Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2)

BACKGROUND: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013)

Introduction: Debates on Experience and Empiricism in Nineteenth Century France

The lasting effects of the debate over canon-formation during the 1980s affected the whole field of Humanities, which became increasingly engaged in interrogating the origin and function of the Western canon (Gorak 1991; Searle 1990). In philosophy, a great deal of criticism was, as a result, directed at the traditional narrative of seventeenth-and eighteenth-century philosophies—a critique informed by postcolonialism (Park 2013) as well as feminist historiography (Shapiro 2016). D. F. Norton (1981), L. Loeb (1981) and many others1 attempted to demonstrate the weaknesses of the tripartite division between rationalism, empiricism and critical philosophy.2 As time went on, symptoms of dissatisfaction with what has been called the “standard narrative” ( Vanzo 2013) and the “epistemological par-adigm” (Haakonssen 2004, 2006) only increased. Indeed, at present, a consensus has been reached that the narrative of the antagonism between “Continental rationalism” and “British empiricism”, and the consequent Aufhebung provided by “German critical philosophy,” has been unable to make sense of the complexity, variety and dynamics of early modern.Fil: Antoine-Mahut, Delphine. Ecole Normale Supérieure; FranciaFil: Manzo, Silvia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; Argentin

Contribution à la prise en compte des incertitudes dans les systèmes mécaniques polyarticulés

En phase d'avant projet, les concepteurs ont aujourd'hui accès à des méthodologies de simulation pour connaître le comportement mécanique de prototypes. Dans le cas particulier des analyses cinématique, statique ou dynamique, le formalisme associé aux systèmes mécaniques polyarticulés constitue un très bon outil de prédiction. Néanmoins, en phase d'avant projet, il est rare que l'on connaisse précisément tous les paramètres de la structure. Il est alors difficile d'estimer la répercussion de ces imprécisions sur le comportement du modèle. Les scientifiques travaillent depuis quelques années à l'intégration des imprécisions dans les modèles mathématiques représentant le modèle de comportement des systèmes mécaniques. Cette recherche s'inscrit dans ce sens puisqu'il s'agit de prendre en compte des incertitudes sur les paramètres géométriques et physiques de systèmes polyarticulés. A partir du formalisme flou, plusieurs méthodes sont développées dans le but de gérer un grand nombre de paramètres incertains sans trop pénaliser les temps de calcul. Les différentes approches sont développées pour trois types de problèmes : les analyses cinématique, statique et dynamique. Différents tests illustrent le potentiel de chacune des méthodes. Enfin, dans le cadre de l'étude du comportement statique d'une colonne vertébrale, une étude est menée dans le but de rechercher les paramètres les plus sensibles aux imprécisions.During the stage of preliminary projetc, some engineers today have access to methodologies of rapid simulation to know the mechanical behaviour of prototypes. In the particular case of kinematic, static or dynamic analyses, the formalism associated to multibody systems is a very good prediction tool. Nevertheless, during the stage of preliminary project, all the parameters of the structure are not often known in a precise way. Then it is difficult to estimate the repercussion of these imprecisions on the model behaviour. Scientists have workes for years on the integration of imprecisions in methematical models that represent the behaviour of mechanical systems. This research is going in this sense because it deals with taking into account some uncertainties about geometrica and physic parameters without penalizing too much the computation time. Different approaches are developed for three types of problems : the kinematic, static and dynamic analyses. Different test illustrate the potential of each method. Finally, with regard to the study of the static behaviour of vertebral spine, a research is carried out in order to search the most sensitive parameters to imprecisionsVALENCIENNES-BU Sciences Lettres (596062101) / SudocSudocFranceF

Choc septique fulminant à Capnocytophaga canimorsus après morsure de chien

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Visualization of adherent cell monolayers by cryo-electron microscopy: A snapshot of endothelial adherens junctions

