Une mesure de l'effet de la délégation sur le prix de l'eau potable en France

Un peu plus de la moitié des communes françaises délègue actuellement la gestion du service de l'eau à des entreprises privées. L'incidence de ce choix du mode de gestion sur le coût du service et l'ampleur des différences observées entre modes de gestion privée ou publique sont des questions d'actualité. Une évaluation des effets sur le niveau des prix de la délégation des services de l'eau potable en France montre que les conditions d'exploitation de ces services permettent d'expliquer en grande partie l'écart de prix existant entre la moyenne des prix pratiqués par les délégataires privés et celle constatée pour les régies en 1998. Ces résultats confortent l'idée que les communes ont tendance à choisir la gestion privée si elles font face à des conditions d'exploitation difficiles.

Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1.

Hepatitis C virus (HCV) infection is closely tied to the lipid metabolism of liver cells. Here we identify the triglyceride-synthesizing enzyme diacylglycerol acyltransferase-1 (DGAT1) as a key host factor for HCV infection. DGAT1 interacts with the viral nucleocapsid core and is required for the trafficking of core to lipid droplets. Inhibition of DGAT1 activity or RNAi-mediated knockdown of DGAT1 severely impairs infectious virion production, implicating DGAT1 as a new target for antiviral therapy

Hepatic differentiation of human pluripotent stem cells in miniaturized format suitable for high-throughput screen

AbstractThe establishment of protocols to differentiate human pluripotent stem cells (hPSCs) including embryonic (ESC) and induced pluripotent (iPSC) stem cells into functional hepatocyte-like cells (HLCs) creates new opportunities to study liver metabolism, genetic diseases and infection of hepatotropic viruses (hepatitis B and C viruses) in the context of specific genetic background. While supporting efficient differentiation to HLCs, the published protocols are limited in terms of differentiation into fully mature hepatocytes and in a smaller-well format. This limitation handicaps the application of these cells to high-throughput assays. Here we describe a protocol allowing efficient and consistent hepatic differentiation of hPSCs in 384-well plates into functional hepatocyte-like cells, which remain differentiated for more than 3weeks. This protocol affords the unique opportunity to miniaturize the hPSC-based differentiation technology and facilitates screening for molecules in modulating liver differentiation, metabolism, genetic network, and response to infection or other external stimuli

Pyrobitumen occurrence and formation in a Cambro–Ordovician sandstone reservoir, Fahud Salt Basin, North Oman

The Cambro–Ordovician Barik Sandstone reservoirs in the Fahud Salt Basin in Oman contain bitumen which may fill up to 40% of the porosity. In well Jaleel-1, this bitumen was isolated (according to kerogen procedure) and typed by NMR, elemental analysis and density measurements. The isolated bitumen is characterized by: (1) a highly aromatic character (NMR 75% CAro, H/C atomic ratio: 0.65), (2) a very high sulphur content (4.2%) and (3) a relatively high density (1.3–1.4 g/cm3). The insolubility and the reflectivity of the bitumen (1.2% Vr) qualify it as a low mature pyrobitumen. The combination of Rock-Eval and density data was used to calculate the actual volume of the pyrobitumen in the rock, as a percentage of porosity. It was found that the pyrobitumen volume shows a negative correlation with total porosity, indicating that small pores are more invaded by bitumen than larger ones. Finally, closed system pyrolysis experiments, performed on oils with different NSO contents, indicate that an in situ oil with a very high content of NSO compounds is required to generate such large amounts of pyrobitumen in the pore system. These observations suggest that the precursor oil of the current pyrobitumen was a very heavy oil tentatively assumed to be the result of a severe biodegradation. Basin modeling shows that the reservoir was charged already in Devonian times. A major uplift brought the oil accumulation near the surface during the Carboniferous and a rather regular burial to the present day position (4500 m, 140°C) (Loosveld et al., 1996). This scenario, involving a residence time at shallow depth, strengthens the biodegradation hypothesis. The numerical modeling, which involves the IFP kinetic model for secondary oil cracking, suggests that pyrobitumen formation is a very recent event. Inclusion of pyrobitumen particles within quartz overgrowth, containing fluid inclusions, provides an upper temperature limit for the beginning of pyrobitumen formation which comforts the result of kinetic modelling

Fleury-sur-Orne – Carrière Saingt

La redécouverte par les archéologues en 2014 de l’une des nombreuses carrières-refuges utilisées par les civils pris sous les bombes lors de la Bataille de Caen (juin-juillet 1944), a offert l’opportunité de mettre en place une opération archéologique à caractère expérimental permettant de confronter différents types d’analyses, au croisement de l’archéologie, de l’histoire et de la sociologie. L’année 2015 a été consacrée à la mise en place du protocole d’étude et aux premiers tests dans plu..

