Profils d'utilisation d'antipsychotiques en conditions réelles dans la population de personnes âgées démentes vivant à domicile : impact des interventions de communication de risque

Les antipsychotiques (APs) sont fréquemment prescrits pour les troubles comportementaux associés à la démence. Or, ces produits ont fait l'objet de trois mises en garde (2002, 2004, 2005) en raison d'une augmentation du risque d'événement cérébrovasculaire et de décès. L’objectif de ce mémoire est d’évaluer l'utilisation d’APs dans la population de personnes âgées démentes vivant à domicile, et de déterminer l’effet des mises en garde sur les profils observés. Une cohorte rétrospective de 10,969 personnes âgées démentes ayant débuté un traitement par AP entre le 1er janvier 2000 et le 31 décembre 2009 fut identifiée à partir des banques de données de la Régie de l'assurance maladie du Québec (RAMQ). Des séries chronologiques segmentées ont permis de quantifier l’effet des mises en garde sur l'utilisation d’APs. L'effet de la mise en garde de 2005 sur les caractéristiques des patients traités ainsi que sur les profils d'utilisation (dose et durée) a été évalué, respectivement par des modèles de régression logistique et de régression linéaire multivariés. Le taux délivrance d'APs atypiques a augmenté au cours du temps jusqu'à la mise en garde de 2005 pour ensuite diminuer de 8.96% (IC 95% : -11.91% – -6.02%). L'analyse par produit a révélé la même tendance pour la rispéridone, le seul AP approuvé au Canada pour les personnes âgées démentes. En revanche, le taux de délivrance de quétiapine, qui est hors-indication, a continué d'augmenter. Le taux d'initiation de traitement par APs a cependant diminué au cours du temps pour tous les produits. Les mises en garde ne semblent pas être associées avec un changement dans les caractéristiques des patients traités, ni avec les doses et durées d’utilisation. Le manque d'efficacité des mises en garde est probablement en partie lié à l'absence d'alternatives thérapeutiques pour le traitement des troubles psychologiques et comportementaux chez les patients atteints de démence.Antipsychotics (APs) are frequently prescribed for the management of behavioural and psychological symptoms of dementia (BPSD). However, three safety warnings have been issued (2002, 2004 and 2005) due to an increased risk of cerebrovascular event and mortality. The aim of this thesis was to evaluate AP usage in the population of community-dwelling elderly with dementia, and to determine the effect of safety warnings on usage patterns. A retrospective cohort of 10,969 elderly with dementia who initiated an AP treatment between January 1st, 2000 and December 31st, 2009 was identified through in the databases of Régie de l’assurance maladie du Québec (RAMQ). Segmented time series analysis was used to quantify the effect of safety warnings on AP dispensing rate. The effect of the 2005 warning on the characteristics of treated patients and on usage patterns (dose and duration) was evaluated, respectively through multivariate logistic and multiple linear regression models. Atypical AP dispensing rates increased until the 2005 safety warning and decreased by 8.96% (95% CI: -11.91% – -6.02%) thereafter. Analysis by individual products yielded similar trends for risperidone, the only AP approved in Canada for elderly with dementia. However, usage of quetiapine, which is off-label, kept increasing. For all products, rate of treatment initiation decreased over time. Safety warnings did not seem to be associated with either changes in prescribed treatment dosage or duration, nor with prescription channeling toward lower risk patients. Apparent lack of efficacy of safety warnings is likely due, in part, to absence of effective treatment alternatives for BPSD

Body odor quality predicts behavioral attractiveness in humans

Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits

Digit ratio (2D:4D) predicts facial, but not voice or body odour, attractiveness in men