Cryo-electron microscopy (cryo-EM) allows the visualization of the cell architecture in its native state. We developed a robust solution to adapt cryo-electron microscopy of vitreous sections (CEMOVIS) to a monolayer of adherent cells using a functionalized polyacrylamide hydrogel growing substrate. We applied this method to reconstitute an endothelial cell monolayer to visualize the morphology of adherens junctions (AJs) which regulate permeability and integrity of the vascular barrier. The fine morphology and ultrastructure of AJs from cultured primary human coronary artery endothelial cells (HCAECs) were analyzed in their native state by using CEMOVIS. Doxycycline and sphingosine-1-phosphate (S1P) are known as efficient regulators of endothelial permeability. Doxycycline and S1P treatments both led to a drastic morphological switch from very uneven to standardized 14-17nm wide AJs over several microns indicative of a better membrane tethering. Repetitive structures were occasionally noticed within the AJ cleft reflecting a local improved structural organization of VE-cadherin molecules. The ultrastructural stabilization of AJs observed upon treatment likely indicates a better adhesion and thus provides structural clues on the mechanism by which these treatments improve the endothelial barrier function. This method was also successfully extended to a thick epithelial barrier model. We expect our strategy to extend the reliable application of CEMOVIS to virtually any adherent cultured cell systems

Hybridization of Poly(oxazoline) and Poly(ethylene oxide)-Based Amphiphilic Copolymers into Thermosensitive Mixed Micelles of Tunable Cloud Point

This paper reports the development in aqueous solution of mixed micelles of tunable cloud point temperature through blending in various proportions of two copolymers of different chemical natures. For that purpose, a lipid-b-poly(2-isopropyl-2-oxazoline) (lipid-b-P(iPrOx)) copolymer, self-assembling into thermosensitive micelles that phase-separate above a cloud point temperature of 38 °C, was blended in various proportions with commercial C18-b-PEOx. The latter was constituted of a hydrophobic saturated C18 chain and a hydrophilic poly(ethylene oxide) (PEO) block with varying polymerization degrees (x) and does not have any thermosensitive properties on the studied temperature range for any value of x. The different blends were thoroughly characterized by light scattering and UV–visible spectroscopy, revealing that hybridization between both copolymers always occurred, independent of the PEO block length. The resulting mixed micelles present TCP values progressively increasing with the C18-b-PEOx proportion, from 38 to 61 °C. This study demonstrates the relevance of the blending approach to tune the phase separation of micellar systems by formulation rather than by more tedious synthetic efforts. Shifting TCP through this approach extends the range of temperature where lipid-b-P(iPrOx) can find an application

Monocore vs multicore magnetic iron oxide nanoparticles: uptake by glioblastoma cells and efficiency for magnetic hyperthermia

PEGylated magnetic iron oxide nanoparticles (IONPs) were synthesised with the aim to provide proof of concept results of remote cancer cell killing by magnetic fluid hyperthermia. The IONPs were produced by the polyol synthetic route also called “forced hydrolysis pathway” yielding highly superparamagnetic, readily-dispersible, and biocompatible IONPs. As shown previously, adjusting parameters of the reaction led to either monocore or multicore IONPs, with on-demand morphology and magnetic properties. Polyethylene glycol (PEG) was grafted onto the nanoparticles in a single final step, using a phosphonic acid-terminated PEG synthesised separately, a strategy named “convergent”. The magnetic properties of the IONPs were preserved in physiological media thanks to this biocompatible shell. The interaction of the PEGylated IONPs with a glioblastoma cell line was studied, from the stability of IONPs in appropriate cell culture medium to the remotely magnetically triggered cell death. Cellular internalisation of the IONPs was studied, along with their fate after application of an alternating magnetic field (AMF). This investigation highlights the superior efficiency of multicore (nanoflowers) vs monocore (nanospheres) IONPs for magnetic hyperthermia, leading to 80 % cancer cells death in medically translatable conditions.Magnéto-Chimiothérapie : Modélisation de la Délivrance Induite par Champ Magnétique Radiofréquence d'Anticancéreux par des Nano-Vésicules Polymères et Suivi par IRM d'un Modèle de GlioblastomeDéveloppment d'une infrastructure française distribuée coordonnéeMultifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therap