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• Introduction: Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing β cells of the pancreas. One immunosuppressive agent that has recently shown promise in the treatment of new-onset T1D subjects aged 12-45 years is ATG, Thymoglobuline®, encouraging further exploration in lower age groups. Methods and analysis: MELD-ATG is a phase 2, multi-centre, randomised, double-blind, placebo-controlled, multi-arm parallel-group trial in participants 5-25 years diagnosed with T1D within 3–9 weeks of planned treatment day 1. A total of 114 participants will be recruited sequentially into seven different cohorts with the first cohort of 30 participants being randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg ATG total dose in a 1:1:1:1:1 allocation ratio. The next six cohorts of 12-15 participants will be randomised to placebo, 2.5 mg/kg, and one or two selected middle ATG total doses in a 1:1:1:1 or 1:1:1 allocation ratio, as dependent on the number of middle doses, given intravenously over 2 consecutive days. The primary objective will be to determine the changes in stimulated C-peptide response over the first 2 hours of a mixed meal tolerance test (MMTT) at 12 months for 2.5mg/kg ATG arm versus the placebo. Conditional on finding a significant difference at 2.5 mg/kg, a minimally effective dose will be sought. Secondary objectives include the determination of the effects of a particular ATG treatment dose on 1) stimulated C-peptide, 2) HbA1c, 3) daily insulin dose, 4) time in range by intermittent continuous glucose monitoring (CGM) measures, 5) fasting and stimulated dry blood spot (DBS) C-peptide measurements. Ethics and dissemination: MELD-ATG received first regulatory and ethical approvals in Belgium in September 2020 and from the German and UK regulators as of February 2021. The publication policy is set in the INNODIA grant agreement (www.innodia.eu)., Union’s Horizon 2020 research and innovation program EFPIA JDRF The Leona M. and Harry B. Helmsley Charitable Trust

On February 8, 2019 the Atmosphere-Space Interaction Monitor (ASIM) passed a thunderstorm system north east of Puerto Rico and observed a TGF and an Elve from the same lightning stroke at the very beginning of a lightning flash. A second Elve was observed 456 ms later but without any signature of a TGF about 300 km south-east of the first Elve. The strokes associated with the two Elve events were detected by WWLLN and Vaisala, which allows for an absolute timing accuracy of the ASIM measurements of at least 100 us. Images of the lighting strokes support the source locations for the Elves and TGF. Both the rise time of the UV pulse by ASIM MMIA photometer and radio measurements from Puerto Rico indicate that the first stroke was an intracloud positive while the latter was a cloud-to-ground stroke. The UV emissions from the Elves preceded the optical emissions in 777 nm by50 us and 90 us, respectively. This can partly be explained by the scattering of 777 nm within the cloud. Current moments derived from radio measurements at Puerto Rico and Duke University indicate a fast (30 us) and large (200 kA) current pulse emitting an electromagnetic wave that produces an Elve and a slow (1-2 ms) current producing the optical signals.

Resume L’objectif de la Table Ronde etait d’aborder la Recherche Pre-competitive pour la premiere fois lors des Rencontres de Giens. Les participants venaient de l’industrie du medicament, des biotech, de l’industrie du dispositif, de l’academie, des services et societes de valorisation, des ministeres, du monde de la recherche clinique et fondamentale. Ils ont fait le constat des changements profonds dans la connaissance des maladies et dans le developpement des medicaments. A l’aide d’exemples dans le monde de la Sante et en dehors, ils ont identifie les principes, les enjeux, les facteurs de succes et de risque de la recherche precompetitive. Les particularites de la gestion de la propriete intellectuelle ont ete plus particulierement etudiees. La Table Ronde a conclu sur les principes de la recherche precompetitive en Sante, une revolution culturelle necessaire. C’est developper une recherche en partenariat fondee sur des principes nouveaux : i) comprendre et partager ; ii) integrer la complexite du vivant ; iii) agir dans l’interdisciplinarite.

Resume Le developpement clinique de medicaments disease-modifiers dans la maladie d’Alzheimer se heurte a des difficultes methodologiques dont temoignent plusieurs echecs recents de medicaments en phase III. Compte-tenu des enjeux financiers inherents au passage en phase III et du risque d’investir en pure perte de l’energie pour l’evaluation d’un mauvais candidat-medicament, la question cruciale reste la decision de go/no go entre la phase II et la phase III dont l’objectif est certes de selectionner une molecule susceptible d’etre efficace en phase III mais plus encore d’ecarter d’un developpement ulterieur les candidats aux effets insuffisants. Aucun consensus n’existe aujourd’hui sur la meilleure conception possible des etudes de phase II pour tenter d’eclairer au mieux la decision de go/nogo. Les difficultes de choix de la meilleure conception d’etude concernent tout aussi bien la population-cible, les criteres de jugement en particulier le recours a des biomarqueurs, le plan experimental ou la duree des etudes. L’objet de la Table Ronde (TR) a ete de rassembler les points de vue d’experts francais issus du monde academique, industriel ou reglementaire afin d’arriver a une proposition consensuelle sur la meilleure conception possible que devraient utiliser les etudes de phase II dans la maladie d’Alzheimer.

The term "theranostics" characterizes a particular combination of the coupled use of a drug therapy with a diagnostic test (called "companion diagnostics"). The diagnostic test marks out the technical means used to identify a biomarker which allows for adjusting the use of the new drug.Theranostics promise a significant step forward for the use of personalized medicine, better tailored for patients in terms of efficacy and tolerance. The development process of theranostics is complex since it requires a proper phasing from development to reimbursement, through a collaborative and controlled approach.The task force's recommendations should form the basis for reflection and action amongst the different players in the field of the development of theranostics.All stages of the system meeting heterogeneous and asynchronous rules should be harmonized to allow for simultaneous availability of, and access to the drug and test. Nevertheless, it is necessary to simplify the regulations to enable a better adaptation of theranostics to the speed of innovation.

Resume Par theranostic, on entend une combinaison particuliere de l’utilisation couplee d’un medicament et d’un test diagnostique (parfois nomme « compagnon diagnostique »). Le test diagnostique designe ici le moyen technique utilise pour identifier un biomarqueur qui permet de moduler l’usage du nouveau medicament. Le theranostic constitue un progres significatif pour une medecine plus personnalisee, mieux adaptee aux patients en termes d’efficacite et de tolerance. Toutefois, le developpement des theranostics est complexe car il necessite un phasage a tous les stades, du developpement au remboursement, avec une approche collaborative et maitrisee. Le groupe de travail a emis des recommandations comme base de reflexion et d’action pour les acteurs impliques dans le developpement de theranostics. En effet, toutes les etapes du systeme repondent a des regles heterogenes et asynchrones qu’il conviendrait d’harmoniser pour permettre une mise a disposition simultanee et un acces generalise au medicament et au test. Des simplifications reglementaires sont necessaires pour permettre une meilleure adaptation du theranostic a l’acceleration de l’innovation.

International audience; This paper introduces an approach how the Sensor Web Enablement (SWE) framework of the Open Geospatial Consortium (OGC) will be used in order to build a franco-lebanese observatory. We present the practical application of SWE services as a source of real-time observation data and the associated technical architecture for making the observations available on the Web to end users near real-time. We discuss the question of crossing sensor data with other data sources, e.g., data provided by human observations. We illustrate our approach with a first use case to monitor the snow weather stations in Lebanese Mountains.

BACKGROUND AND OBJECTIVES: Catheter ablation for atrial fibrillation (AF) has proved to be quite effective in maintaining sinus rhythm without ant-arrhythmic drugs (AA). This procedure has been followed for more than 10 years in our hospital. The aim of our study was to compare our results after one year of follow up with those of other recent publications, and to find the adequate biomarkers of the relevance of this procedure. METHODS: We followed a cohort of 335 consecutive patients with primary ablation between May 2009 and May 2011. A total of 475 ablations were performed: 54% paroxysmal AF, 30% persistent AF, 16% Long standing Persistent AF, Structural heart disease 30%. The bio-markers we evaluated were BNP, CRP and left atrium (LA) volume. RESULTS: After AF procedure sinus rhythm is maintained in 56% after one year follow up for paroxysmal AF, 46% for persistent and 22% for Longstanding Persistent. A major complication (pericardial effusion requiring surgical drainage) occurred in 1,05%. No thrombo-embolic event was reported. There was a good correlation between the success of the procedure and the levels of BNP and CRP, and the LA volume, especially for paroxysmal AF (BNP

The effects of Benfluorex administration on glucose tolerance have been examined in young and old Sprague Dawley rats. The ageing rats were used as a model of insulin resistance. Chronic oral administration of Benfluorex decreased triglycerides levels and normalized glucose tolerance in ageing rats, independently of effects on body weight. Acute intraportal administration of 0.45 mg/kg/h of Benfluorex for 30 min resulted in a 50% increase in glucose tolerance in old rats, but did not modify that in young rats. The improved glucose tolerance brought about by Benfluorex in an animal model of insulin resistance may suggest a wider therapeutic application in man, to include insulin resistant states as type II diabetes or Syndrome X.