Evaluation du projet Loisirs sans tabac du CIPRET-Vaud : Partie 2: Enquête auprès des centres socioculturels, après déploiement du projet

La présente évaluation vise à analyser si les activités prévues dans le cadre du projet ont effectivement été menées et si le projet a atteint ses objectifs. Elle explore également la place de la prévention du tabagisme dans les espaces de loisirs, la constitution d’un réseau de centres socioculturels, la position des centres socioculturels par rapport au tabac et l’appréciation globale du matériel mis à disposition. Le design évaluatif proposé combine un entretien avec la responsable du projet, une enquête en ligne auprès des professionnels de l’animation socioculturelle et des travailleurs sociaux de proximité (n= 21 ; taux de réponse : 24%) et une analyse des données de fréquentation du site Internet. L’évaluation a été réalisée entre le 1er octobre et le 12 décembre 2016. En prenant appui sur les besoins des centres socioculturels identifiés lors de la première phase évaluative, le CIPRET-Vaud a élaboré le site Internet http qui mutualise et valorise les informations et outils existants pour en faciliter l’accès et l’utilisation. Les centres socioculturels et les travailleurs sociaux de proximité ont été invités à une demi-journée de présentation à l'occasion de la journée mondiale sans tabac, le 31 mai 2016 ; une dizaine de personnes y ont effectivement participé. L'ensemble des centres socioculturels et des travailleurs sociaux de proximité a par ailleurs reçu en septembre 2016 un courrier accompagné d’un flyer de présentation du site Internet

TABAC-ALCOOL : Evaluation du projet du CIPRET Vaud "Aborder le tabagisme via d’autres problèmes de santé"

Dans le cadre du programme de prévention du tabagisme 2014-2017 cofinancé par le canton et le Fonds de prévention du tabagisme, le CIPRET-Vaud conduit un projet Aborder le tabagisme via d'autres problèmes de santé visant à apporter une prise en charge spécifique à des personnes fumeuses particulièrement vulnérables en raison d'autres problèmes de santé. Un sous-projet, Tabac-alcool, a été développé afin de favoriser la prise en charge du problème du tabagisme chez les personnes alcoolodépendantes traitées en milieu résidentiel. Deux groupes cibles sont visés, l'un direct, l'autre indirect. Le groupe cible direct est constitué des professionnels socioéducatifs des établissements résidentiels en traitement alcoologique. Le projet vise à les sensibiliser à la problématique, à les former et à les outiller pour offrir aux résidents de leurs centres une information de qualité sur la co-consommation de tabac et d'alcool, une aide spécifique et adaptée, et une orientation éventuelle vers des services spécialisés. Le groupe cible indirect est constitué des résidents de ces établissements. Les objectifs du projet Tabac-alcool tels que définis au démarrage du projet sont les suivants: Fin 2016, les professionnels de trois établissements résidentiels pour personnes alcoolo-dépendantes sont informés et sensibilisés aux liens existant entre la consommation d'alcool et de tabac et sont outillés pour aborder la question dans leur pratique. Fin 2016, les personnes dépendantes à la fois autabac et à l'alcool et traitées en résidentiel (trois établissements) sont informées et sensibilisées sur le lien existant entre le tabac et l'alcool. Parmi elles, les personnes intéressées ont accès à une aide à l'arrêt du tabagisme spécifique et adaptée à leur situation

Neutral evolution of proteins: The superfunnel in sequence space and its relation to mutational robustness.

International audienceFollowing Kimura's neutral theory of molecular evolution [M. Kimura, The Neutral Theory of Molecular Evolution (Cambridge University Press, Cambridge, 1983) (reprinted in 1986)], it has become common to assume that the vast majority of viable mutations of a gene confer little or no functional advantage. Yet, in silico models of protein evolution have shown that mutational robustness of sequences could be selected for, even in the context of neutral evolution. The evolution of a biological population can be seen as a diffusion on the network of viable sequences. This network is called a "neutral network." Depending on the mutation rate mu and the population size N, the biological population can evolve purely randomly (muN1). The stringency of the selection depends not only on the product muN but also on the exact topology of the neutral network, the special arrangement of which was named "superfunnel." Even though the relation between mutation rate, population size, and selection was thoroughly investigated, a study of the salient topological features of the superfunnel that could affect the strength of the selection was wanting. This question is addressed in this study. We use two different models of proteins: on lattice and off lattice. We compare neutral networks computed using these models to random networks. From this, we identify two important factors of the topology that determine the stringency of the selection for mutationally robust sequences. First, the presence of highly connected nodes ("hubs") in the network increases the selection for mutationally robust sequences. Second, the stringency of the selection increases when the correlation between a sequence's mutational robustness and its neighbors' increases. The latter finding relates a global characteristic of the neutral network to a local one, which is attainable through experiments or molecular modeling

Evaluation du projet Loisirs sans tabac du CIPRET-Vaud : Partie 1: Enquête auprès des centres socioculturels, avant déploiement du projet

La plupart des publications disponibles sur des interventions de prévention du tabagisme chez les jeunes concernent des interventions dans le cadre scolaire. Une revue systématique de la littérature sur les programmes de prévention dans les écoles, comprenant 49 cohortes préventives (N=142'447) a montré un effet préventif après plus d'un an de suivi, avec une réduction de l'initiation du tabagisme de 12% comparé aux groupes contrôles. Au Royaume-Uni, le National Institute for Heath and Care Excellence (NICE) recommande la mise en place d'interventions par le personnel dans les écoles, mais aussi par des professionnels externes formés pour travailler avec les enfants et les jeunes sur la problématique du tabac. Les interventions recommandées consistent non seulement à informer les jeunes sur les risques liés au tabagisme, mais aussi un travail avec les jeunes dans le but de les aider à développer leur capacité de décision, leur auto-estime et leur capacité à résister à la pression des médias, de leurs familles, de pairs et de l'industrie du tabac

Neutral evolution of Protein-protein interactions: a computational study using simple models

<p>Abstract</p> <p>Background</p> <p>Protein-protein interactions are central to cellular organization, and must have appeared at an early stage of evolution. To understand better their role, we consider a simple model of protein evolution and determine the effect of an explicit selection for Protein-protein interactions.</p> <p>Results</p> <p>In the model, viable sequences all have the same fitness, following the neutral evolution theory. A very simple, two-dimensional lattice representation of the protein structures is used, and the model only considers two kinds of amino acids: hydrophobic and polar. With these approximations, exact calculations are performed. The results do not depend too strongly on these assumptions, since a model using a 3D, off-lattice representation of the proteins gives results in qualitative agreement with the 2D one. With both models, the evolutionary dynamics lead to a steady state population that is enriched in sequences that dimerize with a high affinity, well beyond the minimal level needed to survive. Correspondingly, sequences close to the viability threshold are less abundant in the steady state, being subject to a larger proportion of lethal mutations. The set of viable sequences has a "funnel" shape, consistent with earlier studies: sequences that are highly populated in the steady state are "close" to each other (with proximity being measured by the number of amino acids that differ).</p> <p>Conclusion</p> <p>This bias in the the steady state sequences should lead to an increased resistance of the population to environmental change and an increased ability to evolve.</p

Recognizing protein-protein interfaces with empirical potentials and reduced amino acid alphabets.

International audienceBACKGROUND: In structural genomics, an important goal is the detection and classification of protein-protein interactions, given the structures of the interacting partners. We have developed empirical energy functions to identify native structures of protein-protein complexes among sets of decoy structures. To understand the role of amino acid diversity, we parameterized a series of functions, using a hierarchy of amino acid alphabets of increasing complexity, with 2, 3, 4, 6, and 20 amino acid groups. Compared to previous work, we used the simplest possible functional form, with residue-residue interactions and a stepwise distance-dependence. We used increased computational resources, however, constructing 290,000 decoys for 219 protein-protein complexes, with a realistic docking protocol where the protein partners are flexible and interact through a molecular mechanics energy function. The energy parameters were optimized to correctly assign as many native complexes as possible. To resolve the multiple minimum problem in parameter space, over 64000 starting parameter guesses were tried for each energy function. The optimized functions were tested by cross validation on subsets of our native and decoy structures, by blind tests on series of native and decoy structures available on the Web, and on models for 13 complexes submitted to the CAPRI structure prediction experiment. RESULTS: Performance is similar to several other statistical potentials of the same complexity. For example, the CAPRI target structure is correctly ranked ahead of 90% of its decoys in 6 cases out of 13. The hierarchy of amino acid alphabets leads to a coherent hierarchy of energy functions, with qualitatively similar parameters for similar amino acid types at all levels. Most remarkably, the performance with six amino acid classes is equivalent to that of the most detailed, 20-class energy function. CONCLUSION: This suggests that six carefully chosen amino acid classes are sufficient to encode specificity in protein-protein interactions, and provide a starting point to develop more complicated energy functions

Computational Protein Design: Validation and Possible Relevance as a Tool for Homology Searching and Fold Recognition

