40 research outputs found

    Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

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    RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Dieu et le mal selon Basile de Césarée, Grégoire de Nysse, Jean Chrysostome (Pères dans la foi 69), Paris 1997

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    MH Congourdeau: direction de l'ouvrage et rédaction de l'introductiontraduction française de textes des Pères de l'Eglise sur la question du mal: Pourquoi Dieu, s'il est bon et tout puissant, permet-il le mal et la souffrance ? Est-ce lui qui envoie le malheur dans le monde ? Ne pouvait-il faire un monde d'où le mal serait absent ? Trois réflexions différentes, où s'expriment trois personnalités, mais qui ont en commun de s'appuyer sur la Bible pour non pas expliquer mais éclairer le mystère d'un monde où les créatures d'un Dieu d'amour ont la liberté de le refuser

    Comparison of bioassays with different exposure time patterns: The added value of dynamic modelling in predictive ecotoxicology

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    International audienceThe purpose of this study was to compare Daphnia magna responses to cadmium between two toxicity experiments performed in static and flow-through conditions. As a consequence of how water was renewed, the two experiments were characterised by two different exposure time patterns for daphnids, time-varying and constant, respectively. Basing on survival, growth and reproduction, we addressed the questions of organism development and sensitivity to cadmium. Classical analysis methods are not designed to deal with the time dimension and therefore not suitable to compare effects of different exposure time patterns. We used instead a dynamic modelling framework taking all timepoints and the time course of exposure into account, making comparable the results obtained from our two experiments. This modelling framework enabled us to detect an improvement of organism development in flow-through conditions compared to static ones and infer similar sensitivity to cadmium for both exposure time patterns. (C) 2011 Elsevier Inc. All rights reserved

    Successful Gene Tagging in Lettuce Using the Tnt1 Retrotransposon from Tobacco

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    The tobacco (Nicotiana tabacum) element Tnt1 is one of the few identified active retrotransposons in plants. These elements possess unique properties that make them ideal genetic tools for gene tagging. Here, we demonstrate the feasibility of gene tagging using the retrotransposon Tnt1 in lettuce (Lactuca sativa), which is the largest genome tested for retrotransposon mutagenesis so far. Of 10 different transgenic bushes carrying a complete Tnt1 containing T-DNA, eight contained multiple transposed copies of Tnt1. The number of transposed copies of the element per plant was particularly high, the smallest number being 28. Tnt1 transposition in lettuce can be induced by a very simple in vitro culture protocol. Tnt1 insertions were stable in the progeny of the primary transformants and could be segregated genetically. Characterization of the sequences flanking some insertion sites revealed that Tnt1 often inserted into genes. The progeny of some primary transformants showed phenotypic alterations due to recessive mutations. One of these mutations was due to Tnt1 insertion in the gibberellin 3β-hydroxylase gene. Taken together, these results indicate that Tnt1 is a powerful tool for insertion mutagenesis especially in plants with a large genome

    Hemocyte Health Status Based on Four Biomarkers to Assess Recovery Capacity in American Lobster (Homarus americanus) after Exposure to Marine Diesel and Diluted Bitumen

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    The growing transportation of petroleum products pose a significant risk of marine diesel or diluted bitumen (dilbit) spills at sea. Despite the economic importance of the American lobster, there have been few studies assessing the impact study of such a spill on their population. In the lobster industry, lobster quality is monitored according to the Brix index of hemolymph. In our research, the effectiveness of three other biomarkers operative in the industry was assessed in hemolymph during contamination (over 96 h) by marine diesel and dilbit (Cold Lake Blend; CLB), as well as in the subsequent recovery period, according to two temperature cycles. At the end of the experiment, chemical and tainting assays were performed. Our results demonstrate that, among the four tested biomarkers, lysosomal stability and ethoxyresorufin O-deethylase (EROD) induction exhibit higher sensitivity. Increasing the temperature did not shorten the recovery period. Viability cellular impacts were greater in lobsters exposed to dilbit than that in those exposed to marine diesel. Marine diesel exposure appears to be more problematic for the lobster fishery, as the cooked lobster meat still presented a hydrocarbon odor even after 3 months of live holding. Finally, the high PAH concentrations measured in lobster eggs suggest potential adverse transgenerational effects of marine diesel exposure

    Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

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    International audienceSynthetic alkyl lipids, such as the ether lipids edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and ohmline (1-O-hexadecyl-2-O-methyl-rac-glycero-3-β-lactose), are forming a class of antitumor agents that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development. In this review, we present the structure-activity relationship of edelfosine and ohmline, and we point out differences and similarities between these two amphiphilic compounds. We also discuss the mechanisms of action of these synthetic alkyl ether lipids (involving, among other structures and molecules, membrane domains, Fas/CD95 death receptor signaling, and ion channels), and highlight a key role for lipid rafts in the underlying process. The reorganization of lipid raft membrane domains induced by these alkyl lipids affects the function of death receptors and ion channels, thus leading to apoptosis and inhibition of cancer cell migration. The possible therapeutic use of these alkyl lipids and the clinical perspectives for these lipids in prevention or/and treatment of tumor development and metastasis are also discussed
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