Glial activation in white matter following ischemia in the neonatal P7 rat brain

This study examines cell death and proliferation in the white matter after neonatal stroke. In post-natal day 7 injured rat, there was a marked reduction in myelin basic protein (MBP) immunostaining mainly corresponding to numerous pyknotic immature oligodendrocytes and TUNEL-positive astrocytes in the ipsilateral external capsule. In contrast, a substantial restoration of MBP, as indicated by the MBP ratio of left-toright, occurred in the cingulum at 48 (1.27 +- 0.12) and 72 (1.30 +- 0.18, p<0.05) hours of recovery as compared to age-matched controls (1.03 +- 0.14). Ki-67 immunostaining revealed a first peak of newly-generated cells in the dorsolateral hippocampal subventricular zone and cingulum at 72 hours after reperfusion. Double immunofluorescence revealed that most of the Ki-67-positive cells were astrocytes at 48 hours and NG2 pre-oligodendrocytes at 72 hours of recovery. Microglia infiltration occurs over several days in the cingulum and a huge quantity of macrophages reached the subcortical white matter where they engulfed immature oligodendrocytes. The overall results suggest that the persistent activation of microglia involves a chronic component of immunoinflammation, which overwhelms repair processes and contributes to cystic growth in the developing brain.Comment: 30 page

Severe pain management in the emergency department: patient pathway as a new factor associated with IV morphine prescription

BackgroundAcross the world, 25–29% of the population suffer from pain. Pain is the most frequent reason for an emergency department (ED) visit. This symptom is involved in approximately 70% of all ED visits. The effective management of acute pain with adequate analgesia remains a challenge, especially for severe pain. Intravenous (IV) morphine protocols are currently indicated. These protocols are based on patient-reported scores, most often after an immediate evaluation of pain intensity at triage. However, they are not systematically prescribed. This aspect could be explained by the fact that physicians individualize opioid pain management for each patient and each care pathway to determine the best benefit–risk balance. Few data are available regarding bedside organizational factors involved in this phenomenon.ObjectiveThis study aimed to analyze the organizational factors associated with no IV morphine prescription in a standardized context of opioid management in a tertiary-care ED.MethodsA 3-month prospective study with a case–control design was conducted in a French university hospital ED. This study focused on factors associated with protocol avoidance despite a visual analog scale (VAS) ≥60 or a numeric rating scale (NRS) ≥6 at triage. Pain components, physician characteristics, patient epidemiologic characteristics, and care pathways were considered. Qualitative variables (percentages) were compared using Fisher’s exact test or the chi-squared tests. Student’s t-test was used to compare continuous variables. The results were expressed as means with their standard deviation (SD). Factors associated with morphine avoidance were identified by logistic regression.ResultsA total of 204 patients were included in this study. A total of 46 cases (IV morphine) and 158 controls (IV morphine avoidance) were compared (3:1 ratio). Pain patterns and patient’s epidemiologic characteristics were not associated with an IV morphine prescription. Regarding NRS intervals, the results suggest a practice disconnected from the patient’s initial self-report. IV morphine avoidance was significantly associated with care pathways. A significant difference between the IV morphine group and the IV morphine avoidance group was observed for “self-referral” [adjusted odds ratio (aOR): 5.11, 95% CIs: 2.32–12.18, p &lt; 0.0001] and patients’ trajectories (Fisher’s exact test; p &lt; 0.0001), suggesting IV morphine avoidance in ambulatory pathways. In addition, “junior physician grade” was associated with IV morphine avoidance (aOR: 2.35, 95% CIs: 1.09–5.25, p = 0.03), but physician gender was not.ConclusionThis bedside case–control study highlights that IV morphine avoidance in the ED could be associated with ambulatory pathways. It confirms the decreased choice of “NRS-only” IV morphine protocols for all patients, including non-trauma patterns. Modern pain education should propose new tools for pain evaluation that integrate the heterogeneity of ED pathways

Le Musée de l'histoire de l'immigration à Paris: une collection et un musée en devenir

