Anomalie isotopique de l'uranium dissous dans le bassin versant de L'Essonne

International audienceL’application de la Directive cadre sur l’eau s’accompagne de mesures de gestion visant le retour à l’état naturel du fonctionnement hydrologique des rivières. L’Essonne (affluent de La Seine) est l’une des rivières pour lesquelles le projet de réhabilitation soulève la question des échanges avec l’eau souterraine. Aussi, l’analyse des eaux est susceptible de faire émerger des outils géochimiques pour tracer et in fine mieux comprendre les échanges nappe/rivière.Dans le cadre de ses travaux d’expertise, de recherche et de surveillance, l’IRSN s’intéresse à l’uranium (U) dissous dans L’Essonne et son affluent L’Œuf [1]. Les résultats montrent que la concentration en U augmente d’aval en amont (238U : 0,08−25,9 µg.L−1) et que cette contribution est associée à un déséquilibre 234U−238U au détriment de 234U ((234U/238U) = 0.42 ± 0.02 min.). A l’échelle d’un bassin versant, les affluents drainant des substrats géologiques contrastés peuvent influer sur la composition isotopique de l’U dans un cours d’eau [2]. Dans L’Essonne, il semblerait que la variation en U soit davantage liée à des apports d’eaux souterraines. En effet, l’analyse de l’eau dans la nappe régionale met en évidence un déséquilibre 234U-238U équivalent et associé à une concentration relativement élevée en U [3]. Le déséquilibre 234U-238U constitue une anomalie isotopique qui a été rarement rapportée dans la littérature [4]. L’anomalie observée est susceptible de fournir un outil de traçage original des apports d’eaux souterraines et donc des échanges nappe/rivière. Pour ce faire il est nécessaire d’investiguer davantage l’origine de l’U ainsi que les mécanismes impliqués dans le déséquilibre 234U−238U

Assessing the conformational changes of pb5, the receptor-binding protein of phage T5, upon binding to its Escherichia coli receptor FhuA

Within tailed bacteriophages, interaction of the receptor-binding protein (RBP) with the target cell triggers viral DNA ejection into the host cytoplasm. In the case of phage T5, the RBP pb5 and the receptor FhuA, an outer membrane protein of Escherichia coli, have been identified. Here, we use small angle neutron scattering and electron microscopy to investigate the FhuA-pb5 complex. Specific deuteration of one of the partners allows the complete masking in small angle neutron scattering of the surfactant and unlabeled proteins when the complex is solubilized in the fluorinated surfactant F6-DigluM. Thus, individual structures within a membrane protein complex can be described. The solution structure of FhuA agrees with its crystal structure; that of pb5 shows an elongated shape. Neither displays significant conformational changes upon interaction. The mechanism of signal transduction within phage T5 thus appears different from that of phages binding cell wall saccharides, for which structural information is available

Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

BackgroundIn the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy.MethodsA FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients.ResultsSamples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0–86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0–117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48–2.26)].ConclusionsThis study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

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

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/)

In silico Comparison of test-and-cull protocols for bovine tuberculosis control in France

Whole depopulation of cattle herds (WHD) confirmed infected by bovine tuberculosis (bTB) has led since the 1950s to a drop of herd incidence in France below 0.1% in 2000, justifying the current officially bTB free (OTF) status of the country. However, this protocol is expensive, ethically questionable, and difficult for breeders to accept because the number of confirmed animals in an infected herd is often very low. A test-and-cull protocol combining at least three screening sessions of the entire herd followed by the slaughter of all the non-negative animals has been used for some years. The aim of this work was to evaluate in silico the epidemiological effectiveness, the public costs and the acceptability to farmers of this test-and-cull protocol as well as of several ones. A stochastic compartmental model of within-herd bTB spread was used. Six test-and-cull protocols were compared: two versions of the official protocol and four alternatives with varying delays between screenings, and varying tests used. Protocols were simulated for an average French beef herd, and compared to WHD. Three key indicators were computed: the failure probability of the protocol (a failure being defined as an herd recovering its OTF status recovery while still infected, indicator of epidemiological effectiveness), its overall public cost and the percentage of farmers who would have dropped it to switch to WHD (indicator of acceptability to farmers). Failure probability ranged from 1.4 to 12.4% and was null (by definition) for WHD. The median cost varied between 2.7 and 78 K€ for the test-and-cull protocols, vs. 120 K€ for WHD. The percentage of dropout ranged from 7.8 to 22%. The optimal tradeoff between epidemiological effectiveness, public costs, and acceptability to farmers was obtained for protocols with an increased delay (6 months instead of 2 in the currently used protocol) between the last two screening sessions, with either 3 or 2 screening sessions. This study may help improving the official test-and-cull protocol applied in France under European Union regulation, by suggesting alternative protocols, very effective, cheaper, and more acceptable than WHD

Caractéristiques et facteurs de risque du paludisme grave d'importation à Plasmodium falciparum chez l'adulte entre 2000 et 2009 en France métropolitaine

Le paludisme d'importation est un enjeu de santé publique dans de nombreux pays industrialisés, de par la fréquence et la létalité des formes graves à p.falciparum. Afin de décrire les caractéristiques des patients ayant présenté des formes graves et de mettre en évidence les facteurs de risque de gravité, nous avons conduit une étude rétrospective sur les cas de paludisme d'importation à p.falciparum en France métropolitaine chez l'adulte entre 2000 et 2009. Les données épidémiologiques, cliniques, et biologiques des patients ont été recueillies par un réseau de 120 correspondants et transmises au CNR Paludisme. La définition OMS 2000 du paludisme grave a été utilisée pour identifier les cas graves. Les facteurs associés à la gravité ont été mis en évidence par régression logistique. Les analyses ont porté sur 20556 patients infectés par p.falciparum, dont 1083 présentaient une forme grave. Les facteurs associés à la gravité étaient: l'absence de chimioprophylaxie, un âge élevé, l'origine caucasienne, un délai symptômes/diagnostic de 4 à 12 jours, une apparition des symptômes avant le retour et un diagnostic en automne/hiver. La proportion de formes graves a augmenté passant de 3,1% en 2000 à 10,5% des patients en 2009. La vigilance doit être accrue chez les patients de plus de 60 ans et les patients caucasiens. Une meilleure connaissance de la maladie par les médecins et une vigilance des voyageurs par rapport aux symptômes sont nécessaires afin de limiter les délais de diagnostic. La chimioprophylaxie doit être préconisée chez tous les voyageurs, notamment les patients d'origine africaine qui représentent une part croissante des patients présentant une forme grave.Imported malaria became an important public health issue in many developed countries, because of severe cases that can quickly lead to complications and death. To explore characteristics and risk factors for severe malaria, we conducted a retrospective study of imported p.falciparum malaria among adults returning to metropolitan France from malaria-endemic areas between 2000 and 2009. Epidemiological, clinical and biological data were collected by a network of 120 laboratories and were reported to the CNR Paludisme. The WHO definition (2000) was used to define the paients with severe malaria. Factors associated with severity were identified by logistic regression. The study evaluated 20,556 patients who presented p.falciparum malaria, including 1083 patients with severe malaria. In multivariate analysis, risk factors independently associated with severity were as follows: absence of chemoprophylaxis, older age, caucasian origin, onset of symptoms prior to return to France, time between onset of symptoms and diagnostis in the range of 4 to 12 days and diagnosis in autumn/winter season. The study period was marked by an increase in the proportion of severe cases from 3,1% in 2000 to 10,5% in 2009.Vigilance should be increased for adults above 60 years and for patients of caucasian origin. Regarding delay in diagnosis, greater physician awareness of the disease and increased vigilance of travellers concerning the symptoms are needed. Increasing compliance with chemoprophylaxis remains necessary for all travelers, including African patients, which represent an increased proportion of severe cases.LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Le rapport transferrine-albumine comme marqueur de carence martiale chez les patients hospitalisés

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Le corps dans la dépression des sujets vieillissants (détours anthropologiques et mises au point psychiatriques)

La dépression des sujets âgés est un problème majeur de santé publique. Elle pose des difficultés diagnostiques et thérapeutiques spécifiques. Le corps y joue un rôle central. Nous replaçons ce trouble dans un décor anthropologique, à savoir l histoire contemporaine des représentations du corps vieillissant. Les bouleversements culturels opérants depuis le XVIIIème siècle et l apparition de la médecine actuelle ont transformé le regard social sur le corps. Par le principe de performance, la dynamique du projet orientée vers l avenir est inventée. Dès lors les corps vieillissants apparaissent comme des antiprojets dont les caractéristiques se cristallisent autour des préoccupations de dépendance et de perte d autonomie. Ainsi nous voyons la dépression des sujets vieillissants potentiellement comme une prophétie autoréalisante de la conception contemporaine du corps. Le défi du temps impose un vécu de trahison et une crise du vieillir. Le trouble dépressif est dans ce contexte banalisé comme une souffrance normale inéluctable. Mais il peut également être masqué par des troubles cognitifs ou la plainte somatique. L enjeu du soin est d une part de repérer les comorbidités et les facteurs précipitants. Une place spécifique doit être faite à l exploration des douleurs. Le travail impose une collaboration interdisciplinaire. Le traitement est multidimensionnel centré sur les choix du sujet et de son entourage. La prescription de traitements médicamenteux doit tenir compte des spécificités pharmacocinétiques et pharmacodynamiques. Les traitements physiques à action centrale ont de ce point de vue une indication intéressante. Les psychothérapies et la psychomotricité permettent de recentrer le sujet sur son être au monde, et de renouer avec une utilité propre.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF