Obesidade é fator de risco para a hipertensão arterial e os mecanismos envolvidos nesta doença não são totalmente esclarecidos. Camundongos C57BL/6J e transgênicos com com deleção em neurônios e glia da via inflamatória do receptor toll-like-NFκB foram submetidos à dieta hiperlipídica (HL) por 8 e 15 semanas e avaliados parâmetros metabólicos, pressão arterial, frequência cardíaca, atividade do sistema nervoso autônomo, fatores inflamatórios e neuropeptídeos no hipotálamo e no tronco encefálico. Os camundongos expostos HL desenvolveram hipertensão arterial acompanhada de disfunção autonômica e aumento de CART no DMH. Os animais transgênicos quando submetidos à dieta HL desenvolveram um quadro de obesidade, porém não apresentaram hipertensão arterial e disfunção autonômica. Além disso, o grupo de animais HL aumentou o RNAm de CCL5 no hipotálamo e de CD86 no tronco-encefálico e a densidade de microglia no NTS caudal. Os resultados sugerem novos mecanismos para a hipertensão e disfunção autonômica secundárias à ingestão de dieta hiperlipídica mostrando o papel do CART o DMH e o envolvimento da via inflamatória do TLR-NFκB em neurônios e glia nos mecanismos desta patologia. / Obesity is a risk factor for high blood pressure and the mechanisms involved in this disease are not fully clarified. C57BL/6J and transgenic mice with toll-like-NFκB receptor inflammatory- pathway deletion in neurons and glia were fed with high-fat diet (HL) for 8 or 15 weeks and assessed metabolic parameters, blood pressure, heart rate, autonomic nervous system activity, inflammatory factors and neuropeptides in the hypothalamus and brainstem. The HL mice developed hypertension accompanied with autonomic dysfunction and increased CART in DMH. Transgenic animals when submitted to HL diet developed obesity, but not showed high blood pressure and autonomic dysfunction. In addition, HL animals had increased CCL5 mRNA in hypothalamus, CD86 mRNA in brainstem and micróglia density in caudal NTS. The results suggest new mechanisms for hypertension and autonomic dysfunction secondary to intake of high-fat diet by showing CART role in DMH and the involvement of the inflammatory pathway TLR-NFκB in neurons and glia.

Obesidade é fator de risco para a hipertensão arterial e os mecanismos envolvidos nesta doença não são totalmente esclarecidos. Camundongos C57BL/6J e transgênicos com com deleção em neurônios e glia da via inflamatória do receptor toll-like-NFκB foram submetidos à dieta hiperlipídica (HL) por 8 e 15 semanas e avaliados parâmetros metabólicos, pressão arterial, frequência cardíaca, atividade do sistema nervoso autônomo, fatores inflamatórios e neuropeptídeos no hipotálamo e no tronco encefálico. Os camundongos expostos HL desenvolveram hipertensão arterial acompanhada de disfunção autonômica e aumento de CART no DMH. Os animais transgênicos quando submetidos à dieta HL desenvolveram um quadro de obesidade, porém não apresentaram hipertensão arterial e disfunção autonômica. Além disso, o grupo de animais HL aumentou o RNAm de CCL5 no hipotálamo e de CD86 no tronco-encefálico e a densidade de microglia no NTS caudal. Os resultados sugerem novos mecanismos para a hipertensão e disfunção autonômica secundárias à ingestão de dieta hiperlipídica mostrando o papel do CART o DMH e o envolvimento da via inflamatória do TLR-NFκB em neurônios e glia nos mecanismos desta patologia. / Obesity is a risk factor for high blood pressure and the mechanisms involved in this disease are not fully clarified. C57BL/6J and transgenic mice with toll-like-NFκB receptor inflammatory- pathway deletion in neurons and glia were fed with high-fat diet (HL) for 8 or 15 weeks and assessed metabolic parameters, blood pressure, heart rate, autonomic nervous system activity, inflammatory factors and neuropeptides in the hypothalamus and brainstem. The HL mice developed hypertension accompanied with autonomic dysfunction and increased CART in DMH. Transgenic animals when submitted to HL diet developed obesity, but not showed high blood pressure and autonomic dysfunction. In addition, HL animals had increased CCL5 mRNA in hypothalamus, CD86 mRNA in brainstem and micróglia density in caudal NTS. The results suggest new mechanisms for hypertension and autonomic dysfunction secondary to intake of high-fat diet by showing CART role in DMH and the involvement of the inflammatory pathway TLR-NFκB in neurons and glia.

La banque de données IMIS (Integrated Management Information System) de l’agence américaine OSHA (Occupational Safety and Health Administration) contient l’ensemble des mesures de l’exposition effectuées par les inspecteurs d’OSHA chargés de vérifier la conformité aux valeurs limites d’exposition. Les résultats analytiques correspondant aux prélèvements effectués par les inspecteurs sont également disponibles dans la banque CEHD (Chemical Exposure Health Data). Ces deux banques représentent une source d’information potentielle majeure sur les conditions d’exposition aux substances chimiques en Amérique du Nord. Cependant, leur représentativité par rapport à la distribution réelle des niveaux d’exposition retrouvés dans les milieux de travail est largement inconnue. L’objectif de cette thèse est d’établir dans quelle mesure les données de contamination de l'air recueillies par l’agence fédérale américaine OSHA peuvent être utilisées pour l’estimation des expositions professionnelles en Amérique du Nord. Les analyses ont porté sur 511 047 et 588 818 mesures d’exposition contenues dans les banques IMIS et CEHD respectivement, pour la période 1979-2011. Premièrement, des modèles additifs généralisés ont été utilisés pour étudier l’association entre les variables reflétant les caractéristiques des établissements visités et des inspections et les niveaux d’exposition pour 77 agents chimiques (90% du contenu d’IMIS). Dans un second temps, une approche de régression de Poisson modifiée a été utilisée pour étudier les facteurs déterminants l’enregistrement ou non des échantillons de CEHD dans la banque IMIS en jumelant les deux banques pour 78 agents chimiques. Finalement, des modèles CART (Classification And Regression Tree) ont été développés permettant de prédire, parmi les résultats non détectés de la banque IMIS, lesquels correspondent à des mesures courte durée ou des moyennes pondérées sur 8 heures (VEMP-8h) en se basant sur les variables communes aux banques IMIS et CEHD. Dans la première analyse, les modèles statistiques ont montré que les niveaux d’exposition étaient plus susceptibles de dépasser la TLV (threshold limit value) pour les mesures effectuées sous un régime OSHA fédéral par rapport au régime OSHA d’État (rapport de cote (RC) de 1,22 à travers les agents). La probabilité de dépasser la TLV augmentait avec le nombre total des amendes reçues par un établissement, indépendamment de la nature des infractions (RC de 1,54 à travers les agents entre les catégories « élevée » et « aucune »). Elle était également plus élevée pour les visites de suivi que pour les visites planifiées (RC de 1,61). Dans la deuxième analyse, la comparaison des banques IMIS et CEHD a montré un taux d’enregistrement global de 38% des données CEHD dans IMIS. Les résultats non détectés (particulièrement ceux mesurés sur un panel d’agents – p. ex. panel de métaux) étaient moins susceptibles d’être enregistrés dans IMIS (risque relatif ~0,6). Finalement, les modèles CART ont prédit plus précisément le type de prélèvement (courte durée, VEMP-8h) pour les résultats non détectés dans IMIS que des méthodes simples d’attribution (p. ex. attribution du type le plus fréquent parmi les résultats détectés) pour les agents les plus pertinents (c.-à-d. ceux ayant une proportion substantielle de mesures ND, courte durée et VEMP-8h). Nos résultats ont montré la présence de plusieurs mécanismes de sélection dans le processus conduisant à l’enregistrement d’une mesure d’exposition dans IMIS, ce qui suggère l’existence de différences systématiques entre les niveaux rapportés dans les banques OSHA et les niveaux moyens d’exposition dans la population de travailleurs. La prise en compte des informations contextuelles aux mesures et l’emploi de méthodes prédictives peuvent aider à pallier partiellement ces biais et ainsi raffiner les portraits d’exposition établis à partir des données d’OSHA. / The Integrated Management Information System (IMIS) contains exposure measurements taken by the U.S. Occupational Safety and Health Administration (OSHA) inspectors to verify compliance with permissible exposure limits. Supplementary data containing analytical results of the field samples are available in the Chemical Exposure Health Database (CEHD). These databanks represent a major potential source of information on exposure conditions in North American workplaces. However, the degree to which they represent the actual distribution of the exposure levels found in the workplace is largely unknown.The objective of this thesis is to examine the extent to which exposure data collected by OSHA can be used for estimating occupational exposure in North America. Analyses focused on 511 047 and 588 818 exposure measurements in IMIS and CEHD respectively, for the period 1979-2011. First, generalized additive models were used to explore associations between exposure levels in IMIS and ancillary variables reflecting characteristics of establishments and inspections for 77 chemical agents (90% of IMIS content). Second, modified Poisson regression was used to identify determinants of recording or not of CEHD samples in IMIS by linking both databanks for 78 agents. Finally, Classification And Regression Tree (CART) models were applied to predict which non-detected (ND) results stored in IMIS are 8-hour time-weighted average (TWA) or short-term samples, based on common variables available in IMIS and CEHD databanks. In the first analysis, statistical modelling showed that measurements collected under federal OSHA plans were more likely to have a sample result exceed the TLV compared