There is growing evidence that human second-to-fourth digit ratio (or 2D:4D) is related to facial features involved in attractiveness, mediated by in utero hormonal effects. The present study extends the investigation to other phenotypic, hormone-related determinants of human attractiveness: voice and body odour. Pictures of faces with a neutral expression, recordings of voices pronouncing vowels and axillary odour samples captured on cotton pads worn for 24 h were provided by 49 adult male donors. These stimuli were rated on attractiveness and masculinity scales by two groups of 49 and 35 females, approximately half of these in each sample using hormonal contraception. Multivariate regression analyses showed that males' lower (more masculine) right 2D:4D and lower right-minus-left 2D:4D (Dr2l) were associated with a more attractive (and in some cases more symmetrical), but not more masculine, face. However, 2D:4D and Dr2l did not predict voice and body odour masculinity or attractiveness. The results were interpreted in terms of differential effects of prenatal and circulating testosterone, male facial shape being supposedly more dependent on foetal levels (reflected by 2D:4D ratio), whereas body odour and vocal characteristics could be more dependent on variation in adult circulating testosterone levels

Distributed Computation of Virtual Coordinates

International audienceSensor networks are emerging as a paradigm for future computing, but pose a number of challenges in the fields of networking and distributed computation. One challenge is to devise a greedy routing protocol – one that routes messages through the network using only information available at a node or its neighbors. Modeling the connectivity graph of a sensor network as a 3-connected planar graph, we describe how to compute on the network in a distributed and local manner a special geometric embedding of the graph. This embedding supports a geometric routing protocol based on the ”virtual” coordinates of the nodes derived from the embedding

Variability of Affective Responses to Odors: Culture, Gender, and Olfactory Knowledge

Emotion and odor scales (EOS) measuring odor-related affective feelings were recently developed for three different countries (Switzerland, United Kingdom, and Singapore). The first aim of this study was to investigate gender and cultural differences in verbal affective response to odors, measured with EOS and the usual pleasantness scale. To better understand this variability, the second aim was to investigate the link between affective reports and olfactory knowledge (familiarity and identification). Responses of 772 participants smelling 56-59 odors were collected in the three countries. Women rated odors as more intense and identified them better in all countries, but no reliable sex differences were found for verbal affective responses to odors. Disgust-related feelings revealed odor-dependent sex differences, due to sex differences in identification and categorization. Further, increased odor knowledge was related to more positive affects as reported with pleasantness and odor-related feeling evaluations, which can be related to top-down influences on odor representation. These top-down influences were thought, for example, to relate to beliefs about odor properties or to categorization (edible vs. nonedible). Finally, the link between odor knowledge and olfactory affect was generally asymmetrical and significant only for pleasant odors, not for unpleasant ones that seemed to be more resistant to cognitive influences. This study, for the first time using emotional scales that are appropriate to the olfactory domain, brings new insights into the variability of affective responses to odors and its relationship to odor knowledg

The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins

The Dot/Icm system of the intracellular pathogen Legionella pneumophila has the capacity to deliver over 270 effector proteins into host cells during infection. Important questions remain as to spatial and temporal mechanisms used to regulate such a large array of virulence determinants after they have been delivered into host cells. Here we investigated several L. pneumophila effector proteins that contain a conserved phosphatidylinositol-4-phosphate (PI4P)-binding domain first described in the effector DrrA (SidM). This PI4P binding domain was essential for the localization of effectors to the early L. pneumophila-containing vacuole (LCV), and DrrA-mediated recruitment of Rab1 to the LCV required PI4P-binding activity. It was found that the host cell machinery that regulates sites of contact between the plasma membrane (PM) and the endoplasmic reticulum (ER) modulates PI4P dynamics on the LCV to control localization of these effectors. Specifically, phosphatidylinositol-4-kinase IIIalpha (PI4KIIIalpha) was important for generating a PI4P signature that enabled L. pneumophila effectors to localize to the PM-derived vacuole, and the ER-associated phosphatase Sac1 was involved in metabolizing the PI4P on the vacuole to promote the dissociation of effectors. A defect in L. pneumophila replication in macrophages deficient in PI4KIIIalpha was observed, highlighting that a PM-derived PI4P signature is critical for biogenesis of a vacuole that supports intracellular multiplication of L. pneumophila. These data indicate that PI4P metabolism by enzymes controlling PM-ER contact sites regulate the association of L. pneumophila effectors to coordinate early stages of vacuole biogenesis

Metatranscriptome analysis of the reef-building coral Orbicella faveolata indicates holobiont response to coral disease

White Plague Disease (WPD) is implicated in coral reef decline in the Caribbean and is characterized by microbial community shifts in coral mucus and tissue. Studies thus far have focused on assessing microbial communities or the identification of specific pathogens, yet few have addressed holobiont response across metaorganism compartments in coral disease. Here, we report on the first metatranscriptomic assessment of the coral host, algal symbiont, and microbial compartment in order to survey holobiont structure and function in healthy and diseased samples from Orbicella faveolata collected at reef sites off Puerto Rico. Our data indicate holobiont-wide as well as compartment-specific responses to WPD. Gene expression changes in the diseased coral host involved proteins playing a role in innate immunity, cytoskeletal integrity, cell adhesion, oxidative stress, chemical defense, and retroelements. In contrast, the algal symbiont showed comparatively few expression changes, but of large magnitude, of genes related to stress, photosynthesis, and metal transport. Concordant with the coral host response, the bacterial compartment showed increased abundance of heat shock proteins, genes related to oxidative stress, DNA repair, and potential retroelement activity. Importantly, analysis of the expressed bacterial gene functions establishes the participation of multiple bacterial families in WPD pathogenesis and also suggests a possible involvement of viruses and/or phages in structuring the bacterial assemblage. In this study, we implement an experimental approach to partition the coral holobiont and resolve compartment- and taxa-specific responses in order to understand metaorganism function in coral disease

Affective semantic space of scents. Towards a universal scale to measure self-reported odor-related feelings

Measuring self-reported affective feelings to odors and odorous products is a recent challenge for the food and cosmetic field, requiring the development of suited instruments. This paper finalizes a line of studies aimed at developing Emotion and Odor Scales (EOSs) in several cultures. Previously available for Switzerland, the United Kingdom and Singapore, new EOSs are presented here for the United States, Brazil, and China. These scales, developed with 350-540 participants per country, have been conceived to allow the measurement of affective feelings (e.g., emotions, moods, attitudes) in response to a wide range of odors including pleasant and unpleasant, food and non-food ones. Several affective categories were recurrent in the countries examined here: Disgust/Irritation, Happiness/Well-being, Sensuality/Desire, Energy, but also Soothing/Peacefulness and Hunger/Thirst, indicating a potential link between emotion and adaptive universal functions of olfaction such as danger avoidance, ingestion and social communication. For these common categories, similarity in affective responses generally reflected geographic proximity indicating also a strong influence of cultural aspects. Exceptions to this pattern were Singapore and China, with affective responses of Singaporeans being closer to those of Europeans. This series of studies allows us to propose a universal scale (UniGEOS) that might be used in the future for examination of other cultures. This scale comprises affective categories that we found to be culturally shared, enclosing the most frequently shared affective terms, and several culture-specific aspects that may be relevant in other cultures. This tool can be used in its complete form (25 affective terms) or as a short version with nine categories entitled Unpleasant feelings, Happiness/Delight, Sensuality/Desire, Energy, Soothing/ Peacefulness, Hunger/Thirst, Interest, Nostalgia and Spirituality

Identification of a Unique TGF-β Dependent Molecular and Functional Signature in Microglia

Microglia are myeloid cells of the central nervous system (CNS) that participate both in normal CNS function and disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia vs. myeloid and other immune cells. Out of 239 genes, 106 were enriched in microglia as compared to astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS and was also observed in human microglia. Based on this signature, we found a crucial role for TGF-β in microglial biology that included: 1) the requirement of TGF-β for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia; and 2) the absence of microglia in CNS TGF-β1 deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling which provides insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease