188: Prevalence of early repolarization in congenital long QT syndrome A combination of early and delayed repolarization

Introductionearly repolarization (ER) in Brugada or short QT syndrome is common and has been associated to a less favourable outcome. Even if apparently paradoxical, ER can also be seen in long QT (LQT) but prevalence and correlations to other variables are unknown.Methods12 lead ECG of 37 LQT pts (19 men, 39±21 yo) and 80 matched controls were reviewed. LQT pts were selected by a positive genetic testing (n=27) or by showing abnormal T wave and long QT interval (n=10) either spontaneously or during epinephrin infusion. ER was defined by >1mm J point elevation in the inferior or lateral leads with notch or slurring pattern. Presence of ER was correlated to the clinical and ECG characteristics and results genetic analysis.ResultsQT was 409±53 msec in pts and 372±24 in controls (p<0.0001) (QTc 476±52 vs 392±26 msec, p<0.0001). Two LQT pts presented with resuscitated sudden death and 4 with syncope at the time of diagnosis.14/37 LQT pts (38%) had ER compared to 17/80 (21%) controls (p=0.05).ER was more frequent in men (12/19, 63%) compared to women (2/18, 11%) (p=0.001) but was not correlated to age. Pts with ER had slower heart rate (63±10 vs 75±18 bpm, p=0.02).ER was not correlated to symptoms or cardiac events (no ER in the 2 pts with SD and in 2/4 pts with syncope).QT were longer in pts with ER (450±68 vs 397±54 msec in V2, p=0.01) but there was no correlations between ER and corrected QT intervals.ER was more often seen in pts with or without mutations although non significantly (8/27 vs 6/10, p=0.09), but there was a trend toward more frequent ER in case of HeRG mutations (6/12) than KCNQ1 or KCNJ2 mutations (2/11 and 0/4) (p=0.09).ConclusionER is very common in LQT pts and is related to the gender and to the heart rate but not to the corrected QT duration. ER does not seem to be correlated to cardiac events in this series but may be linked to some gene mutations. Further studies are needed for demonstrating additional mutations/ variants or the existence of an early transient voltage gradient due to altered kinetics in muted potassium channels with loss of function

Composition de la trousse d'urgence du médecin généraliste en Haute-Garonne en 2007

La composition de la trousse d'urgence du médecin généraliste en Haute-Garonne en 2007 a été analysée dans cette étude au travers d'un questionnaire soumis à 118 médecins généralistes du département. Ceci a permis de mettre en évidence : des disparités selon le type d'exercice médical ; mais aussi le matériel et les médicaments les plus fréquemment retrouvés qui permettent de déterminer les urgences qui sont le plus souvent rencontrées en médecine générale ; et enfin certaines lacunes dans la composition des trousses d'urgence vis-à-vis de la prise en charge d'urgences vitales rares mais auxquelles le médecin généraliste doit pouvoir faire face. Dans ce travail, nous proposons également une trousse d'urgence minimale dédiée à la prise en charge des urgences vitales en médecine générale, que chaque médecin pourra compléter en fonction de sa pratique.TOULOUSE3-BU Sciences (315552104) / SudocPARIS-BIUM (751062103) / SudocTOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

A simple widespread computer help improves nutrition support orders and decreases infection complications in critically ill patients.

AIMS: To assess the impact of a simple computer-based decision-support system (computer help) on the quality of nutrition support orders and patients' outcome in Intensive-Care Unit (ICU). METHODS: This quality-improvement study was carried out in a 16-bed medical-surgical ICU in a French university hospital. All consecutive patients who stayed in ICU more than 10 days with non-oral feeding for more than 5 days were retrospectively included during two 12-month periods. Prescriptions of nutrition support were collected and compared to French national guidelines as a quality-improvement process. A computer help was constructed using a simple Excel-sheet (Microsoft(TM)) to guide physicians' prescriptions according to guidelines. This computer help was displayed in computers previously used for medical orders. Physicians were informed but no systematic protocol was implemented. Patients included during the first (control group) and second period (computer help group) were compared for achievement of nutrition goals and ICU outcomes. RESULTS: The control and computer help groups respectively included 71 and 95 patients. Patients' characteristics were not significantly different between groups. In the computer help group, prescriptions achieved significantly more often 80% of nutrition goals for calorie (45% vs. 79% p<0.001) and nitrogen intake (3% vs. 37%, p<0.001). Incidence of nosocomial infections decreased significantly between the two groups (59% vs. 41%, p = 0.03). Mortality did not significantly differ between control (21%) and computer help groups (15%, p = 0.30). CONCLUSIONS: Use of a widespread inexpensive computer help is associated with significant improvements in nutrition support orders and decreased nosocomial infections in ICU patients. This computer-help is provided in electronic supplement

Fostering the use of methods for geosimulation models sensitivity analysis and validation

International audienceIn recent years, there has been a significant increase in the development of methods to explore, validate, calibrate and optimize geosimulation models. These methods and tools remain, however, underused by simulation communities, despite an ever improved and easier access to high performance computation facilities. The OpenMOLE model exploration software (Reuillon et al., 2013) is one of the reliable approaches fully dedicated to promote these techniques. This presentation offers some feedback on the recent initiative of a researcher school in model validation, focused around models and practices linked to the OpenMOLE platform. We present the iterative exploration and validation protocol developed during the school, with methods of increasing refinement deployed on a toy geosimulation model (spatialized prey-predator agent-based model of a zombie infection, with multi-modeling paradigms to include diverse processes for agent behavior). First, we illustrate classical sensitivity analysis methods (stochasticity, design of experiments, global sensitivity indices), and then specific methods to study spatial configuration sensitivity, evolutionary computation methods for calibration and diversity search, and Bayesian calibration methods. They are applied on diverse specific submodels, highlighting specific mechanisms of the model, in order to answer associated thematic questions. We also illustrate the comparison with competing model ontologies by calibrating an ODE-based model on data generated by the simulation model. We finally synthesize lessons learned in the final challenge part of the school, consisting of the autonomous exploration of a new model instance by participants, including defining a thematic question and applying appropriate validation methods. This experiment both introduces a broad overview of new geosimulation model methods, and suggests ways to disseminate these into the modeling communities through similar pedagogical implementations

c-Jun/p38MAPK/ASIC3 pathways specifically activated by NGF through TrkA is crucial for mechanical allodynia development

International audienceMechanical allodynia is a cardinal sign of several inflammatory pain disorders where Nerve Growth Factor, a prototypic neurotrophin, plays a crucial role by binding to TrkA receptors. Here, we took the advantage of our generated knock-in mouse model expressing a chimeric TrkA/TrkC receptor that seems to not specifically develop mechanical allodynia following inflammation, to identify the TrkA downstream pathways involved in this phenomenon. We confirmed and extended that disrupting TrkA specific pathways leads to a specific deficit in mechanical hypersensitivity development following somatic (systemic NGF administration and paw incision) and to a lesser extent, visceral injuries. Despite a deficit in thin, mainly peptidergic, fibres innervation in TrkAC mice, thermal hyperalgesia development was not different from WT mice. Inflammatory reaction (oedema, IL-6 content), pain behaviours following intraplantar capsaicin as well as TRPV1 calcium imaging response of DRG neurons were similar between TrkAC and WT mice. This deficiency in mechanical allodynia development in TrkAC mice is likely due to the alteration of the expression of different TrkA transduction pathways (i.e. Akt, p38 MAPK and c-Jun) especially p38 MAPK, in the DRG cell bodies, ultimately leading to an alteration of at least, ASIC3 channel overexpression, known to participate in nociceptor mechanosensory function

Retour d'expérience de l'école OpenMOLE "ExModelo", organisée en partenariat avec le méso-centre du CRIANN

International audienceOpenMOLE (Reuillon et al., 2013) est une plateforme d’exploration automatique de modèles numériques. Elle permet d’étudier des programmes développés dans une très large gamme de langages. OpenMOLE permet aussi de distribuer la charge de calcul sur la plupart des environnements de calcul (serveur, clusters, grille de calcul, cloud). La description de ces expériences sont décrits à l’aide DSL à destination d’utilisateurs non-informaticiens et non-spécialistes des environnements HPC. Alors que cette plateforme fête sa 10ème release salué par une communauté d’utilisateur en forte croissance, un nouveau pas vient d’être franchi avec l’organisation en 2019 d’une première école d’été dédiée à “l’exploration de modèles”. Durant la formation, la plateforme et l’écosystème de méthodes d’exploration qui l’accompagne sont utilisés de manière intensive. Les travaux pratiques mettent en oeuvre l’exploration d’un modèle “jouet” de dynamiques complexes développé pour l’occasion. Il s’agit d’un modèle multi-agent spatialisé de type proie/prédateur sur la thématique des zombies. Les apprenants pourront découvrir l’usage et la spécificité de chacune des méthodes d’explorations intégrés dans la plateforme de façon interactive : analyses de sensibilité (Saltelli, Morris), calibrage et optimisation (Profiles, NSGA2, ABC), diversité (PSE). Lors des deux derniers jours, les participants sont invités à formuler des questions sur le modèle de Zombies et à en proposer une étude en utilisant les outils découverts les jours précédents. La mise en oeuvre rapide de ces méthodes n’étant possible qu’avec l’appui d’un environnement HPC, un partenariat avec l’UMR IDEES et le méso-centre Normand du CRIANN a été mis en place pour assurer un accès rapide aux ressources de calcul nécessaires (1000 coeurs / 25 participants) pour les explorations menées pendant les 5 jours d’école. Développé avant tout pour accéder à des ressources de type grille, OpenMOLE s’est constamment adapté pour offrir des connecteurs capable de suivre l’offre croissante et très diversifiée en environnements de calcul. Il s’agit d’ajouter à la fois des nouveaux connecteurs (PBS, SLURM, etc.) mais aussi de nouveaux moyens d’encapsulation et de déploiement des programmes utilisateurs (Kubernetes, UDocker, PRoot, etc.). La collaboration entre les deux équipes du CRIANN et d’OpenMOLE s’inscrit dans ce cadre. Bénéfique pour les deux parties, elle a permis de soulever et résoudre des points de blocages représentatifs des diversités de pratiques qui peuvent exister sur le plan matériel et logiciels (Fortran/C vs Java/R/Python) entre les deux communautés (Grille / Cluster). Dans cette présentation nous proposons de faire une synthèse des résultats obtenus par les groupes sur le modèle jouet, ainsi qu’un retour sur cette collaboration originale entre les deux équipes techniques d’OpenMOLE et du CRIANN.Reuillon, R., Leclaire, M., and Rey-Coyrehourcq, S. (2013). Openmole, a workflow engine specifically tailored for the distributed exploration of simulation models. Future Generation Computer Systems, 29(8):1981–1990

Discussion de l'article 5 du projet de décret du comité de Constitution sur la police municipale, lors de la séance du 5 juillet 1791

Démeunier Jean Nicolas, Pervinquiere Mathieu-Joseph-Séverin, Delay ou Delley d'Agier Claude Pierre de, Martineau Louis Simon, Ramel de Nogaret Dominique-Vincent, Prieur (de la Marne). Discussion de l'article 5 du projet de décret du comité de Constitution sur la police municipale, lors de la séance du 5 juillet 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXVII - Du 6 juin au 5 juillet 1791. Paris : Librairie Administrative P. Dupont, 1887. p. 745