Nonparametric Evaluation of Quantitative Traits in Population-Based Association Studies when the Genetic Model is Unknown

Statistical association between a single nucleotide polymorphism (SNP) genotype and a quantitative trait in genome-wide association studies is usually assessed using a linear regression model, or, in the case of non-normally distributed trait values, using the Kruskal-Wallis test. While linear regression models assume an additive mode of inheritance via equi-distant genotype scores, Kruskal-Wallis test merely tests global differences in trait values associated with the three genotype groups. Both approaches thus exhibit suboptimal power when the underlying inheritance mode is dominant or recessive. Furthermore, these tests do not perform well in the common situations when only a few trait values are available in a rare genotype category (disbalance), or when the values associated with the three genotype categories exhibit unequal variance (variance heterogeneity). We propose a maximum test based on Marcus-type multiple contrast test for relative effect sizes. This test allows model-specific testing of either dominant, additive or recessive mode of inheritance, and it is robust against variance heterogeneity. We show how to obtain mode-specific simultaneous confidence intervals for the relative effect sizes to aid in interpreting the biological relevance of the results. Further, we discuss the use of a related all-pairwise comparisons contrast test with range preserving confidence intervals as an alternative to Kruskal-Wallis heterogeneity test. We applied the proposed maximum test to the Bogalusa Heart Study dataset, and gained a remarkable increase in the power to detect association, particularly for rare genotypes. Our simulation study also demonstrated that the proposed non-parametric tests control family-wise error rate in the presence of non-normality and variance heterogeneity contrary to the standard parametric approaches. We provide a publicly available R library nparcomp that can be used to estimate simultaneous confidence intervals or compatible multiplicity-adjusted p-values associated with the proposed maximum test.

Essays in asset price bubbles

This thesis studies the field of asset price bubbles. It is comprised of three independent chapters. Each of these chapters either directly or indirectly analyse the existence or implications of asset price bubbles. The type of bubbles assumed in each of these chapters is consistent with rational expectations. Thus, the kind of price bubbles investigated here are known as rational bubbles in the literature. The following describes the three chapters. Chapter 1: This chapter attempts to explain the recent US housing price bubble by developing a heterogeneous agent endowment economy asset pricing model with risky housing, endogenous collateral and defaults. Investment in housing is subject to an idiosyncratic risk and some mortgages are defaulted in equilibrium. We analytically derive the leverage or the endogenous loan to value ratio. This variable comes from a limited participation constraint in a one period mortgage contract with monitoring costs. Our results show that low values of housing investment risk produces a credit easing effect encouraging excess leverage and generates credit driven rational price bubbles in the housing good. Conversely, high values of housing investment risk produces a credit crunch characterized by tight borrowing constraints, low leverage and low house prices. Furthermore, the leverage ratio was found to be procyclical and the rate of defaults countercyclical consistent with empirical evidence. Chapter 2: It is widely believed that financial assets have considerable persistence and are susceptible to bubbles. However, identification of this persistence and potential bubbles is not straightforward. This chapter tests for price bubbles in the United States housing market accounting for long memory and structural breaks. The intuition is that the presence of long memory negates price bubbles while the presence of breaks could artificially induce bubble behaviour. Hence, we use procedures namely semi-parametric Whittle and parametric ARFIMA procedures that are consistent for a variety of residual biases to estimate the value of the long memory parameter, d, of the log rent-price ratio. We find that the semi-parametric estimation procedures robust to non-normality and heteroskedasticity errors found far more bubble regions than parametric ones. A structural break was identified in the mean and trend of all the series which when accounted for removed bubble behaviour in a number of regions. Importantly, the United States housing market showed evidence for rational bubbles at both the aggregate and regional levels. In the third and final chapter, we attempt to answer the following question: To what extend should individuals participate in the stock market and hold risky assets over their lifecycle? We answer this question by employing a lifecycle consumption-portfolio choice model with housing, labour income and time varying predictable returns where the agents are constrained in the level of their borrowing. We first analytically characterize and then numerically solve for the optimal asset allocation on the risky asset comparing the return predictability case with that of IID returns. We successfully resolve the puzzles and find equity holding and participation rates close to the data. We also find that return predictability substantially alter both the level of risky portfolio allocation and the rate of stock market participation. High factor (dividend-price ratio) realization and high persistence of factor process indicative of stock market bubbles raise the amount of wealth invested in risky assets and the level of stock market participation, respectively. Conversely, rare disasters were found to bring down these rates, the change being severe for investors in the later years of the life-cycle. Furthermore, investors following time varying returns (return predictability) hedged background risks significantly better than the IID ones.

Desacoplamento mitocondrial e estresse oxidativo em espermatozoides suínos resfriados

A espécie suína (Sus scropha domesticus) possui relevância nos âmbitos da pesquisa, da xenotransplantação e da produção de carnes. O resfriamento de sêmen é capaz de reduzir o metabolismo celular e possibilitar o armazenamento dos gametas, sendo auxiliar durante práticas de reprodução assistida. Contudo, os espermatozoides suínos são sensíveis ao estresse oxidativo gerado durante o processo de resfriamento. O 2,4 dinitrofenol (DNP) poderia gerar o desacoplamento mitocondrial reduzindo o estresse oxidativo e prolongando indiretamente a viabilidade e capacidade fertilizante de espermatozoides suínos resfriados pela diminuição de espécies reativas de oxigênio. O objetivo do presente estudo foi avaliar os efeitos do desacoplamento mitocondrial induzido pelo DNP e os efeitos desse desacoplamento sobre as de fluidez e integridade de membrana plasmática, funcionalidade de mitocôndria, motilidade espermática, além dos parâmetros de estresse oxidativo de lipoperoxidação e produção de espécies reativas de oxigênio, durante o resfriamento a 17 °C de 24 até 96 horas. Utilizou-se 22 ejaculados expostos ao diluente Betsville Thawing Solution (BTS) (controle) e ao mesmo diluente acrescido das concentrações de 0,01 µM (T1); 0,1 µM (T2); 1,0 µM (T3) e 10 µM (T4) de DNP. Através do teste de Shapiro-Wilk as variáveis que não apresentaram normalidade, tiveram suas médias comparadas pelo teste de KruskalWallis. As análises estatísticas demonstraram que o DNP não se diferiu do controle independente do tempo de armazenamento, para nenhuma das variáveis analisadas. Possivelmente, a falta de ação sobre as mitocôndrias, ou seja, a não promoção do desacoplamento mitocondrial foi o motivo principal para a falta dos efeitos do DNP. Acredita-se que a utilização do DNP em temperaturas mais elevadas por estas promoverem aumento da fluidez de membrana e/ou o aumento das concentrações de DNP poderiam gerar efeitos significativos sobre as mitocôndrias e demais variáveis analisadas. Finalmente, o DNP nas concentrações testadas não se diferiu do controle em todas as variáveis analisadas independente do tempo de armazenamento.

Avaliação das concentrações hepáticas e séricas de retinol em bovinos e do consumo habitual de fígado por gestantes

The vitamin A is essential to animals because of its participation in a great number of biological functions. The investigation of this vitamin s concentrations is important to serve as reference to normality parameters. This study had as aim to analyse the serics and hepatics concentrations of vitamin A in two groups of bovines and to compare the hepatics concentrations to the present requeriments of vitamin A for pregnant women. It was also appraised the consume habit of bovine liver by pregnant women through of the alimentary frequency quest. Two groups of bovine were studied and the first was formad by Nelore bovine breed and the second by bovine without defined breed (WDB). It was analysed 120 samples: 60 of liver and 60 of serum. The method used to dose retinol was High Performance Liquid Cromatography (HPLC). The average (+ sd) of retinol concentrations in Nelore breed bovine and WDB liver were 16947,8 + 6866,9 and 5213,1 + 2517,2 µg of retinol/100g and at serum 39,6 + 17,9 e 28,6 + 9,4 µg of retinol/dL, respectively. No statistically significant correlation was found between hepatic and the serum retinol. The bovines in this study had adequate vitamin A levels. Independently of animal breed, the daily ingestion of bovine liver is not advised for pregnant women who show adequate support of vitamin A. The consume of bovine liver by pregnant women consulted on school maternity hospital Januário Cicco, UFRN, Natal RN, was considered high

Le pilocentrisme de la France d’Ancien Régime : évolution des représentations de la pilosité de François 1er à Louis XVI

Thèse réalisée en cotutelle avec la direction de Jean-Jacques Courtine à l'Université de Paris III Sorbonne Nouvelle sous la discipline anthropologie et avec la direction de Dominique Deslandres à l'Université de Montréal sous la discipline histoire

Change-point detection in environmental time series based on the informational approach

In this study, the Schwarz Information Criterion (SIC) is applied in order to detect change-points in the time series of surface water quality variables. The application of change-point analysis allowed detecting change-points in both the mean and the variance in series under study. Time variations in environmental data are complex and they can hinder the identification of the so-called change-points when traditional models are applied to this type of problems. The assumptions of normality and uncorrelation are not present in some time series, and so, a simulation study is carried out in order to evaluate the methodology’s performance when applied to non-normal data and/or with time correlation.

Avaliação do efeito da megadose de vitamina A no colostro humano

The mothers supplementation of vitamin A in the postpartum comes being a measure of intervention sufficiently used in the combat to the vitamin deficiency. The objective of this work was to evaluate the effect of the mother megadose of vitamin A under the levels of retinol in colostrum of postpartum mothers receiving care at the Januário Cicco Maternity School (MEJC), Natal, RN, as well as analyzing the influence of the maternal nutritional status in the reply to this supplementation. The study it was transversal type, with participation of 91 women in labor divided in group had participated of the study have controlled (44 women) and supplemented group (47 women). In the period of the morning blood and milk had been collected (milk 0h). After that a capsule of retinil palmitate of (200 000 UI or 60 mg) was supplied to the supplemented group. Another aliquot of colostro was after gotten 24h of the first collection (milk 24h). Retinol in milk and serum was quantified through the High Pressure Liquid Chromatography. The vitamin ingestion was evaluated by the questionnaire of frequency of alimentary consumption. The levels of serum retinol were 40.6 ± 10.6 and 35.9 ± 10.9 µg/dL in the groups controlled and supplemented, respectively. The women had presented a satisfactory average ingestion of vitamin (1492,4 µgRAE/dia), however with high prevalence of inadequate consumption (23%). Average values of retinol in milk 0h had been found and 24h of 93.5 ± 50.3 µg/dL and 99.1 ± 49.3 µg/dL has the group controlled group, respectively (p>0.05). After the supplementation had a significant increase in the levels of retinol of the supplemented group, being found values of 102.0 ± 56.0 µg/dL and 196.1 ± 74.0 µg/dL for milk 0h and 24h, respectively (p<0.0001). The women in labor presented different answers to the supplementation influenced for the basal levels of retinol in colostrum. It was possible to verify that women with deficient levels of retinol in milk had transferred more retinol to milk 24h than ones with adjusted levels, showing a percentage of reply equivalent to 326.1% and 86.5% of increase, respectively (p< 0.0001). Although the apparent normality found in the serum, the studied women are considered of risk to the development of the vitamin deficiency, and megadose was efficient in first 24h after the supplementation and wakes up with the mechanisms considered for transference of vitamin A to the milk

Méthodes de Bootstrap pour les modèles à facteurs

Cette thèse développe des méthodes bootstrap pour les modèles à facteurs qui sont couram- ment utilisés pour générer des prévisions depuis l'article pionnier de Stock et Watson (2002) sur les indices de diffusion. Ces modèles tolèrent l'inclusion d'un grand nombre de variables macroéconomiques et financières comme prédicteurs, une caractéristique utile pour inclure di- verses informations disponibles aux agents économiques. Ma thèse propose donc des outils éco- nométriques qui améliorent l'inférence dans les modèles à facteurs utilisant des facteurs latents extraits d'un large panel de prédicteurs observés. Il est subdivisé en trois chapitres complémen- taires dont les deux premiers en collaboration avec Sílvia Gonçalves et Benoit Perron. Dans le premier article, nous étudions comment les méthodes bootstrap peuvent être utilisées pour faire de l'inférence dans les modèles de prévision pour un horizon de h périodes dans le futur. Pour ce faire, il examine l'inférence bootstrap dans un contexte de régression augmentée de facteurs où les erreurs pourraient être autocorrélées. Il généralise les résultats de Gonçalves et Perron (2014) et propose puis justifie deux approches basées sur les résidus : le block wild bootstrap et le dependent wild bootstrap. Nos simulations montrent une amélioration des taux de couverture des intervalles de confiance des coefficients estimés en utilisant ces approches comparativement à la théorie asymptotique et au wild bootstrap en présence de corrélation sérielle dans les erreurs de régression. Le deuxième chapitre propose des méthodes bootstrap pour la construction des intervalles de prévision permettant de relâcher l'hypothèse de normalité des innovations. Nous y propo- sons des intervalles de prédiction bootstrap pour une observation h périodes dans le futur et sa moyenne conditionnelle. Nous supposons que ces prévisions sont faites en utilisant un ensemble de facteurs extraits d'un large panel de variables. Parce que nous traitons ces facteurs comme latents, nos prévisions dépendent à la fois des facteurs estimés et les coefficients de régres- sion estimés. Sous des conditions de régularité, Bai et Ng (2006) ont proposé la construction d'intervalles asymptotiques sous l'hypothèse de Gaussianité des innovations. Le bootstrap nous permet de relâcher cette hypothèse et de construire des intervalles de prédiction valides sous des hypothèses plus générales. En outre, même en supposant la Gaussianité, le bootstrap conduit à des intervalles plus précis dans les cas où la dimension transversale est relativement faible car il prend en considération le biais de l'estimateur des moindres carrés ordinaires comme le montre une étude récente de Gonçalves et Perron (2014). Dans le troisième chapitre, nous suggérons des procédures de sélection convergentes pour les regressions augmentées de facteurs en échantillons finis. Nous démontrons premièrement que la méthode de validation croisée usuelle est non-convergente mais que sa généralisation, la validation croisée «leave-d-out» sélectionne le plus petit ensemble de facteurs estimés pour l'espace généré par les vraies facteurs. Le deuxième critère dont nous montrons également la validité généralise l'approximation bootstrap de Shao (1996) pour les regressions augmentées de facteurs. Les simulations montrent une amélioration de la probabilité de sélectionner par- cimonieusement les facteurs estimés comparativement aux méthodes de sélection disponibles. L'application empirique revisite la relation entre les facteurs macroéconomiques et financiers, et l'excès de rendement sur le marché boursier américain. Parmi les facteurs estimés à partir d'un large panel de données macroéconomiques et financières des États Unis, les facteurs fortement correlés aux écarts de taux d'intérêt et les facteurs de Fama-French ont un bon pouvoir prédictif pour les excès de rendement.

Estudio in vitro de la resistencia adhesiva en la interfaz de resina entre la base del pad y el resinoso utilizado en cementación indirecta de la técnica lingual

Con el fin de aminorar retrasos por descementación de cualquier accesorio durante el tratamiento de Ortodoncia Lingual, se ha considerado que la fuerza de adhesión es muy importante, especialmente cuando está ubicada en las diferentes interfaces presentes entre el bracket y la resina del PAD; entre la resina del PAD y el cemento resinoso fotopolimerizable y entre este cemento y el esmalte dental. Por lo que este estudio se ha enfocado en determinar la resistencia adhesiva en la interfaz localizada entre la resina de la base del PAD y el cemento resinoso fotopolimerizable utilizando ácido fluorhídrico y óxido de aluminio como tratamiento de superficie previo a la cementación indirecta de la técnica lingual. MATERIALES Y METODOS: El tipo de estudio fue experimental "in vitro", con una muestra de 30 cuerpos de prueba hechos con resina Transbond XT, utilizando para su confección un blíster de brackets, se siguieron tres protocolos diferentes; G1 o grupo control sin ninguna preparación, G2 con aplicación de óxido de aluminio, 50 micrones durante 10 segundos en la superficie del cuerpo de prueba, G3 con aplicación de ácido fluorhídrico al 9% en la superficie del cuerpo de prueba durante 10 minutos. Previo al test de resistencia adhesiva, se realizó los cortes de precisión en cada cuerpo de prueba, obteniendo así 45 tiras de prueba, cada una de las muestras fue adherida a un porta muestra para la prueba de micro tracción, la misma que fue realizada con la máquina universal Mini-Instron modelo 5942, a una velocidad de deformación constante de 0.5 mm/min. Los datos fueron sometidos al test de Normalidad de residuos de Shapiro Wilk (p>0,05) y de LEVENE para el análisis de homogeneidad de las varianzas. La resistencia adhesiva fue comparada entre los grupos por medio del Análisis de Varianza (ANOVA) como factor único para el procesamiento de los datos. Para todos los análisis el nivel de significancia fue del 5% (p< 0,05) con un nivel de confianza del 95% (IC95%). Se consideró estadísticamente significativo valores por debajo de 0,05. RESULTADOS Y CONCLUSIONES: El resultado del test de ANOVA, reveló que el factor de tratamiento de superficie F(2,12)=2,52;p=0,12 no es significante, por lo tanto los diferentes tratamientos de superficie (óxido de aluminio y ácido fluorhídrico) utilizados son equivalentes al grupo control, indicando que no ejercen influencia de manera significativa en los valores de Resistencia Adhesiva (RA) en la preparación de la interfaz localizada entre la resina de la base del PAD y el cemento resinoso fotopolimerizable; concluyendo que se puede utilizar cualquier protocolo de tratamiento de superficie indicado en la presente investigación.

Efeitos do treinamento resistido com máquinas pneumáticas e resistência elástica progressiva na força, capacidade funcional e equilíbrio em mulheres idosas : um ensaio clínico randomizado

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Educação Física, Programa de Pós-Graduação Strictu-Sensu em Educação Física, 2015.

Abdominal hyperalgesia in secretory phospholipase A(2)-induced rat pancreatitis: Distinct roles of NK1 receptors

We investigated the potential of secretory phospholipase A(2) (sPLA(2))-induced pancreatitis to promote abdominal hyperalgesia, as well as to depolarize sensory fibres in vitro using a grease-gap technique. Pancreatitis was induced by the injection of sPLA(2) from Crotalus durissus terrificus (sPLA(2) Cdt, 300 mu g kg(-1)) venom into the common bile duct of rats. Pancreatic inflammatory signs, serum amylase levels and abdominal hyperalgesia were evaluated in rats treated or not with SR140333, a tachykinin NK1 receptor antagonist. Injection of sPLA(2) Cdt caused pancreatic oedema formation and increased pancreatic neutrophil infiltration and serum amylase at 4 h, which returned to normality by 24 h, except for the neutrophil infiltration, which was still increased at this time point. Animals injected with sPLA(2) exhibited a lower withdrawal threshold to electronic von Frey stimulation in the upper abdominal region at 4 h, but not 24 h, post-injection when compared with saline-injected rats. Pre-treatment of animals with SR140333 significantly reduced the sPLA(2) Cdt-induced abdominal hyperalgesia, without affecting the other parameters. Neither sPLA(2) Cdt nor sPLA(2) from Naja mocambique mocambique venom depolarized capsaicin-sensitive sensory fibres from rat vagus nerve, but they decreased the propagated compound action potentials in both A and C fibres. These data show for the first time that NK1 receptors play an important role in the early abdominal hyperalgesia in a rat model of sPLA(2)-induced pancreatitis, suggesting that these receptors are of importance in the development of pain in the pancreatitis condition. We also provide evidence that sPLA(2)s do not directly depolarize sensory fibres in vitro. (C) 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Bahadur representation of linear kernel quantile estimator of VaR under mixing assumptions

Bahadur representation and its applications have attracted a large number of publications and presentations on a wide variety of problems. Mixing dependency is weak enough to describe the dependent structure of random variables, including observations in time series and longitudinal studies. This note proves the Bahadur representation of sample quantiles for strongly mixing random variables (including ½-mixing and Á-mixing) under very weak mixing coe±cients. As application, the asymptotic normality is derived. These results greatly improves those recently reported in literature.

Body composition by dual X-ray absorptiometry in Mexican schoolchildren with or without obesity

Objective: Apply dual X-ray absorptiometry (DXA) to determine the amount of fat mass, lean mass, and bone mineral density in Mexican schoolchildren with and without obesity. Material and methods: We performed an observational, analytical, comparative, cross-sectional study of 80 Mexican schoolchildren who attended the Nutrition Clinic of the Pediatric Medical Center in Monterrey, Mexico during the period of January to April 2005. Body mass index (BMI) was determined to classify the participants according to the growth charts of the Centers for Disease Control and Prevention. Two groups of 40 children each (with and without obesity) were formed and DXA was carried out on each individual. Cronbach’s Alpha was used to determine instrument reliability and the Kolmogorov-Smirnov test was used to test the normality of numerical variables. Means were compared using Student´s t test. Results: Statistically signiicant differences were found in fat mass (p≤0.001) and lean mass (p≤0.001), but not in bone mineral content (p=0.051) between both groups. Conclusions: Differences exist in fat mass and lean mass in both groups, but not in bone mineral content between both groups. A signiicant positive correlation was found between fat mass, determined by DXA, and BMI in schoolchildren with and without obesity

The medico-legal importance of establishing human identity by palatal rugoscopy: evaluation of the immutability and individuality of palatal rugae under the influence of ante mortem orthodontic treatment

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

As forças armadas e a segurança interna

A Constituição da República Portuguesa desde 1982, e após sete revisões constitucionais, faz a distinção vincada entre o que é Segurança Interna e Defesa Nacional. Assim, reserva para a primeira a intervenção das Forças da Segurança e para a segunda a as Forças Armadas, permitindo apenas a intervenção destas na Segurança Interna em estados de excepção, como o estado de emergência e o estado de sítio. Dada a delicadeza do tema optou-se pela construção de um questionário, para que as pessoas possam pronunciar-se de forma isenta sobre o tema, sem constrangimentos institucionais. Optou-se por uma abordagem qualitativa. Com base num guião, entrevistaram-se quatro peritos no assunto de forma a obter respostas sobre a viabilidade da intervenção das Forças Armadas na Segurança Interna, num estado de normalidade democrática. As respostas depois de transcritas constituíram o corpus que foi submetido a análise de conteúdo. Com base nesta análise de conteúdo, a partir dos excertos de discursos codificados nas categorias e subcategorias, procedeu-se à construção dos itens que figurarão numa primeira versão do questionário. A primeira versão do questionário apresenta-se em torno de quatro eixos (categorias), que se dividem em subcategorias: intervenção das Forças Armadas na Segurança Interna; legislação; mudança do paradigma de segurança; e, definição conceptual.