Évaluation de l'impact clinique et économique du développement d'un traitement pour la schizophrénie

Contexte : Les stratégies pharmacologiques pour traiter la schizophrénie reçoivent une attention croissante due au développement de nouvelles pharmacothérapies plus efficaces, mieux tolérées mais plus coûteuses. La schizophrénie est une maladie chronique présentant différents états spécifiques et définis par leur sévérité. Objectifs : Ce programme de recherche vise à: 1) Évaluer les facteurs associés au risque d'être dans un état spécifique de la schizophrénie, afin de construire les fonctions de risque de la modélisation du cours naturel de la schizophrénie; 2) Développer et valider un modèle de Markov avec microsimulations de Monte-Carlo, afin de simuler l'évolution naturelle des patients qui sont nouvellement diagnostiqués pour la schizophrénie, en fonction du profil individuel des facteurs de risque; 3) Estimer le coût direct de la schizophrénie (pour les soins de santé et autres non reliés aux soins de santé) dans la perspective gouvernementale et simuler l’impact clinique et économique du développement d’un traitement dans une cohorte de patients nouvellement diagnostiqués avec la schizophrénie, suivis pendant les cinq premières années post-diagnostic. Méthode : Pour le premier objectif de ce programme de recherche, un total de 14 320 patients nouvellement diagnostiqués avec la schizophrénie ont été identifiés dans les bases de données de la RAMQ et de Med-Echo. Les six états spécifiques de la schizophrénie ont été définis : le premier épisode (FE), l'état de dépendance faible (LDS), l’état de dépendance élevée (HDS), l’état stable (Stable), l’état de bien-être (Well) et l'état de décès (Death). Pour évaluer les facteurs associés au risque de se trouver dans chacun des états spécifiques de la schizophrénie, nous avons construit 4 fonctions de risque en se basant sur l'analyse de risque proportionnel de Cox pour des risques compétitifs. Pour le deuxième objectif, nous avons élaboré et validé un modèle de Markov avec microsimulations de Monte-Carlo intégrant les six états spécifiques de la schizophrénie. Dans le modèle, chaque sujet avait ses propres probabilités de transition entre les états spécifiques de la schizophrénie. Ces probabilités ont été estimées en utilisant la méthode de la fonction d'incidence cumulée. Pour le troisième objectif, nous avons utilisé le modèle de Markov développé précédemment. Ce modèle inclut les coûts directs de soins de santé, estimés en utilisant les bases de données de la Régie de l'assurance maladie du Québec et Med-Echo, et les coûts directs autres que pour les soins de santé, estimés à partir des enquêtes et publications de Statistique Canada. Résultats : Un total de 14 320 personnes nouvellement diagnostiquées avec la schizophrénie ont été identifiées dans la cohorte à l'étude. Le suivi moyen des sujets était de 4,4 (± 2,6) ans. Parmi les facteurs associés à l’évolution de la schizophrénie, on peut énumérer l’âge, le sexe, le traitement pour la schizophrénie et les comorbidités. Après une période de cinq ans, nos résultats montrent que 41% des patients seront considérés guéris, 13% seront dans un état stable et 3,4% seront décédés. Au cours des 5 premières années après le diagnostic de schizophrénie, le coût direct moyen de soins de santé et autres que les soins de santé a été estimé à 36 701 $ canadiens (CAN) (95% CI: 36 264-37 138). Le coût des soins de santé a représenté 56,2% du coût direct, le coût de l'aide sociale 34,6% et le coût associé à l’institutionnalisation dans les établissements de soins de longue durée 9,2%. Si un nouveau traitement était disponible et offrait une augmentation de 20% de l'efficacité thérapeutique, le coût direct des soins de santé et autres que les soins de santé pourrait être réduit jusqu’à 14,2%. Conclusion : Nous avons identifié des facteurs associés à l’évolution de la schizophrénie. Le modèle de Markov que nous avons développé est le premier modèle canadien intégrant des probabilités de transition ajustées pour le profil individuel des facteurs de risque, en utilisant des données réelles. Le modèle montre une bonne validité interne et externe. Nos résultats indiquent qu’un nouveau traitement pourrait éventuellement réduire les hospitalisations et le coût associé aux établissements de soins de longue durée, augmenter les chances des patients de retourner sur le marché du travail et ainsi contribuer à la réduction du coût de l'aide sociale.

Recherche d'un neutrino lourd avec le détecteur ATLAS au LHC

Ce mémoire de maîtrise a pour objet une recherche de leptons lourds de quatrième génération avec les données prises par le détecteur ATLAS au LHC dans les collisions pp à $\sqrt{s}$ = 7 TeV et avec une luminosité intégrée de 1.02 fb$^{-1}$. Le processus étudié est la production au singulet de leptons lourds neutres de quatrième génération (N) par la voie du courant chargé suivi de la désintégration du celui-ci en un électron et un boson W : $ pp \to W \to N e \to e W e \to e e \nu_{\ell} \ell $ ($\ell$ = $e$ ou $\mu$), et dépend d'un paramètre de mélange $\xi^{2}$ avec un lepton léger. L'analyse passe par plusieurs étapes, soit l'utilisation de FeynRules pour construire le modèle pour ensuite générer des événements par MadGraph 5.1.2.4. Comme hypothèse de référence, on a choisi une masse de 100 GeV pour le lepton lourd neutre et $\xi_{Ne}^2$ = 0.19, donnant une section efficace de 0.312 pb pour une énergie au centre de masse de 7 TeV. Puisque la génération du signal s'est faite de manière privée à Montréal et non par la collaboration ATLAS, les résultats ne peuvent pas être reconnus officiellement. Sur la base de la simulation, avec des données correspondant à 1 fb$^{-1}$, la limite supérieure attendue à un niveau de confiance de $95\%$ sur la section efficace du signal est de 0.145 pb avec 0.294 pb pour un écart type($\sigma$) et 0.519 pb pour 2$\sigma$. La limite supérieure attendue à un niveau de confiance de $95\%$ sur $\xi_{Ne}^{2}$ de 0.09 pour une masse de 100 GeV.

Femtosecond real-time probing of reactions. 12. Vectorial dynamics of transition states

Femtosecond time-resolved techniques with KETOF (kinetic energy time-of-flight) detection in a molecular beam are developed for studies of the vectorial dynamics of transition states. Application to the dissociation reaction of IHgI is presented. For this system, the complex [I---Hg---I](++)* is unstable and, through the symmetric and asymmetric stretch motions, yields different product fragments: [I---Hg---I](++)* -> HgI(X^2/sigma^+) + I(^2P_3/2) [or I*(^2P_l/2)] (1a); [I---Hg---I](++)* -> Hg(^1S_0) + I(^2P_3/2) + I(^2P_3/2) [or I* (^2P_1/2)] (1 b). These two channels, (1a) and (1b), lead to different kinetic energy distributions in the products. It is shown that the motion of the wave packet in the transition-state region can be observed by MPI mass detection; the transient time ranges from 120 to 300 fs depending on the available energy. With polarized pulses, the vectorial properties (transition moments alignment relative to recoil direction) are studied for fragment separations on the femtosecond time scale. The results indicate the nature of the structure (symmetry properties) and the correlation to final products. For 311-nm excitation, no evidence of crossing between the I and I* potentials is found at the internuclear separations studied. (Results for 287-nm excitation are also presented.) Molecular dynamics simulations and studies by laser-induced fluorescence support these findings.

Análisis en componentes principales de la Obesidad-Adiposidad y su asociación con factores de riesgo cardiometabólico en mujeres. Estudio transversal en un entorno laboral

Los factores de riesgo para el desarrollo de eventos cardiometabólicos, constituyen un set de variables útiles como predictores de enfermedades cardiovasculares y metabólicas. Uno de los factores de riesgo que recibe mayor atención en la deteccion y prevencion de eventos cardiometabolicos, es la obesidad y la herramienta más común para diagnosticarla es el índice de masa corporal. Sin embargo, existen imprecisiones y sesgos en su concepto actual y en la forma de medirla. Nuevas alternativas de valoracion y tamizaje deben incluir porcentaje de grasa corporal y su distribución, dada la relevancia que adquiere la adiposidad en la definicion de obesidad y por ende en la mejoría del pronóstico de eventos cardiometabólicos. Los entornos laborales son ambientes vulnerables que se beneficiarían ampliamente de la aplicación de estas nuevas alternativas para predecir e intervenir tempranamente el riesgo cardiometabólico desde el correcto tamizaje de obesidad, dado el volumen poblacional que se puede abordar.

La construcción de identidades en una muestra de adolescentes de la Universidad Intercultural de Chiapas. Funciones de la identidad y mecanismos psicosociales implicados.

En este estudio se explora la construcción narrativa de la identidad personal y social en adolescentes de la Universidad Intercultural de Chiapas. El objetivo general es mostrar e ilustrar un modelo teórico que intenta explicar dos funciones que tiene la identidad en la adolescencia, así como los mecanismos psicosociales que están implicados en su construcción. Se analiza información recogida a través de distintos instrumentos metodológicos (triangulación). Específicamente, usamos cuatro medidas: el cuestionario de funciones de la identidad y percepción entre grupos (FI-PG), la escala de identidad étnica multigrupo (EIEM), ambos instrumentos cuantitativos, entrevistas historia de vida (HV) y dibujos identitarios (DI), ambas cualitativas. En el estudio cuantitativo participan 331 adolescentes (144 mestizos y 187 indígenas). La media de edad es de 21.7 años (DS = 2.65; rango: 17-40). Los resultados sugieren una conclusión general. Hay diferencias identitarias entre los mestizos e indígenas de la Universidad Intercultural de Chiapas.

Cyclamen: time, sea and speciation biogeography using a temporally calibrated phylogeny

Aim The Mediterranean region is a species-rich area with a complex geographical history. Geographical barriers have been removed and restored due to sea level changes and local climatic change. Such barriers have been proposed as a plausible mechanism driving the high levels of speciation and endemism in the Mediterranean basin. This raises the fundamental question: is allopatric isolation the mechanism by which speciation occurs? This study explores the potential driving influence of palaeo-geographical events on the speciation of Cyclamen (Myrsinaceae), a group with most species endemic to the Mediterranean region. Cyclamen species have been shown experimentally to have few genetic barriers to hybridization. Location The Mediterranean region, including northern Africa, extending eastwards to the Black Sea coast. Methods A generic level molecular phylogeny of Myrsinaceae and Primulaceae is constructed, using Bayesian approximation, to produce a secondary age estimate for the stem lineage of Cyclamen. This estimate is used to calibrate temporally an infrageneric phylogeny of Cyclamen, built with nrDNA ITS, cpDNA trnL-F and cpDNA rps16 sequences. A biogeographical analysis of Cyclamen is performed using dispersal-vicariance analysis. Results The emergence of the Cyclamen stem lineage is estimated at 30.1-29.2 Ma, and the crown divergence at 12.9-12.2 Ma. The average age of Cyclamen species is 3.7 Myr. Every pair of sister species have mutually exclusive, allopatric distributions relative to each other. This pattern appears typical of divergence events throughout the evolutionary history of the genus. Main conclusions Geographical barriers, such as the varying levels of the Mediterranean Sea, are the most plausible explanation for speciation events throughout the phylogenetic history of Cyclamen. The genus demonstrates distributional patterns congruent with the temporally reticulate palaeogeography of the Mediterranean region.

Ab initio prediction of the infrared-absorption spectrum of the C2Cl radical

The three lowest (1(2)A('), 2(2)A('), and 1(2)A(')) potential-energy surfaces of the C2Cl radical, correlating at linear geometries with (2)Sigma(+) and (2)Pi states, have been studied ab initio using a large basis set and multireference configuration-interaction techniques. The electronic ground state is confirmed to be bent with a very low barrier to linearity, due to the strong nonadiabatic electronic interactions taking place in this system. The rovibronic energy levels of the (CCCl)-C-12-C-12-Cl-35 isotopomer and the absolute absorption intensities at a temperature of 5 K have been calculated, to an upper limit of 2000 cm(-1), using diabatic potential-energy and dipole moment surfaces and a recently developed variational method. The resulting vibronic states arise from a strong mixture of all the three electronic components and their assignments are intrinsically ambiguous. (c) 2005 American Institute of Physics.

Ab initio prediction of the infrared absorption spectrum of the C2Br radical

The first three electronic states (1(2)A', 2(2)A', 1(2)A '') of the C2Br radical, correlating at linear geometries with (2)Sigma(+) and (2)Pi states, have been studied ab initio, using Multi Reference Configuration Interaction techniques. The electronic ground state is found to have a bent equilibrium geometry, R-CC = 1.2621 angstrom, R-CBr = 1.7967 angstrom, < CCBr 156.1 degrees, with a very low barrier to linearity. Similarly to the valence isoelectronic radicals C2F and C2Cl, this anomalous behaviour is attributed to a strong three-state non-adiabatic electronic interaction. The Sigma, Pi(1/2), Pi(3/2) vibronic energy levels and their absolute infrared absorption intensities at a temperature of 5K have been calculated for the (CCBr)-C-12-C-12-Br-79 isotopomer, to an upper limit of 2000 cm(-1), using ab initio diabatic potential energy and dipole moment surfaces and a recently developed variational method.

Proceedings of the Rank Forum on Vitamin D

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations . 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

Effects of dietary polyunsaturated fatty acid supplementation on fatty acid composition in muscle and subcutaneous adipose tissue of lambs

Lambs (n = 48) were used in a 2 × 2 factorial arrangement of treatments to evaluate effects of inclusion of oil containing PUFA in high-concentrate diets (with or without) and duration of oil supplementation (pre- vs. postweaning) on CLA concentration of muscle and adipose tissue. Lambs were fed preweaning creep diets (with or without oil) corresponding to the dietary lactation treatment diet (with or without oil) of the dam. Dams blocked by lambing date and rearing type were randomly assigned to 1 of 2 lactation dietary treatments with or without oil supplementation. Creep diets contained approximately 70% concentrate and 30% roughage and were provided to lambs for ad libitum intake. At weaning (58.7 ± 2.5 d of age), lambs (n = 48) were randomly assigned within preweaning treatment groups to 1 of 2 postweaning dietary treatments (with or without oil) and 16 pens in a randomized block design, blocked by sex and BW. Postweaning diets were formulated to contain approximately 80% concentrate and 20% roughage and were fed once daily for ad libitum intake. Soybean and linseed oil (2:1, respectively) replaced ground corn and provided 3% additional fat in pre- and postweaning diets. Lambs were slaughtered at 60.3 ± 4.2 kg of BW. A subcutaneous fat (SQ) sample was obtained within 1 h postmortem and a LM sample at the 12th rib was obtained 24 h postmortem, and both were analyzed for fatty acid profile. Feedlot performance and carcass measurements were not affected (P ≥ 0.26) by oil supplementation. Total CLA content of LM and SQ was not affected (P ≥ 0.08) by oil supplementation pre- or postweaning, but trans-10, cis-12 CLA was greater (P = 0.02) in SQ from lambs supplemented with oil postweaning. Total PUFA content in LM was greater (P = 0.02) in lambs supplemented with oil pre- or postweaning as a result of increased concentrations of 18:2cis-9, cis-12 and longer chain PUFA. Conversely, pre- and postweaning oil supplementation resulted in less (P = 0.04) MUFA content in LM. Only postweaning oil supplementation increased (P = 0.001) SQ PUFA content. Feeding oils containing PUFA to lambs pre- and postweaning did not increase CLA content of muscle, whereas postweaning oil supplementation minimally increased CLA concentration of SQ fat. Inclusion of soybean and linseed oil in pre- and postweaning diets increased total PUFA content of SQ fat and muscle tissue without adversely affecting growth performance or carcass characteristics.

