Asthma is a chronic disease of airway hyper-responsiveness, airway inflammation and episodic bronchoconstriction. With asthma forecasted to increase by an additional 100 million cases by 2025, there is a critical and immediate need to address new asthma therapies. Guidelines for asthma treatment in the emergency department conditionally recommend intravenous magnesium sulfate (MgSO4). However, some investigations have failed to demonstrate beneficial effects. Ethical constraints limit evaluation of the bronchodilatory effects of MgSO4 alone in patients with acute asthma exacerbation, independent of other conventional therapeutics. To address this ethical dilemma, this study consisted of two phases: 1) quantification of the independent pulmonary effect of three doubling doses of MgSO4 in the spontaneous equine model of asthma during naturally occurring exacerbations of bronchoconstriction, and 2) evaluation of arterial blood gas parameters in response to administration of MgSO4 at a dose identified in phase 1 that yielded greatest efficacy without deleterious side effects.

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Pulmonary surfactant is synthesized in the alveoli and lines the respiratory epithelium of the airways. Phospholipids, the main component of surfactant, confer it its ability to lower surface tension and to prevent alveolar collapse. Airway surfactant helps maintain smaller airway patency, improves muco-ciliary clearance, decreases bronchoconstriction, and modulates pulmonary immunity. Surfactant alterations in human asthma are therefore believed to contribute to the severity of airway obstruction. The goal of our first study was to characterize surfactant phospholipid composition and function in healthy horses, and to investigate the influence of age and bronchoalveolar lavage fluid (BALF) sample characteristics on surfactant. For that purpose, BALF was collected from 17 healthy horses and evaluated for BALF recovery percentage, cell count, and cell differential. BALF was separated into crude surfactant pellets (CSP) and supernatant and was analyzed for phospholipid content, protein content, phospholipid composition, and surface tension. Interestingly, phospholipid (surfactant) content in CSP significantly decreased with age. BALF recovery percentage, nucleated cell count, and cytological profile did not affect surfactant composition or function. The hypothesis of our second study was that surfactant alterations in RAO-affected horses are related to clinical stage of RAO. The objectives were 1) to compare surfactant phospholipid composition and function between Non-RAO and RAO horses at clinical stages and 2) to investigate relationships between surfactant alterations and variables assessing clinical stage of RAO. Seven horses with confirmed RAO and seven Non-RAO horses were evaluated in pairs (RAO/Non-RAO) at baseline, during exposure to hay, and post-exposure. Assessments included: clinical scoring, measure of maximal change in pleural pressure (ΔPplmax), airway endoscopy, and BALF cell counts and differentials. Samples were processed and analyzed as described above. Phospholipid levels in BALF were significantly lower in RAO versus Non-RAO horses, even in the absence of clinical signs. In the group of RAO horses, phospholipid content was significantly lower during exposure versus baseline. Furthermore, exposure to hay led to an increase in the protein versus phospholipid ratio in BALF from RAO horses. No significant differences were found in BALF protein content, phospholipid composition, or surface tension between or within groups of horses. Phosphatidylglycerol percentage had a tendency to be lower in RAO horses with higher clinical scores. Supernatant protein content was related to BALF neutrophilia in RAO crisis and overall ΔPplmax . In conclusion, our study demonstrated that surfactant alterations in RAO horses are present in remission and are exacerbated following exposure to hay. It is conceivable that a lower amount of surfactant in bronchioli of RAO horses may contribute to the horses' propensity to develop airway obstruction, mucous accumulation, and bronchial hyperresponsiveness. This may be exacerbated during crisis by a relatively higher protein versus phospholipid ratio. Furthermore, a progressive decrease of surfactant levels in older horses may contribute to a worsening of clinical signs in older RAO-affected horses. / Ph. D.

L'utilisation de stents urétéraux (endoprothèses urétérales) pour soulager l'obstruction des voies urinaires est toujours entravée par le problème de l'infection, de l'incrustation et de la compression, qui nécessitent une procédure de retrait. Un nouveau type de stents urétéraux biodégradables en matér iaux polymères a été proposé pour surmonter ces problèmes. Des travaux récents ont proposé des métaux biodégradables à base de magnésium, comme nouveaux matériaux offrant à la fois résistance et biodégradation. Ce travail propose des alliages à base de zinc dont la cytocompatibilité avec les cellules urothéliales humaines normales a été évaluée par des tests 2D et 3D. Pour ce faire, les cellules ont été exposées à différentes concentrations d'extraits de métaux, 15 mg/ml de ZM21, 10 mg/ml de Zn-1Mg et 8,75 mg/ml de Zn-0,5Al. La mort cellulaire a été observée après 24 h, quoique en proportion différente pour chaque métal. Des modifications du cytosquelette des cellules a également été observée par immunofluorescence contre les cytokératines cependant, un processus de récupération des cellules a été noté au jour 3. La toxicité directe sur les cellules a été évaluée sur une construction de tissu urétéral 3D non tubulaire. Le résultat a montré que les cellules urothéliales pouvaient former un urothelium présentant des couches similaire à un tissu natif. Les protéines telles que la jonction serrée ZO-1 au niveau des couches superficielles et la laminine au niveau de la lame basale montre que le tissu reste sain au voisinage des disques métalliques après 7 jours de traitement. L'observation par MEB a montré que les cellules basales étaient attachées à la surface des métaux et observées dans un état d'étalement naturel, montrant que les pseudopodes et la morphologie fusiforme indiquent que les échantillons de métal sont non toxiques. / The use of ureteral stents to relieve urinary tract obstruction is still challenged by the problem of infection, encrustation and compression leading to the need for removal procedure. A new type of biodegradable ureteral stents made of polymeric materials has been proposed to overcome the problems. Recent works proposed magnesium-based biodegradable metals as new materials offering both biodegradation and strength. This work proposes zinc-based alloys by firstly evaluating their cytocompatibility toward normal human urothelial cells using 2D and 3D assays. Cells were exposed by different concentration of metals extracts, 15 mg/ml of ZM21, 10 mg/ml of Zn-1Mg and 8.75 mg/ml of Zn-0.5Al. Induction of cell death was observed after 24 h, resulting in reduced cell viability at different percentages for each metal. The cytoskeleton of cells was also affected as observed by immunofluorescence of cytokeratins however, the recovery process of cells was noted at day 3. Direct cell toxicity was evaluated on a non-tubular 3D ureteral tissue construct. The results showed that urothelial cells could form a multilayered urothelium as in a native tissue, with the presence of tight junction ZO-1 in superficial layer and laminin in the basal layer indicating that the tissue is healthy in the presence of the metal disks even after 7 days of treatment. SEM observation showed basal cells were found attached to the metal surface and seen as in a natural spreading state, showing pseudopodia and fusiform morphology indicating that the metal specimens are non-toxic.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Résumé : La réduction du bruit tonal des ventilateurs basse vitesse est un défi très important pour l’industrie. Lorsqu’il émerge du bruit large bande, ce rayonnement est la source de gênes auprès de la population, que ce soit pour de petits ventilateurs d’ordinateurs ou de gros ventilateur miniers. Afin de contrôler le bruit tonal, de nombreuses techniques ont été développées au fil de ces dernières décennies. Une méthode alliant simplicité et efficacité se démarque néanmoins : le contrôle par obstruction de l’écoulement. Malgré les études menées jusqu’alors, les mécanismes aéroacoustiques de réduction du bruit associés à cette méthode restent mal compris. Pour répondre à cette problématique, ce projet de Doctorat s’intéresse à l’étude de l’intéraction entre l’obstruction et le ventilateur au moyen de simulations aéro-acoustiques. De plus, une méthodologie numérique de design de l’obstruction est proposée afin de réduire les coûts associés aux multiples test expérimentaux. / Abstract : Tonal noise radiated by low-speed fans is a prime challenge for many industries. When this component emerges from the broadband noise, the acoustic radiation is particularly harsh for the human ear, whether it comes from a small computer cooling fan or from a large mine ventilation fan. Several methods have been developed over the last decades to control tonal noise. Nevertheless, one simple and efficient technique stands out: the adaptive passive control with flow obstruction. Despite all the research conducted on this method, the aeroacoustic mechanisms responsible for the noise reduction are not fully understood. Therefore, the present thesis aims at investing the obstruction-fan interaction using aeroacoustic simulations. Moreover, a numerical design methodology is proposed to reduce the cost induced by extensive experimental tests.

Le thème principal de cette thèse est l’interaction entre le “comportement” des points rationnels sur certaines classes de variétés définies sur des corps globaux et locaux, et la cohomologie de ces variétés.Dans la partie I, on étudie l’obstruction de Brauer-Manin à la validité des principes locaux-globaux (comme le principe de Hasse et l’approximation faible) qui vient du groupe de Brauer d’une variété. Dans certains cas, pour des fibrations en torseurs sous un tore constant défini sur un corps de nombres, on démontre que l’obstruction de Brauer-Manin est suffisante pour expliquer le défaut des principes locaux-globaux. On donne également des nouveaux examples de variétés pour lesquelles l’obstruction de Brauer-Manin et ses raffinements ne suffisent pas pour expliquer le défaut du principe de Hasse.Dans la partie II, on étudie la relation entre le volume rationnel d’une variété lisse, projective sur un corps strictement local, et la trace de l’opérateur de monodromie modérée sur la cohomologie étale de la variété. Ceci est motivé par un travail de Nicaise-Sebag sur une formule de traces pour l’invariant de Serre motivique, inspiré par la formule de Grothendieck-Lefschetz pour les variétés sur les corps fini. On utilise ici le formalisme de la géométrie logarithmique. / The main theme of this thesis is the interplay between the “behaviour” of the rational points on certain classes of algebraic varieties defined over global and local fields, andthe cohomology of these varieties. Part I studies the Brauer-Manin obstruction to the validity of local-global principles (such as the Hasse principle and weak approximation) coming from the Brauer groupof a variety. In some cases, for certain families of torsors under a constant torusdefined over a number field, we prove that the Brauer-Manin obstruction is sufficientto explain the failure of these local-global principles. We also give new examples of varieties for which the Brauer-Manin obstruction and its refinements are insufficientto explain the failure of the Hasse principle.In Part II, we investigate the relationship between the rational volume of a smooth, projective variety defined over a strictly local field, and the trace of the tame monodromy operator on the étale cohomology of this variety. The motivation is work of Nicaise–Sebag on a trace formula for the motivic Serre invariant, inspired by the Grothendieck–Lefschetz trace formula for varieties over finite fields. We study this relationship using the framework of logarithmic geometry.

Nosso objetivo neste trabalho é estudar a obstrução de Euler de uma função, este conceito foi definido por J.-P. Brasselet, D. Massey, A. J. Parameswaran e J. Seade, e generaliza dois conceitos importantes, a obstrução de Euler definida por R. D. MacPherson assim como o número de Milnor de uma função. O resultado principal deste trabalho mostra a relação existente entre a obstrução de Euler e a obstrução de Euler de uma função / Our goal in this work is to study the Euler obstruction of a function, this concept was defined by J.-P. Brasselet, D. Massey, A. J. Parameswaran and J. Seade, and it generalizes two important concepts, the Euler obstruction defined by R. D. MacPherson and the Milnor number of a function. The main result of this study shows the relation between the Euler obstruction and the Euler obstruction of a function

L’IRM cardiaque a une capacité unique d’étudier le remodelage ventriculaire gauche (VG) après infarctus du myocarde. Les objectifs principaux de ce travail étaient de caractériser le tissue de l’infarctus par IRM et d’évaluer les facteurs associés au remodelage du VG. Nous avons étudié prospectivement 114 patients présentant un premier infarctus du myocarde avec sus-décalage du segment ST et ayant subi une angioplastie primaire. Des IRM cardiaques ont été réalisées dans les 2 à 4 jours et à 6 mois suivant la revascularisation. Premièrement, nous avons réalisé une analyse comparative de différentes méthodes de segmentation de l’infarctus sur l’imagerie de rehaussement tardive (RT). Deuxièmement, nous avons étudié l’évolution des différentes composantes de la zone RT au cours des six mois, et observé que la réduction de la zone RT (33,8%) était représentée par l’extension de la zone grise initiale. Troisièmement, nous avons évalué le rôle clinique de la zone grise. Elle s’est révélée protectrice vis-à-vis du remodelage délétère. Quatrièmement, nous avons étudié l’influence de l’obstruction microvasculaire (OMV) sur le remodelage local du VG. Différents motifs ont été observés entre les patients atteints de l’OMV et ceux ne présentant pas d’OMV: un rétrécissement uniforme à travers le VG chez les patients sans OMV lorsque les sujets avec OMV présentaient une dilatation globale significative, ainsi qu’une dilatation plus importante dans les régions atteint d’OMV / Cardiac MRI (CMR) has the unique ability to study left ventricular remodeling after myocardial infarction. The main objectives of this work were to characterize infarct tissue by CMR and to evaluate factors associated with LV remodeling. We prospectively studied 114 patients with a first ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty. CMR was performed within 2-4 days and at 6 months after the revascularization. First, we compared different methods for the segmentation of myocardial infarcts on late gadolinium enhancement (LGE) imaging. Second, we described the evolution of different components of LGE area during 6 months. We found that the decrease of LGE area (33.8%) matched the extent of initial gray zone. Third, we studied the clinical role of gray zone. The gray zone was found to be a protective factor for adverse remodeling. Fourth, we studied the influence of microvascular obstruction (MVO) on local LV remodeling and observed distinct remodeling patterns in patients with and without MVO: equally-distributed shrinkage throughout the LV cavity in patients without MVO whereas significant dilation occurring in those with MVO, tending to be greater in myocardial regions containing MVO