Introdução: A doença de Machado-Joseph (DMJ) ou ataxia espinocerebelar tipo 3 (SCA3) é causada por uma expansão de trinucleotídeos CAG no gene ATXN3, que leva à degeneração de múltiplos sistemas neurológicos. Seu curso é invariavelmente progressivo, não havendo tratamento específico. Objetivos: Descrever novos biomarcadores, aspectos não motores e definir quais escalas clínicas devem ser utilizadas como desfechos principais nos futuros ensaios clínicos randomizados (ECR) para a DMJ/SCA3. Além de avaliar se o tratamento com carbonato de lítio é seguro e efetivo em reduzir a progressão desta condição. Métodos: Em estudo caso-controle avaliamos: 1) a relação dos sintomas depressivos na DMJ/SCA3, pelo inventário de Beck (BDI), com aspectos de gravidade clínica e molecular; 2) alterações no índice de massa corporal (IMC) e sua correlação com aspectos clínico-moleculares e de neuroimagem; e 3) o Sistema Insulina/ IGF-1 (IIS) e o potencial de seus componentes como biomarcadores. Fizemos uma revisão sistemática sobre os aspectos psicométricos das escalas clínicas de SCAs já descritas, para em seguida iniciarmos um ECR, duplo-cego, paralelo, placebo-controlado de fase 2/3. Para este estudo foram randomizados 62 pacientes com diagnóstico molecular prévio de DMJ/SCA3 com marcha independente e ≤ 10 anos de doença (1:1) para tratamento com carbonato de lítio (0.5-0.8mEq/L) ou placebo. Resultados: Os escores do BDI foram mais elevados na DMJ/SCA3 (p= 0.012) e correlacionaram-se significativamente apenas com as escalas SARA (R=0.359, p=0.01) e NESSCA (R=0.412, p=0.003). Os pacientes com DMJ/SCA3 (N=46) apresentaram IMC menor (24.4 ± 4.1) do que os indivíduos controle (N=42, 27.1± 4.5, p=0.01), havendo correlação inversa (R=−0.396, p=0.015) entre o IMC e o tamanho da sequencia repetitiva CAG (CAGn). Encontramos uma maior sensibilidade periférica à insulina (HOMA2-%S, p=0.003, corrigido pelo IMC) e níveis séricos mais elevados da proteína ligante do IGF-1, IGFBP-1 (p=0.001) na DMJ/SCA3. A IGFBP1 correlacionou-se diretamente à CAGn (R=0.452; p = 0.006) e a sensibilidade à insulina inversamente à idade de início dos sintomas (R=-0.444; P = 0.003). Concluímos, na revisão sistemática, que as escalas semi-quantitativas SARA e NESSCA, e as quantitativas SCAFI e CCFS seriam os melhores desfechos para um ECR. O uso de lítio foi seguro após 24 semanas de tratamento, não havendo diferenças no número total de eventos adversos entre os grupos lítio (50,3%) e placebo (49,7%, p=1.00). O grupo placebo apresentou maior progressão (que não foi significativa) nos escores NESSCA (0.35 pontos, 95% IC -1.0 a 1.7, p=0.222, desfecho primário de efetividade) e SARA (0.96 pontos, 95% IC -0.46 a 2.38, p=0.329), após 48 semanas de tratamento. A gravidade da ataxia de marcha (p=0.008), as provas funcionais quantitativas: PATA rate (p=0.002) e Click Test ND (p=0.023), e os escores compostos SCAFI (p=0.015) e CCFS (p=0.029) apresentaram menor progressão no grupo tratado com lítio durante as 48 semanas. Conclusão: Os resultados destes estudos ajudam no entendimento da depressão e alterações nutricionais da DMJ/SCA3 e apontam a IGFBP-1 como biomarcador e a sensibilidade periférica insulínica como modificador do fenótipo. Houve efetividade do tratamento com carbonato de lítio nos desfechos secundários do ECR, sendo necessária confirmação por ensaios clínicos multicêntricos. / Background: Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is caused by a CAG repeat expansion at ATXN3 gene, leading to progressive degeneration of multiple neurological systems. MJD/SCA3 is an invariably progressive disorder, with no current treatment. Objectives: To describe new disease biomarkers, non-motor aspects and to define the clinical SCA scales to be utilized as main outcomes in future randomized controlled trials (RCT) on MJD/SCA3. And further assess safety and effectiveness of lithium carbonate in reducing the progression of this condition. Methods: We performed a case-control study to evaluate: 1) the relation of MJD/SCA3 depressive symptoms, through Beck depression Inventory (BDI), with other clinical and molecular findings; 2) the Body Mass Index (BMI) of MJD/SCA3 patients and the correlation with other clinical, molecular and neuroimaging findings; and 3) the Insulin/IGF-1 system (IIS) in MJD/SCA3 and the possible biomarker properties of its components. We further performed a systematic review on the psychometric properties of the described SCAs scales in order to initiate the double-blind, parallel, placebo-controlled phase 2/3 clinical trial. 62 independently ambulatory MJD/SCA3 patients with ≤ 10 years of disease duration were randomly assigned in the RCT (1:1) to lithium (0.5-0.8mEq/L) or placebo. Results: BDI scores were higher in MJD/SCA3 patients (p= 0.012), with significant correlations only with the scales SARA (R=0.359, p=0.01) and NESSCA (R=0.412, p=0.003). MJD/SCA3 patients (N=46) presented lower BMI (24.4 ± 4.1) than control individuals (N=42, 27.1± 4.5, p=0.01). BMI correlated inversely with the length of the expanded CAG repeat (CAGn). We found higher peripheral sensitivity to insulin (HOMA2-%S, p=0.003, corrected for BMI) and serum levels of the IGF-1 binding protein, IGFBP-1 (p=0.001) in MJD/SCA3. IGFBP-1 correlated with CAGn (R=0.452; p = 0.006) and insulin sensitivity with the age of disease onset (R=-0.444; P = 0.003). In the systematic review we concluded that the semiquantitative SCA scales SARA and NESSCA and the quantitative instruments SCAFI and CCFS would be the most appropriate outcomes for the RCT. After 24 weeks, there were no differences in the number of adverse events in lithium (50.3%) and placebo (40.7%) groups (p=1.00) in the RCT. The placebo group presented a non-significant faster progression on NESSCA (0.35 points, 95% CI -1.0 to 1.7, p=0.612, primary effectiveness outcome) and SARA (0.96 points, 95% CI -0.46 to 2.38, p=0.186), after 48 weeks of treatment. Gait ataxia severity (p=0.008), the quantitative performance tasks: PATA rate (p=0.002) and Click Test ND (p=0.023), and the composite scores SCAFI (p=0.015) and CCFS (p=0.029) presented a slower progression under lithium therapy in the overall 48 weeks period. Conclusion: These studies added to the understanding of depressive and nutritional manifestations of MJD/SCA3 and points IGFBP-1 as a biomarker and peripheral insulin sensitivity as a disease phenotype modifier. The effectiveness of lithium carbonate treatment shown in secondary outcomes of the RCT opened a perspective for an effective therapy for this untreatable disorder that must be confirmed by large multicentric clinical trials.

Made available in DSpace on 2017-07-10T18:13:12Z (GMT). No. of bitstreams: 1 Aldo Tovo Neto.pdf: 648463 bytes, checksum: b133940cbe853e6bbd59b51fbcfa544e (MD5) Previous issue date: 2013-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of the study was to evaluate ractopamine increasing levels (0, 4, 8, 12 and 16 mg kg-1) as an additive in diet of Nile tilapia (Oreochromis niloticus) in final growout period (750-920 g), during 38 days of feeding. The fishes (400) were distributed in 20 experimental units in a completely randomized design with five treatments and four replications. Were evaluated: the morphometric relations, growth performance, beef cuts yield and chemical composition of fish flesh and organs. The results were submitted to analysis of variance (ANOVA) with multiple comparisons of means (Tukey). Ractopamine is a feed additive with potential for use in diets for Nile tilapia, 8 mg kg-1 did not cause any decrease in performance parameters and demonstrated positive effect in reducing fat content of abdominal muscles to growout period (750-920 g). / O objetivo do estudo foi avaliar a inclusão da ractopamina como aditivo na dieta da tilápia do Nilo (Oreochromis niloticus), no período final de engorda (750 a 920 g), em níveis crescentes de inclusão (0, 4, 8, 12 e 16 mg kg-1) durante 38 dias de alimentação. Foram distribuídos 400 peixes em 20 unidades experimentais, em um delineamento inteiramente casualizado com cinco tratamentos e quatro repetições. Foram avaliados: as relações morfométricas, desempenho zootécnico, rendimento de cortes e composição química da carne e órgãos dos peixes. Os resultados obtidos foram submetidos à análise de variância (ANOVA) com teste de comparação múltipla de médias (Tukey). A ractopamina é um aditivo com potencial para a utilização em rações para a tilápia do Nilo, e o nível 8 mg kg-1 não causou nenhum decréscimo nos parâmetros de desempenho e demonstrou efeito positivo na redução do teor de gordura da musculatura abdominal no período final de engorda (750 a 920 g).

