As investigações sobre as bases genéticas de doenças complexas em Genômica utilizam diversos tipos de informação. Diversos sintomas são avaliados de maneira a diagnosticar a doença, os indivíduos apresentam padrões de agrupamento baseados, por exemplo no seu parentesco ou ambiente comum e uma quantidade imensa de características dos indivíduos são medidas por meio de marcadores genéticos. No presente trabalho, um modelo multiníveis da teoria de resposta ao item (TRI) é proposto de forma a integrar todas essas fontes de informação e caracterizar doenças complexas através de uma variável latente. Além disso, a quantidade de marcadores moleculares induz um problema de seleção de variáveis, para o qual uma seleção baseada nos métodos da busca estocástica e do LASSO bayesiano são propostos. Os parâmetros do modelo e a seleção de variáveis são realizados sob um paradigma bayesiano, no qual um algoritmo Monte Carlo via Cadeias de Markov é construído e implementado para a obtenção de amostras da distribuição a posteriori dos parâmetros. O mesmo é validado através de estudos de simulação, nos quais a capacidade de recuperação dos parâmetros, de escolha de variáveis e características das estimativas pontuais dos parâmetros são avaliadas em cenários similares aos dados reais. O processo de estimação apresenta uma recuperação satisfatória nos parâmetros estruturais do modelo e capacidade de selecionar covariáveis em espaços de dimensão elevada apesar de um viés considerável nas estimativas das variáveis latentes associadas ao traço latente e ao efeito aleatório. Os métodos desenvolvidos são então aplicados aos dados colhidos no estudo de associação familiar \'Corações de Baependi\', nos quais o modelo multiníveis se mostra capaz de caracterizar a síndrome metabólica, uma série de sintomas associados com o risco cardiovascular. O modelo multiníveis e a seleção de variáveis se mostram capazes de recuperar características conhecidas da doença e selecionar um marcador associado. / Recent investigations about the genetic architecture of complex diseases use diferent sources of information. Diferent symptoms are measured to obtain a diagnosis, individuals may not be independent due to kinship or common environment and their genetic makeup may be measured through a large quantity of genetic markers. In the present work, a multilevel item response theory (IRT) model is proposed that unifies all these diferent sources of information through a latent variable. Furthermore, the large ammount of molecular markers induce a variable selection problem, for which procedures based on stochastic search variable selection and the Bayesian LASSO are considered. Parameter estimation and variable selection is conducted under a Bayesian framework in which a Markov chain Monte Carlo algorithm is derived and implemented to obtain posterior distribution samples. The estimation procedure is validated through a series of simulation studies in which parameter recovery, variable selection and estimation error are evaluated in scenarios similar to the real dataset. The estimation procedure showed adequate recovery of the structural parameters and the capability to correctly nd a large number of the covariates even in high dimensional settings albeit it also produced biased estimates for the incidental latent variables. The proposed methods were then applied to the real dataset collected on the \'Corações de Baependi\' familiar association study and was able to apropriately model the metabolic syndrome, a series of symptoms associated with elevated heart failure and diabetes risk. The multilevel model produced a latent trait that could be identified with the syndrome and an associated molecular marker was found.

Harmony search method based optimum topology design algorithm is presented for single layer lamella domes. The harmony search method is a numerical optimization technique developed recently that imitates the musical performance process which takes place when a musician searches for a better state of harmony. Jazz improvisation seeks to find musically pleasing harmony similar to the optimum design process which seeks to find the optimum solution. The optimum design algorithm developed imposes the behavioral and performance constraints in accordance with LRFD-AISC. The optimum number of rings, the height of the crown and the tubular cross-sectional designations for dome members are treated as design variables. The member grouping is allowed so that the same section can be adopted for each group. The design algorithm developed has a routine that build the data for the geometry of the dome automatically that covers the numbering of joints, and member incidences, and the computation of the coordinates of joints. Due to the slenderness and the presence of imperfections in dome structures it is necessary to consider the geometric nonlinearity in the prediction of their response under the external loading. Design examples are considered to demonstrate the efficiency of the algorithm presented.

Joint models for the association of a longitudinal binary and a longitudinal continuous process are proposed for situations in which their association is of direct interest. The models are parameterized such that the dependence between the two processes is characterized by unconstrained regression coefficients. Bayesian variable selection techniques are used to parsimoniously model these coefficients. A Markov chain Monte Carlo (MCMC) sampling algorithm is developed for sampling from the posterior distribution, using data augmentation steps to handle missing data. Several technical issues are addressed to implement the MCMC algorithm efficiently. The models are motivated by, and are used for, the analysis of a smoking cessation clinical trial in which an important question of interest was the effect of the (exercise) treatment on the relationship between smoking cessation and weight gain.

Indiana University-Purdue University Indianapolis (IUPUI) / Randomized studies are designed to estimate the average treatment effect (ATE) of an intervention. Individuals may derive quantitatively, or even qualitatively, different effects from the ATE, which is called the heterogeneity of treatment effect. It is important to detect the existence of heterogeneity in the treatment responses, and identify the different sub-populations. Two corresponding statistical methods will be discussed in this talk: a hypothesis testing procedure and a mixture-model based approach. The hypothesis testing procedure was constructed to test for the existence of a treatment effect in sub-populations. The test is nonparametric, and can be applied to all types of outcome measures. A key innovation of this test is to build stochastic search into the test statistic to detect signals that may not be linearly related to the multiple covariates. Simulations were performed to compare the proposed test with existing methods. Power calculation strategy was also developed for the proposed test at the design stage. The mixture-model based approach was developed to identify and study the sub-populations with different treatment effects from an intervention. A latent binary variable was used to indicate whether or not a subject was in a sub-population with average treatment benefit. The mixture-model combines a logistic formulation of the latent variable with proportional hazards models. The parameters in the mixture-model were estimated by the EM algorithm. The properties of the estimators were then studied by the simulations. Finally, all above methods were applied to a real randomized study in a low ejection fraction population that compared the Implantable Cardioverter Defibrillator (ICD) with conventional medical therapy in reducing total mortality.

Steel space frames having irregular shapes when subjected to lateral loads caused by wind or earthquakes undergo twisting as a result of their unsymmetrical topology. As a result, torsional moment comes out which is required to be resisted by the three dimensional frame system. The members of such frame are generally made out of steel I sections which are thin walled open sections. The simple beam theory is not adequate to predict behavior of such thin-walled sections under torsional moments due to the fact that the large warping deformations occur in the cross section of the member. Therefore, it is necessary to consider the effect of warping in the design of the steel space frames having members of thin walled steel sections is significant. In this study the optimum design problem of steel space frames is formulated according to the provisions of LRFD-AISC (Load and Resistance factor design of American Institute of Steel Construction) in which the effect of warping is also taken into account. Ant colony optimization and harmony search techniques two of the recent methods in stochastic search techniques are used to obtain the solution of the design problem. Number of space frame examples is designed by the algorithms developed in order to demonstrate the effect of warping in the optimum design.

Cellular beams became increasingly popular as an efficient structural form in steel construction since their introduction. Their sophisticated design and profiling process provides greater flexibility in beam proportioning for strength, depth, size and location of circular holes. The purpose of manufacturing these beams is to increase overall beam depth, the moment of inertia and section modulus, which results in greater strength and rigidity. Cellular beams are used as primary or secondary floor beams in order to achieve long spans and service integration. They are also used as roof beams beyond the range of portal-frame construction, and are the perfect solution for curved roof applications, combining weight savings with a low-cost manufacturing process. The purpose of the current research is to study optimum design, ultimate load capacity under applied load and finite element analysis of non-composite cellular beams. The first part of the research program focuses on the optimum design of steel cellular beams using one of the stochastic search methods called &ldquo / harmony search algorithm&rdquo / . The minimum weight is taken as the design objective while the design constraints are implemented from the Steel Construction Institute. Design constraints include the displacement limitations, overall beam flexural capacity, beam shear capacity, overall beam buckling strength, web post flexure and buckling, vierendeel bending of upper and lower tees and local buckling of compression flange. The design methods adopted in this publication are consistent with BS5950. In the second part of the research, which is the experimental work, twelve non-composite cellular beams are tested to determine the ultimate load carrying capacities of these beams under using a hydraulic plug to apply point load. The tested cellular beam specimens have been designed by using harmony search algorithm. Finally, finite element analysis program is used to perform elastic buckling analysis and predict critical loads of all steel cellular beams. Finite element analysis results are then compared with experimental test results for each tested cellular beam.