Des scandales à la vertu : gouvernance interne et reddition de comptes des OBNL à Laval

Le scandale de la corruption dans l’octroi de contrats publics qui a mené à l’arrestation de l’ex-maire Gilles Vaillancourt en 2013 a conduit la Ville de Laval à réformer en profondeur ses mécanismes de gouvernance. Pourquoi et comment s’est effectué ce virage? Cette table ronde vise à présenter les multiples facettes de la mise en oeuvre des bonnes pratiques en matière de gouvernance selon deux volets, soit la gouvernance des instances consultatives internes et la reddition de comptes des organismes à but non lucratif (OBNL) recevant un appui financier direct ou indirect de la Ville

228 Blood pressure in HIV-infected patients

ObjectifveTo determine the prevalence of hypertension in a cohort of HIV-infected patients (HIV+).MethodsHIV+ patients were enrolled consecutively at ambulatory cardiology consultation. We evaluated:cardiovascular risk factors,office blood pressure,24 hours ambulatory blood pressure monitoring (ABPM).We identified patients with known hypertension, masked hypertension and white-coat effect.Results258 HIV+ patients (mean age 49±7 ans, 91% men) were consecutively included in this study between 2005 and 2009. Cardiovascular risk factors were as follows: 52% had dyslipidemia, 51% were active smokers, 40% with known hypertension and 9% were diabetics. Body mass index of the entire cohort was 24±4kg/mΣ and 89% were under antiretrovirals. Data on blood pressure are depicted in Table 1. 19% (29) were discovered to have hypertension.ConclusionHypertension is frequent in HIV-infected patients and more and more common with aging. The number of non-dipper HIV+ was high in this cohort. Studies on the impact of HIV infection and antiretrovirals on the autonomic nervous system should be performed.ParametersN=258Office systolic BP, mmHg131±19Office diastolic BP, mmHg81±10Mean 24h-systolic BP, mmHg125±13Mean 24-diastolic BP, mmHg77±9Daytime systolic BP, mmHg129±13Daytime diastolic BP, mmHg80±9Nighttime systolic BP, mmHg115±17Nighttime diastolic BP, mmHg68±10BP profile in known hypertensive patientsN=103Number of patients with appropriate BP control, %45%Number of patients with white-coat effect, %17%Non dipper, %43% in known hypertensive patients 39% in unknown hypertensive patient

Former à s’informer : développer l’esprit critique ! Comment éduquer et accompagner les adolescents et les jeunes adultes dans l’univers médiatique contemporain pour les aider à grandir ?

Les contenus pédagogiques ont été réalisés dans le cadre du projet Former des médiateurs EMI pour adolescents et jeunes adultes, déposé en 2020 par l’Enssib et l’Inspé Université Claude Bernard Lyon 1. Ce projet s’inscrit dans le Plan EMI développé et financé par le Ministère de la Culture

Rescue of Advanced Pompe Disease in Mice with Hepatic Expression of Secretable Acid α-Glucosidase.

Pompe disease is a neuromuscular disorder caused by disease-associated variants in the gene encoding for the lysosomal enzyme acid α-glucosidase (GAA), which converts lysosomal glycogen to glucose. We previously reported full rescue of Pompe disease in symptomatic 4-month-old Gaa knockout (Gaa-/-) mice by adeno-associated virus (AAV) vector-mediated liver gene transfer of an engineered secretable form of GAA (secGAA). Here, we showed that hepatic expression of secGAA rescues the phenotype of 4-month-old Gaa-/- mice at vector doses at which the native form of GAA has little to no therapeutic effect. Based on these results, we then treated severely affected 9-month-old Gaa-/- mice with an AAV vector expressing secGAA and followed the animals for 9 months thereafter. AAV-treated Gaa-/- mice showed complete reversal of the Pompe phenotype, with rescue of glycogen accumulation in most tissues, including the central nervous system, and normalization of muscle strength. Transcriptomic profiling of skeletal muscle showed rescue of most altered pathways, including those involved in mitochondrial defects, a finding supported by structural and biochemical analyses, which also showed restoration of lysosomal function. Together, these results provide insight into the reversibility of advanced Pompe disease in the Gaa-/- mouse model via liver gene transfer of secGAA.This work was supported by Genethon, the French Muscular Dystro-phy Association (AFM), and Spark Therapeutics. It was also sup-ported by the European Union’s Research and Innovation Programunder grant agreement number 667751 (to F.M.), the EuropeanResearch Council Consolidator Grant under grant agreement number617432 (to F.M.), and Marie Skłodowska-Curie Actions-IndividualFellowship (MSCA-IF) grant agreement number 797144 (to U.C.)S

Newborn screening in metachromatic leukodystrophy – European consensus-based recommendations on clinical management

Introduction: Metachromatic leukodystrophy (MLD) is a rare autosomal recessive lysosomal storage disorder resulting from arylsulfatase A enzyme deficiency, leading to toxic sulfatide accumulation. As a result affected individuals exhibit progressive neurodegeneration. Treatments such as hematopoietic stem cell transplantation (HSCT) and gene therapy are effective when administered pre-symptomatically. Newborn screening (NBS) for MLD has recently been shown to be technically feasible and is indicated because of available treatment options. However, there is a lack of guidance on how to monitor and manage identified cases. This study aims to establish consensus among international experts in MLD and patient advocates on clinical management for NBS-identified MLD cases. Methods: A real-time Delphi procedure using eDELPHI software with 22 experts in MLD was performed. Questions, based on a literature review and workshops, were answered during a seven-week period. Three levels of consensus were defined: A) 100%, B) 75–99%, and C) 50–74% or >75% but >25% neutral votes. Recommendations were categorized by agreement level, from strongly recommended to suggested. Patient advocates participated in discussions and were involved in the final consensus. Results: The study presents 57 statements guiding clinical management of NBS-identified MLD patients. Key recommendations include timely communication by MLD experts with identified families, treating early-onset MLD with gene therapy and late-onset MLD with HSCT, as well as pre-treatment monitoring schemes. Specific knowledge gaps were identified, urging prioritized research for future evidence-based guidelines. Discussion: Consensus-based recommendations for NBS in MLD will enhance harmonized management and facilitate integration in national screening programs. Structured data collection and monitoring of screening programs are crucial for evidence generation and future guideline development. Involving patient representatives in the development of recommendations seems essential for NBS programs

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

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Le retour des forêts françaises

Au cours des 150 dernières années, la surface forestière française a doublé, la France est devenue le troisième pays européen le plus boisé, après la Finlande et la Suède. Les forêts ont conquis 6 millions d’hectares entre 1908 et 2009, soit en moyenne 60 000 hectares par an. Les forêts occupent actuellement 28% du territoire, presque 16 millions d'hectares, elles sont en croissance de 26 m2 chaque seconde, soit de 82 000 hectares et 85 à 110 millions de m3 chaque année. Entre 1985 et 1995, l..

O retorno das matas francesas

Nos últimos 150 anos, a área florestal francesa dobrou, a França tornou-se o terceiro país europeu mais arborizado, depois da Finlândia e da Suécia. As florestas conquistaram 6 milhões de hectares entre 1908 e 2009, com uma média de 60.000 hectares por ano. As florestas ocupam atualmente 28% do território, quase 16 milhões de hectares, estão crescendo 26 m2 a cada segundo, ou 82.000 hectares e 85 a 110 milhões de m3 por ano. Entre 1985 e 1995, a floresta francesa cresceu a uma taxa anual de 3..