Introduction

International audienceGlobalization, as a process of accelerated commercial exchanges between different types of universality, is a long-term phenomenon that is often seen as part of the 15th century’s Age of Discovery (Grataloup, 2006; Boucheron, 2009). This was the period when ‘world economies’ first began to be organized structurally through trade which led to the launch of international commerce as a form of capitalism with the Mediterranean as one of the main marketplaces (Braudel, 1993a, 1993b). In the 19th century, colonization and new industrial revolutions provided the bases for greater and more concentrated movements of people and goods (Wallerstein, 2006)

Decrypting the programming of β-methylation in virginiamycin M biosynthesis

During biosynthesis by multi-modular trans-AT polyketide synthases, polyketide structural space can be expanded by conversion of initially-formed electrophilic ß-ketones into ß-alkyl groups. These multi-step transformations are catalysed by 3-hydroxy-3-methylgluratryl synthase cassettes of enzymes. While mechanistic aspects of these reactions have been delineated, little information is available concerning how the cassettes select the specific polyketide intermediate(s) to target. Here we use integrative structural biology to identify the basis for substrate choice in module 5 of the virginiamycin M trans-AT polyketide synthase. Additionally, we show in vitro that module 7, at minimum, is a potential additional site for ß-methylation. Indeed, analysis by HPLC-MS coupled with isotopic labelling and pathway inactivation identifies a metabolite bearing a second ß-methyl at the expected position. Collectively, our results demonstrate that several control mechanisms acting in concert underpin ß-branching programming. Furthermore, variations in this control – whether natural or by design – open up avenues for diversifying polyketide structures towards high-value derivatives

Atlas des migrations en Méditerranée. De l'Antiquité à nos jours

Au travers de deux cents cartes, des illustrations, des extraits de sources historiques et des textes de synthèse rédigés par plus de soixante-dix spécialistes, historiens, géographes, anthropologues ou politologues, l’Atlas des migrations en Méditerranée de l’Antiquité à nos jours montre comment les migrations ont façonné les sociétés et les cultures méditerranéennes sur la longue durée. Il évoque les territoires et structures qui encadrent, contrôlent ou accompagnent les migrations (routes, frontières, ports, lieux d’accueil, cadres politiques et juridiques), les différents acteurs des mobilités (marchands, travailleurs, esclaves, hommes d’État, exilés et bannis, religieux, intellectuels, touristes ou artistes), avant de porter attention aux modalités de contact entre les migrants et les sociétés d’arrivée (invasions, colonisations, transferts, cosmopolitismes, xénophobie). Dans chacun des seize chapitres, les doubles pages thématiques, où se croisent les époques, laissent le choix d’une lecture continue ou fractionnée. L’ouvrage s’adresse à un lectorat curieux de mettre en perspective le phénomène migratoire qui, sous les feux de l’actualité, suscite des discours aux formules lapidaires et parfois outrancières

Pratique actuelle pour le retour au sport après une entorse de cheville: Sondage de médecins francophones

