Investigating the effects of the disease-modifying anti-rheumatic drug methotrexate on the vascular endothelium

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that associates with increased mortality from cardiovascular disease (CVD). Methotrexate (MTX), a folate analogue used as disease-modifying anti-rheumatic drug (DMARD), reduces CVD morbidity and mortality in RA patients, possibly by improving endothelial function. The aim of this study was to investigate the molecular effects of MTX in quiescent and activated vascular endothelial cells (EC). In EC pre-treated with tumour necrosis factor (TNF)-alpha, MTX independently increased the activity of mitogen-activated protein kinase (MAPK) p38 and Akt and caused cell cycle arrest due to folate depletion. In contrast, MTX did not affect cell signalling, proliferation or gene expression in EC exposed to different types of shear stress. To tease out the underlying mechanism, folate or one carbon metabolism (OCM) was investigated in EC cultivated under static or shear stress conditions. Endothelial OCM was fundamentally altered by shear stress, with potentially important implications for MTX uptake and function. Using endothelial colony forming cells (ECFC) isolated from RA patients before and after treatment initiation with MTX and hydroxychloroquine, it was shown that systemic inflammation primes ECFC towards a pro-inflammatory state that may be reversible with DMARD treatment. These data suggest that MTX acts on vascular EC in a folate-dependent manner. However, since endothelial OCM was largely downregulated by shear stress, this implies that MTX may have limited direct effects on EC in vivo and provides a potential explanation for the controversies around the vascular effects of folate and anti-folate therapy. Although findings in ECFC from patients with RA support anti-inflammatory effects of MTX containing therapy, the data in this thesis do not support a direct MTX-mediated anti-atherogenic effect on the endothelium but suggest that the drug may limit EC dysfunction in combination with other drugs indirectly by reducing systemic inflammation.Open Acces

Functional Limit Theorem for the Empirical Process of a Class of Bernoulli Shifts with Long Memory

International audienceWe prove a functional central limit theorem for the empirical process of a stationary process $X_t = Y_t + V_t$, where $Y_t$ is a long memory moving average in i.i.d. r.v.'s $\zeta_s, s\le t$, and $V_t = V(\zeta_t, \zeta_{t-1}, \dots )$ is a weakly dependent nonlinear Bernoulli shift. Conditions of weak dependence of $V_t$ are written in terms of $L^2-$norms of shift-cut differences $V(\zeta_t, \dots, \zeta_{t-n}, 0, \dots, ) - V(\zeta_t, \dots, \zeta_{t-n+1}, 0, \dots )$. Examples of Bernoulli shifts are discussed. The limit empirical process is a degenerated process of the form $f(x) Z$, where $f$ is the marginal p.d.f. of $X_0$ and $Z$ is a standard normal r.v. The proof is based on a uniform reduction principle for the empirical process

The role of the CO2 laser in the management of laryngotracheal stenosis: a survey of 100 cases

Over the last decade, improvement of CO2 lasers with the microspot and ultrapulse technologies has broadened the indications for endoscopic CO2-laser resection of benign laryngotracheal stenosis (LTS). This article reviews 100 patients treated solely by endoscopic means for a LTS. There were 47 grade III, 41 grade II and 12 grade I stenoses according to the Myer-Cotton classification. The postoperative results show that the improvement to a nearly normal (>80% luminal size) airway declines from 92% (11/12 patients) for grade I to 46% (19/41 patients) for grade II and 13% (6/47 patients) for grade III stenoses. When compared to open surgery for more severe grades of stenosis (31 grade IV, 66 grade III and 3 grade II stenoses), the results of the endoscopy group is much less favorable: 36% of patients in the endoscopy group versus 76% of patients in the open surgery group were rehabilitated to a normal respiration without exertional dyspnea and 38% versus 5% patients remained tracheotomy dependent. However, if strict selection and therapeutic criteria are respected, a significant number of grade I and II stenoses, and to a lesser degree of grade III stenoses, can be improved to a nearly normal airway by endoscopic means only. The endoscopic treatment is potentially less invasive and risky and only needs a short hospital stay. To try this as a first treatment modality in a selected group of patients is worthwhile, provided that this endoscopic treatment is not repeated a second time, if the stenosis recurs to its initial grade after a primary CO2-laser treatment. Some guidelines for safe endoscopic treatment modalities with of the CO2 laser, dilatation and/or stenting are propose

Compact preference representation and Boolean games

International audienceGame theory is a widely used formal model for studying strategical in- teractions between agents. Boolean games[23, 22] yield a compact rep- resentation of 2-player zero-sum static games with binary preferences: an agent's strategy consists of a truth assignment of the propositional variables she controls, and a player's preferences are expressed by a plain propositional formula. These restrictions (2-player, zero-sum, binary preferences) strongly limit the expressivity of the framework. We first generalize the framework to n-player games which are not necessarily zero-sum. We give simple char- acterizations of Nash equilibria and dominated strategies, and investigate the computational complexity of the associated problems. Then, we relax the last restriction by coupling Boolean games with a representation, namely,CP-nets

La réception des textes de magazines à caractère sexuel chez les adolescentes au Québec et au Nouveau-Brunswick : adhésion, ignorance ou contestation?

Au cours des dernières années, de nombreux journalistes et chercheurs ont tenté de relier le phénomène d'hypersexualisation à certains contenus médiatiques nord-américains, en particulier en ce qui concerne les magazines pour adolescentes. Il s'en est suivi beaucoup d'études de contenu, dont quelques-unes au Québec, mais très peu d'études de réception, et surtout très peu portant explicitement sur les textes à caractère sexuel que contiennent ces magazines. Cette recherche avait pour but d'étudier la façon dont étaient reçus les textes à caractère sexuel du magazine Adorable par des adolescentes franco-canadiennes âgées entre 15 et 17 ans. Elle a tenté de déterminer dans quelle mesure ce type de textes les intéressait de même que ce qu'elles recherchaient dans ces articles, c'est-à-dire si elles les lisaient dans une optique de plaisir ou plutôt d'accès à la connaissance. Enfin, elle a cherché à examiner si la relation qu'elles entretenaient avec ces textes témoignait d'une imprégnation idéologique, d'une ignorance ou d'une résistance. Alliant une méthode inspirée du système d'annotation de lecture de Debras (2003) à des entretiens individuels et de petits groupes, cette recherche a permis une analyse sur trois plans: 1. l'intérêt suscité par les articles; 2. les fonctions remplies par ceux-ci chez les participantes; et 3. le type de réception qu'elles en faisaient (dominante, négociée, oppositionnelle ou ignorée, selon une codification inspirée de Hall [1973]). Les résultats tendent à montrer que les adolescentes interrogées s'intéressent en effet aux textes à caractère sexuel et les lisent à la fois pour apprendre, pour le plaisir et pour se rassurer. Si les participantes ont majoritairement fait une lecture dominante des textes, l'étude a également permis de montrer que les participantes sont capables de faire montre d'un esprit critique envers certains d'entre eux

Radiographic pelvimetry in free-ranging Eurasian lynx (Lynx lynx carpathicus) from Switzerland

The observation of pelvic anomalies in two Eurasian lynx (subspecies Lynx lynx carpathicus) from a population reintroduced to Switzerland raised the question of the frequency of such anomalies, but no anatomical reference values were available for comparison. This study aimed at providing baseline data on the pelvic morphology of Carpathian lynx from Switzerland, and at detecting potential pelvic anomalies. Measurements of 10 pelvic parameters were performed on the radiographs of 56 lynx taken from 1997–2015. Two ratios (vertical diameter/acetabula; sagittal diameter/transversal diameter) and two areas (pelvic outlet and inlet) were calculated to describe pelvic shape. The results showed that the Eurasian lynx has a mesatipellic pelvis, with a pelvic length corresponding to approximatively 20% of the body length. We found growth-related pelvis size diferences among age classes and evidence of sexual dimorphism in adults: two parameters refecting pelvic width were larger in females, likely to meet the physiological requirements of parturition. By contrast, pelvis length, conjugata vera, diagonal conjugata, sagittal diameter, and tendentially also vertical diameter, were larger in males, in agreement with their larger body size. Outliers were found in fve individuals but apparently without clinical signifcance. Extreme values were likely due to inter-individual diferences and the limited sample size rather than to possible congenital or developmental pathological morphology of the pelvic cavity. We present baseline data of the pelvic morphology, including growth and sexual dimorphism, which may be useful for health monitoring and for determination of age and sex in skeletal remains of Carpathian lynx

La recherche d'informations sexuelles sur le Web par de jeunes Franco-Canadiennes et ses liens avec l'expression de leur agentivité sexuelle