International audienceBACKGROUND: Protein fold recognition usually relies on a statistical model of each fold; each model is constructed from an ensemble of natural sequences belonging to that fold. A complementary strategy may be to employ sequence ensembles produced by computational protein design. Designed sequences can be more diverse than natural sequences, possibly avoiding some limitations of experimental databases. METHODOLOGY/PRINCIPAL FINDINGS: WE EXPLORE THIS STRATEGY FOR FOUR SCOP FAMILIES: Small Kunitz-type inhibitors (SKIs), Interleukin-8 chemokines, PDZ domains, and large Caspase catalytic subunits, represented by 43 structures. An automated procedure is used to redesign the 43 proteins. We use the experimental backbones as fixed templates in the folded state and a molecular mechanics model to compute the interaction energies between sidechain and backbone groups. Calculations are done with the Proteins@Home volunteer computing platform. A heuristic algorithm is used to scan the sequence and conformational space, yielding 200,000-300,000 sequences per backbone template. The results confirm and generalize our earlier study of SH2 and SH3 domains. The designed sequences ressemble moderately-distant, natural homologues of the initial templates; e.g., the SUPERFAMILY, profile Hidden-Markov Model library recognizes 85% of the low-energy sequences as native-like. Conversely, Position Specific Scoring Matrices derived from the sequences can be used to detect natural homologues within the SwissProt database: 60% of known PDZ domains are detected and around 90% of known SKIs and chemokines. Energy components and inter-residue correlations are analyzed and ways to improve the method are discussed. CONCLUSIONS/SIGNIFICANCE: For some families, designed sequences can be a useful complement to experimental ones for homologue searching. However, improved tools are needed to extract more information from the designed profiles before the method can be of general use

Testing the Coulomb/Accessible Surface Area solvent model for protein stability, ligand binding, and protein design

<p>Abstract</p> <p>Background</p> <p>Protein structure prediction and computational protein design require efficient yet sufficiently accurate descriptions of aqueous solvent. We continue to evaluate the performance of the Coulomb/Accessible Surface Area (CASA) implicit solvent model, in combination with the Charmm19 molecular mechanics force field. We test a set of model parameters optimized earlier, and we also carry out a new optimization in this work, using as a target a set of experimental stability changes for single point mutations of various proteins and peptides. The optimization procedure is general, and could be used with other force fields. The computation of stability changes requires a model for the unfolded state of the protein. In our approach, this state is represented by tripeptide structures of the sequence Ala-X-Ala for each amino acid type X. We followed an iterative optimization scheme which, at each cycle, optimizes the solvation parameters and a set of tripeptide structures for the unfolded state. This protocol uses a set of 140 experimental stability mutations and a large set of tripeptide conformations to find the best tripeptide structures and solvation parameters.</p> <p>Results</p> <p>Using the optimized parameters, we obtain a mean unsigned error of 2.28 kcal/mol for the stability mutations. The performance of the CASA model is assessed by two further applications: (i) calculation of protein-ligand binding affinities and (ii) computational protein design. For these two applications, the previous parameters and the ones optimized here give a similar performance. For ligand binding, we obtain reasonable agreement with a set of 55 experimental mutation data, with a mean unsigned error of 1.76 kcal/mol with the new parameters and 1.47 kcal/mol with the earlier ones. We show that the optimized CASA model is not inferior to the Generalized Born/Surface Area (GB/SA) model for the prediction of these binding affinities. Likewise, the new parameters perform well for the design of 8 SH3 domain proteins where an average of 32.8% sequence identity relative to the native sequences was achieved. Further, it was shown that the computed sequences have the character of naturally-occuring homologues of the native sequences.</p> <p>Conclusion</p> <p>Overall, the two CASA variants explored here perform very well for a wide variety of applications. Both variants provide an efficient solvent treatment for the computational engineering of ligands and proteins.</p

The Influence of Personality, Safety Attitudes, and Risk Perception of Pilots: A Modeling and Mediation Perspective

Objective: The purpose of the current study was to assess the influence of personality traits on safety attitudes and risk perceptions. Background: The ability to accurately assess risk remains a focal point of aviation training. This research seeks to understand if safety attitudes serve as a mediator. Method: Using a sample of 2,857 pilots, a statistical model was created through two independent stages. In stage 1, approximately 50% of the data were used to create the model using structural equation modeling techniques, and in stage 2, the model was independently validated. Results: The findings indicated that personality factors positively influenced risk perception, whereas personality increased, so did the pilot\u27s perception of the risk level. Self-confidence was negatively related to risk perceptions, indicating that a pilot\u27s self-confidence increases their perception of risk decreases. Additionally, self-confidence was a significant mediator to the relationship between personality factors and risk perception. Conclusion: The original scales had some validity issues, but the re-specified model provided some meaningful findings, especially in the relationships between personality traits, self-confidence, and risk perception. The model explained 26.4% of the variance in self-confidence and 9.5% of risk perception variance. Application: The findings highlight the importance for pilots to be aware of how increased self-confidence may influence their perceptions of risk. As pilots gain experience and self-confidence, care needs to be given to ensure greater risks are not taken, offsetting the value of the experience and self-confidence