Comparison of polar ozone loss rates simulated by one-dimensional and three-dimensional models with Match observations in recent Antarctic and Arctic winters

Simulations of ozone loss rates using a three-dimensional chemical transport model and a box model during recent Antarctic and Arctic winters are compared with experimental loss rates. The study focused on the Antarctic winter 2003, during which the first Antarctic Match campaign was organized, and on Arctic winters 1999/2000, 2002/2003. The maximum ozone loss rates retrieved by the Match technique for the winters and levels studied reached 6 ppbv/sunlit hour and both types of simulations could generally reproduce the observations at 2-sigma error bar level. In some cases, for example, for the Arctic winter 2002/2003 at 475 K level, an excellent agreement within 1-sigma standard deviation level was obtained. An overestimation was also found with the box model simulation at some isentropic levels for the Antarctic winter and the Arctic winter 1999/2000, indicating an overestimation of chlorine activation in the model. Loss rates in the Antarctic show signs of saturation in September, which have to be considered in the comparison. Sensitivity tests were performed with the box model in order to assess the impact of kinetic parameters of the ClO-Cl2O2 catalytic cycle and total bromine content on the ozone loss rate. These tests resulted in a maximum change in ozone loss rates of 1.2 ppbv/sunlit hour, generally in high solar zenith angle conditions. In some cases, a better agreement was achieved with fastest photolysis of Cl2O2 and additional source of total inorganic bromine but at the expense of overestimation of smaller ozone loss rates derived later in the winter.

Visceral and central abdominal fat and anthropometry in relation to diabetes in Asian Indians

OBJECTIVE: The objective of the study was to examine body fat distribution using computed tomography (CT), dual-energy X-ray absorptiometry (DEXA), and anthropometry in relation to type 2 diabetes in urban Asian Indians. RESEARCH DESIGN AND METHODS: This is a case-control study of 82 type 2 diabetic and 82 age- and sex-matched nondiabetic subjects from the Chennai Urban Rural Epidemiology Study, an ongoing epidemiological study in southern India. Visceral, subcutaneous, and total abdominal fat were measured using CT, while DEXA was used to measure central abdominal and total body fat. Anthropometric measures included BMI, waist circumference, sagittal abdominal diameter (SAD), and waist-to-hip ratio. RESULTS: Visceral and central abdominal fat showed a strong correlation with each other (P <0.0001), and kappa analysis revealed a fairly good agreement between tertiles of visceral and central abdominal fat (kappa=0.44, P <0.0001). Diabetic subjects had significantly higher visceral (P=0.005) and central abdominal (P=0.011) fat compared with nondiabetic subjects. Waist circumference and SAD showed a strong correlation with visceral (P <0.01) and central abdominal (P <0.0001) fat in both diabetic and nondiabetic subjects. Logistic regression analysis revealed visceral (odds ratio [OR] 1.011, P=0.004) and central abdominal (OR 1.001, P=0.013) fat to be associated with diabetes, even after adjusting for age and sex. CONCLUSIONS: Visceral and central abdominal fat showed a strong association with type 2 diabetes. Both measures correlated well with each other and with waist circumference and SAD in diabetic and nondiabetic urban Asian Indians.

Evaluating adjusted forcing and model spread for historical and future scenarios in the CMIP5 generation of climate models

We utilize energy budget diagnostics from the Coupled Model Intercomparison Project phase 5 (CMIP5) to evaluate the models' climate forcing since preindustrial times employing an established regression technique. The climate forcing evaluated this way, termed the adjusted forcing (AF), includes a rapid adjustment term associated with cloud changes and other tropospheric and land-surface changes. We estimate a 2010 total anthropogenic and natural AF from CMIP5 models of 1.9 ± 0.9 W m−2 (5–95% range). The projected AF of the Representative Concentration Pathway simulations are lower than their expected radiative forcing (RF) in 2095 but agree well with efficacy weighted forcings from integrated assessment models. The smaller AF, compared to RF, is likely due to cloud adjustment. Multimodel time series of temperature change and AF from 1850 to 2100 have large intermodel spreads throughout the period. The intermodel spread of temperature change is principally driven by forcing differences in the present day and climate feedback differences in 2095, although forcing differences are still important for model spread at 2095. We find no significant relationship between the equilibrium climate sensitivity (ECS) of a model and its 2003 AF, in contrast to that found in older models where higher ECS models generally had less forcing. Given the large present-day model spread, there is no indication of any tendency by modelling groups to adjust their aerosol forcing in order to produce observed trends. Instead, some CMIP5 models have a relatively large positive forcing and overestimate the observed temperature change.

Glacial-interglacial temperature change in the tropical West Pacific: a comparison of stalagmite-based paleo-thermometers

In the tropics, geochemical records from stalagmites have so far mainly been used to qualitatively reconstruct changes in precipitation, but several new methods to reconstruct past temperatures from stalagmite material have emerged recently: i) liquid–vapor homogenization of fluid inclusion water ii) noble gas concentrations in fluid inclusion water, iii) the partitioning of oxygen isotopes between fluid inclusion water and calcite, and iv) the abundance of the 13C18O16O (‘clumped’) isotopologue in calcite. We present, for the first time, a direct comparison of these four paleo-thermometers by applying them to a fossil stalagmite covering nearly two glacial–interglacial cycles (Marine Isotope Stages (MIS) 12–9) and to two modern stalagmites, all from northern Borneo. The temperature estimates from the different methods agree in most cases within errors for both the old and recent samples; reconstructed formation temperatures of the recent samples match within 2-sigma errors with measured cave temperatures. However, slight but systematic deviations are observed between noble gas and liquid–vapor homogenization temperatures. Whereas the temperature sensitivity of fluid inclusion δ18O and clumped isotopes is currently debated, we find that the calibration of Tremaine et al. (2011) for fluid inclusion δ18O and a synthetic calcite-based clumped isotope calibration (Ziegler et al., in prep.) yield temperature estimates consistent with the other methods. All methods (with the potential exception of clumped isotopes) show excellent agreement on the amplitude of glacial–interglacial temperature change, indicating temperature shifts of 4–5 °C. This amplitude is similar to the amplitude of Mg/Ca-based regional sea surface temperature records, when correcting for sea level driven changes in cave elevation. Our reconstruction of tropical temperature evolution over the time period from 440 to 320 thousand years ago (ka) adds support to the view that climate sensitivity to varying greenhouse forcing is substantial also in the deep tropics.

An accelerating cosmology without dark energy

The negative pressure accompanying gravitationally-induced particle creation can lead to a cold dark matter (CDM) dominated, accelerating Universe (Lima et al. 1996 [1]) without requiring the presence of dark energy or a cosmological constant. In a recent study, Lima et al. 2008 [2] (LSS) demonstrated that particle creation driven cosmological models are capable of accounting for the SNIa observations [3] of the recent transition from a decelerating to an accelerating Universe, without the need for Dark Energy. Here we consider a class of such models where the particle creation rate is assumed to be of the form Gamma = beta H + gamma H(0), where H is the Hubble parameter and H(0) is its present value. The evolution of such models is tested at low redshift by the latest SNe Ia data provided by the Union compilation [4] and at high redshift using the value of z(eq), the redshift of the epoch of matter - radiation equality, inferred from the WMAP constraints on the early Integrated Sachs-Wolfe (ISW) effect [5]. Since the contributions of baryons and radiation were ignored in the work of LSS, we include them in our study of this class of models. The parameters of these more realistic models with continuous creation of CDM are constrained at widely-separated epochs (z(eq) approximate to 3000 and z approximate to 0) in the evolution of the Universe. The comparison of the parameter values, {beta, gamma}, determined at these different epochs reveals a tension between the values favored by the high redshift CMB constraint on z(eq) from the ISW and those which follow from the low redshift SNIa data, posing a potential challenge to this class of models. While for beta = 0 this conflict is only at less than or similar to 2 sigma, it worsens as beta increases from zero.