AI-based diagnosis in mandibulofacial dysostosis with microcephaly using external ear shapes

IntroductionMandibulo-Facial Dysostosis with Microcephaly (MFDM) is a rare disease with a broad spectrum of symptoms, characterized by zygomatic and mandibular hypoplasia, microcephaly, and ear abnormalities. Here, we aimed at describing the external ear phenotype of MFDM patients, and train an Artificial Intelligence (AI)-based model to differentiate MFDM ears from non-syndromic control ears (binary classification), and from ears of the main differential diagnoses of this condition (multi-class classification): Treacher Collins (TC), Nager (NAFD) and CHARGE syndromes.MethodsThe training set contained 1,592 ear photographs, corresponding to 550 patients. We extracted 48 patients completely independent of the training set, with only one photograph per ear per patient. After a CNN-(Convolutional Neural Network) based ear detection, the images were automatically landmarked. Generalized Procrustes Analysis was then performed, along with a dimension reduction using PCA (Principal Component Analysis). The principal components were used as inputs in an eXtreme Gradient Boosting (XGBoost) model, optimized using a 5-fold cross-validation. Finally, the model was tested on an independent validation set.ResultsWe trained the model on 1,592 ear photographs, corresponding to 1,296 control ears, 105 MFDM, 33 NAFD, 70 TC and 88 CHARGE syndrome ears. The model detected MFDM with an accuracy of 0.969 [0.838–0.999] (p < 0.001) and an AUC (Area Under the Curve) of 0.975 within controls (binary classification). Balanced accuracies were 0.811 [0.648–0.920] (p = 0.002) in a first multiclass design (MFDM vs. controls and differential diagnoses) and 0.813 [0.544–0.960] (p = 0.003) in a second multiclass design (MFDM vs. differential diagnoses).ConclusionThis is the first AI-based syndrome detection model in dysmorphology based on the external ear, opening promising clinical applications both for local care and referral, and for expert centers

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

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/)

Production de virus de l'hépatite C infectieux en culture primaire d'hépatocytes humains adultes

L infection par le Virus de l Hépatite C (VHC) représente un grave problème de santé publique à travers le monde. Bien que la production de virus en culture cellulaire (VHCcc) ait été rendue possible en utilisant des sous clones de la lignée Huh7 issue d un hépatocarcinome humain, les recherches basiques et appliquées sur le virus restent pénalisées par l absence d un modèle de culture cellulaire capable de reproduire le cycle viral complet dans les cellules hôtes naturelles du VHC, c'est-à-dire les hépatocytes humains primaires, cellules normales, quiescentes et hautement différenciées. Ici nous avons développé un système permettant de cultiver le VHC en culture primaire d hépatocytes humains adultes. Tout en maintenant l expression de leurs marqueurs de différenciation, les hépatocytes humains primaires inoculés avec des particules virales VHCcc permettaient une réplication intracellulaire forte du génome viral. Surtout, ces hépatocytes normaux produisaient de nouveaux virions infectieux (appelés VHCpc, pour virus produits en culture primaire) avec des titres comparables à ceux obtenus avec les cellules transformées Huh7. Cependant, les VHCpc présentaient une meilleure infectiosité spécifique et une densité plus faible que les VHCcc, reproduisant plus précisément les caractéristiques des complexes virus/lipoprotéines produits durant l infection in vivo. Ces deux propriétés étaient perdues après re-culture en cellules Huh7, suggérant que les virions authentiques ne peuvent être produits qu en culture d hépatocytes normaux. En conclusion, nous avons établi un système de culture cellulaire simple mais robuste permettant de reproduire le cycle viral complet du VHC dans des hépatocytes humains hautement différenciés, constituant ainsi un modèle in vitro plus pertinent pour l étude des interactions du VHC avec sa cellule hôte naturelle et permettant la validation de traitements antiviraux candidats dans le contexte d une physiologie hépatocytaire authentique.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF