
2018

39. Research frontiers for improving our understanding of drought-induced tree and forest mortality

Author

Jasper Bloemen, Michael O'Brien, Catarina F. Moura, Steven Jansen, Thorsten E. E. Grams, Hendrik Davi, Henry D. Adams, Jan Wunder, Nadine K. Ruehr, Henrik Hartmann, Richard Cobb, Stefan K. Arndt, Maxime Cailleret, Markus Kautz, William R. L. Anderegg, David W. Galbraith, Arthur Gessler, Craig D. Allen, Yann Salmon, Katinka X. Ruthrof, Francisco Lloret, David D. Breshears, Max Planck Institute for Biogeochemistry (MPI-BGC), Max-Planck-Gesellschaft, Universidade de Coimbra, Universidade Técnica de Lisboa, Dept Biol, Utah State University (USU), Karlsruhe Institute of Technology (KIT), University of Helsinki, University of Edinburgh, University of Melbourne, University of Arizona, Dept Ecol & Evolutionary Biol, University of Toronto, Ecologie des Forêts Méditerranéennes (URFM), Institut National de la Recherche Agronomique (INRA), Univ Leeds, Sch Geog, Leeds LS2 9JT, W Yorkshire, England, Partenaires INRAE, Murdoch University, Botanic Gardens & Parks Authority, Swiss Federal Institute for Forest, Snow and Landscape Research WSL, University of Auckland [Auckland], Oklahoma State Univ, Dept Plant Biol Ecol & Evolut, 301 Phys Sci, Stillwater, OK 74078 USA, Univ Innsbruck, Inst Ecol, Sternwartestr 15, A-6020 Innsbruck, Austria, Univ Antwerp, Dept Biol, B-2610 Antwerp, Belgium, Institute of Animal Science, California State Polytechnic University - San Luis Obispo, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Inst Systemat Bot & Ecol, Universität Ulm - Ulm University [Ulm, Allemagne], Centre de Recerca Ecològica i Aplicacions Forestals - Centre for Ecological Research and Forestry Applications, Universitat Autònoma de Barcelona (UAB), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Portuguese Foundation for Science and Technology (FCT) SFRH/BPD/47131/2008, PTDC/AAG-MAA/3699/2014,UID/BIA/04004/2013, NERC RA0929, Academy of Finland 1284701, German Federal Ministry of Education and Research (BMBF) RU 1657/2-1 National Science Foundation NSF CNH 1714972,NSF EF-1340624,EF-1550756,EAR-1331408, USDA National Institute of Food and Agriculture, 2017-05521, Spanish MINECO CGL2015-67419-R, Catalonian Government AGAUR 2014-SGR-00453, ANR 310030L_156661, European Project: 603542,EC:FP7:ENV,FP7-ENV-2013-two-stage,LUC4C(2013), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Leeds, Universität Innsbruck [Innsbruck], and University of Antwerp (UA)

Subjects
0106 biological sciences, 010504 meteorology & atmospheric sciences, Physiology, Mortality Map, tree death, Climate change, Plant Science, Forests, 01 natural sciences, Trees, Ecosystem services, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Ecosystem, Political authorities, Biology, monitoring network, Probability, carbon-water cycling, 0105 earth and related environmental sciences, Geography, business.industry, Environmental resource management, Global change, Models, Theoretical, 15. Life on land, Droughts, Tree (data structure), 13. Climate action, Scale (social sciences), insects and pathogens, dynamic vegetation models, business, Forecasting, 010606 plant biology & botany
Abstract

International audience; nitori Accumulating evidence highlights increased mortality risks for trees during severe drought, particularly under warmer temperatures and increasing vapour pressure deficit (VPD). Resulting forest die-off events have severe consequences for ecosystem services, biophysical and biogeochemical land-atmosphere processes. Despite advances in monitoring, modelling and experimental studies of the causes and consequences of tree death from individual tree to ecosystem and global scale, a general mechanistic understanding and realistic predictions of drought mortality under future climate conditions are still lacking. We update a global tree mortality map and present a roadmap to a more holistic understanding of forest mortality across scales. We highlight priority research frontiers that promote: (1) new avenues for research on key tree ecophysiological responses to drought; (2) scaling from the tree/plot level to the ecosystem and region; (3) improvements of mortality risk predictions based on both empirical and mechanistic insights; and (4) a global mong network of forest mortality. In light of recent and anticipated large forest die-off events such a research agenda is timely and needed to achieve scientific understanding for realistic predictions of drought-induced tree mortality. The implementation of a sustainable network will require support by stakeholders and political authorities at the international level.

Published
2018

40. Before the ICU: does emergency room hyperoxia affect outcome?

Author

Peter Radermacher, Martin Wepler, Enrico Calzia, Julien Demiselle, Pierre Asfar, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Universitätsklinikum Ulm - University Hospital of Ulm, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Universität Ulm - Ulm University [Ulm, Allemagne]

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], MEDLINE, Hospital mortality, Hyperoxia, Critical Care and Intensive Care Medicine, Affect (psychology), Outcome (game theory), 03 medical and health sciences, Hospital, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Hospital Mortality, ComputingMilieux_MISCELLANEOUS, Emergency Service, business.industry, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Oxygen, Editorial, Emergency medicine, medicine.symptom, business, Emergency Service, Hospital
Abstract

International audience

Published
2018

41. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Guideline development process for the updated guidelines

Author

S. Lohner, Koen F. M. Joosten, Mary Fewtrell, R. Shamir, Magnus Domellöf, Miguel Saenz de Pipaon, Thibault Senterre, Tamás Decsi, Dieter Mesotten, Jiang Wu, Christine Prell, Jean Charles Picaud, Nicholas D. Embleton, Sanja Kolaček, K. Mihályi, Vlasselaers Dirk, Arieh Riskin, J.B. van Goudoever, Anne A.M.W. van Kempen, Frank Jochum, Jiri Bronsky, Szimonetta Lohner, Sascha Verbruggen, Antonia Nomayo, Virgilio P. Carnielli, Sissel J. Moltu, A. Lapillonne, Olivier Goulet, Weihui Yan, Merit M. Tabbers, Christian Braegger, W. Mihatsch, M. Fewtrell, Krisztina Mihalyi, Silvia Iacobelli, Susan Hill, Janusz Ksiazyk, Raanan Shamir, Berthold Koletzko, Iva Hojsak, Francis B. Mimouni, Johannes B. van Goudoever, John W L Puntis, Alexandre Lapillonne, Walter A. Mihatsch, Venetia Simchowitz, Chris H. B. van den Akker, Dominique Darmaun, Nataša Fidler Mis, Corina Hartman, Axel R. Franz, Wei Cai, Cristina Campoy, Peter Szitanyi, Christian Mølgaard, Paediatrics, ARD - Amsterdam Reproduction and Development, AGEM - Digestive immunity, Paediatric Gastroenterology, AGEM - Re-generation and cancer of the digestive system, Neonatology, Universität Ulm - Ulm University [Ulm, Allemagne], Tel Aviv University [Tel Aviv], Vrije Universiteit Amsterdam [Amsterdam] (VU), Institute of Child London (UCL), Moorfields Eye Hospital, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), University of Pecs, Centre d'Études Périnatales de l'Océan Indien (CEPOI), Université de La Réunion (UR)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Sud Saint Pierre [Ile de la Réunion], Pediatric surgery, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, Amsterdam Reproduction & Development (AR&D), and Pediatrics

Subjects
0301 basic medicine, medicine.medical_specialty, Parenteral Nutrition, Consensus, Adolescent, [SDV]Life Sciences [q-bio], MEDLINE, Clinical nutrition, Online voting, Critical Care and Intensive Care Medicine, 03 medical and health sciences, Paediatric gastroenterology, Medicine, Humans, Guideline development, Child, ComputingMilieux_MISCELLANEOUS, Extremely premature, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, development process, Infant, Newborn, Infant, Pediatric parenteral nutrition, Guideline, 3. Good health, Parenteral nutrition, Family medicine, Child, Preschool, Practice Guidelines as Topic, business, Child Nutritional Physiological Phenomena
Abstract

Background: Previous guidelines on Paediatric Parenteral Nutrition (PN) were published in 2010, by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR) were published. The aim of the present paper was to provide up-to-date evidence for health professionals working with infants, children and adolescents receiving PN. Methods: The current document is a revision of the 2005 guidelines produced by the same 3 organizations (ESPEN, ESPGHAN, ESPR) together with the Chinese Society of Parenteral and Enteral Nutrition (CSPEN). Experts participating in the guideline updating process were all professionals with extensive experience in managing PN from a wide range of European countries, Israel and China. The guideline development process was coordinated by a guideline steering committee. Each chapter of the guideline was prepared by a separate author group. These author groups were responsible for screening titles and abstracts identified by a systematic literature search for inclusion, for conducting additional expert searches (including secondary sources such as other published valid guidelines), for evaluating the quality of studies included in the given chapter and assigning evidence levels to the literature. Based on the evidence level of included studies experts formulated and graded recommendations. A consensus conference was held in February 2015. All chapter manuscripts were revised following the recommendations of the consensus conference and then reviewed and edited by the project steering committee. Final consensus on each individual guideline and its individual recommendations was achieved and assessed by online voting. This process lasted until January 2018. Funding for the consensus conference (including travel expenses for participants) was provided by all participating societies. No other funding was received for the guideline updating process and participants received no payment. Support was provided by the Hungarian Cochrane organization. Results/conclusions: The present document provides guideline for the use of PN across the wide range of pediatric patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg [1]. It covers their individual macro- and micronutrient needs [2], [3], [4], [5], [6], [7], [8], fluid requirements [9], venous access [10], organizational aspects [11], home parenteral nutrition [12], standardized vs. individualized PN [13], and last but not least a wide range of safety considerations for prevention and management of complications such central line associated bloodstream infections (CLABSI)

Published
2018

42. ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—update on methodological approaches and results interpretation

Author

Richard Rosenquist, Eugen Tausch, Thorsten Zenz, M. Gonzalez Diaz, D. Rossi, Lesley-Ann Sutton, K. Stamatopoulos, Frederic Davi, S. Stilgenbauer, Carsten Utoft Niemann, Carol Moreno, Gianluca Gaidano, Šárka Pospíšilová, David Gonzalez, Arnon P. Kater, Jitka Malčíková, Thierry Soussi, Paolo Ghia, CCA - Cancer biology and immunology, Experimental Immunology, Clinical Haematology, AII - Amsterdam institute for Infection and Immunity, AII - Inflammatory diseases, Malcikova, J., Tausch, E., Rossi, D., Sutton, L. A., Soussi, T., Zenz, T., Kater, A. P., Niemann, C. U., Gonzalez, D., Davi, F., Gonzalez Diaz, M., Moreno, C., Gaidano, G., Stamatopoulos, K., Rosenquist, R., Stilgenbauer, S., Ghia, P., Pospisilova, S., Masaryk University, Universität Ulm - Ulm University [Ulm, Allemagne], Oncology Institute of Southern Switzerland (IOSI), Uppsala University, Karolinska Institutet [Stockholm], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cancer Center Karolinska [Karolinska Institutet] (CCK), University hospital of Zurich [Zurich], University of Zürich [Zürich] (UZH), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Rigshospitalet [Copenhagen], Queen's University [Belfast] (QUB), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Universidad de Salamanca, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona [Barcelona] (UAB), CERTH, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), Universita Vita Salute San Raffaele (UniSR), Masaryk University [Brno] (MUNI), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universität Zürich [Zürich] = University of Zurich (UZH), Copenhagen University Hospital, Service d'Hématologie clinique [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), Universitat Autònoma de Barcelona (UAB), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), University of Zurich, and Ghia, P

Subjects
0301 basic medicine, medicine.medical_specialty, Cancer Research, endocrine system diseases, Chronic lymphocytic leukemia, 2720 Hematology, DNA Mutational Analysis, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, 610 Medicine & health, Review, Review Article, Tp53 mutation, 03 medical and health sciences, 0302 clinical medicine, Chemoimmunotherapy, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Journal Article, Humans, In patient, 1306 Cancer Research, Hematologi, Intensive care medicine, neoplasms, Cancer och onkologi, Hematology, business.industry, breakpoint cluster region, High-Throughput Nucleotide Sequencing, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Clinic for Hematology, medicine.disease, Genes, p53, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Europe, Leukemia, 030104 developmental biology, Anesthesiology and Pain Medicine, Oncology, 030220 oncology & carcinogenesis, Cancer and Oncology, 10032 Clinic for Oncology and Hematology, 2730 Oncology, business
Abstract

