30 research outputs found

    Adoption des pratiques agroforestières en France, quelles perspectives ?

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    Equipe AMPLUS : Analyse et Modélisation du champ cultivé PLUrispécifiqueAdoption des pratiques agroforestières en France, quelles perspectives

    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/)

    Mathematical models of radiation action on living cells: From the target theory to the modern approaches. A historical and critical review

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    International audienceCell survival is conventionally defined as the capability of irradiated cells to produce colonies. It is quantified by the clonogenic assays that consist in determining the number of colonies resulting from a known number of irradiated cells. Several mathematical models were proposed to describe the survival curves, notably from the target theory. The Linear-Quadratic (LQ) model, which is to date the most frequently used model in radiobiology and radiotherapy, dominates all the other models by its robust- ness and simplicity. Its usefulness is particularly important because the ratio of the values of the adjustable parameters, α and β, on which it is based, predicts the occurrence of post-irradiation tissue reactions. However, the biological interpretation of these parameters is still unknown.Throughout this review, we revisit and discuss historically, mathematically and biologically, the different models of the radiation action by providing clues for resolving the enigma of the LQ model

    The pATM Immunofluorescence assay: a high-performance radiosensitivity assay to predict post radiotherapy overreactions.

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    International audiencePurpose dentifying prior treatment, the patients who will overreact to radiotherapy (RT) would have sound positive clinical implications. By focusing on DNA double-strand breaks (DSB) recognition and repair proteins after irradiation, we recently demonstrated that the maximal number of pATM nuclear foci in the first hour (pATMmax) after ex vivo irradiation correlated with post-RT toxicity severity. We aimed to carry out additional analyses on our whole collection of fibroblast lines to refine the predictive performance of our assay

    Fast and binary assay for predicting radiosensitivity based on the nucleoshuttling of ATM protein: development, validation and performances

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    International audiencePurposeThe societal and clinical impact of post-radiotherapy adverse tissue events (AE) has highlighted the need of molecular parameters to predict individual radiosensitivity. Recent studies have stressed the role of the phosphorylated forms of the ATM protein (pATM) and its nucleoshuttling in response to radiation. The statistical performance of the pATM immunofluorescence assay to predict AE is promising. However, immunofluorescence requires a time-consuming amplification of cells. The purpose of this study was to develop a predictive assay based on the ELISA technique that renders faster the previous approach.Materials and methodsThis study was performed on 30 skin fibroblasts from 9 radioresistant and 21 AE patients. Patients were divided in 2 groups, radioresistant (toxicity grade<2) and radiosensitive (toxicity grade ≥2). The quantity of nuclear pATM molecules was assessed by ELISA method at 10 min and 1 h after 2 Gy and compared to pATM immunofluorescence data.ResultsThe pATM ELISA data were found in quantitative agreement with the immunofluorescence ones. A ROC analysis was applied first to two data sets (a training (n=14) and a validating (n=16) one) and thereafter to the whole data with a 2-fold cross-validation method. The assay showed an AUC value higher than 0.8, a sensitivity of 0.8 and a specificity ranging from 0.75 and 1, which strongly document the predictive power of the pATM ELISA assay.ConclusionThis study showed that the assessment of nuclear pATM quantity after 2 Gy via ELISA technique can be the basis of a predictive assay with the highest statistical performance among the available predictive approaches

    Hyperpolarization of Frozen Hydrocarbon Gases by Dynamic Nuclear Polarization at 1.2 K

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    International audienceABSTRACT: We report a simple and general method for the hyperpolarization of condensed gases by dynamic nuclear polarization (DNP). The gases are adsorbed in the pores of structured mesoporous silica matrices known as HYPSOs (HYper Polarizing SOlids) that have paramagnetic polarizing agents covalently bound to the surface of the mesopores. DNP is performed at low temperatures and moderate magnetic fields (T = 1.2 K and B0 = 6.7 T). Frequency-modulated microwave irradiation is applied close to the electron spin resonance frequency (f = 188.3 GHz), and the electron spin polarization of the polarizing agents of HYPSO is transferred to the nuclear spins of the frozen gas. A proton polarization as high as P(1H) = 70% can be obtained, which can be subsequently transferred to 13C in natural abundance by cross-polarization, yielding up to P(13C) = 27% for ethylene

    Filterable Agents for Hyperpolarization of Water, Metabolites, and Proteins

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    International audienceHyperpolarization is generated by dissolution dynamic nuclear polarization (d-DNP) using a polymer-based polarizing agent dubbed FLAP (filterable labeled agents for polarization). It consists of a thermo-responsive poly(N-isopropylacrylamide), also known as pNiPAM-COOH, labeled with nitroxide radicals. The polymer powder is impregnated with an arbitrary solution of interest and frozen as is. Dissolution is followed by a simple filtration, leading to hyperpolarized solutions free from any contaminants. We demonstrated the use of FLAP to hyperpolarize partially deuterated water up to P(1H)=6 % with a long relaxation T1 >36 s characteristic of high purity. Water hyperpolarization can be transferred to drugs, metabolites, or proteins that are waiting in an NMR spectrometer, either by exchange of labile protons or through intermolecular Overhauser effects. We also show that FLAPs are suitable polarizing agents for 13C-labeled metabolites such as pyruvate, acetate, and alanine
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