34 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/)

    Resilience and Life Expectations of Perinatally HIV-1 Infected Adolescents in France

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    International audienceBackground: Resilience of perinatally HIV-infected youth in European countries is poorly studied. Life satisfaction and expectations for adulthood are rarely examined.Objective: This cross-sectional, descriptive study of a French cohort of 54 perinatally HIV-infected adolescents raised in France (age 14-20 years) aimed to (1) evaluate their psychosocial adjustment, (2) identify their expectations for adulthood and (3) delineate risk and protective factors associated with mental health, life satisfaction, and HIV-1 viral load level.Method: Medical evaluation, psychological semi-structured interview, and self-report questionnaires were used.Results: All the adolescents had been receiving Highly Active Anti-Retroviral Therapy (HAART) for 9 to 11 years and 2/3 were healthy with controlled viral load (<50 copies/mL). The majority had medium to high levels of life satisfaction. They viewed HIV as having only minor impact on their current daily life and had positive expectations for adulthood. However, 46% exhibited psychiatric symptomatology. Multivariable analysis showed that having a deceased parent and current worries about HIV were substantial risk factors for psychiatric symptoms. Having two living parents and being satisfied with life were protective factors for mental health. Good quality of caregiver-adolescent relationships and high life satisfaction were significant protective factors for controlled viral load.Conclusion: These data indicate psychosocial resilience among perinatally HIV-1 infected adolescents with 10 years of HAART treatment. These findings demonstrate the influence of life satisfaction, parent’s life status and quality of caregiver-adolescent relationships on resilience and health outcomes in these patients. We conclude that healthcare providers should attend to these factors

    Metastable ferroelectric phase and crossover in the Ba2NdFeNb4−xTaxO15 TTB solid solution

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    In the framework of the crystal chemical investigation of Tetragonal Tungsten Bronze (TTB) niobates, the Ba2NdFeNb4−xTaxO15 solid solution has been investigated in order to gain insights on the relaxor to ferroelectric crossover and its features. Single-phase ceramics were synthesised by conventional two-step firing and sintering and they underwent extended chemical, structural, microstructural and physical characterizations. For Nb-rich compositions (x ≤ 0.5), the temperature dependence of the dielectric permittivity, the pyroelectric coefficient, and also the ferroelectric hysteresis loops revealed a nonconventional relaxor to ferroelectric crossover, which was confirmed by piezoelectric measurements for x ≤ 0.1. A thermal hysteresis of the ferroelectric transition revealed the existence of a metastable ferroelectric phase in these TTB niobates. An accurate and reliable dielectric phase diagram is established from these observations, which allows discussing the original sequence of dielectric phase transitions encountered in this solid solution.Croissance Cristalline d'Oxydes Dielectrique

    RAR/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements

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    International audienceIn mouse embryonic cells, ligand-activated retinoic acid receptors (RARs) play a key role in inhibiting pluripotency-maintaining genes and activating some major actors of cell differentiation. To investigate the mechanism underlying this dual regulation, we performed joint RAR/RXR ChIP-seq and mRNA-seq time series during the first 48 h of the RA-induced Primitive Endoderm (PrE) differentiation process in F9 embryonal carcinoma (EC) cells. We show here that this dual regulation is associated with RAR/RXR genomic redistribution during the differentiation process. In-depth analysis of RAR/RXR binding sites occupancy dynamics and composition show that in undifferentiated cells, RAR/RXR interact with genomic regions characterized by binding of pluripotency-associated factors and high prevalence of the non-canonical DR0-containing RA response element. By contrast, in differentiated cells, RAR/RXR bound regions are enriched in functional Sox17 binding sites and are characterized with a higher frequency of the canonical DR5 motif. Our data offer an unprecedentedly detailed view on the action of RA in triggering pluripotent cell differentiation and demonstrate that RAR/RXR action is mediated via two different sets of regulatory regions tightly associated with cell differentiation status

    Original crystal-chemistry behaviors in (Ba, Sr)2Ln(Fe, Nb, Ta)5O15 tetragonal tungsten bronze: anion-driven properties evidenced by cationic substitutions

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    From room-temperature composite multiferroics to relaxor to ferroelectric crossovers, many original behaviors were recently evidenced in compounds and/or solid solutions related to the Ba2LnFeNb4O15 (Ln = rare earth) family of tetragonal tungsten bronze (TTB) materials. We show how an empirical crystal chemistry approach, while yielding unexpected results, allowed for a better understanding of these original and sometimes specific behaviors. A survey of the dielectric properties of four solid solutions derived from the Ba2NdFeNb4O15 ferroelectric TTB is presented. We also show how the diversity of compositions and chemical substitution patterns unveils the anionic driving force behind the relaxor to ferroelectric crossovers. We finally discuss the probable involvement of aperiodic modulations in these crossovers and the fact that these modulations may constitute an additional degree of freedom to control the properties of TTB structured functional materials.Croissance Cristalline d'Oxydes Dielectrique

    Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study

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    International audienceBackground: The early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been thoroughly investigated in children over five years of age or adolescents. Here, we describe the levels of naive CD4 and CD8 T lymphocytes (CD4/CD8TN), reflecting the quality of immune reconstitution, as a function of the timing of ART initiation (early (<6 months) versus late (≥24 months of age)).Methods: The ANRS-EP59-CLEAC study enrolled 27 children (5-12 years of age) and nine adolescents (13-17 years of age) in the early-treatment group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-treatment group. T lymphocytes were analyzed by flow cytometry and plasma markers were analyzed by ELISA. Linear regression analysis was performed with univariate and multivariate models.Results: At the time of evaluation, all patients were on ART and had a good immunovirological status: 83% had HIV RNA loads below 50 copies/mL and the median CD4 T-cell count was 856 cells/µL (interquartile range: 685-1236 cells/µL). In children, early ART was associated with higher CD8TN percentages (medians: 48.7% vs. 31.0%, P = 0.001), and a marginally higher CD4TN (61.2% vs. 53.1%, P = 0.33). In adolescents, early ART was associated with low CD4TN percentages and less differentiated memory CD8 T cells. CD4TN and CD8TN levels were inversely related to cellular activation and gut permeability.Conclusion: In children and adolescents, the benefits of early ART for CD8TN were clear after long-term ART. The impact of early ART on CD4TN appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the de novo production of TN cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on TN levels
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