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Class of 2012 Abstract / Specific Aims: To evaluate the in vitro throat deposition and respirable mass of the QVAR® pressurized metered-dose inhaler (pMDI) alone or coupled to an accessory device, such as the AeroChamber Valved Holding ChamberTM or various nonconventional accessory devices. Methods: The performance of the AeroChamber and nonconventional accessory devices, including a toilet paper roll, paper towel roll, rolled paper, plastic bottle spacer, plastic bottle reverse-flow holding chamber, and nebulizer reservoir tubing, were compared to no accessory device. Throat deposition and respirable mass were evaluated using a United States Pharmacopeia (USP) inlet ("throat") coupled to instrumentation for particle size analysis. Each configuration was tested with three actuations and repeated in quadruplicate. The amount of drug deposition was quantified using high-performance liquid chromatography. The data were analyzed using multiple independent t-tests assuming unequal variances. An a priori α-threshold of 0.05 was used with a Bonferroni corrected α of 0.007. Main Results: Compared to the pMDI alone, all of the accessory devices had significantly lower throat deposition (p < 0.001) and significantly higher respirable fraction (p < 0.001). Differences in respirable mass were not significant for any accessory device (p ≥ 0.049), except the paper towel roll and the nebulizer reservoir tubing (p < 0.001). Conclusions: Under these testing circumstances, nonconventional accessory devices, such as the toilet paper roll, rolled paper, plastic bottle spacer, and plastic bottle reverse-flow holding chamber, effectively reduce throat deposition and maintain respirable mass compared to a QVAR pMDI alone. Therefore, they may be suitable alternatives to commercial spacers.

A formulação convencional do Método dos Elementos Finitos (MEF) baseada em aproximação do campo de deslocamentos apresenta limitações conhecidas como, por exemplo, em problemas que envolvam regiões com singularidade e problemas de elasticidade quase incompressível. Quando a utilização do MEF convencional inclui a análise de propagação de fissuras ou de dano evolutivo, faz-se recurso a mudança contínua da rede de elementos finitos, tornando as simulações onerosas em termos computacionais. Assim, justifica-se a procura por metodologias que combinem boa capacidade de aproximação com baixo custo computacional. Neste trabalho as formulações estudadas são dos tipos híbrido-mista e puramente mista, ambas combinadas com técnicas de enriquecimento das soluções proporcionadas pelo Método dos Elementos Finitos Generalizados (MEFG). A metodologia numérica resultante é aplicada às análises de sólidos em regime de ruptura modelados pela Mecânica do Dano. Vale ressaltar que a aproximação do campo de tensões, dada por estas formulações não convencionais, pode permitir melhor estimativa da danificação da estrutura, frente ao MEF convencional. Isto se dá porque os critérios de danificação empregados são quase sempre baseados na estimativa do campo de tensões atuantes. Nas análises numéricas, aplica-se uma estratégia incremental-iterativa convencional e propõe-se uma estratégia simplificada não iterativa, que permite uma estimativa do dano utilizando-se os resultados de uma análise linear. O trabalho é finalizado com a comparação entre resultados de simulações desenvolvidas mediante as estratégias simplificada e não linear completa, comprovando-se que o modelo simplificado pode ser empregado nas situações de dano localizado em pequenas regiões do domínio. / The conventional Finite Element Method (FEM) based on displacement field approximation presents limitations e. g. problems involving regions with singularity and problems of quasi-incompressible elasticity. When the conventional FEM utilization includes the crack growth analysis or damage evolution is made resort of the continuous change of finite element mesh, rendering costly simulations in computational terms. Thus, it is justified the search of methodologies which combine good approximation capacity with low computational cost. In this research the studied formulations are of hybrid-mixed and purely mixed types, both combined with enrichment techniques of solutions offered by the Generalized Finite Element Method (GFEM). The numerical resultant methodology is applied to solid analyses in rupture regime modeled using Damage Mechanics. It is noteworthy that the approximation of stress field, given with these nonconventional formulations, may allow better damage estimative of structure, compared to conventional FEM. This is because the employed damage criteria are almost always based on active stress field estimative. In the numerical analyses it is applied a conventional incremental-iterative strategy and it is proposed a non-iterative simplified strategy which allows damage estimative using the results of a linear analysis. The research is finalized with the comparison between results of developed simulations through the simplified and nonlinear strategies, proving that the simplified model may be employed in situations where the damage is located in small regions in domain.

A formulação convencional do Método dos Elementos Finitos (MEF) baseada em aproximação do campo de deslocamentos apresenta limitações conhecidas como, por exemplo, em problemas que envolvam regiões com singularidade e problemas de elasticidade quase incompressível. Quando a utilização do MEF convencional inclui a análise de propagação de fissuras ou de dano evolutivo, faz-se recurso a mudança contínua da rede de elementos finitos, tornando as simulações onerosas em termos computacionais. Assim, justifica-se a procura por metodologias que combinem boa capacidade de aproximação com baixo custo computacional. Neste trabalho as formulações estudadas são dos tipos híbrido-mista e puramente mista, ambas combinadas com técnicas de enriquecimento das soluções proporcionadas pelo Método dos Elementos Finitos Generalizados (MEFG). A metodologia numérica resultante é aplicada às análises de sólidos em regime de ruptura modelados pela Mecânica do Dano. Vale ressaltar que a aproximação do campo de tensões, dada por estas formulações não convencionais, pode permitir melhor estimativa da danificação da estrutura, frente ao MEF convencional. Isto se dá porque os critérios de danificação empregados são quase sempre baseados na estimativa do campo de tensões atuantes. Nas análises numéricas, aplica-se uma estratégia incremental-iterativa convencional e propõe-se uma estratégia simplificada não iterativa, que permite uma estimativa do dano utilizando-se os resultados de uma análise linear. O trabalho é finalizado com a comparação entre resultados de simulações desenvolvidas mediante as estratégias simplificada e não linear completa, comprovando-se que o modelo simplificado pode ser empregado nas situações de dano localizado em pequenas regiões do domínio. / The conventional Finite Element Method (FEM) based on displacement field approximation presents limitations e. g. problems involving regions with singularity and problems of quasi-incompressible elasticity. When the conventional FEM utilization includes the crack growth analysis or damage evolution is made resort of the continuous change of finite element mesh, rendering costly simulations in computational terms. Thus, it is justified the search of methodologies which combine good approximation capacity with low computational cost. In this research the studied formulations are of hybrid-mixed and purely mixed types, both combined with enrichment techniques of solutions offered by the Generalized Finite Element Method (GFEM). The numerical resultant methodology is applied to solid analyses in rupture regime modeled using Damage Mechanics. It is noteworthy that the approximation of stress field, given with these nonconventional formulations, may allow better damage estimative of structure, compared to conventional FEM. This is because the employed damage criteria are almost always based on active stress field estimative. In the numerical analyses it is applied a conventional incremental-iterative strategy and it is proposed a non-iterative simplified strategy which allows damage estimative using the results of a linear analysis. The research is finalized with the comparison between results of developed simulations through the simplified and nonlinear strategies, proving that the simplified model may be employed in situations where the damage is located in small regions in domain.

Le traitement d'images numériques a suivi l'évolution de l'électronique et de l'informatique. Il est maintenant courant de manipuler des images à valeur non pas dans {0,1}, mais dans des variétés ou des distributions de probabilités. C'est le cas par exemple des images couleurs où de l'imagerie du tenseur de diffusion (DTI). Chaque type d'image possède ses propres structures algébriques, topologiques et géométriques. Ainsi, les techniques existantes de traitement d'image doivent être adaptés lorsqu'elles sont appliquées à de nouvelles modalités d'imagerie. Lorsque l'on manipule de nouveaux types d'espaces de valeurs, les précédents opérateurs peuvent rarement être utilisés tel quel. Même si les notions sous-jacentes ont encore un sens, un travail doit être mené afin de les exprimer dans le nouveau contexte. Cette thèse est composée de deux parties indépendantes. La première, « Morphologie mathématiques pour les images non standards », concerne l'extension de la morphologie mathématique à des cas particuliers où l'espace des valeurs de l'image ne possède pas de structure d'ordre canonique. Le chapitre 2 formalise et démontre le problème de l'irrégularité des ordres totaux dans les espaces métriques. Le résultat principal de ce chapitre montre qu'étant donné un ordre total dans un espace vectoriel multidimensionnel, il existe toujours des images à valeur dans cet espace tel que les dilatations et les érosions morphologiques soient irrégulières et incohérentes. Le chapitre 3 est une tentative d'extension de la morphologie mathématique aux images à valeur dans un ensemble de labels non ordonnés.La deuxième partie de la thèse, « Estimation de densités de probabilités dans les espaces de Riemann » concerne l'adaptation des techniques classiques d'estimation de densités non paramétriques à certaines variétés Riemanniennes. Le chapitre 5 est un travail sur les histogrammes d'images couleurs dans le cadre de métriques perceptuelles. L'idée principale de ce chapitre consiste à calculer les histogrammes suivant une approximation euclidienne local de la métrique perceptuelle, et non une approximation globale comme dans les espaces perceptuels standards. Le chapitre 6 est une étude sur l'estimation de densité lorsque les données sont des lois Gaussiennes. Différentes techniques y sont analysées. Le résultat principal est l'expression de noyaux pour la métrique de Wasserstein. / Digital image processing has followed the evolution of electronic and computer science. It is now current to deal with images valued not in {0,1} or in gray-scale, but in manifolds or probability distributions. This is for instance the case for color images or in diffusion tensor imaging (DTI). Each kind of images has its own algebraic, topological and geometric properties. Thus, existing image processing techniques have to be adapted when applied to new imaging modalities. When dealing with new kind of value spaces, former operators can rarely be used as they are. Even if the underlying notion has still a meaning, a work must be carried out in order to express it in the new context.The thesis is composed of two independent parts. The first one, "Mathematical morphology on non-standard images", concerns the extension of mathematical morphology to specific cases where the value space of the image does not have a canonical order structure. Chapter 2 formalizes and demonstrates the irregularity issue of total orders in metric spaces. The main results states that for any total order in a multidimensional vector space, there are images for which the morphological dilations and erosions are irregular and inconsistent. Chapter 3 is an attempt to generalize morphology to images valued in a set of unordered labels.The second part "Probability density estimation on Riemannian spaces" concerns the adaptation of standard density estimation techniques to specific Riemannian manifolds. Chapter 5 is a work on color image histograms under perceptual metrics. The main idea of this chapter consists in computing histograms using local Euclidean approximations of the perceptual metric, and not a global Euclidean approximation as in standard perceptual color spaces. Chapter 6 addresses the problem of non parametric density estimation when data lay in spaces of Gaussian laws. Different techniques are studied, an expression of kernels is provided for the Wasserstein metric.