Altres ajuts: Supported by the IMI 2 HARMONY JU under GA No 116026, this JU receives support from the EU's H2020 R&I program and EFPIA. Further supported by the EU Horizon 2020 projects MEDGENET 692298, AEGLE 644906, projects CEITEC 2020 (LQ1601), NCMG research infrastructure (LM2015091 funded by MEYS CR), project FNBr 65269705, FM MU ROZV/24/LF/2016, DFG (SFB1074, projects B1 and B2, and EU (FIRE CLL)), and the Swedish Cancer Society and the Swedish Research Council. Publication reflects only the authors' views and the Commission is not responsible for any use that may be made of the information it contains. In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i.e., inhibitors of B-cell receptor (BcR) signaling and anti-apoptotic BCL2 family members, owing to their efficacy in patients with TP53 defects. In this report, the TP53 Network of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) presents updated recommendations on the methodological approaches for TP53 mutation analysis. Moreover, it provides guidance to ensure that the analysis is performed in a timely manner for all patients requiring treatment and that the data is interpreted and reported in a consistent, standardized, and accurate way. Since next-generation sequencing technologies are gaining prominence within diagnostic laboratories, this report also offers advice and recommendations for the interpretation of TP53 mutation data generated by this methodology.

Published
2018
Full Text
View/download PDF

43. White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation

Author

Henrik Zetterberg, Kaj Blennow, Martin R Turner, Charlotte E. Teunissen, Sylvain Lehmann, Armand Perret-Liaudet, Markus Otto, Hayrettin Tumani, Sanna-Kaisa Herukka, Marcel M. Verbeek, Lucilla Parnetti, Sebastiaan Engelborghs, Piotr Lewczuk, Jens Wiltfang, Alberto Lleó, VU University Medical Center [Amsterdam], Universität Ulm - Ulm University [Ulm, Allemagne], University of Eastern Finland, Plateforme de Protéomique Clinique, CHU Saint-Eloi, 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), 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), Universität Duisburg-Essen [Essen], University of Gothenburg (GU), and Neurology

Subjects
0301 basic medicine, Education Biomarkers, Neurology, [SDV]Life Sciences [q-bio], Disease, Review, lcsh:RC346-429, 0302 clinical medicine, White paper, Medizinische Fakultät, Medicine, Biomarker discovery, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), ComputingMilieux_MISCELLANEOUS, Clinical implementation, Medicine(all), Clinical neurochemistry, Assay development, Neurochemistry, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, cerebrospinal fluid [Alzheimer Disease], Cerebrospinal fluid, Body fluids, cerebrospinal fluid [Biomarkers], Biomarker (medicine), medicine.medical_specialty, Cognitive Neuroscience, education, Society, Neurology (clinical), lcsh:RC321-571, 03 medical and health sciences, Alzheimer Disease, Humans, ddc:610, Intensive care medicine, Biology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, business.industry, Clinical study design, 030104 developmental biology, Human medicine, business, 030217 neurology & neurosurgery, Geriatric psychiatry, Biomarkers
Abstract

Altres ajuts: C. E. Teunissen PhD received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer's Drug Discovery Foundation, Alzheimer Netherlands. M. Otto MD PhD received funding from the EU, German ministry of science and technology (KNDD/FTLD) the Baden-Wuertemberg Foundation. Sebastiaan Engelborghs MD, PhD received funding from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant number 115372); the University Research Fund of the University of Antwerp; the Flemish Impulse Financing of Networks for Dementia Research (VIND); and Flanders Innovation & Entrepreneurship (VLAIO). Sanna-Kaisa Herukka MD, PhD received funding from Finnish Medical Foundation and Finnish Medical Society Duodecim. Sylvain Lehmann MD, PhD has received support from "France Alzheimer", the National French Alzheimer effort ("Plan Alzheimer"). Piotr Lewczuk MD, PhD has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement number 115372, resources of which are composed of financia contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in kind contribution. Hayrettin Tumani MD received research support from Hertie-Stiftung, BMBF, University of Ulm and Landesstiftung BW. Martin R. Turner MBBS, PhD is supported by the Medical Research Council & Motor Neurone Disease Association Lady Edith Wolfson Senior Clinical Fellowship (MR/K01014X/1). MM Verbeek PhD received grants from Alzheimer Nederland (number 14502) and the CAVIA project, which has been made possible by ZonMW (number 733050202). The CAVIA project is part of 'Memorabel', the research and innovation programme for dementia, as part of the Dutch national 'Deltaplan for Dementia': zonmw.nl/dementiaresearch. The CAVIA project is a consortium of Radboudumc, LUMC, Erasmus MC, VUmc, ADX Neurosciences, Philips Healthcare, Stony Brook University and Massachusetts General Hospital. Jens Wiltfang is supported by an Ilídio Pinho professorship and iBiMED (UID/BIM/04501/2013), at the University of Aveiro, Portugal. Lucilla Parnetti MD, PhD, received grants from EU-FP 6 and 7 (cNeupro, PharmaCog), MJFF, Italian Ministry of University and Research and Italian Ministry of Health. K Blennow MD, PhD holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences. Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e.g. initial mass spectrometry proteomic low-throughput studies into immunoassays for widespread clinical implementation; iii) lack of interaction among all stakeholders to optimise and adapt study designs throughout the biomarker development process to medical needs, which may change during the long period needed for biomarker development. The Society for CSF Analysis and Clinical Neurochemistry (established in 2015) has been founded as a concerted follow-up of large standardisation projects, including BIOMARKAPD and SOPHIA, and the BioMS-consortium. The main aims of the CSF society are to exchange high level international scientific experience, to facilitate the incorporation of CSF diagnostics into clinical practice and to give advice on inclusion of CSF analysis into clinical guidelines. The society has a broad scope, as its vision is that the gaps in development and implementation of biomarkers are shared among almost all neurological diseases and thus they can benefit from the activities of the society.

Published
2018

44. Human milk oligosaccharides: 2-Fucosyllactose (2-FL) and Lacto-N-Neotetraose (LNnT) in infant formula

Author

Virgilio P. Carnielli, Hanna Lagström, Jean-Charles Picaud, Manuel Sánchez Luna, Martin Wabitsch, Yvan Vandenplas, Janusz Ksiazyk, N.B. Migacheva, Jean-Marc Mosselmans, Bernard Berger, Mike Possner, Atul Singhal, Vrije Universiteit Brussel (VUB), Nestec Ltd, Polytechnic University of Marche, The Children’s Memorial Health Institute, Department of Public Health, Turku University Hospital (TYKS)-University of Turku, Turku University Hospital (TYKS), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Samara National Research University, Independent, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Nestlé, UCL Great Ormond Street Institute of Child Health, Partenaires INRAE, Universität Ulm - Ulm University [Ulm, Allemagne], Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nestlé S.A., ProdInra, Migration, Clinical sciences, Growth and Development, and Pediatrics

Subjects
0301 basic medicine, Oligosaccharides, Physiology, bifidobacteria, Review, formula feeding, Gut flora, Health benefits, chemistry.chemical_compound, Child Development, Lactation, human milk oligosaccharide, Medicine, Intestinal Mucosa, Infant Nutritional Physiological Phenomena, health care economics and organizations, Nutrition and Dietetics, biology, Brain, Infant Formula, 3. Good health, medicine.anatomical_structure, breast feeding, 2-fucosyllactose, Alimentation et Nutrition, lcsh:Nutrition. Foods and food supply, Nutritive Value, Lacto-N-neotetraose, Nutritional Status, lcsh:TX341-641, 03 medical and health sciences, 2'-Fucosyllactose, Immune system, 2'-fucosyllactose, microbiota, Animals, Humans, Food and Nutrition, Immunity, Mucosal, 030109 nutrition & dietetics, Milk, Human, business.industry, Infant, Newborn, biology.organism_classification, Gastrointestinal Microbiome, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, chemistry, Infant formula, business, Trisaccharides, Breast feeding, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 2′-fucosyllactose, Food Science
Abstract

The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies. The still limited data of trials evaluating the effect of mainly 2′-fucosyllactose (2′-FL) on the addition of some of HMOs to infant formula were also reviewed. PubMed was searched from January 1990 to April 2018. The amount of HMOs in mother’s milk is a dynamic process as it changes over time. Many factors, such as duration of lactation, environmental, and genetic factors, influence the amount of HMOs. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. The limited clinical data suggest that the addition of HMOs to infant formula seems to be safe and well tolerated, inducing a normal growth and suggesting a trend towards health benefits. HMOs are one of the major differences between cow’s milk and human milk, and available evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk. More prospective, randomized trials in infants are need to evaluate the clinical benefit of supplementing infant formula with HMOs.

Published
2018

45. Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial

Author

Nicola Baldini, Elena Veronesi, Nathalie Chevallier, Enrique Gómez-Barrena, Philippe Rosset, Pierre Layrolle, Philippe Hernigou, Cristina Avendaño-Solá, Gabriela Ciapetti, Sandrine Fleury, Massimo Dominici, Tiziana Montemurro, Rosaria Giordano, José Cordero-Ampuero, Jose Rafael Cabrera, M.N. Fernández, Hélène Rouard, Juan Carlos Rubio-Suárez, Ramin Lotfi, Markus Rojewski, Christian Ehrnthaller, Luc Sensebé, Hubert Schrezenmeier, Markus Huber-Lang, Florian Gebhard, Charles Henri Flouzat-Lachaniette, Norma G. Padilla-Eguiluz, Julien Stanovici, Davide Maria Donati, Carmen Panaitescu, Rosa Gonzalo-Daganzo, Eduardo García-Rey, Servicio de Cirugía Ortopédica y Traumatología [Madrid, Spain], Universidad Autonoma de Madrid (UAM)-Hospital Universitario La Paz-IdiPAZ and Facultad de Medicina [Madrid, Spain], Service de Chirurgie Orthopédique et Traumatologique 2 [CHU Tours], Hôpital Trousseau (Tours)-Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery [Ulm, Germany], Universität Ulm - Ulm University [Ulm, Allemagne]-Center of Surgery [Ulm, Germany], Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine [Bologna, Italy], University of Bologna-Department of Biomedical and Neuromotor Sciences [Bologna, Italy], Istituto Ortopedico Rizzoli [Bologna, Italy]-Istituto Ortopedico Rizzoli [Bologna, Italy], Etablissement Français du Sang Ile de France (EFS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Servicio de Hematología [Madrid, Spain], Universidad Autonoma de Madrid (UAM)-Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Cell Factory, Center for Cellular Therapy and Cryobiology [Milano, Italy], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Victor Babes University of Medicine and Pharmacy [Timisoara, Romania], Laboratory of Cellular Therapies [Modena, Italy], University - Hospital of Modena and Reggio Emilia [Modena, Italy]- Department of Medical and Surgical Sciences for Children & Adults [Modena, Italy], Institute for Clinical Transfusion Medicine and Immunogenetic Ulm [Ulm, Germany], Institut für Klinische Transfusionsmedizin und Immungenetik Ulm -IKT [Ulm, Germany], Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876)., Hospital Universitario La Paz-IdiPAZ and Facultad de Medicina [Madrid, Spain]-Universidad Autonoma de Madrid (UAM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université Francois Rabelais [Tours]-Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Victor Babeş University of Medicine and Pharmacy (UMFT), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), UAM. Departamento de Cirugía, UAM. Departamento de Farmacología, UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours]-Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Gómez-Barrena, Enrique, Rosset, Philippe, Gebhard, Florian, Hernigou, Philippe, Baldini, Nicola, Rouard, Helène, Sensebé, Luc, Gonzalo-Daganzo, Rosa M., Giordano, Rosaria, Padilla-Eguiluz, Norma, García-Rey, Eduardo, Cordero-Ampuero, José, Rubio-Suárez, Juan Carlo, Stanovici, Julien, Ehrnthaller, Christian, Huber-Lang, Marku, Flouzat-Lachaniette, Charles Henri, Chevallier, Nathalie, Donati, Davide Maria, Ciapetti, Gabriela, Fleury, Sandrine, Fernandez, Manuel-Nicolá, Cabrera, José-Rafael, Avendaño-Solá, Cristina, Montemurro, Tiziana, Panaitescu, Carmen, Veronesi, Elena, Rojewski, Markus Thoma, Lotfi, Ramin, Dominici, Massimo, Schrezenmeier, Hubert, Layrolle, Pierre, Universidad Autónoma de Madrid (UAM)-Hospital Universitario La Paz-IdiPAZ and Facultad de Medicina [Madrid, Spain], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours], University of Bologna/Università di Bologna-Department of Biomedical and Neuromotor Sciences [Bologna, Italy], Universidad Autónoma de Madrid (UAM)-Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), and maurice, sandrine