Globalization and the emergence of political issues in the European Union have propelled the topic of immigration into the center of the current political climate. In this contemporary context, museums that are focused on immigration are gaining more importance due to the impetus for preserving and providing visibility for the heritage of immigrants. In Paris during October 2007 the Cité nationale de l'Histoire de l'Immigration (CNHI) opened its doors but in 2013 it changed its name to Musée de l'histoire de l'immigration (MHI). The museum presents a historical and cultural approach to immigration as well as displaying contemporary works of art that deal with the theme of immigration. In this paper we will analyze how this museum is an attempt to integrate the History of immigration as a national heritage.Com a globalização e o surgimento da Comunidade Europeia, a questão das migrações se apresenta no centro das preocupações políticas mundiais contemporâneas. E nesse contexto histórico de países de imigração ou de emigração organizam-se os museus de estudos das migrações que pertencem à categoria dos museus de história e de sociedade. Em outubro de 2007, é criada, em Paris, a Cité nationale de l'Histoire de l'Immigration (CNHI) que desde 2013 passou a se chamar Musée de l'histoire de l'immigration (MHI): um museu que apresenta ao público uma abordagem histórica e cultural da imigração assim como obras de arte contemporânea que tratam do tema. Neste artigo, bucaremos compreender como este museu constitui uma tentativa de reconhecimento do patrimônio da imigração como um patrimônio nacional.Avec la mondialisation et l'émergence de nouvelles politiques d'immigration dans la Communauté Européenne, la question des migrations est centrale dans le monde politique d'aujourd'hui. C'est dans ce contexte historique de pays d'immigration ou d'émigration que se met en place et s'organise l'étude des musées d'immigration qui appartiennent à la catégorie des musées d'histoire et de société. En France, la Cité nationale de l'Histoire de l'Immigration, qui a ouvert ses portes en octobre 2007, depuis 2013 Musée de l'histoire de l'immigration (MHI), se distingue, dans ce contexte mondial, par l'originalité de son projet et les discussions qu'il suscite dans divers domaines (aussi bien dans le milieu académique que dans les réseaux d'associations qui s'occupent des immigrés en France). Le musée présente au public une approche historique et culturelle de l'immigration ainsi que des œuvres d'art contemporain sur ce sujet. Dans cet article, on s'interrogera sur comment ce musée constitue une tentative de reconnaître le patrimoine de l'immigration comme un patrimoine national

Comparative in vitro activity of Meropenem, Imipenem and Piperacillin/tazobactam against 1071 clinical isolates using 2 different methods: a French multicentre study

<p>Abstract</p> <p>Background</p> <p>Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The major objective of the present study was to assess the <it>in vitro </it>activity of meropenem compared to imipenem and piperacillin/tazobactam, against 1071 non-repetitive isolates collected from patients with bacteremia (55%), pneumonia (29%), peritonitis (12%) and wound infections (3%), in 15 French hospitals in 2006. The secondary aim of the study was to compare the results of routinely testings and those obtained by a referent laboratory.</p> <p>Method</p> <p>Susceptibility testing and Minimum Inhibitory Concentrations (MICs) of meropenem, imipenem and piperacillin/tazobactam were determined locally by Etest method. Susceptibility to meropenem was confirmed at a central laboratory by disc diffusion method and MICs determined by agar dilution method for meropenem, imipenem and piperacillin/tazobactam.</p> <p>Results</p> <p>Cumulative susceptibility rates against <it>Escherichia coli </it>were, meropenem and imipenem: 100% and piperacillin/tazobactam: 90%. Against other <it>Enterobacteriaceae</it>, the rates were meropenem: 99%, imipenem: 98% and piperacillin/tazobactam: 90%. All <it>Staphylococci</it>, <it>Streptococci </it>and anaerobes were susceptible to the three antibiotics. Against non fermeters, meropenem was active on 84-94% of the strains, imipenem on 84-98% of the strains and piperacillin/tazobactam on 90-100% of the strains.</p> <p>Conclusions</p> <p>Compared to imipenem, meropenem displays lower MICs against <it>Enterobacteriaceae</it>, <it>Escherichia coli </it>and <it>Pseudomonas aeruginosa</it>. Except for non fermenters, MICs90 of carbapenems were <4 mg/L. Piperacillin/tazobactam was less active against <it>Enterobacteriaceae </it>and <it>Acinetobacter </it>but not <it>P. aeruginosa</it>. Some discrepancies were noted between MICs determined by Etest accross centres and MICs determined by agar dilution method at the central laboratory. Discrepancies were more common for imipenem testing and more frequently related to a few centres. Overall MICs determined by Etest were in general higher (0.5 log to 1 log fold) than MICs by agar dilution.</p