Dans les études anglophones sur les jeunes femmes, on fait de plus en plus appel à un concept relativement récent en sciences sociales : l’agentivité sexuelle (sexual agency). Terme peu usité en anglais, et encore moins en français, l’agentivité sexuelle fait référence à l’idée de « contrôle » de sa propre sexualité, c’est-à-dire à la capacité de prendre en charge son corps et sa sexualité. L’une des façons de prendre une part active dans sa sexualité est de s’y intéresser et chercher des réponses à ses questions. Par le biais de blogues « privés » de recherche sur Internet et d’entrevues individuelles, nous avons interrogé 30 jeunes femmes âgées de 17 à 21 ans sur leurs façons d’utiliser Internet pour répondre à leurs questions sur la sexualité. Nous avons ensuite poussé plus loin la question de l’agentivité en interrogeant la façon dont les jeunes participantes manifestent de l’agentivité dans diverses situations en lien avec leur sexualité. Ce rapport de recherche doctorale propose une définition du concept d’agentivité sexuelle, décrit la méthodologie novatrice utilisée et présente ensuite de façon qualitative les résultats. Nous avons pu observer qu’Internet constitue un moyen de choix pour répondre aux questions des participantes sur la sexualité, mais qu’en certaines situations angoissantes, Internet présente certaines limites. Bien qu’Internet leur semble une solution rapide, efficace et anonyme pour répondre à leurs questions d’ordre « physique », elles utilisent très peu le Web pour répondre à leurs besoins d’ordre plus « psychologique » ou « relationnel ». Elles n’accordent pas non plus aux sources Web le même crédit qu’à leurs parents, médecins ou amis. Nous avons également constaté que les participantes, dans leurs pratiques, ont bien intégré certaines notions de contrôle (notamment que « non », c’est « non »), mais éprouvent plus de difficulté à exercer du pouvoir quand leur partenaire est insistant ou a plus d’expérience qu’elles. Nous verrons enfin que la méthode du blogue « privé », jumelée à des entretiens individuels, présente de nombreux avantages sur les méthodes de recherche plus « traditionnelles », notamment lorsqu’il est question de sujets délicats comme la sexualité.In the last few years, the concept of sexual agency has been used by many English-language studies on youth and women to describe the ability to take control of one’s own body and sexuality. While the term is rarely used in informal English, it appears even less frequently in French. One way that young women can exercise their sexual agency is for them to take an active role by seeking answers to their questions about their own sexuality. Using an innovative "private" blog method, combined with in-depth interviews, we sought to determine how teenage girls and young women ages 17 to 21 are using the Internet to learn about sexuality. We then interviewed the participants about the situations where they exercise (or refrain to exercise) sexual agency in their lives. In this thesis, we propose a definition of sexual agency, describe the method we have developed, and then discuss our results. We show that the participants use the Internet to gather information on a wide variety of sexual topics, but using the Internet has some limitations when a participant's situation is worrisome or taboo. Although Internet seems to serve well their needs related to "physical" matters, the participants don’t really use Internet to address their more "psychological" or "relational" concerns. They also do not grant the same credence to some Internet sources as they do to their friends, doctors or parents. We also show that the participants, in their sexual encounters, have integrated some agentic messages, such as "No means no", but show some lack of sexual agency when their partner is more experienced or insistent. Finally, we will see that our method of private blogs mixed with in-depth interviews is an ideal method for gathering qualitative data on sensitive topics such as sexuality

First IJCAI International Workshop on Graph Structures for Knowledge Representation and Reasoning (GKR@IJCAI'09)

International audienceThe development of effective techniques for knowledge representation and reasoning (KRR) is a crucial aspect of successful intelligent systems. Different representation paradigms, as well as their use in dedicated reasoning systems, have been extensively studied in the past. Nevertheless, new challenges, problems, and issues have emerged in the context of knowledge representation in Artificial Intelligence (AI), involving the logical manipulation of increasingly large information sets (see for example Semantic Web, BioInformatics and so on). Improvements in storage capacity and performance of computing infrastructure have also affected the nature of KRR systems, shifting their focus towards representational power and execution performance. Therefore, KRR research is faced with a challenge of developing knowledge representation structures optimized for large scale reasoning. This new generation of KRR systems includes graph-based knowledge representation formalisms such as Bayesian Networks (BNs), Semantic Networks (SNs), Conceptual Graphs (CGs), Formal Concept Analysis (FCA), CPnets, GAI-nets, all of which have been successfully used in a number of applications. The goal of this workshop is to bring together the researchers involved in the development and application of graph-based knowledge representation formalisms and reasoning techniques