Subjects
Calcium Phosphates, Biocompatible Materials, 02 engineering and technology, Bone tissue engineering, Fractures, Bone, Femur, media_common, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 021001 nanoscience & nanotechnology, 3. Good health, Clinical trial, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Mechanics of Materials, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, medicine.medical_specialty, Bioceramic, Medicina, Biophysics, Ceramics and Composite, Bioengineering, Mesenchymal Stem Cell Transplantation, Non-union, Transplantation, Autologous, Non union, Expanded autologous BM-hMSC, Biomaterials, 03 medical and health sciences, medicine, media_common.cataloged_instance, Humans, Humerus, Tibia, European union, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, 030304 developmental biology, Cell Proliferation, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Mesenchymal stem cell, Mesenchymal Stem Cells, ATMP, Biomaterial, Surgery, [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, Biophysic, Fractures, Ununited, Ceramics and Composites, Feasibility Studies, Bone marrow, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. Methods: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5–10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. Findings: With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). Interpretation: Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. Funding: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876)., The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/FP7-HEALTH-2009); REBORNE Project (GA: 241876)

Published
2017

46. On the Use of Emojis in Mobile Authentication

Author

Marcel Walch, Sebastian Möller, Lydia Kraus, Florian Schaub, Robert Schmidt, Technische Universität Berlin (TU), Universität Ulm - Ulm University [Ulm, Allemagne], University of Michigan [Ann Arbor], University of Michigan System, Sabrina De Capitani di Vimercati, Fabio Martinelli, and TC 11

Subjects
Scheme (programming language), Mobile authentication, Emoji, Computer science, Usability, 02 engineering and technology, Computer security, computer.software_genre, User experience design, 020204 information systems, Lightweight Extensible Authentication Protocol, 0202 electrical engineering, electronic engineering, information engineering, [INFO]Computer Science [cs], computer.programming_language, Password, Authentication, User experience, business.industry, Chip Authentication Program, ComputingMilieux_MANAGEMENTOFCOMPUTINGANDINFORMATIONSYSTEMS, Security, 020201 artificial intelligence & image processing, business, computer
Abstract

Part 5: User Authentication and Policies; International audience; Mobile authentication methods protect smartphones from unauthorized access, but also require users to remember and frequently enter PINs, passwords, or graphical patterns. We propose the EmojiAuth scheme with which we study the effects of Emoji use on the usability and user experience of mobile authentication. We conducted two between-subjects studies (lab study: n = 53; field study: n = 41) comparing EmojiAuth to standard PIN entry. We find that EmojiAuth provides good memorability for short passwords and reasonable memorability for longer passwords. Moreover, we identify diverse Emoji-password selection strategies and provide insights on the practical security of Emoji-based mobile authentication. Our results suggest that Emoji-based authentication constitutes a practical alternative to traditional PIN authentication.

Published
2017

47. Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis : a randomised, double-blind, placebo-controlled, phase 2 trial

Author

Stephen DeWall, Karen E. Morrison, Alain Destée, Andrea Calvo, Annelot M. Dekker, Francesca Barbieri, Philip Van Damme, James D. Berry, Robert D. Henderson, Claude Desnuelle, Johannes Dorst, Linda O. Nichols, Jerzy Daniluk, Sonja Koerner, Adriano Chiò, Kristiana Salmon, Pierre-François Pradat, Albert C. Ludolph, Genevieve Matte, Harutoshi Fujimura, Gaëlle Bruneteau, Stewart Bates, Giuseppe Fuda, Torsten Grehl, Usha Gungabissoon, Andrea Sylvia Winkler, Byung Jo Kim, Eleanor Ramsey, Christen Shoesmith, Peggy Ho, Matthew C. Kiernan, Rodrigo Refoios Camejo, Saiju Jacob, Rob Stubbs, Thomas M. Ringer, Jonathan Bullman, Stephan A Botez, Michael A. van Es, Xenia Kobeleva, Stefano Milleri, Wim Robberecht, William Huynh, Mary Lou Watson, Mieko Ogino, Seung Hyun Kim, Chris Parkinson, Diane Boswell, Stephen J. Kolb, Jeremy M. Shefner, Katja Kollewe, Jane R. Temple, Paul Rees, Julian Grosskreutz, Deven Chauhan, K. Nishiyama, Leonard H. van den Berg, Marloes Stam, Susanne Petri, Rami Massie, Darryl Menezes, Tino Prell, Anthony Lynch, Raul Juntas-Morales, Andreas Funke, P. Nigel Leigh, Lawrence Korngut, Angela Genge, Cathy Alsop, Margie C. Zoing, Arseniy Lavrov, Rajat Mohindra, Anne E. Visser, Susanne Abdulla, Veronique Danel-Brunaud, William Camu, Matt Davies, Amy Lee, Erik Steinberg, Lorne Zinman, Jeffrey Price, Marie Helene Soriani, Matthew S Devine, Vincent Meininger, Géraldine Lautrette, Herman Sullivan, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], University Medical Center [Utrecht], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Universität Ulm - Ulm University [Ulm, Allemagne], Università degli studi di Torino (UNITO), Brighton and Sussex Medical School (BSMS), The University of Sydney, Barrow Neurological Institute, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), University of Birmingham [Birmingham], University of Southampton, Hannover Medical School [Hannover] (MHH), GlaxoSmithKline, Glaxo Smith Kline, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Neurologie [CHU Limoges], CHU Limoges, McGill University, and Université Côte d'Azur (UCA)

Subjects
0301 basic medicine, Male, International Cooperation, law.invention, Clinical Trial, Phase II, Electrocardiography, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Depression (differential diagnoses), Aged, 80 and over, Age Factors, Middle Aged, Clinical Trial, Phase II, 3. Good health, Multicenter Study, Treatment Outcome, RC0346, Randomized Controlled Trial, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, psychological phenomena and processes, Adult, medicine.medical_specialty, Adolescent, Nogo Proteins, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Young Adult, Double-Blind Method, Internal medicine, mental disorders, Journal Article, Humans, Immunologic Factors, Adverse effect, Aged, business.industry, Ozanezumab, Amyotrophic Lateral Sclerosis, Survival Analysis, Surgery, Discontinuation, Clinical trial, 030104 developmental biology, Respiratory failure, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Summary Background Neurite outgrowth inhibitor A (Nogo-A) is thought to have a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). A monoclonal antibody against Nogo-A showed a positive effect in the SOD1 G93A mouse model of ALS, and a humanised form of this antibody (ozanezumab) was well tolerated in a first-in-human trial. Therefore, we aimed to assess the safety and efficacy of ozanezumab in patients with ALS. Methods This randomised, double-blind, placebo-controlled, phase 2 trial was done in 34 centres in 11 countries. Patients aged 18–80 years with a diagnosis of familial or sporadic ALS were randomly assigned (1:1), centrally according to a computer-generated allocation schedule, to receive ozanezumab (15 mg/kg) or placebo as intravenous infusions over 1 h every 2 weeks for 46 weeks, followed by assessments at week 48 and week 60. Patients and study personnel were masked to treatment assignment. The primary outcome was a joint-rank analysis of function (ALS Functional Rating Scale-Revised) and overall survival, analysed at 48 weeks in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01753076, and with GSK-ClinicalStudyRegister.com, NOG112264, and is completed. Findings Between Dec 20, 2012, and Nov 1, 2013, we recruited 307 patients, of whom 303 were randomly assigned to receive placebo (n=151) or ozanezumab (n=152). The adjusted mean of the joint-rank score was −14·9 (SE 13·5) for the ozanezumab group and 15·0 (13·6) for the placebo group, with a least squares mean difference of −30·0 (95% CI −67·9 to 7·9; p=0·12). Overall, reported adverse events, serious adverse events, and adverse events leading to permanent discontinuation of study drug or withdrawal from study were similar between the treatment groups, except for dyspepsia (ten [7%] in the ozanezumab group vs four [3%] in the placebo group), depression (11 [7%] vs five [3%]), and diarrhoea (25 [16%] vs 12 [8%]). Respiratory failure was the most common serious adverse event (12 [8%] vs seven [5%]). At week 60, the number of deaths was higher in the ozanezumab group (20 [13%]) than in the placebo group (16 [11%]), mainly as a result of respiratory failure (ten [7%] vs five [3%]). Two deaths were considered related to the study drug (bladder transitional cell carcinoma in the ozanezumab group and cerebrovascular accident in the placebo group). Interpretation Ozanezumab did not show efficacy compared with placebo in patients with ALS. Therefore, Nogo-A does not seem to be an effective therapeutic target in ALS. Funding GlaxoSmithKline.

Published
2017

48. EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research

Author

Eva De Smedt, Bieke Soen, Marta Monguió-Tortajada, Jasper Anckaert, Erminia Romano, Els Beghein, Hina Kalra, Alessandra Lo Cicero, Michael W. Pfaffl, Laurence Bertier, Bert Dhondt, Edward Geeurickx, Özden Akay, Lorraine O'Driscoll, Frederik J. Verweij, Alan Van Goethem, Dominik Buschmann, Olivier De Wever, Zoraida Andreu Martinez, Susanne G. van der Grein, Carina Leonelli, Vincent Hyenne, Shu Liu, Prabhu Mathiyalagan, Guillaume van Niel, Andrew D Foers, Niels Vandamme, Joeri Tulkens, Petra Leidinger, Jan Van Deun, James Brian Byrd, Suzanne Vanhauwaert, David Kim, Patrizia Agostinis, Seyma Demirsoy, Esther N. M. Nolte-‘t Hoen, Stephanie Boukouris, Aleksandra M. Dudek, Michel Bremer, Anna Cmoch, Sandra Kraemer, Kathrin Gärtner, Clotilde Théry, Hetty Helsmoortel, Farzaneh Ghazavi, Pieter Mestdagh, Dillon C. Muth, Jo Vandesompele, Grace V. Hancock, Lien Lippens, Tom Groot Kormelink, Tom A. P. Driedonks, Abdou ElSharawy, Sushma Anand, Marijke I. Zonneveld, Benjamin J. Scicluna, Joanna Kowal, Susmita Sahoo, Lesley Cheng, Safia Thaminy, Isabel Van Audenhove, Suresh Mathivanan, Ilaria Floris, Glenn Vergauwen, Geert Berx, Jan Gettemans, Johannes V. Swinnen, Yaxuan Liang, Victoria Depoorter, Shaun Martin, Alexander R. van Vliet, Natalia G. Sampaio, Martijn J. C. van Herwijnen, Bernd Giebel, Abhishek D. Garg, Bjarke Primdal-Bengtson, An Hendrix, Gloria Milani, Tamás Matusek, Liselot Mus, Annelynn Wallaert, Andrew F. Hill, Roberta Palmulli, Maarit Takatalo, Tine Baetens, Clara Casert, Janneke Boere, Monisha Samuel, Marca H. M. Wauben, Nadine Van Roy, Delphine Daveloose, Anneleen Steels, Andrea Németh, Kenneth W. Witwer, Quentin Rousseau, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Center for Medical Genetics, Cancer Research Institute Ghent (CRIG), Bioinformatics Institute Ghent (BIG), Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain = Catholic University of Louvain (UCL), Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Department of Biochemistry, Faculty of Medicine and Health Sciences, Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University [Utrecht], Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Animal Physiology and Immunology, School of Life Sciences, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Laboratory of Cytometry, Department of Internal Medicine, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Biochemistry, Hôpital Lapeyronie, Institute of Clinical Molecular Biology, Kiel University, Faculty of Sciences, Division of Biochemistry, Chemistry Department, Damietta University, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Department of Biochemistry, Microbiology and Immunology, University of Ottawa [Ottawa], Inflammation Division, The Walter and Eliza Hall Institute of Medical Research (WEHI), Department of Medical Biology, Hacettepe University Faculty of Medicine, Partner site Munich, German Centre for Infection Research (DZIF), Research Unit Gene Vectors, Helmholtz-Zentrum München (HZM), Department of Molecular and Comparative Pathobiology and Department of Neurology, Johns Hopkins University School of Medicine, Fédération de Médecine Translationelle de Strasbourg (FMTS), LabEx Medalis, Université de Strasbourg (UNISTRA), U1109, MN3T, Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Department of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen, Institute of Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], German Center for Neurodegenerative Diseases, Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (IBV), 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), REMAR-IVECAT Group, Germans Trias i Pujol Health Science Research Institute, Department of Genetics, Cell- and Immunobiology, Semmelweis University, School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Population Health and Immunity Division, Laboratory of Lipid Metabolism and Cancer, Department of Oncology, LKI - Leuven Cancer Institute, Faculty of Biological and Environmental Sciences [Helsinki], University of Helsinki, Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, National Cancer Center, Fund for Scientific Spearheads of the Ghent University Hospital, Concerted Research Actions from Ghent University, Stichting tegen Kanker, Kom Op Tegen Kanker, H2020/COST ME-HaD, Fund for Scientific Research Flanders (FWO), Krediet aan Navorsers from FWO, Universiteit Gent = Ghent University (UGENT), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Helmholtz Zentrum München = German Research Center for Environmental Health, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 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), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Van Deun J., Mestdagh P., Agostinis P., Akay O., Anand S., Anckaert J., Martinez Z.A., Baetens T., Beghein E., Bertier L., Berx G., Boere J., Boukouris S., Bremer M., Buschmann D., Byrd J.B., Casert C., Cheng L., Cmoch A., Daveloose D., De Smedt E., Demirsoy S., Depoorter V., Dhondt B., Driedonks T.A.P., Dudek A., Elsharawy A., Floris I., Foers A.D., Gartner K., Garg A.D., Geeurickx E., Gettemans J., Ghazavi F., Giebel B., Kormelink T.G., Hancock G., Helsmoortel H., Hill A.F., Hyenne V., Kalra H., Kim D., Kowal J., Kraemer S., Leidinger P., Leonelli C., Liang Y., Lippens L., Liu S., Lo Cicero A., Martin S., Mathivanan S., Mathiyalagan P., Matusek T., Milani G., Monguio-Tortajada M., Mus L.M., Muth D.C., Nemeth A., Nolte-'T Hoen E.N.M., O'Driscoll L., Palmulli R., Pfaffl M.W., Primdal-Bengtson B., Romano E., Rousseau Q., Sahoo S., Sampaio N., Samuel M., Scicluna B., Soen B., Steels A., Swinnen J.V., Takatalo M., Thaminy S., Thery C., Tulkens J., Van Audenhove I., Van Der Grein S., Van Goethem A., Van Herwijnen M.J., Van Niel G., Van Roy N., Van Vliet A.R., Vandamme N., Vanhauwaert S., Vergauwen G., Verweij F., Wallaert A., Wauben M., Witwer K.W., Zonneveld M.I., De Wever O., Vandesompele J., Hendrix A., Ghent University [Belgium] (UGENT), Université Catholique de Louvain, Technical University of Munich (TUM), Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), University of Ottawa [Ottawa] (uOttawa), Walter and Eliza Hall Institute of Medical Research (WEHI), Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PSL Research University (PSL), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-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)-Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)

Subjects
0301 basic medicine, minimum information, blood-plasma, physiology [Extracellular Vesicles], Biomedical Research, Internationality, Computer science, phenotype, [SDV]Life Sciences [q-bio], Medizin, exosomes, Crowdsourcing, Bioinformatics, Biochemistry, 03 medical and health sciences, Extracellular Vesicles, ultracentrifugation, Biological property, cancer, ddc:610, resolution flow-cytometry, Molecular Biology, subpopulations, business.industry, biological-properties, Cell Biology, Extracellular vesicle, Data science, Databases, Bibliographic, Replication (computing), 030104 developmental biology, cells, business, Biotechnology
Abstract

We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice.

Published
2017

49. Determinants of diet and physical Activity (DEDIPAC): a summary of findings

Author

Matthias B. Schulze, Massimo Lanza, Jürgen M. Steinacker, Hidde P. van der Ploeg, Ulf Ekelund, Nanna Lien, Lene Frost Andersen, Mario Mazzocchi, Johannes Brug, Sebastien F. M. Chastin, Britta Renner, Matthijs van den Berg, Anne Loyen, Oliver Allais, Marie H. Murphy, Gun Roos, Donal J. O’Gorman, Pablo Monsivais, Marieke De Craemer, Antje Hebestreit, Paul Finglas, Karien Stronks, Ciaran MacDonncha, Dorothee Volkert, Marion Flechtner-Mors, Ilse De Bourdeaudhuij, Jeroen Lakerveld, Greet Cardon, Wolfgang Ahrens, Laura Capranica, Alan E. Donnelly, Mary Nicolaou, Thomas Kubiak, Ute Nöthlings, Persuasive Communication (ASCoR, FMG), ASCoR (FMG), Brug, Johanne, van der Ploeg, Hidde P., Loyen, Anne, Ahrens, Wolfgang, Allais, Oliver, Andersen, Lene F., Cardon, Greet, Capranica, Laura, Chastin, Sebastien, De Bourdeaudhuij, Ilse, De Craemer, Marieke, Donnelly, Alan, Ekelund, Ulf, Finglas, Paul, Flechtner-Mors, Marion, Hebestreit, Antje, Kubiak, Thoma, Lanza, Massimo, Lien, Nanna, MacDonncha, Ciaran, Mazzocchi, Mario, Monsivais, Pablo, Murphy, Marie, Nicolaou, Mary, Nöthlings, Ute, O'Gorman, Donal J., Renner, Britta, Roos, Gun, van den Berg, Matthij, Schulze, Matthias B., Steinacker, Jürgen M., Stronks, Karien, Volkert, Dorothee, Lakerveld, Jeroen, University of Amsterdam [Amsterdam] (UvA), VU University Medical Center [Amsterdam], Sydney School of Public Health, The University of Sydney, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Alimentation et sciences sociales (ALISS), Institut National de la Recherche Agronomique (INRA), Department of Nutrition [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Department of Movement and Sports Sciences, Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Movement, Human and Health Sciences, Università degli Studi di Roma 'Foro Italico', Glasgow Caledonian University (GCU), Centre for Physical Activity and Health Research, University of Limerick (UL), Norwegian institute for public health, Institute of Food Research, Universität Ulm - Ulm University [Ulm, Allemagne], Johannes Gutenberg - Universität Mainz (JGU), University of Verona (UNIVR), Health Research Institute, Department of Statistical Sciences, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of Cambridge [UK] (CAM), Ulster University, Department of Nutrition and Food Science, Rheinische Friedrich-Wilhelms-Universität Bonn, Dublin City University, Department of Psychology, University of Konstanz, Akershus University College, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Institute for Biomedicine of Aging, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Joint Programming Initiative 'Healthy Diet for a Healthy Life', Austria: Austrian Federal Ministry of Science and Research, Belgium: Research Foundation - Flanders, France: Institut National de la Recherche Agronomique (INRA), Germany: Federal Ministry of Education and Research, Italy: Ministry of Education, University and Research/ Ministry of Agriculture Food and Forestry Policies, Ireland: The Health Research Board (HRB), Netherlands: The Netherlands Organisation for Health Research and Development (ZonMw), Norway: The Research Council of Norway, Division for Society and Health, Poland: The National Centre for Research and Development, Spain: Carlos III Institute of Health (ISCIII), United Kingdom: The Medical Research Council (MRC), APH - Methodology, APH - Health Behaviors & Chronic Diseases, Public and occupational health, Other departments, ACS - Heart failure & arrhythmias, Lakerveld , Jeroen, Epidemiology and Data Science, Lakerveld, Jeroen [0000-0002-8551-6748], Apollo - University of Cambridge Repository, Brug, Johannes [0000-0002-1904-7349], van der Ploeg, Hidde P [0000-0002-3719-5249], Ahrens, Wolfgang [0000-0003-3777-570X], Allais, Oliver [0000-0002-4849-5255], Cardon, Greet [0000-0003-4983-6557], Capranica, Laura [0000-0003-3073-7655], De Craemer, Marieke [0000-0002-5220-7850], Donnelly, Alan [0000-0002-6874-0991], Kubiak, Thomas [0000-0003-0095-9265], MacDonncha, Ciaran [0000-0001-7999-4930], Mazzocchi, Mario [0000-0002-0498-8031], Monsivais, Pablo [0000-0002-7088-6674], O'Gorman, Donal J [0000-0002-8228-1488], Renner, Britta [0000-0001-8385-2839], Roos, Gun [0000-0001-8551-2491], Schulze, Matthias B [0000-0002-0830-5277], and Steinacker, Jürgen M [0000-0001-8901-9450]

Subjects
0301 basic medicine, Gerontology, Debate, Health Behavior, Psychological intervention, Medicine (miscellaneous), Disease, determinants of health behaviours, dietary behaviour, Europe, interventions, physical activity, policy evaluation, sedentary behaviour, [SHS]Humanities and Social Sciences, Cohort Studies, 0302 clinical medicine, ddc:150, Medizinische Fakultät, Medicine, 030212 general & internal medicine, lcsh:RC620-627, Interventions, Nutrition and Dietetics, lcsh:Public aspects of medicine, Benchmarking, Public relations, Dietary behaviour, Physical activity, Sedentary behaviour, Determinants of health behaviours, Policy evaluation, lcsh:Nutritional diseases. Deficiency diseases, Work (electrical), Life course approach, Diet, Healthy, Behavioural sciences, Intervention, Physical Therapy, Sports Therapy and Rehabilitation, 03 medical and health sciences, Humans, ddc:610, Exercise, 030109 nutrition & dietetics, business.industry, Research, lcsh:RA1-1270, Diet, Action (philosophy), Determinants of health behaviour, Sedentary Behavior, business, DEDIPAC consortium
Abstract

The establishment of the Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub, 2013 – 2016, was the first action taken by the ‘ Healthy Diet for a Healthy Life ’ European Joint Programming Initiative. DEDIPAC aimed to provide better insight into the determinants of diet, physical activity and sedentary behaviour across the life course, i.e. insight into the causes of the causes of important, non-commu nicable diseases across Europe and beyond. DEDIPAC was launched in late 2013, and delivered its final report in late 2016. In this paper we give an overview of what was achieved in terms of furthering measurement and monitoring, providing overviews of the state-of-the-art in the field, and building toolboxes for further research and pr actice. Additionally, we propose some of the next steps that are now required to move forward in this field, arguing in favour of 1) sustaining the Knowledge Hub and developing it into a European virtual research institute and knowledge cen tre for determinants of behavi oural nutrition and physical activity with close links to other parts of the world; 2) establi shing a cohort study of families across all regions of Europe focusing specifically on the individual and contextual determinants of major, non-communicable disease; and 3) furthering DEDIPAC ’ s work on nutrition, physical activity, and sedentary behaviour policy evaluation and benchmarking across Europe by aligning with other international initiatives and by supporting harmonisation of pan-European surveillance. Norges forskningsråd 236215 Norges forskningsråd 236216

Published
2017

50. Multi-trial Guruswami–Sudan decoding for generalised Reed–Solomon codes

Author

Johan Sebastian Rosenkilde Nielsen, Alexander Zeh, Department of Applied Mathematics and Computer Science [Lyngby] (DTU Compute), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Institute of Communications Engineering [Ulm] (INT - University of Ulm.), Universität Ulm - Ulm University [Ulm, Allemagne], Geometry, arithmetic, algorithms, codes and encryption (GRACE), Laboratoire d'informatique de l'École polytechnique [Palaiseau] (LIX), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Technion - Israel Institute of Technology [Haifa], Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'informatique de l'École polytechnique [Palaiseau] (LIX), and École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)

Subjects
FOS: Computer and information sciences, Minimisation (psychology), Iterative method, Computer Science - Information Theory, List decoding, Cryptography, Data_CODINGANDINFORMATIONTHEORY, 0102 computer and information sciences, 02 engineering and technology, [INFO.INFO-DM]Computer Science [cs]/Discrete Mathematics [cs.DM], 01 natural sciences, Reed--Solomon Codes, [INFO.INFO-CR]Computer Science [cs]/Cryptography and Security [cs.CR], [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], Reed–Solomon error correction, [MATH.MATH-CO]Mathematics [math]/Combinatorics [math.CO], 0202 electrical engineering, electronic engineering, information engineering, Multi-Trial, Computer Science::Information Theory, Mathematics, Guruswami-Sudan, Guruswami--Sudan, Reed-Solomon codes, business.industry, Information Theory (cs.IT), Applied Mathematics, [MATH.MATH-IT]Mathematics [math]/Information Theory [math.IT], 020206 networking & telecommunications, [MATH.MATH-NT]Mathematics [math]/Number Theory [math.NT], Computer Science Applications, [INFO.INFO-IT]Computer Science [cs]/Information Theory [cs.IT], 010201 computation theory & mathematics, Iterated function, Re-encoding transformation, List Decoding, business, Algorithm, Decoding methods
Abstract

An iterated refinement procedure for the Guruswami-Sudan list decoding algorithm for Generalised Reed-Solomon codes based on Alekhnovich's module minimisation is proposed. The method is parametrisable and allows variants of the usual list decoding approach. In particular, finding the list of closest codewords within an intermediate radius can be performed with improved average-case complexity while retaining the worst-case complexity. We provide a detailed description of the module minimisation, reanalysing the Mulders-Storjohann algorithm and drawing new connections to both Alekhnovich's algorithm and Lee-O'Sullivan's. Furthermore, we show how to incorporate the re-encoding technique of K\"otter and Vardy into our iterative algorithm., Comment: Design Codes and Cryptography (2014)

Published
2014

Catalog

Books, media, physical & digital resources
See catalog results