to measurements collected under state OSHA plans (odds ratio (OR) of 1,22 across agents). An increase in the total amount of penalty assessed to a company was associated with higher odds of having a sample result exceed the TLV (OR of 1,54 across agents for « high » vs. « none »). Follow-up inspections were more likely to have a sample result exceed the TLV compared to planned inspections (OR of 1,61 across agents). In the second analysis, linkage between CEHD and IMIS showed a 38% overall proportion of CEHD samples recorded into IMIS. Non-detects (especially ND records corresponding to analytical panels – e.g. panel of metals) were less likely to be recorded in IMIS (relative risk ~0,6). Finally, CART models predicted more accurately which IMIS ND results were TWA or short-term samples compared to simple methods of assignment (e.g. assignment of the most frequent category from detected values) for the most relevant agents (i.e. with high proportions of ND, short-term, and TWA results). Our findings showed the presence of several selection mechanisms in the process leading up to the recording of a sample in IMIS, which suggest systematic differences exist between OSHA measurements and actual occupational exposures in the general U.S. working population. These biases can be partially controlled by using ancillary information on exposure measurements together with predictive methods, thus helping to draw more accurate portraits of exposure levels from OSHA data.

In the shift to a globalised creative economy where innovation and creativity are increasingly prized, many studies have documented direct and indirect social and economic benefits of the arts. In addition, arts workers have been argued to possess capabilities which are of great benefit both within and outside the arts, including (in addition to creativity) problem solving abilities, emotional intelligence, and team working skills (ARC Centre of Excellence for Creative Industries and Innovation, 2007). However, the labour force characteristics of professional artists in Australia and elsewhere belie their importance. The average earnings of workers in the arts sector are consistently less than other workers with similar educational backgrounds, and their rates of unemployment and underemployment are much higher (Australian Bureau of Statistics, 2005; Caves, 2000; Throsby & Hollister, 2003). Graduating students in the arts appear to experience similar employment challenges and exhibit similar patterns of work to artists in general. Many eventually obtain work unrelated to the arts or go back to university to complete further tertiary study in fields unrelated to arts (Graduate Careers Council of Australia, 2005a). Recent developments in career development theory have involved discussion of the rise of boundaryless careers amongst knowledge workers. Boundaryless careers are characterised by non-linear career progression occurring outside the bounds of a single organisation or field (Arthur & Rousseau, 1996a, 1996b). The protean career is an extreme form of the boundaryless career, where the careerist also possesses strong internal career motivations and criteria for success (Baruch, 2004; Hall, 2004; Hall & Mirvis, 1996). It involves a psychological contract with one's self rather than an organisation or organisations. The boundaryless and protean career literature suggests competencies and dispositions for career self-management and career success, but to date there has been minimal empirical work investigating the predictive value of these competencies and dispositions to career success in the boundaryless or protean career. This program of research employed competencies and dispositions from boundaryless and protean career theory to predict career success in professional artists and tertiary arts graduates. These competencies and dispositions were placed into context using individual and contextual career development influences suggested by the Systems Theory Framework of career development (McMahon & Patton, 1995; Patton & McMahon, 1999, 2006a). Four substantive studies were conducted, using online surveys with professional artists and tertiary arts students / graduates, which were preceded by a pilot study for measure development. A largely quantitative approach to the program of research was preferred, in the interests of generalisability of findings. However, at the time of data collection, there were no quantitative measures available which addressed the constructs of interest. Brief scales of Career Management Competence based on the Australian Blueprint for Career Development (Haines, Scott, & Lincoln, 2003), Protean Career Success Orientation based on the underlying dispositions for career success suggested by protean career theory, and Career Development Influences based on the Systems Theory Framework of career development (McMahon & Patton, 1995; Patton & McMahon, 1999, 2006a) were constructed and validated via a process of pilot testing and exploratory factor analyses. This process was followed by confirmatory factor analyses with data collected from two samples: 310 professional artists, and 218 graduating arts students who participated at time 1 (i.e., at the point of undergraduate course completion in October, 2005). Confirmatory factor analyses via Structural Equation Modelling conducted in Study 1 revealed that the scales would benefit from some respecification, and so modifications were made to the measures to enhance their validity and reliability. The three scales modified and validated in Study 1 were then used in Studies 3 and 4 as potential predictors of career success for the two groups of artists under investigation, along with relevant sociodemographic variables. The aim of the Study 2 was to explore the construct of career success in the two groups of artists studied. Each participant responded to an open-ended question asking them to define career success. The responses for professional artists were content analysed using emergent coding with two coders. The codebook was later applied to the arts students' definitions. The majority of the themes could be grouped into four main categories: internal definitions; financial recognition definitions; contribution definitions; and non-financial recognition definitions. Only one third of the definition themes in the professional artists' and arts graduates' definitions of career success were categorised as relating to financial recognition. Responses within the financial recognition category also indicated that many of the artists aspired only to a regular subsistence level of arts income (although a small number of the arts graduates did aspire to fame and fortune). The second section of the study investigated the statistical relationships between the five different measures of career success for each career success definitional category and overall. The professional artists' and arts graduates' surveys contained several measures of career success, including total earnings over the previous 12 months, arts earnings over the previous 12 months, 1-6 self-rated total employability, 1-6 self-rated arts employability, and 1-6 self-rated self-defined career success. All of the measures were found to be statistically related to one another, but a very strong statistical relationship was identified between each employability measure and its corresponding earnings measure for both of the samples. Consequently, it was decided to include only the earnings measures (earnings from arts, and earnings overall) and the self-defined career success rating measure in the later studies. Study 3 used the career development constructs validated in Study 1, sociodemographic variables, and the career success measures explored in Study 2 via Classification and Regression Tree (CART - Breiman, Friedman, Olshen, & Stone, 1984) style decision trees with v-fold crossvalidation pruning using the 1 SE rule. CART decision trees are a nonparametric analysis technique which can be used as an alternative to OLS or hierarchical regression in the case of data which violates parametric statistical assumptions. The three optimal decision trees for total earnings, arts earnings and self defined career success ratings explained a large proportion of the variance in their respective target variables (R2 between 0.49 and 0.68). The Career building subscale of the Career Management Competence scale, pertaining to the ability to manage the external aspects of a career, was the most consistent predictor of all three career success measures (and was the strongest predictor for two of the three trees), indicating the importance of the artists' abilities to secure work and build the external aspects of a career. Other important predictors included the Self management subscale of the Career Management Competence scale, Protean Career Success Orientation, length of time working in the arts, and the positive role of interpersonal influences, skills and abilities, and interests and beliefs from the Career Development Influences scale. Slightly different patterns of predictors were found for the three different career success measures. Study 4 also involved the career development constructs validated in Study 1, sociodemographic variables, and the career success measures explored in Study 2 via CART style decision trees. This study used a prospective repeated measures design where the data for the attribute variables were gathered at the point of undergraduate course completion, and the target variables were measured one year later. Data from a total of 122 arts students were used, as 122 of the 218 students who responded to the survey at time 1 (October 2005) also responded at time 2 (October 2006). The resulting optimal decision trees had R2 values of between 0.33 and 0.46. The values were lower than those for the professional artists' decision trees, and the trees themselves were smaller, but the R2 values nonetheless indicated that the arts students' trees possessed satisfactory explanatory power. The arts graduates' Career building scores at time 1 were strongly predictive of all three career success measures at time 2, a similar finding to the professional artists' trees. A further similarity between the trees for the two samples was the strong statistical relationship between Career building, Self management, and Protean Career Success Orientation. However, the most important variable in the total earnings tree was arts discipline category. Technical / design arts graduates consistently earned more overall than arts graduates from other disciplines. Other key predictors in the arts graduates' trees were work experience in arts prior to course completion, positive interpersonal influences, and the positive influence of skills and abilities and interests and beliefs on career development. The research program findings represent significant contributions to existing knowledge about artists' career development and success, and also the transition from higher education to the world of work, with specific reference to arts and creative industries programs. It also has implications for theory relating to career success and protean / boundaryless careers.

In this thesis a number of statistical methods have been developed and applied to habitat suitability modelling for rare and threatened species. Data available on these species are typically limited. Therefore, developing these models from these data can be problematic and may produce prediction biases. To address these problems there are three aims of this thesis. The _rst aim is to develop and implement frequentist and Bayesian statistical modelling approaches for these types of data. The second aim is develop and implement expert elicitation methods. The third aim is to apply these novel approaches to Australian rare and threatened species case studies with the intention of habitat suitability modelling. The _rst aim is ful_lled by investigating two innovative approaches for habitat suitability modelling and sensitivity analysis of the second approach to priors. The _rst approach is a new multilevel framework developed to model the species distribution at multiple scales and identify excess zeros (absences outside the species range). Applying a statistical modelling approach to the identi_cation of excess zeros has not previously been conducted. The second approach is an extension and application of Bayesian classi_cation trees to modelling the habitat suitability of a threatened species. This is the _rst `real' application of this approach in ecology. Lastly, sensitivity analysis of the priors in Bayesian classi_cation trees are examined for a real case study. Previously, sensitivity analysis of this approach to priors has not been examined. To address the second aim, expert elicitation methods are developed, extended and compared in this thesis. In particular, one elicitation approach is extended from previous research, there is a comparison of three elicitation methods, and one new elicitation approach is proposed. These approaches are illustrated for habitat suitability modelling of a rare species and the opinions of one or two experts are elicited. The _rst approach utilises a simple questionnaire, in which expert opinion is elicited on whether increasing values of a covariate either increases, decreases or does not substantively impact on a response. This approach is extended to express this information as a mixture of three normally distributed prior distributions, which are then combined with available presence/absence data in a logistic regression. This is one of the _rst elicitation approaches within the habitat suitability modelling literature that is appropriate for experts with limited statistical knowledge and can be used to elicit information from single or multiple experts. Three relatively new approaches to eliciting expert knowledge in a form suitable for Bayesian logistic regression are compared, one of which is the questionnaire approach. Included in this comparison of three elicitation methods are a summary of the advantages and disadvantages of these three methods, the results from elicitations and comparison of the prior and posterior distributions. An expert elicitation approach is developed for classi_cation trees, in which the size and structure of the tree is elicited. There have been numerous elicitation approaches proposed for logistic regression, however no approaches have been suggested for classi_cation trees. The last aim of this thesis is addressed in all chapters, since the statistical approaches proposed and extended in this thesis have been applied to real case studies. Two case studies have been examined in this thesis. The _rst is the rare native Australian thistle (Stemmacantha australis), in which the dataset contains a large number of absences distributed over the majority of Queensland, and a small number of presence sites that are only within South-East Queensland. This case study motivated the multilevel modelling framework. The second case study is the threatened Australian brush-tailed rock-wallaby (Petrogale penicillata). The application and sensitivity analysis of Bayesian classi_cation trees, and all expert elicitation approaches investigated in this thesis are applied to this case study. This work has several implications for conservation and management of rare and threatened species. Novel statistical approaches addressing the _rst aim provide extensions to currently existing methods, or propose a new approach, for identi _cation of current and potential habitat. We demonstrate that better model predictions can be achieved using each method, compared to standard techniques. Elicitation approaches addressing the second aim ensure expert knowledge in various forms can be harnessed for habitat modelling, a particular bene_t for rare and threatened species which typically have limited data. Throughout, innovations in statistical methodology are both motivated and illustrated via habitat modelling for two rare and threatened species: the native thistle Stemmacantha australis and the brush-tailed rock wallaby Petrogale penicillata.

Ett av de mest hotande problemen idag är vad som händer med miljö. Ett stort problem är utsläpp. En stor bidragande faktor är den tanklösa användningen av fordon drivna av fossila bränslen. Ett sätt att kunna ta ett litet steg i rätt riktning, är att anpassa våran livstil och till exempel minska på användningen av bilen. Men även att allmänt göra mer medvetna val i vardagen. Målet med detta projektet är att göra just detta lite enklare. Att hjälpa dig transportera dina matvaror exempelvis från mataffären till hemmet.Processen för att komma fram till det som blev slutprodukten, började med intervjuer av användare. Därefter producerades skisser som visades för en testgrupp, för att samla feedback. Fysiska tester utfördes, innan det slutgiltiga konceptet nåtts: En vagn man kan använda på fyra sätt. Man kan skjuta den framför sig medan man går, eller dra den efter sig, man kan använda den som sparkcykel eller man kan koppla den till en cykel. / One of the most threatening issues today is what is happening to our environment. A consi- derable problem for these issues are the emissions. A tremendous contributing factor is the insensible use of fossil fuel driven vehicles. A way of taking a small step i the right direction is to adjust our lifestyle and reduce the use of the car. But also by making more conscious choises in our everyday lives. The aim of this project is to make this a little easier. To help you transport your groceries from for example the store to your home.The process of coming up with what later became the end product, started with interviewing users. Following that, sketches were made and showed to a test group to gather feedback.Physical tests executed, before the final concept was reached: A wagon you cam utilise infour ways. It can be pushed in front of you, while walking. It can be dragged behind, while walking. it can be used as a kick bike and it can be connected to a bicycle.

This thesis deals with the MIMO system analysis, with a comparison of a different frequency charactersitics, and including singular values characteristic. The H2 and H norms are defined for signals and a MIMO systems. A MIMO optimal control using an LQG, an H2 and an H control is defined and described. Their general advantages, disadvantages and similarities are summed up. An H2 and an H state controller and state observer synthesis is implemented in a MATLAB using linear matrix inequalities. Control of an inverted pendulum is designed using the H optimal cascade control, the H2 state control and the H state control. The results are compared with each other. The theoretical possibility of same H2 and H optimal state controller design is presented.

Indiana University-Purdue University Indianapolis (IUPUI) / Symptoms of post-traumatic stress disorder (PTSD) are a common comorbidity in veterans seeking treatment of chronic musculoskeletal pain (CMP). However, little is known regarding the mutual influence of PTSD and CMP in this population. Using cross-sectional and longitudinal data from a randomized clinical trial evaluating a stepped care intervention for CMP in Iraq/Afghanistan veterans (ESCAPE), this dissertation examined the relationships between PTSD and CMP along with other factors including depression, anxiety, catastrophizing and health-related quality of life. The Classification and Regression Tree (CART) analysis was conducted to identify key factors associated with baseline PTSD besides CMP severity. A series of statistical analyses including logistical regression analysis, mixed model repeated measure analysis, confirmatory factor analysis and cross-lagged panel analysis via structural equation modeling were conducted to test five competing models of PTSD symptom clusters, and to examine the mutual influences of PTSD symptom clusters and CMP outcomes. Results showed baseline pain intensity and pain disability predicted PTSD at 9 months. And baseline PTSD predicted improvement of pain disability at 9 months. Moreover, direct relationships were found between PTSD and the disability component of CMP, and indirect relationships were found between PTSD, CMP and CMP components (intensity and disability) mediated by depression, anxiety and pain catastrophizing. Finally, the coexistence of PTSD and more severe pain was associated with worse SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Together these findings provided empirical support for the mutual maintenance theory.

Indiana University-Purdue University Indianapolis (IUPUI) / Magnetic resonance (MR) spectroscopy is a neuroimaging technique. It is widely used to quantify the concentration of important metabolites in a brain tissue. Imbalance in concentration of brain metabolites has been found to be associated with development of neurological impairment. There has been increasing trend of using MR spectroscopy as a diagnosis tool for neurological disorders. We established statistical methodology to analyze data obtained from the MR spectroscopy in the context of the HIV associated neurological disorder. First, we have developed novel methodology to study the association of marker of neurological disorder with MR spectrum from brain and how this association evolves with time. The entire problem fits into the framework of scalar-on-function regression model with individual spectrum being the functional predictor. We have extended one of the existing cross-sectional scalar-on-function regression techniques to longitudinal set-up. Advantage of proposed method includes: 1) ability to model flexible time-varying association between response and functional predictor and (2) ability to incorporate prior information. Second part of research attempts to study the influence of the clinical and demographic factors on the progression of brain metabolites over time. In order to understand the influence of these factors in fully non-parametric way, we proposed LongCART algorithm to construct regression tree with longitudinal data. Such a regression tree helps to identify smaller subpopulations (characterized by baseline factors) with differential longitudinal profile and hence helps us to identify influence of baseline factors. Advantage of LongCART algorithm includes: (1) it maintains of type-I error in determining best split, (2) substantially reduces computation time and (2) applicable even observations are taken at subject-specific time-points. Finally, we carried out an in-depth analysis of longitudinal changes in the brain metabolite concentrations in three brain regions, namely, white matter, gray matter and basal ganglia in chronically infected HIV patients enrolled in HIV Neuroimaging Consortium study. We studied the influence of important baseline factors (clinical and demographic) on these longitudinal profiles of brain metabolites using LongCART algorithm in order to identify subgroup of patients at higher risk of neurological impairment. / Partial research support was provided by the National Institutes of Health grants U01-MH083545, R01-CA126205 and U01-CA086368