Modeling of Large Pharmacokinetic Data Using Nonlinear Mixed-Effects: A Paradigm Shift in Veterinary Pharmacology. A Case Study With Robenacoxib in Cats

The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed‐effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects. A bicompartmental disposition model with simultaneous zero and first‐order absorption best described robenacoxib PKs in blood. Clearance was 0.502 L/kg/h and the bioavailability was high (78%). The absorption constant point estimate (Ka = 0.68 h−1) was lower than beta (median, 1.08 h−1), unveiling flip‐flop kinetics. No dosing adjustment based on available covariates information is advocated. This modeling work constitutes the first application of NLME in a large feline population

Caractérisation du complexe Lre1p/Gsp1p chez la levure Saccharomyces cerevisiae

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

The dependence of dijet production on photon virtuality in ep collisions at HERA

The dependence of dijet production on the virtuality of the exchanged photon, Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 < 2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of 38.6 pb^-1. Dijet cross sections were measured for jets with transverse energy E_T^jet > 7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon momentum entering the hard process, was used to enhance the sensitivity of the measurement to the photon structure. The Q^2 dependence of the ratio of low- to high-xg^obs events was measured. Next-to-leading-order QCD predictions were found to generally underestimate the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models based on leading-logarithmic parton-showers, using a partonic structure for the photon which falls smoothly with increasing Q^2, provide a qualitative description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.

Développement de la sensibilité des neurones du collicule supérieur à la durée de la stimulation auditive

Chez plusieurs espèces, les neurones auditifs sensibles à la durée de la stimulation sont présents au niveau des collicules inférieurs. Toutefois, le décours temporel de leur développement fonctionnel est inconnu. Étant donné que le collicule supérieur est l’un des principaux relais sous-cortical impliqué dans l’intégration des stimuli audio-visuels, nous voulons déterminer si le collicule supérieur du rat contient de tels neurones et s’ils sont sensibles et sélectifs à différentes durées de stimulation auditive. De plus, l'originalité de cette étude est de déterminer les étapes de leur maturation fonctionnelle. Des enregistrements neuronaux unitaires et extra-cellulaires sont effectués dans le collicule supérieur de rats juvéniles (P15-P18, P21-P24, P27-P30) et adultes anesthésiés. La sensibilité à la durée est déterminée lors de la présentation de bruits gaussiens (2-10 dB SPL au-dessus du seuil) de durées variables (3-100 ms). Seulement un faible pourcentage des neurones du collicule supérieur est de type passe-bande (3-9% des neurones parmi les ratons et 20% chez les rats adultes). Une différence significative de la distribution entre les différents types de neurones auditifs sensibles à la durée est présente au cours du développement: les neurones de type passe-haut (63-75%) sont présents en majorité chez les groupes juvéniles alors que 43% des neurones sont de type insensible à la durée de la stimulation auditive chez les rats adultes. Ces résultats montrent qu’une population importante de neurones auditifs du collicule supérieur du rat est sensible à la durée des signaux sonores et qu’un développement fonctionnel important survient au cours du premier mois postnatal.In many species, duration-sensitive neurons which could possibly analyse species-specific vocalizations are encountered in the inferior colliculus. However, their postnatal development is unknown. Since the superior colliculus is one of the most important subcortical relay implicated in the audiovisual integration, we sought to gain insight on whether the SC of the rat contains such neurons and, if so, whether they are sensitive and selective to duration. Furthermore, the originality of this study is to determine their fonctional maturation. Extracellular single-unit recordings were assessed in the deep layers of the superior colliculus of anesthetized rats throughout postnatal days (P15 – P18, P21 – P24, P27 – P30) and at adulthood. Gaussian noises of different durations (3-100 ms) were presented in free-field in pseudo-random order (2 – 10 dB SPL above threshold). Only few neurons are band-pass: about 3 – 9% across the different age groups (P15 – P30) and 20 % in adults. Thus, in terms of categories of duration-sensitive neurons profiles, a significant difference was evident across postnatal development: long-pass (63-75%) neurons were mostly encountered in the different groups of pups relative to all-pass (43%) in adult rats. These results demonstrate that a large population of neurons in the superior colliculus of the rat is sensitive to noise durations and that important development changes occur during postnatal maturation

Beauty photoproduction measured using decays into muons in dijet events in ep collisions at s\sqrt{s}=318 GeV

The photoproduction of beauty quarks in events with two jets and a muon has been measured with the ZEUS detector at HERA using an integrated luminosity of 110 pb$^{- 1}$. The fraction of jets containing b quarks was extracted from the transverse momentum distribution of the muon relative to the closest jet. Differential cross sections for beauty production as a function of the transverse momentum and pseudorapidity of the muon, of the associated jet and of $x_{\gamma}^{jets}$, the fraction of the photon's momentum participating in the hard process, are compared with MC models and QCD predictions made at next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September 200

FATORES DE IMPLEMENTAÇÃO DA POLÍTICA DE QUALIDADE DO ENSINO SUPERIOR EM MOÇAMBIQUE: O CASO DO SINAQES

The present research was guided by the objective of investigating the factors of implementation of the National System of Assessment, Accreditation and Quality Assurance – “SINAQES” in Mozambique, as a public policy for Higher Education. Thus, a Documentary Research was carried out, based on the content analysis of official documents. The establishment of a colonial educational system, the post-independence conversion of the educational system, and the introduction of the market economy were identified as relevant contextual determinants under which SINAQES is introduced. Moreover, its implementation is based on the articulation of different actors, among them: political actors, bureaucrats, experts, interest groups, and initiative recipients, under an implementation model that has shown to focus on the top-down conception. KEYWORDS: Education Quality Policy. Higher Education. Implementation. Mozambique.  La presente investigación estuvo guiada por el objetivo de investigar los factores de implementación del Sistema Nacional de Evaluación, Acreditación y Garantía de Calidad – “SINAQES” en Mozambique, como política pública de Educación Superior. Así, se llevó a cabo una Investigación Documental, basada en el análisis de contenido de documentos oficiales. El establecimiento de un sistema educativo colonial, la conversión del sistema educativo posterior a la independencia y la introducción de la economía de mercado fueron identificados como determinantes contextuales relevantes bajo los cuales se introdujo el SINAQES. Además, su implementación se basa en la articulación de diferentes actores, entre ellos: actores políticos, burócratas, expertos, grupos de interés y beneficiarios de la iniciativa, bajo un modelo de implementación que ha demostrado centrarse en la concepción top-down.  PALABRAS CLAVE: Política de Educación de Calidad. Educación Superior. Aplicación. Mozambique.A presente pesquisa orientou-se pelo objetivo de investigar os fatores de implementação do Sistema Nacional de Avaliação, Acreditação e Garantia de Qualidade – SINAQES em Moçambique, como política pública para o Ensino Superior. Procedeu-se a realização de uma Pesquisa Documental, baseando-se na análise de conteúdo de documentos oficiais. Identificou-se a instauração de um sistema educacional colonial, sua conversão para o período pós-independência, e a introdução da economia de mercado como determinantes contextuais relevantes, sob os quais o SINAQES é introduzido. Sua implementação encontrou-se em torno da articulação de diferentes atores: atores políticos, burocratas, especialistas, grupos de interesse e destinatários da iniciativa, sob um modelo que demonstrou concentrar-se numa concepção top-down. PALAVRAS-CHAVE: Política de Qualidade da Educação. Ensino Superior. Implementação. Moçambique

Avaliação da qualidade do ensino superior em Moçambique

A presente investigação teve como objetivo identificar como a implementação de um sistema de avaliação do Ensino Superior tem contribuído para o desenvolvimento de um ensino tecnológico e inovador em Moçambique. Para tanto, realizou-se uma pesquisa de abordagem mista, que coletou a percepção de 16 dirigentes de IES localizadas nas províncias de Manica, Tete, Sofala e Zambézia, através da realização de entrevistas. Ademais, as percepções de 99 professores e 326 estudantes foram, também, coletadas, a partir da aplicação de questionários. Identificou-se, a destacar, melhorias nas infraestruturas de ensino, nos currículos dos cursos, e na formação de pessoal, especificamente, de docentes. Todavia, determinados desafios foram evidenciados, como a disponibilidade de recursos financeiros e o acesso de docentes a cursos de doutorado

Search for Resonance Decays to Lepton+jet at DESY HERA and Limits on Leptoquarks

A search for narrow-width resonances that decay into electron+jet or neutrino+jet has been performed with the ZEUS detector at the DESY ep collider HERA operating at center-of-mass energies of 300 and 318 GeV. An integrated e+p luminosity of 114.8 pb-1 and e-p luminosity of 16.7 pb-1 were used. No evidence for any resonance was found. Limits were derived on the Yukawa coupling λ as a function of the mass of a hypothetical resonance that has arbitrary decay branching ratios into eq or vq. These limits also apply to squarks predicted by R-parity-violating supersymmetry. Limits for the production of leptoquarks described by the Buchmüller-Rückl-Wyler model were also derived for masses up to 400 GeV. For λ = 0.1, leptoquark masses up to 290 GeV are excluded