INTRODUCTION: The prevalence of obesity is increasing in the United States and globally, and impacts many aspects of health. To understand the contribution of body weight to chronic diseases such as diabetes, it is necessary to characterize secular and longitudinal weight trends prior to evaluating the weight effects that may result from medical interventions. The cross-sectional National Health and Nutrition Examination Survey (NHANES) indicates that mean body weight in the adult population increased from 152 lb (69 kg) to 181 lb (82 kg) between 1959 and 2008. However, there are no previously published studies on secular or longitudinal weight trends in a veteran population. OBJECTIVES: The purpose of this study is to describe secular and longitudinal trends in body weight for a large population of male and female individuals with and without diabetes in the Veterans Administration (VA) healthcare system, the largest integrated healthcare system in the United States. METHODS: Retrospective observational analysis of data from VA facilities throughout the United States, in patients who had at least 4 outpatient visits within any consecutive 4-year interval during 2000–2014. The dataset included men and women with and without type 2 diabetes. The primary outcomes were longitudinal trends in body weight stratified by birth cohort, sex, and diabetes status. RESULTS: A total of 4,680,735 unique patients, 1,666,346 with diabetes, were included in the analysis. Regressions were performed on the patient-level data and segmented by birth cohort. A total of 176,034,543 weight observations were included in the analysis, with a median of 15 to 36 weight observations per patient in individuals without diabetes, and a median of 22 to 49 weight observations in individuals with diabetes across birth cohorts. In the year 2000, the y-intercept for the regression equations indicated a mean body weight for men without diabetes of 188 lb (85 kg), for women without diabetes of 166 lb (75 kg), for men with diabetes of 213 lb (97 kg), and for women with diabetes of 195 lb (88 kg). Secular trends in body weight during the study period had median linear increases of 0.53 lb/y (0.24 kg/y) in men with diabetes, 0.50 lb/y (0.23 kg/y) in women with diabetes, 0.53 lb/y (0.24 kg/y) in men without diabetes, and 0.86 lb/y (0.39 kg/y) among women without diabetes, respectively. In cohorts born before 1940, body weight decreased. In the cohorts born between 1940-1949, body weight was stable. In all cohorts born after 1950, body weight increased. Across birth cohorts, the rate of weight increase accelerated from older to younger groups, with higher rates in the groups with diabetes than in the groups without diabetes: β2 = 0.0260 lb2/y (0.01179 kg2/y) in men without diabetes, 0.0398 lb2/y (0.01805 kg2/y) in men with diabetes, 0.0127 lb2/y (0.00576 kg2/y) in women without diabetes, and 0.0895 lb2/y (0.04060 kg2/y) in women with diabetes. CONCLUSIONS: This is the first report of secular and longitudinal weight trends in a large, contemporary veteran population that includes both men and women. Consistent with findings from the Normative Aging Study, a longitudinal study of male veterans from the northeastern United States, weight changes varied from decreases among the oldest birth cohorts to increases in the youngest birth cohorts. Secular changes in body weight by birth cohort were consistent with the patterns reported in the Global Burden of Disease Study. The rate of weight change is accelerated in all younger birth cohorts relative to all older birth cohorts, with the highest rates in women with diabetes. Further analyses of this dataset are recommended to elucidate clinical characteristics associated with longitudinal weight change among individuals with and without diabetes in the veteran population.

Adolescence is a crucial period for bone development and exercise can enhance bone acquisition during this period of life. However, there is a lack of scientific evidence on how different loading sports practiced during adolescence can affect bone development in males. The present thesis is part of the PRO-BONE study and aimed to investigate the cross-sectional and longitudinal effects of participation in football (osteogenic sport), swimming and cycling (non-osteogenic sports) on bone mass, bone geometry, texture and bone metabolism in adolescent males. An active control group has been included too. Additionally, the thesis examined the effect of a 9-month jumping intervention programme on bone outcomes in adolescent males involved these sports. Cross-sectional findings from Chapter 4 show that footballers have better bone status than swimmers, cyclists and controls (7 to 21 %), and that there are no differences between participants of non-osteogenic sports and controls. Chapter 5 identifies that lean mass is the strongest determinant of bone outcomes, followed by football participation and height in adolescent male athletes, whereas the contribution of the other predictors, such as nutrition, physical activity and fitness, is site specific. Longitudinal evidence in Chapters 6 and 7 show that bone mass (5 to 8 %) and geometry (4 to 10 %) is higher in adolescent male footballers compared to swimmers and cyclists after one year of sport specific training, and that there are no differences in bone development between non-osteogenic sports groups and controls. Chapters 8 and 9 indicate that a 9-month jumping intervention programme can improve bone outcomes only in male adolescents participating in swimming and cycling (4 to 13 %), but not in those engaged in football, while it can improve fitness outcomes in all 4 groups (4 to 8 %). Collectively, the present thesis contributes to the literature by providing novel evidence in adolescent male athletes on the effects of popular sports such as football, swimming and cycling on bone status and development, and that a jumping intervention programme can improve bone development in those involved in non-osteogenic sports.

The economic wellbeing, physical and mental health of the ageing population in the United Kingdom is associated with continued participation in the labour force. Encouraging later life employment is therefore a key policy issue. Research into older person's employment trajectories is concentrated on male working patterns, and often takes an individualistic approach that does not account for the domestic context. Previous research on women's labour force participation has been informed by small scale qualitative studies that do consider the household domain but these findings cannot be generalized to the wider population. This research investigates the factors associated with the continued employment of women aged 50 to 59 using data from the English Longitudinal Study of Ageing (ELSA). Transition rates out of employment between 2001 and 2011 are modeled using multilevel discrete time event history specifications that permit the inclusion of time varying covariates. Retirement is characterized as an ageing process which allows the impact of predictors on transition rates to be assessed and measured as women approach state pension age. Alternative time structures are considered, with parameter estimates from an age baseline model compared with those from a time on study specification. Results illustrate the sensitivity of parameter estimates in discrete time event history models to the measurement of time, and emphasize the importance of adopting a time metric that is commensurate with the theoretical representation of retirement as a dynamic ageing process. The domestic context is realised as sampled women and their male partners are positionedwithin a household structure, and asymmetric effects of predictors on the transition rate of each gender are considered. Own poor health, caring responsibilities and a retired or inactive spouse accelerate labour market exit for women whilst high levels of accrued pension wealth predict earlier transitions for their male partners. The age of employment exit for females is independent of pension wealth, but pension resources do predict the retirement pathway taken following any transition that does occur. Women residing in the wealthiest households are more likely to report as voluntary retired prior to state pension age whilst those in the poorest of couples are at higher risk of following an involuntary pathway into an alternative inactive state. These findings emphasize the importance of conducting research into later life employment trajectories on a household, rather than individual, basis.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically significant viral diseases facing the global swine industry. Viraemia profiles of PRRS virus challenged pigs reflect the severity and progression of infection within the host and provide crucial information for subsequent control measures. In this thesis we analyse the largest longitudinal PRRS viraemia dataset from an in-vivo experiment, and corresponding immune measures in the form of cytokine data and neutralising antibodies. In the PRRS Host Genetic Consortium (PHGC) trials, pigs were challenged with one of two PRRSV isolates (NVSL and KS06, respectively). In Chapter 2 we derive a statistical description of the temporal changes in viraemia and determine the influence of diverse factors (e.g. PRRSV strain, pig genetic background, resistance genotype, etc.) on viraemia profiles. The well-established methodology of linear mixed modelling with a repeated measures model and fitting a linearized Wood’s function, a gamma-type function, is applied to the viraemia dataset. The virus isolate had a significant impact on the viraemia profiles which was captured by statistically significant differences in model parameters via both statistical methods. The more virulent NVSL isolate had higher early viraemia predictions and a faster rate of decline than KS06. In line with previous studies the WUR “resistance” genotype, associated with lower AUC viraemia found in previous studies, also resulted in lower viraemia predictions in the statistical models. The typical time trends of the viraemia profiles were a rise to a peak followed by a period of decline with dynamics and magnitude influenced by the virus isolate. Both uni and bimodal viraemia profiles were observed. The Wood’s model appeared a suitable candidate model for the data associated with uni-modal profiles and captured the time trends concisely in only three model parameters which also had a biological relevance. Overall the best fitting Wood’s model (y=atbe-ct) was when there was a random effect in Wood’s parameters b and c. Bimodal profiles significantly reduced the model fit, particularly in the later phase of infection resulting in large model residuals. However bimodal profiles did not impact upon the significance of the differences between the LSM repeated measures estimates nor the LSM linearized Wood’s model parameter estimates. The longitudinal viraemia measures from the PRRSV challenge experiment revealed substantial differences in the viraemia profiles between hosts infected with the same PRRSV challenge dose, pointing to considerable variation in the host response to PRRSV infections. In Chapter 3 we provide a suitable mathematical description of all viraemia profiles with biologically meaningful parameters for quantitative analysis of profile characteristics. The Wood’s function and a biphasic extended Wood’s function were fit to the individual profiles using Bayesian inference with a likelihood framework in Chapter 3. Using maximum likelihood inference and numerous fit criteria, we established that the broad spectrum of viraemia trends could be adequately represented by either uni-or biphasic Wood’s functions. Three viraemic categories emerged: cleared (uni-modal and below detection within 42 days post infection(dpi)), persistent (transient experimental persistence over 42 dpi) and rebound (biphasic within 42 dpi). The convenient biological interpretation of the model parameters estimates, allowed us not only to quantify inter-host variation, but also to establish common viraemia curve characteristics and their predictability. The convenient biological interpretation of the model parameters estimates, allowed us not only to quantify inter-host variation, but also to establish common viraemia curve characteristics and their predictability, which were utilized in subsequent quantitative genetic analyses to identify genomic regions associated with these new resistance traits. The Bayesian approach for curve fitting in Chapter 3 led to better model fits than the classical linear mixed models approach of Chapter 2. Furthermore in Chapter 4 we explored the association between the observed PRRS viraemia profile characteristics and the corresponding measures of the immune response in the form of: neutralising antibody (nAb) cross protection data and longitudinal cytokine profiles. Statistical analysis of the profile characteristics revealed that persistent profiles were distinguishable already within the first 21 dpi, whereas it is not possible to predict the onset of viraemia rebound. Analysis of the neutralizing antibody (nAb) data indicated that there was a ubiquitous strong response to the homologous PRRSV challenge, but high variability in the range of cross-protection of the nAbs. Persistent pigs were found to have a significantly higher nAb cross-protectivity than pigs that either cleared viraemia or experienced rebound within 42 dpi. We determined the typical features and time trends of each cytokine profile, examined the associations between cytokines, and characterised the cytokine response. A stronger association was found in the direction of cytokines driving the ensuing viraemia characteristics as opposed to vice versa. It was found that viraemia class differences were best captured in the anti-viral cytokine IFNA and also the chemokine CCL2, furthermore these key cytokines were the most strongly associated with viraemia measures. The breadth of the cytokine responsiveness was associated with viral profile class and genetic background but not the WUR genotype. The statistical categorization of pigs from each PHGC trial through model fitting provides a critical basis for the generation of new desirable host phenotypes, and of potential use in the genetic selection of pigs with favourable infection traits. Our study provides novel insights into the nature and degree of variation of hosts’ responses to infection as well as new informative traits for subsequent genetic and modelling studies.

abstract: When analyzing longitudinal data it is essential to account both for the correlation inherent from the repeated measures of the responses as well as the correlation realized on account of the feedback created between the responses at a particular time and the predictors at other times. A generalized method of moments (GMM) for estimating the coefficients in longitudinal data is presented. The appropriate and valid estimating equations associated with the time-dependent covariates are identified, thus providing substantial gains in efficiency over generalized estimating equations (GEE) with the independent working correlation. Identifying the estimating equations for computation is of utmost importance. This paper provides a technique for identifying the relevant estimating equations through a general method of moments. I develop an approach that makes use of all the valid estimating equations necessary with each time-dependent and time-independent covariate. Moreover, my approach does not assume that feedback is always present over time, or present at the same degree. I fit the GMM correlated logistic regression model in SAS with PROC IML. I examine two datasets for illustrative purposes. I look at rehospitalization in a Medicare database. I revisit data regarding the relationship between the body mass index and future morbidity among children in the Philippines. These datasets allow us to compare my results with some earlier methods of analyses. / Dissertation/Thesis / Arizona Medicare Data on Rehospitalization / Philippine Data on Children's Morbidity / M.S. Statistics 2012

El presenta trabajo de investigación titulado “Modelamiento Geomecanico de la Veta Daniela” en la zona de profundización de Minera Aurífera Retamas, tiene como objetivo principal optimizar el criterio de estabilidad de las excavaciones mineras. El proyecto se encuentra emplazada dentro del Batolito de Pataz, el cual es el cuerpo intrusivo dominante en la región, con un ancho de 2.5 a 5 Km, tiene una forma alargada aproximadamente 160 km con orientación N3O°W, en este intrusivo se hospedan las vetas auríferas. Los dominios litológicos en la zona de estudio son 4: Diorita, Pórfido Granítico, Pórfido Tonalitico y Granito. Presenta un sistema de fallamiento longitudinal NW-SE, de rumbo sub-paralelo y/o paralelo a las vetas, que originan ensanchamientos (cabalgamiento), acuñamientos y discontinuidad local de las estructuras mineralizadas, muchos de estos son ND (Falla NW-2), ID (Falla Sistema Chilcas), con desplazamientos desde centímetros a varios metros. Presenta otro sistema de fallamiento N-S (Diagonales- Transversales), las cuales son de rumbo N a N-W y alto buzamiento al W, son fallas que se presentan muchas veces agrupadas en bloque como la Falla Los Loros, Falla Chilcas y Falla Sistema Chilcas. Presenta un sistema de fracturamiento local, en forma paralela al sistema de fallas. La veta Daniela presenta un sistema NW-SE. Las estructuras mineralizadas presentan esfuerzos de comprensión en la dirección NE- SW, pero no sólo en una etapa sino en repetidas actividades orogénicas. Las vetas comúnmente se presentan fracturadas y/o craqueladas. El esfuerzo vertical in-situ, para un profundidad aproximada de 1200 metros es de 4.21 MPa, el valor de la constante “k” = 1.75; el esfuerzo horizontal estaría en el rango de 7.37 MPa. Según el estudio de mediciones Over Coring realizadas en la Unidad, el esfuerzo principal tiene una dirección N15°E-S15°W. Para excavaciones con orientación de avance paralela al rumbo de la estructura mineralizada, se tiene la formación de cuñas con criterio de falla por deslizamiento. Y para orientación de avance perpendicular al rumbo de la estructura mineralizada, se tiene la formación de cuñas con criterio de falla por gravedad. Según el análisis de estabilidad controlada por estructuras, el arreglo estructural de la distribución de fallas y diaclasamientos está definido por 3 sistemas principales. El sistema de discontinuidades dominante, tiene un rumbo NW-SE, con orientación paralela a las estructuras mineralizadas, lo cual indica condiciones de estabilidad muy desfavorable. El segundo sistema de discontinuidades, tiene un rumbo NE-SW, con orientación perpendicular al rumbo de las estructurales mineralizadas, lo cual indica condiciones de estabilidad favorable. Según el análisis de estabilidad controlada por esfuerzos, el comportamiento tenso- deformacional del macizo rocoso, presenta un Strength Factor mayor a 1.00 en labores insitu y un Strength Factor menor a 1.00 en labores de explotación, indicando que el vector de deformación presenta mayor concentración en la zona de explotación y por lo cual se contrasta una mayor zona plástica. La trayectoria de los esfuerzos principales se concentra en las coronas de las excavaciones y en el nivel base de la zona de explotación.

Normative age differences and declines in cognition may be overestimated due to influences reflecting impending mortality. The terminal decline hypothesis posits that accelerated cognitive decline for older adults is a function of proximity to death. Although previous research has demonstrated mortality-cognition associations, key questions remain unresolved. This study examined five neglected aspects of terminal decline research: (a) are mortality deficits uniform across age? (b) does impending mortality differentially influence cognitive domains? (c) does cause of death influence magnitude of mortality deficits? (d) do individuals closer to death show accelerated cognitive declines? and (e) do mortality deficits share associations with indicators of neurological disturbance such as performance inconsistency? The sample consisted of 707 adults from the Victoria Longitudinal Study (VLS) who completed between 1 to 5 waves of measurement over a 12-year period. Participants were classified as either Young-Old (59 to 79 years, M = 71.86) or Old-Old (80 to 95 years, M = 83.66). A total of 442 Survivors completed all waves and relevant measures compared with 265 Decedents who participated on at least one occasion and subsequently died. An extensive battery of tests was administered including measures of verbal speed, working memory, episodic memory, semantic memory, and crystallized verbal ability. Results were informative for each of the five research questions. First, mortality-related cognitive deficits were magnified with increasing age. Old-Old decedents exhibited steeper decline compared with similarly aged and younger survivors. Further, multilevel analyses demonstrated that Decedents declined at significantly faster rates per year increase in age. For the second research question, terminal decline was found to differentially influence select cognitive measures. Relative to Survivors, Old-Old Decedents displayed large variation across measures exhibiting poorer performance for verbal speed and episodic memory with considerably better performance for vocabulary. Results for the third research goal demonstrated that specific cause of death differentially influenced cognitive performance. Greater cross-sectional differences and declines were found for those who died of cardiovascular disease (CVD). A fourth contribution to the terminal decline literature found that the shape of cognitive decline for Decedents was accelerated in closer proximity to death. Evidence for the final research question revealed that impending death, presence of CVD, and older age were all associated with increased performance inconsistency. Considered together, these results provide both converging evidence and novel contributions to the terminal decline literature. / Graduate

The development of academic English proficiency and the time it takes to reclassify to fluent English proficient status are key issues in monitoring achievement of English learners. Yet, little is known about academic English language development at the domain-level (listening, speaking, reading, and writing), or how English language development is associated with time-to-reclassification as an English proficient student. Although the substantive findings surrounding English proficiency and reclassification are of great import, the main focus of this dissertation was methodological: the exploration and testing of joint modeling methods for studying both issues. The first joint model studied was a multilevel, multivariate random effects model that estimated the student-specific and school-specific association between different domains of English language proficiency. The second model was a multilevel shared random effects model that estimated English proficiency development and time-to-reclassification simultaneously and treated the student-specific random effects as latent covariates in the time-to-reclassification model. These joint modeling approaches were illustrated using annual English language proficiency test scores and time-to-reclassification data from a large Arizona school district. Results from the multivariate random effects model revealed correlations greater than .5 among the reading, writing and oral English proficiency random intercepts. The analysis of English proficiency development illustrated that some students had attained proficiency in particular domains at different times, and that some students had not attained proficiency in a particular domain even when their total English proficiency score met the state benchmark for proficiency. These more specific domain score analyses highlight important differences in language development that may have implications for instruction and policy. The shared random effects model resulted in predictions of time-to-reclassification that were 97% accurate compared to 80\% accuracy from a conventional discrete-time hazard model. The time-to-reclassification analysis suggested that use of information about English language development is critical for making accurate predictions of the time a student will reclassify in this Arizona school district.

A proposta deste trabalho consiste na aplicação de dados de concentração de sedimentos em suspensão, na zona de arrebentação das ondas, para quantificar o transporte longitudinal que ocorre no Litoral Norte do Estado do Rio Grande do Sul – Brasil. Os dados de suspensão foram coletados a partir de uma estrutura construída perpendicularmente à linha de praia (Plataforma de Pesca de Tramandaí). As amostragens foram feitas, de modo a cobrir a zona de arrebentação, para diferentes distâncias do fundo. Verificou-se ao longo do trabalho, que o valor médio da concentração de sedimentos em suspensão (C) em quilogramas massa por metro linear de praia, apresentou como propriedade principal, uma forte proporcionalidade com a área da seção (S), ao longo do perfil, (C(kg;m) = 3,10-4 S2 + 0,1173 S). Utilizando esta particularidade, foi proposto um modelo utilizando as equações do perfil de equilíbrio de Dean (1977) para gerar o perfil de fundo. O limite deste foi obtido pela profundidade do ponto de arrebentação, determinada através da metodologia proposta por Herbich (2000). A área foi obtida por integração da equação de Dean, entre a linha de praia e o limite da zona de arrebentação. Através da propriedade citada acima, obteve-se a concentração total de sedimento entre a linha de praia e a arrebentação. O fluxo de sedimento foi obtido pelo produto da concentração total pela velocidade de corrente obtida pela aplicação da equação de Longuet-Higgins (1970). Os dados de ondas utilizados foram obtidos a partir de previsões fornecidas pela NOAA (National Oceanic Atmospheric Administration), para o ano de 2009. Observou-se ainda, que a direção do transporte resultante foi de SW para NW, em acordo com observações geológicas. O valor encontrado foi 314.799,10 m3/ano. / The purpose of this work is the application of data of suspended sediment concentration in the breaking zone waves, to quantify the longitudinal transport that occurs on the northern coast of Rio Grande do Sul - Brazil. The data of suspended sediment were collected from a structure built perpendicular to the beach line (Fishing Platform Tramandaí). The samples were taken so as to cover the breaking zone for different distances from the bottom. It was found during the study, the mean value of the suspended sediment concentration (C) in kg weight per linear meter of sand, presented as a main property, a strong proportionality to the sectional area (S) along the profile (C (kg/m) = 3.10-4 S2 + 0,1173S). Utilizing this characteristic, we propose a model using Dean’s (1977) equations of equilibrium profile, to generate the bottom profile. The limit of this was obtained by the depth of the point of breaking, determined using the methodology proposed by Herbich (2000). The area was obtained by integrating the equation Dean between the beach line and the limit of the breaking zone. Through the property mentioned above, there was obtained a total concentration of sediment between the beach line and breaking zone. The flux of sediment was obtained by the product of total concentration and the velocity of flux obtained by applying the equation Longuets-Higgins (1970). The wave data used were obtained from forecasts provided by NOAA (National Oceanic Atmospheric Administration) for the year 2009. It was also observed that the direction of transport resulting from SW to NW, in agreement with geological observations. The value found was 314799,10 m3/year.

abstract: This paper investigates a relatively new analysis method for longitudinal data in the framework of functional data analysis. This approach treats longitudinal data as so-called sparse functional data. The first section of the paper introduces functional data and the general ideas of functional data analysis. The second section discusses the analysis of longitudinal data in the context of functional data analysis, while considering the unique characteristics of longitudinal data such, in particular sparseness and missing data. The third section introduces functional mixed-effects models that can handle these unique characteristics of sparseness and missingness. The next section discusses a preliminary simulation study conducted to examine the performance of a functional mixed-effects model under various conditions. An extended simulation study was carried out to evaluate the estimation accuracy of a functional mixed-effects model. Specifically, the accuracy of the estimated trajectories was examined under various conditions including different types of missing data and varying levels of sparseness. / Dissertation/Thesis / Masters Thesis Psychology 2016