peer reviewedBackground: Recommendations are available for assessment criteria for safe return-to-play (RTP) after a lateral ankle sprain. However, their current use among physicians is unknown. Methods: French-speaking physicians in Belgium, France and Switzerland were asked to complete an online survey and report their clinical assessment of selected RTP criteria. Results:The respondent sample (n = 109) included physicians with and without Sports Medicine education, varied level of experience and proportion of athletes in their practice population. Pain was the most selected criterion for safe RTP (90% of physicians), followed by ability to engage in functional tasks (82%), functional instability (73%), range of motion (61%), proprioception (47%), mechanical instability (39%), strength (38%) and swelling (31%). A low proportion of physicians use quantitative measures to assess these criteria (between 4% and 53%). Conclusions: A large proportion of physicians consider the recommended criteria for RTP decisions. However, physicians do not frequently use quantitative measures.Introduction: Il existe des recommandations concernant les critères d'évaluation pour un retour au sport (RTS) réussi à la suite d'une entorse latérale de la cheville. Cependant, leur utilisation actuelle par les médecins est inconnue. Méthodes: Des médecins francophones de Belgique, de France et de Suisse ont été invités à répondre à une enquête en ligne et à faire part de leur évaluation clinique de certains critères de RTS. Résultats: L'échantillon de répondants (n = 109) comprenait des médecins avec et sans formation en médecine du sport, un niveau d'expérience varié et une proportion d'athlètes différente dans leur patient. La douleur était le critère le plus sélectionné pour une RTS réussi (90 % des médecins), suivi de la capacité à s'engager dans des tâches fonctionnelles (82 %), de l'instabilité fonctionnelle (73 %), de l'amplitude des mouvements (61 %), de la proprioception (47 %), de l'instabilité mécanique (39 %), de la force (38 %) et du gonflement (31 %). Une faible proportion de médecins utilise des mesures quantitatives pour évaluer ces critères (entre 4% et 53%). Conclusions: Une grande proportion de médecins prend en compte les critères recommandés pour autoriser le RTS. Cependant, les médecins n'utilisent pas fréquemment des mesures quantitatives

Health-related quality of life in French adolescents and adults: norms for the DUKE Health Profile

<p>Abstract</p> <p>Background</p> <p>The continual monitoring of population health-related quality of life (HRQoL) with validated instruments helps public health agencies assess, protect, and promote population health. This study aimed to determine norms for the French adolescent and adult general population for the Duke Health Profile (DUKE) questionnaire in a large representative community sample.</p> <p>Methods</p> <p>We randomly selected 17,733 French people aged 12 to 75 years old in 2 steps, by households and individuals, from the National Health Barometer 2005, a periodic population study by the French National Institute for Prevention and Health Education. Quality of life and other data were collected by computer-assisted telephone interview.</p> <p>Results</p> <p>Normative data for the French population were analyzed by age, gender and self-reported chronic disease. Globally, function scores (best HRQoL=100) for physical, mental, social, and general health, as well as perceived health and self-esteem, were 72.3 (SEM 0.2), 74.6 (0.2), 66.8 (0.1), 71.3 (0.1), 71.3 (0.3), 76.5 (0.1), respectively. Dysfunction scores (worst HRQoL=100) for anxiety, depression, pain and disability domains were 30.9 (0.1), 27.6 (0.2), 34.3 (0.3), 3.1 (0.1), respectively.</p> <p>Conclusion</p> <p>The French norms for adolescents and adults for the DUKE could be used as a reference for other studies assessing HRQoL, for specific illnesses, in France and for international comparisons.</p

The BioMart community portal: an innovative alternative to large, centralized data repositories.

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations

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/)

Place des essais cliniques de phases précoces dans le développement des médicaments (cas particulier de la phase 0)

Le développement d'un nouveau médicament est un processus long et de plus en plus coûteux. Il est séparé en plusieurs phases précliniques et cliniques. Ce schéma standard présente un fort taux d'attrition puisque seulement 10% des molécules testées en phase I se retrouveront sur le marché. Pour contrer cela, la FDA et l'EMEA ont posé les fondements d'un nouveau concept faisant le pont entre les essais précliniques et les essais de phase I et permettant d'obtenir des informations sur le comportement du composé plus précocement chez l'Homme : les essais de phase 0. Cette restructuration du protocole de développement intervient également au moment où les médicaments issus des biotechnologies prennent leur essor et pour lesquels ce protocole classique semblait montrer ses limites. Notre travail montre quels sont les fondements de ces nouveaux protocoles, les outils nécessaires et les enjeux pour des composés issus des biotechnologies tels que les anticorps monoclonaux développés pour l'oncologie. La phase 0 offre de nouvelles perspectives d'évaluation d'un composé chez l'Homme et permet une prise de décision de manière plus précoce et plus sûre. Elle permet également de répondre aux limites du protocole actuel de phase I dans le développement d'entités issues des biotechnologies et des anticorps monoclonaux en particulier.DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF