Institution
University of Lorraine
Education•Nancy, France•
About: University of Lorraine is a education organization based out in Nancy, France. It is known for research contribution in the topics: Population & Nonlinear system. The organization has 11942 authors who have published 25010 publications receiving 425227 citations. The organization is also known as: Lorraine University.
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TL;DR: Theoretical approaches such as molecular modeling provide a significant insight into the processes affecting the integrity of lipid cell membranes when these are subject to voltage gradients under similar conditions as those used in experiments, and progress made so far using such simulations to model membrane—lipid bilayer—electroporation is reported.
Abstract: The permeability of cell membranes can be transiently increased following the application of external electric fields. Theoretical approaches such as molecular modeling provide a significant insight into the processes affecting, at the molecular level, the integrity of lipid cell membranes when these are subject to voltage gradients under similar conditions as those used in experiments. This article reports on the progress made so far using such simulations to model membrane—lipid bilayer—electroporation. We first describe the methods devised to perform in silico experiments of membranes subject to nanosecond, megavolt-per-meter pulsed electric fields and of membranes subject to charge imbalance, mimicking therefore the application of low-voltage, long-duration pulses. We show then that, at the molecular level, the two types of pulses produce similar effects: provided the TM voltage these pulses create are higher than a certain threshold, hydrophilic pores stabilized by the membrane lipid headgroups form within the nanosecond time scale across the lipid core. Similarly, when the pulses are switched off, the pores collapse (close) within similar time scales. It is shown that for similar TM voltages applied, both methods induce similar electric field distributions within the membrane core. The cascade of events following the application of the pulses, and taking place at the membrane, is a direct consequence of such an electric field distribution.
156 citations
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TL;DR: In this paper, the authors present a systematic experimental study of the relative contributions of the martensite volume fraction, morphology and carbon content to the overall strength and ductility of dual-phase steels.
156 citations
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DBV Technologies1, Icahn School of Medicine at Mount Sinai2, Harvard University3, University of Ottawa4, University of Toronto5, Children's Hospital of Philadelphia6, Stanford University7, University of California, San Diego8, Children's Memorial Hospital9, Cincinnati Children's Hospital Medical Center10, University of Texas Southwestern Medical Center11, University of Pittsburgh12, Erasmus University Rotterdam13, Utrecht University14, University of Lorraine15, Boston Children's Hospital16, Medical University of Łódź17, Paris Descartes University18, Necker-Enfants Malades Hospital19
TL;DR: A dose-ranging trial of a peanut patch in peanut-allergic patients and a double-blind, placebo-controlled food challenge to establish changes in eliciting dose to determine the optimal dose, adverse events (AEs), and efficacy of aanut patch for peanut allergy treatment.
Abstract: IMPORTANCE: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. OBJECTIVE: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. DESIGN, SETTING, AND PARTICIPANTS: Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein. INTERVENTIONS: Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 μg (n = 53), 100 μg (n = 56), or 250 μg (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was percentage of treatment responders (eliciting dose: 10-times increase and/or reaching 1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs). RESULTS: Of 221 patients randomized (median age, 11 years [quartile 1, quartile 3: 8, 16]; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-μg (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-μg patch. Because of statistical testing hierarchical rules, the 50-μg patch was not compared with placebo. Interaction by age group was only significant for the 250-μg patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-μg (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-μg (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, −11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-μg patch = 100%, 100-μg patch = 98.2%, 250-μg patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%. CONCLUSIONS AND RELEVANCE: In this dose-ranging trial of peanut-allergic patients, the 250-μg peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01675882.
155 citations
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Technical University of Berlin1, Washington State University2, University of Potsdam3, Tufts University4, Imperial College London5, London Metropolitan University6, German Aerospace Center7, Leibniz Association8, Instituto Nacional de Técnica Aeroespacial9, University of Lorraine10, University of Duisburg-Essen11, Ames Research Center12, Free University of Berlin13, University of Antofagasta14, University of Westminster15, Johns Hopkins University16, University of Tübingen17, University of California, Davis18, Heidelberg University19, University of Bremen20
TL;DR: It is shown that even the hyperarid Atacama Desert can provide a habitable environment for microorganisms that allows them to become metabolically active following an episodic increase in moisture and that once it decreases, so does the activity of the microbiota.
Abstract: Traces of life are nearly ubiquitous on Earth. However, a central unresolved question is whether these traces always indicate an active microbial community or whether, in extreme environments, such as hyperarid deserts, they instead reflect just dormant or dead cells. Although microbial biomass and diversity decrease with increasing aridity in the Atacama Desert, we provide multiple lines of evidence for the presence of an at times metabolically active, microbial community in one of the driest places on Earth. We base this observation on four major lines of evidence: (i) a physico-chemical characterization of the soil habitability after an exceptional rain event, (ii) identified biomolecules indicative of potentially active cells [e.g., presence of ATP, phospholipid fatty acids (PLFAs), metabolites, and enzymatic activity], (iii) measurements of in situ replication rates of genomes of uncultivated bacteria reconstructed from selected samples, and (iv) microbial community patterns specific to soil parameters and depths. We infer that the microbial populations have undergone selection and adaptation in response to their specific soil microenvironment and in particular to the degree of aridity. Collectively, our results highlight that even the hyperarid Atacama Desert can provide a habitable environment for microorganisms that allows them to become metabolically active following an episodic increase in moisture and that once it decreases, so does the activity of the microbiota. These results have implications for the prospect of life on other planets such as Mars, which has transitioned from an earlier wetter environment to today's extreme hyperaridity.
155 citations
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University of Lorraine1, Campbell University2, Hannover Medical School3, University of Glasgow4, University of Gothenburg5, University of Dundee6, University of Groningen7, Complutense University of Madrid8, University of Chicago9, Duke University10, Northwestern University11, University of Paris12, Pierre-and-Marie-Curie University13, National and Kapodistrian University of Athens14, University of Picardie Jules Verne15, Paul Sabatier University16, Henry Ford Health System17, Virginia Commonwealth University18, University of Michigan19
TL;DR: Although serious hyperkalaemia events were reported in the major MRA clinical trials, these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up.
Abstract: Mineralocorticoid receptor antagonists (MRAs) improve survival and reduce morbidity in patients with heart failure, reduced ejection fraction (HF–REF), and mild-to-severe symptoms, and in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction. These clinical benefits are observed in addition to those of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers. The morbidity and mortality benefits of MRAs may be mediated by several proposed actions, including antifibrotic mechanisms that slow heart failure progression, prevent or reverse cardiac remodelling, or reduce arrhythmogenesis. Both eplerenone and spironolactone have demonstrated survival benefits in individual clinical trials. Pharmacologic differences exist between the drugs, which may be relevant for therapeutic decision making in individual patients. Although serious hyperkalaemia events were reported in the major MRA clinical trials, these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up. When used appropriately, MRAs significantly improve outcomes across the spectrum of patients with HF–REF.
155 citations
Authors
Showing all 12161 results
Name | H-index | Papers | Citations |
---|---|---|---|
Jonathan I. Epstein | 138 | 1121 | 80975 |
Peter Tugwell | 129 | 948 | 125480 |
David Brown | 105 | 1257 | 46827 |
Faiez Zannad | 103 | 839 | 90737 |
Sabu Thomas | 102 | 1554 | 51366 |
Francis Martin | 98 | 733 | 43991 |
João F. Mano | 97 | 822 | 36401 |
Jonathan A. Epstein | 94 | 299 | 27492 |
Muhammad Imran | 94 | 3053 | 51728 |
Laurent Peyrin-Biroulet | 90 | 901 | 34120 |
Athanase Benetos | 83 | 391 | 31718 |
Michel Marre | 82 | 444 | 39052 |
Bruno Rossion | 80 | 337 | 21902 |
Lyn March | 78 | 367 | 62536 |
Alan J. M. Baker | 76 | 234 | 26080 |