ARE THERE DISCRETE GAMMA SUB-BANDS IN HIPPOCAMPAL NETWORKS DURING SPATIAL LEARNING ?

International audienc

A second wind for the cholinergic system in Alzheimer’s therapy:

Notwithstanding tremendous research efforts, the cause of Alzheimer’s disease (AD) remains elusive and there is no curative treatment. The cholinergic hypothesis presented 35 years ago was the first major evidence-based hypothesis regarding AD etiology. It proposed that the depletion of brain acetylcholine was a primary cause of cognitive decline in advanced age and AD. It relied on a series of observations obtained in aged animals, elderly and AD patients which pointed to dysfunctions of cholinergic basal forebrain, similarities between cognitive impairments induced by anticholinergic drugs and those found in advanced age and AD, and beneficial effects of drugs stimulating cholinergic activity. This review comes back on these major results to show how this hypothesis provided the drive for the development of anticholinesterase inhibitor-based therapies of AD, the almost exclusive approved treatment in use despite transient and modest efficacy. New ideas for improving cholinergic therapies are also compared and discussed in light of the current revival of the cholinergic hypothesis based on two sets of evidence from new animal models and refined imagery techniques in humans. First, human and animal studies agree on detecting signs of cholinergic dysfunctions much earlier than initially thought. Second, alterations of the cholinergic system are deeply intertwined with its reactive responses providing the brain with efficient compensatory mechanisms to delay the conversion to AD. Active research in this field should give new insight to develop multi-therapies incorporating cholinergic manipulation, as well as early biomarkers of AD allowing earlier diagnostics. This is of prime importance to counteract a disease that is now recognized to start early in adult life

Estimation and Inference for a Spline-Enhanced Population Pharmacokinetic Model

This article is motivated by an application where subjects were dosed three times with the same drug and the drug concentration profiles appeared to be the lowest after the third dose. One possible explanation is that the pharmacokinetic (PK) parameters vary over time. Therefore, we consider population PK models with time-varying PK parameters. These time-varying PK parameters are modeled by natural cubic spline functions in the ordinary differential equations. Mean parameters, variance components, and smoothing parameters are jointly estimated by maximizing the double penalized log likelihood. Mean functions and their derivatives are obtained by the numerical solution of ordinary differential equations. The interpretation of PK parameters in the model and its flexibility are discussed. The proposed methods are illustrated by application to the data that motivated this article. The model's performance is evaluated through simulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65539/1/j.0006-341X.2002.00601.x.pd

Novelty and anxiolytic drugs dissociate two components of hippocampal theta in behaving rats

Hippocampal processing is strongly implicated in both spatial cognition and anxiety and is temporally organized by the theta rhythm. However, there has been little attempt to understand how each type of processing relates to the other in behaving animals, despite their common substrate. In freely moving rats, there is a broadly linear relationship between hippocampal theta frequency and running speed over the normal range of speeds used during foraging. A recent model predicts that spatial-translation-related and arousal/anxiety-related mechanisms of hippocampal theta generation underlie dissociable aspects of the theta frequency–running speed relationship (the slope and intercept, respectively). Here we provide the first confirmatory evidence: environmental novelty decreases slope, whereas anxiolytic drugs reduce intercept. Variation in slope predicted changes in spatial representation by CA1 place cells and novelty-responsive behavior. Variation in intercept predicted anxiety-like behavior. Our findings isolate and doubly dissociate two components of theta generation that operate in parallel in behaving animals and link them to anxiolytic drug action, novelty, and the metric for self-motion

Qualité qualifiante et modèle de l'anticipation - réalisation - contrôle (application au circuit hospitalier du médicament)

Objectif : élaborer une théorie de la qualité, la théorie de la qualité qualifiante, appicable au circuit hospitalier du médicament (CHM), puis en vérifier le bien-fondé à travers douze applicatifs. Modélisation : le CHM est considéré comme un système général, complexe, ouvert, à haut risque, évolutif, chaotique, autofinalisant et autoorganisant où le médicament est à la fois un flux de matière et un flux d'information. L'amélioration de la qualité s'y déroule sur base d'un algorithme récurrent, le cycle qualifié Anticipation-Réalisation-Contrôle, et ce à tous les niveaux d'organisation. Il exige de chaque processus d'être anticipé, réalisé (exécuté consciemment) puis contrôlé. Chaque acteur doit établir des relations triurnes impliquant les aspects énergétiques, émotionnel, et computationnel. La stratégie des hypercycles transforme alors l'organisation passive en organisé-organisant et une qualité qualifiante en émerge, qui bénéficie autant à celui qui la fait qu'à celui qui la reçoit. Celle-ci qualifie ainsi les six types d'acteurs du CHM :le prestataire, son patient, ses collègues, son établissement, la société, et la nature. Mise en pratique : pour solutionner des situations complexes. Dans la phase d'Anticipation, notre méthodologie permet l'inclusion raisonnée d'un médicament au formulaire thérapeutique et son analyse médico-économique. La phase réalisation étudie la constitution de réseaux fractaux intra- et inter-services et de la relation pharmacien-patient en pharmacie transmurale. Dans la phase de contrôle, un logiciel original de suivi de prescription étudie la pharmacoéconomie des antidépresseurs, la pharmacoépidémiologie des anxiolytiques et des somnifères et la relation entre consommation d'antibiotiques et résistance nosocomiale. Trois applicatifs à long terme portent sur la conception d'une poche de perfusion, la sélection d'une bande de contention et l'optimisation d'ampoules injectables.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Urbanisme et sécurité : Analyse de l'application des principes de sécurité urbaine dans le cadre de la rénovation de la Place Communale de Molenbeek-Saint-Jean

Master [120] en criminologie, Université catholique de Louvain, 201