Perception of inappropriate cardiopulmonary resuscitation by clinicians working in emergency departments and ambulance services : The REAPPROPRIATE international, multi-centre, cross sectional survey

Introduction: Cardiopulmonary resuscitation (CPR) is often started irrespective of comorbidity or cause of arrest. We aimed to determine the prevalence of perception of inappropriate CPR of the last cardiac arrest encountered by clinicians working in emergency departments and out-of-hospital, factors associated with perception, and its relation to patient outcome. Methods: A cross-sectional survey was conducted in 288 centres in 24 countries. Factors associated with perception of CPR and outcome were analyzed by Cochran-Mantel-Haenszel tests and conditional logistic models. Results: Of the 4018 participating clinicians, 3150 (78.4%) perceived their last CPR attempt as appropriate, 548 (13.6%) were uncertain about its appropriateness and 320 (8.0%) perceived inappropriateness; survival to hospital discharge was 370/2412 (15.3%), 8/481 (1.7%) and 8/294 (2.7%) respectively. After adjusting for country, team and clinician's characteristics, the prevalence of perception of inappropriate CPR was higher for a non-shockable initial rhythm (OR 3.76 [2.13-6.64]; P 79 years) and in case of a "poor" first physical impression of the patient (3.45 [2.36-5.05]; P 79 years) and a "poor" first physical impression (0.26 [0.19-0.35]; P <0.0001). Conclusions: The perception of inappropriate CPR increased when objective indicators of poor prognosis were present and was associated with a low survival to hospital discharge. Factoring clinical judgment into the decision to (not) attempt CPR may reduce harm inflicted by excessive resuscitation attempts.Peer reviewe

Death and the Societies of Late Antiquity

Ce volume bilingue, comprenant un ensemble de 28 contributions disponibles en français et en anglais (dans leur version longue ou abrégée), propose d’établir un état des lieux des réflexions, recherches et études conduites sur le fait funéraire à l’époque tardo-antique au sein des provinces de l’Empire romain et sur leurs régions limitrophes, afin d’ouvrir de nouvelles perspectives sur ses évolutions possibles. Au cours des trois dernières décennies, les transformations considérables des méthodologies déployées sur le terrain et en laboratoire ont permis un renouveau des questionnements sur les populations et les pratiques funéraires de l’Antiquité tardive, période marquée par de multiples changements politiques, sociaux, démographiques et culturels. L’apparition de ce qui a été initialement désigné comme une « Anthropologie de terrain », qui fut le début de la démarche archéothanatologique, puis le récent développement d’approches collaboratives entre des domaines scientifiques divers (archéothanatologie, biochimie et géochimie, génétique, histoire, épigraphie par exemple) ont été décisives pour le renouvellement des problématiques d’étude : révision d’anciens concepts comme apparition d’axes d’analyse inédits. Les recherches rassemblées dans cet ouvrage sont articulées autour de quatre grands thèmes : l’évolution des pratiques funéraires dans le temps, l’identité sociale dans la mort, les ensembles funéraires en transformation (organisation et topographie) et les territoires de l’empire (du cœur aux marges). Ces études proposent un réexamen et une révision des données, tant anthropologiques qu’archéologiques ou historiques sur l’Antiquité tardive, et révèlent, à cet égard, une mosaïque de paysages politiques, sociaux et culturels singulièrement riches et complexes. Elles accroissent nos connaissances sur le traitement des défunts, l’emplacement des aires funéraires ou encore la structure des sépultures, en révélant une diversité de pratiques, et permettent au final de relancer la réflexion sur la manière dont les sociétés tardo-antiques envisagent la mort et sur les éléments permettant d’identifier et de définir la diversité des groupes qui les composent. Elles démontrent ce faisant que nous pouvons véritablement appréhender les structures culturelles et sociales des communautés anciennes et leurs potentielles transformations, à partir de l’étude des pratiques funéraires.This bilingual volume proposes to draw up an assessment of the recent research conducted on funerary behavior during Late Antiquity in the provinces of the Roman Empire and on their borders, in order to open new perspectives on its possible developments. The considerable transformations of the methodologies have raised the need for a renewal of the questions on the funerary practices during Late Antiquity, a period marked by multiple political, social, demographic and cultural changes. The emergence field anthropology, which was the beginning of archaeothanatology, and then the recent development of collaborative approaches between various scientific fields (archaeothanatology, biochemistry and geochemistry, genetics, history, epigraphy, for example), have been decisive. The research collected in this book is structured around four main themes: Evolution of funerary practices over time; Social identity through death; Changing burial grounds (organisation and topography); Territories of the Empire (from the heart to the margins). These studies propose a review and a revision of the data, both anthropological and archaeological or historical on Late Antiquity, and reveal a mosaic of political, social, and cultural landscapes singularly rich and complex. In doing so, they demonstrate that we can truly understand the cultural and social structures of ancient communities and their potential transformations, based on the study of funerary practices

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Antibiothérapie initiale des péritonites graves en réanimation chirurgicale (évaluation des pratiques et intérêt de l'antibiogramme chromogène)

Une antibiothérapie rapide et couvrant tous les germes en cause est un facteur de survie dans les infections abdominales graves. La pression de sélection exercée par ce traitement doit être réduite au strict nécessaire. Objectif : évaluer les pratiques de prescription et d'adaptation des antibiothérapies aux résultats bactériologiques dans les péritonites graves dans un service de Réanimation Chirurgicale d'un Centre Hospitalier Universitaire. Déterminer l'intérêt potentiel d'un antibiogramme chromogène systématique et son apport pour les prescriptions quotidiennes. Matériel et méthodes : Tous les patients hospitalisés en Réanimation chirurgicale en 2005 au CHU de Rouen, ayant présenté une infection intra abdominale grave et chez qui a été réalisé au moins un prélèvement intra péritonéal ont été inclus de façon rétrospective. Les données épidémiologiques, cliniques et les résultats bactériologiques ont été recueillis rétrospectivement. Les résultats bactériologiques disponibles chaque jour ont été confrontés aux prescriptions d'antibiotiques afin de déterminer : - si l'antibiothérapie initiale couvrait tous les germes pathogènes identifiés - si toutes les rétrocessions souhaitables ont été réalisées et dans quel délai - si l'utilisation du métronidazole aurait pu réduire encore la pression de sélection. - s'il y a eu des journées supplémentaires indues de couverture des germes anaérobies. - l'apport potentiel d'un antibiogramme chromogène direct.Résultats : Quarante-quatre patients ayant présenté 68 épisodes infectieux intra-abdominaux ont été inclus. La mortalité, l'étiologie des épisodes infectieux et les données microbiologiques sont concordantes avec les données de la littérature. L'examen direct n'apporte jamais d'information faisant modifier l'antibiothérapie initiale. Dans 29,4% des cas l'antibiothérapie initiale était insuffisante (pendant 3,2+-1,5 jours). 61% des rétrocessions souhaitables ont été faites (41% le jour même, 27% à 24h, 13,5% à 48h, 13,5% à 72h, 5% au-delà). Une antibiothérapie à spectre trop large a été maintenue pendant 6,6+-5 jours. Seules 10% des possibilités de réduction du spectre en utilisant le métronidazole ont été saisies. Le traitement anti-anaérobies a été poursuivi indûment dans 13,2% des cas pendant 3,4+-1,2 jours. L'antibiogramme chromogène aurait permis de modifier l'antibiothérapie dans 50% des cas, 2,4 jours plus tôt en moyenne. Conclusion : cet audit montre la nécessité d'amélioration de nos antibiothérapies dans les infections abdominales graves, en particulier par une plus grande réactivité aux résultats bactériologiques disponibles. Le potentiel de réductionde la pression de sélection par l'utilisation du métronidazole est sous-exploité. L'antibiogramme chromogène semble avoir un potentiel important pour améliorer nos prescriptions, qui devrait être évalué par les études prospectives.ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L'organisation de la permanence des soins libérale en France (un enjeu pour le médecine générale. A propos du groupement de coopération sanitaire de Neufchatel en Bray)

La permanence de soins en France est devenue un enjeu de santé publique ces 10 dernières années. Depuis 2001 et la grève des médecins généralistes, des notions importantes sont apparues, comme celles du volontariat, de la sectorisation et de la régulation téléphonique. Malgré cela l'organisation de l'offre de soins non programmés est loin d'être aboutie et de nombreuses disparités persistent. II sera difficile d'envisager l'avenir de la médecine générale comme acteur essentiel de l'offre de soins si sa juste place dans ce dispositif ne peut être trouvée. La création récente des agences régionales de santé devrait permettre une meilleure coordination de tous les acteurs de santé, et rationnaliser une offre de soins non programmés libérale inégalitaire et fragile. A Neufchâtel en Bray (Seine-Maritime), depuis 1999, les médecins généralistes ont développé une activité inédite de permanence de soins de proximité. Ils ont choisi d'étendre l'offre de soins habituellement réservée aux maisons médicales de garde et de collaborer dans le cadre d'un groupement de coopération sanitaire avec le centre hospitalier local qui met à leur disposition leur plateau technique. L'objectif de cette thèse est de décrire le dispositif Neufchâtelois après l'avoir situé dans le contexte régional et national et d'en tirer des éléments de réflexion sur ce que pourrait être le rôle du médecin généraliste dans l'organisation des soins non programmés.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Nebulized versus intravenous morphine titration for the initial treatment of severe acute pain in the emergency department: study protocol for a multicenter, prospective randomized and controlled trial, CLIN-AEROMORPH

International audienceBACKGROUND: Intravenous morphine titration (IVMT) is the French gold standard for opioid treatment in the emergency department (ED). Nebulized morphine titration (NMT) may represent an alternative without venous access, but it has not been adequately studied in adults. We test the hypothesis that NMT is at least as effective as IVMT to initially manage severe acute pain in the ED.METHODS/DESIGN: We designed a multicenter (10 French EDs), single-blind, randomized and controlled trial. Adults between 18 and 75 years with visual analog scale (VAS) ≥ 70/100 or numeric rating scale (NRS) ≥ 7/10 will be enrolled. We will randomize 850 patients into two groups to compare two routes of MT as long as VAS >  30 or NRS >  3. In group A (425), patients will receive an initial NMT for 5-25 min associated with titration of an intravenously (IV) administered placebo of physiologic serum (PS). In group B (425), patients will receive IVMT plus nebulized PS placebo. NMT is defined as a minimum of 1 and a maximum of 3 5-min nebulized boluses of 10 mg or 15 mg (weight ≥ 60 kg), at 10-min fixed intervals. IVMT is defined as a minimum of 1 and a maximum of 6 boluses of 2 mg or 3 mg (weight ≥ 60 kg), at 5-min fixed intervals. Nebulized placebo titration will be performed every 10 min. IV titration of PS will be performed every 5 min. In both groups, after 25 min, if VAS > 30/100 or NRS > 3/10, routine IVMT will be continued until pain relief. Pain severity, vital signs, bronchospasm, and Ramsay score will be recorded every 5 min. The primary outcome is the rate of relief obtained 1 h from the start of drug administration. Complete pain relief in both groups will be compared with a non-inferiority design. Secondary outcomes are pain relief at 30 min (the end of NMT) and at 2 h and median pain relief. We will compare final doses, and study the feasibility and tolerance of NMT (protocol deviations, respiratory or hemodynamic depression, sedation, and minor vegetative side effects). Co-analgesia will be recorded. Discharge criteria from the ED and hospital are defined.DISCUSSION: This trial is the first multicenter randomized and controlled NMT protocol for severe pain in the ED using the titration concept. We propose an original approach of combined titration with an endpoint at 1 h and a non-inferiority design