Den här är en korpusbaserad studie över sammansättningar med efterledet -bubbla under 2000–2014. Följande ord har studerats ingående: bostadsbubbla, lånebubbla, finansbubbla, aktiebubbla, småbolagsbubbla, husbubbla, lönebubbla och hyresbubbla. Studien har funnit att sammansättningarna är etablerade, att metaforiken bubbla är konventionaliserad att sammansättningarna används i en ekonomisk diskurs och mer allmänt. Studien för även en vidare diskussion kring nyord och metaforik och föreslår en offentlig konversation med ekonomijournalister och språkforskare. / This is a corpus-based study of compound words with the modifier -bubble in texts from 2000 to 2014. The following compound words were studied closely: housing bubble, credit bubble, the financial bubble, the stock bubble, small cap bubble, real estate bubble, salary bubble and the rental bubble. Results indicate that these compound words are established, that the metaphor bubble is conventionalized, and that the compound words are used both in economic discourse and more generally. Further, new words and metaphors are discussed. A public conversation with financial journalists and linguists is suggested.

Mesoscopic spin systems can be designed and fabricated using modern nano-fabrication techniques. These systems can contain large numbers of patterned ferromagnetic elements, for which the shape will generally determine their effective mesospin dimensionality. The lateral arrangement of these mesospins can be further used to tune the interactions between them. With an appropriate choice of material, it is possible to define a temperature range where thermal fluctuations of these mesospins are experimentally accessible. To actively define this range, we use δ-doped Palladium, a three-layer system of Palladium—Iron—Palladium, for which the Curie-temperature scales with the Iron layer thickness. The patterned mesoscopic elements used in this work have a stadium-like shape that promotes a single magnetic domain state, thus making these islands behave as one-dimensional Ising-like mesospins that can be observed using magnetic imaging techniques. We investigate the impact on the magnetic order resulting from modifications of the square spin ice geometry. By adding, removing and merging elements in the square artificial spin ice architecture, energy-landscape variations can be realized. Firstly, an added interaction modifier is used to equilibrate the interactions between the mesospins at the vertex level, which can restore the degenerate ground state of the square spin ice model. Secondly, the removal of elements can lead to topologically frustrated spin systems, as not all building blocks can simultaneously be in their lowest energy state. Furthermore, the merging results in multiple element sizes in the mesospin system. As the magnetization reversal barrier is dependent on the element size, these mesospin systems have different energy barriers. The thermal ordering process in such a system differs from a single-size element system with its unique energy barrier. Using reciprocal space analysis tools like the magnetic spin structure factor we show that systems with multiple element sizes achieve a higher short-range order then their single-size element references. The magnetic order in mesoscopic spin systems could successfully be tailored by modifications of the lattice geometry.

The thesis deals with composite systems, with a focus on matrix resistant to extreme conditions. The aim of this work was to research and development matrix, resistant to high temperatures, typical in case of fire. Used theoretical knowledge were realized with subsequent laboratory research. Attention was paid matrices based binder mixed with any alkali activation of alternative raw materials and geopolymers. Scattered reinforcement featured polypropylene fibers. The subject of the practical part of the two alternatives, including a matrix based on basic ingredients - cement, alternative raw materials - high fly ash, blast furnace slag, geopolymer and polymeric components incl. combinations thereof. Laboratory research conducted by determining the fundamental material properties such as density, strengths, etc., after heat exposure. The developed materials were subjected to a temperature 1400 ° C. The conclusion was selected several recipes that were based on the resulting values found to be optimal.

This work describes important periods of making application on editing 3D scene. It concerns a program which makes possible visualization of objects and simulation graphic scene. The introduction of this document is dedicated to theorical analysis, which is oriented on objects presentation in computer graphic with detailed orientation on Boundary Representation. The following chapter is about transformations and manipulators. Design part introduces basic problems and apprises with exercise solutions on general level. In the part of the implementation, we find detailed description of actual solution for particular phase of proposal. It states description of advanced camera system and transformation of objects by the help of graphic manipulators. The next chapter discuss implement effects, modifications and solution for graphical user interface.

Contexte : Un accès adéquat aux aliments sains dans les environnements résidentiels peut contribuer aux saines habitudes alimentaires. Un tel accès est d’autant plus important pour les personnes âgées, où les changements associés au vieillissement peuvent accentuer leur dépendance aux ressources disponibles dans le voisinage. Cependant, cette relation n’a pas encore été établie chez les aînés. Objectifs : La présente thèse vise à quantifier les associations entre l’environnement alimentaire local et les habitudes alimentaires de personnes âgées vivant à domicile en milieu urbain. La thèse s’est insérée dans un projet plus large qui a apparié les données provenant d’une cohorte d’aînés québécois vivant dans la région métropolitaine montréalaise avec des données provenant d’un système d’information géographique. Trois études répondent aux objectifs spécifiques suivants : (1) développer des indices relatifs de mixité alimentaire pour qualifier l’offre d’aliments sains dans les magasins d’alimentation et l’offre de restaurants situés dans les quartiers faisant partie du territoire à l’étude et en examiner la validité; (2) quantifier les associations entre la disponibilité relative de magasins d’alimentation et de restaurants près du domicile et les habitudes alimentaires des aînés; (3) examiner l’influence des connaissances subjectives en nutrition dans la relation entre l’environnement alimentaire près du domicile et les habitudes alimentaires chez les hommes et les femmes âgés. Méthodes : Le devis consiste en une analyse secondaire de données transversales provenant de trois sources : les données du cycle 1 pour 848 participants de l’Étude longitudinale québécoise « La nutrition comme déterminant d’un vieillissement réussi » (2003-2008), le Recensement de 2001 de Statistique Canada et un registre privé de commerces et services (2005), ces derniers regroupés dans un système d’information géographique nommé Mégaphone. Des analyses bivariées non paramétriques ont été appliquées pour répondre à l’objectif 1. Les associations entre l’exposition aux commerces alimentaires dans le voisinage et les habitudes alimentaires (objectif 2), ainsi que l’influence des connaissances subjectives en nutrition dans cette relation (objectif 3), ont été vérifiées au moyen d’analyses de régression linéaires. Résultats : Les analyses ont révélé trois résultats importants. Premièrement, l’utilisation d’indices relatifs pour caractériser l’offre alimentaire s’avère pertinente pour l’étude des habitudes alimentaires, plus particulièrement pour l’offre de restaurants-minute. Deuxièmement, l’omniprésence d’aspects défavorables dans l’environnement, caractérisé par une offre relativement plus élevée de restaurants-minute, semble nuire davantage aux saines habitudes alimentaires que la présence d’opportunités d’achats d’aliments sains dans les magasins d’alimentation. Troisièmement, un environnement alimentaire plus favorable aux saines habitudes pourrait réduire les écarts quant à la qualité de l’alimentation chez les femmes ayant de plus faibles connaissances subjectives en nutrition par rapport aux femmes mieux informées. Conclusion : Ces résultats mettent en relief la complexité des liens entre l’environnement local et l’alimentation. Dans l’éventualité où ces résultats seraient reproduits dans des recherches futures, des stratégies populationnelles visant à résoudre un déséquilibre entre l’accès aux sources d’aliments sains par rapport aux aliments peu nutritifs semblent prometteuses. / Context: Adequate access to healthful foods in residential environments may contribute to healthful dietary practices. Such access is important for older adults where changes associated with aging may accentuate their dependence on resources available in their residential neighborhood. However, this relationship has not been established for seniors. Objectives: This thesis aims to quantify associations between the local food environment and dietary patterns of independent urban-dwelling older adults. The thesis is part of a larger project involving the linkage of data from a cohort of Québec seniors living in the Montréal metropolitan area and data from a geographic information system. Three studies addressed the following specific objectives: (1) to develop relative indices of local-area food sources outlets to qualify stores potentially selling healthful foods and supply of restaurants in neighborhoods that were part of the study area, (2) to quantify associations between the relative availability of food stores and restaurants in residential area and dietary patterns of members of the cohort, (3) to examine the influence of subjective nutrition knowledge in the relationship between the residential food environment and dietary patterns among older men and women. Methods: Cross-sectional analysis of data from three different sources was performed: (1) person-level data on 848 participants from cycle 1 of the Québec Longitudinal Study on Nutrition and Successful Aging , (2) 2001 Census data from Statistics Canada and (3) data from private businesses and services registry (2005), these two gathered in a geographic information system called Megaphone. Nonparametric bivariate analyses were applied to address objective 1. Associations between exposure to residential-area food sources and dietary patterns (objective 2), as well as moderating effect of nutrition knowledge (objective 3), were tested using linear regression analyses. Results: Analyses revealed three important results. First, the use of relative indices to characterize availability of local-area food sources is relevant to the study of dietary patterns, particularly regarding the supply of fast food restaurants. Second, the ubiquity of unfavorable aspects in the food environment, characterized by relatively higher fast food restaurants offer seem more detrimental to healthful eating habits that the presence of opportunities to buy healthful foods in food stores. Third, a residential food environment more favorable to healthful dietary patterns could reduce disparities in diet quality between women with low nutrition knowledge compared to women more knowledgeable. Conclusion: These results highlight the complex links between local environment and diet. If findings can be replicated in future research, population-based strategies to address an imbalance between accessibility to healthful food sources relative to unhealthful food sources, would be promising.

No description available.

Contexte : Un accès adéquat aux aliments sains dans les environnements résidentiels peut contribuer aux saines habitudes alimentaires. Un tel accès est d’autant plus important pour les personnes âgées, où les changements associés au vieillissement peuvent accentuer leur dépendance aux ressources disponibles dans le voisinage. Cependant, cette relation n’a pas encore été établie chez les aînés. Objectifs : La présente thèse vise à quantifier les associations entre l’environnement alimentaire local et les habitudes alimentaires de personnes âgées vivant à domicile en milieu urbain. La thèse s’est insérée dans un projet plus large qui a apparié les données provenant d’une cohorte d’aînés québécois vivant dans la région métropolitaine montréalaise avec des données provenant d’un système d’information géographique. Trois études répondent aux objectifs spécifiques suivants : (1) développer des indices relatifs de mixité alimentaire pour qualifier l’offre d’aliments sains dans les magasins d’alimentation et l’offre de restaurants situés dans les quartiers faisant partie du territoire à l’étude et en examiner la validité; (2) quantifier les associations entre la disponibilité relative de magasins d’alimentation et de restaurants près du domicile et les habitudes alimentaires des aînés; (3) examiner l’influence des connaissances subjectives en nutrition dans la relation entre l’environnement alimentaire près du domicile et les habitudes alimentaires chez les hommes et les femmes âgés. Méthodes : Le devis consiste en une analyse secondaire de données transversales provenant de trois sources : les données du cycle 1 pour 848 participants de l’Étude longitudinale québécoise « La nutrition comme déterminant d’un vieillissement réussi » (2003-2008), le Recensement de 2001 de Statistique Canada et un registre privé de commerces et services (2005), ces derniers regroupés dans un système d’information géographique nommé Mégaphone. Des analyses bivariées non paramétriques ont été appliquées pour répondre à l’objectif 1. Les associations entre l’exposition aux commerces alimentaires dans le voisinage et les habitudes alimentaires (objectif 2), ainsi que l’influence des connaissances subjectives en nutrition dans cette relation (objectif 3), ont été vérifiées au moyen d’analyses de régression linéaires. Résultats : Les analyses ont révélé trois résultats importants. Premièrement, l’utilisation d’indices relatifs pour caractériser l’offre alimentaire s’avère pertinente pour l’étude des habitudes alimentaires, plus particulièrement pour l’offre de restaurants-minute. Deuxièmement, l’omniprésence d’aspects défavorables dans l’environnement, caractérisé par une offre relativement plus élevée de restaurants-minute, semble nuire davantage aux saines habitudes alimentaires que la présence d’opportunités d’achats d’aliments sains dans les magasins d’alimentation. Troisièmement, un environnement alimentaire plus favorable aux saines habitudes pourrait réduire les écarts quant à la qualité de l’alimentation chez les femmes ayant de plus faibles connaissances subjectives en nutrition par rapport aux femmes mieux informées. Conclusion : Ces résultats mettent en relief la complexité des liens entre l’environnement local et l’alimentation. Dans l’éventualité où ces résultats seraient reproduits dans des recherches futures, des stratégies populationnelles visant à résoudre un déséquilibre entre l’accès aux sources d’aliments sains par rapport aux aliments peu nutritifs semblent prometteuses. / Context: Adequate access to healthful foods in residential environments may contribute to healthful dietary practices. Such access is important for older adults where changes associated with aging may accentuate their dependence on resources available in their residential neighborhood. However, this relationship has not been established for seniors. Objectives: This thesis aims to quantify associations between the local food environment and dietary patterns of independent urban-dwelling older adults. The thesis is part of a larger project involving the linkage of data from a cohort of Québec seniors living in the Montréal metropolitan area and data from a geographic information system. Three studies addressed the following specific objectives: (1) to develop relative indices of local-area food sources outlets to qualify stores potentially selling healthful foods and supply of restaurants in neighborhoods that were part of the study area, (2) to quantify associations between the relative availability of food stores and restaurants in residential area and dietary patterns of members of the cohort, (3) to examine the influence of subjective nutrition knowledge in the relationship between the residential food environment and dietary patterns among older men and women. Methods: Cross-sectional analysis of data from three different sources was performed: (1) person-level data on 848 participants from cycle 1 of the Québec Longitudinal Study on Nutrition and Successful Aging , (2) 2001 Census data from Statistics Canada and (3) data from private businesses and services registry (2005), these two gathered in a geographic information system called Megaphone. Nonparametric bivariate analyses were applied to address objective 1. Associations between exposure to residential-area food sources and dietary patterns (objective 2), as well as moderating effect of nutrition knowledge (objective 3), were tested using linear regression analyses. Results: Analyses revealed three important results. First, the use of relative indices to characterize availability of local-area food sources is relevant to the study of dietary patterns, particularly regarding the supply of fast food restaurants. Second, the ubiquity of unfavorable aspects in the food environment, characterized by relatively higher fast food restaurants offer seem more detrimental to healthful eating habits that the presence of opportunities to buy healthful foods in food stores. Third, a residential food environment more favorable to healthful dietary patterns could reduce disparities in diet quality between women with low nutrition knowledge compared to women more knowledgeable. Conclusion: These results highlight the complex links between local environment and diet. If findings can be replicated in future research, population-based strategies to address an imbalance between accessibility to healthful food sources relative to unhealthful food sources, would be promising.

The diploma thesis is focused on fire-resistant repair mortar with fine-grained filler. The aim of this work is the research and development of fine-grained Mortars resistant to high temperatures, which are characteristic at the beginning of the fire. The theoretical knowledge with subsequently realized laboratory verification was used. At-tention was paid to the masses based on the mixed binder comprising cement and blast furnace slag, respectively. high-temperature ash. Cellulose fibres were used as the dis-persed reinforcement. Two kinds of aggregate were assessed - fly ash agloporit and am-phibolite incl. combinations thereof. Laboratory tests were carried out via determination of basic material properties (density, strength, consistency, dimensional changes etc.) after exposure to extreme temperatures. A substantial part of the research was also study of different cooling conditions - slow and fast (water and air). Selected formulations were subjected to temperatures up to 1200 ° C. In the conclusion is selected several recipes that have been found to be optimal for continuing research on the basis of the results and findings.