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The aim of this thesis is to explore the role of common genetic variation, identified through genome-wide association (GWA) studies, in human traits and diseases, using height as a model polygenic trait, type 2 diabetes as a model common polygenic disease, and maturity onset diabetes of the young (MODY) as a model monogenic disease. The wave of the initial GWA studies, such as the Wellcome Trust Case-Control Consortium (WTCCC) study of seven common diseases, substantially increased the number of common variants associated with a range of different multifactorial traits and diseases. The initial excitement, however, seems to have been followed by some disappointment that the identified variants explain a relatively small proportion of the genetic variance of the studied trait, and that only few large effect or causal variants have been identified. Inevitably, this has led to criticism of the GWA studies, mainly that the findings are of limited clinical, or indeed scientific, benefit. Using height as a model, Chapter 2 explores the utility of GWA studies in terms of identifying regions that contain relevant genes, and in answering some general questions about the genetic architecture of highly polygenic traits. Chapter 3 takes this further into a large collaborative study and the largest sample size in a GWA study to date, mainly focusing on demonstrating the biological relevance of the identified variants, even when a large number of associated regions throughout the genome is implicated by these associations. Furthermore, it shows examples of different features of the genetic architecture, such as allelic heterogeneity and pleiotropy. Chapter 4 looks at the predictive value and, therefore, clinical utility, of variants found to associate with type 2 diabetes, a common multifactorial disease that is increasing in prevalence despite known environmental risk factors. This is a disease where knowledge of the genetic risk has potentially substantial clinical relevance. Finally, Chapter 5 approaches the monogenic-polygenic disease bridge in the direction opposite to that approached in the past: most studies have investigated genes mutated in monogenic diseases as candidates for harboring common variants predisposing to related polygenic diseases. This chapter looks at the common type 2 diabetes variants as modifiers of disease onset in patients with a monogenic but clinically heterogeneous disease, maturity onset diabetes of the young (MODY).

The general aims of the thesis were to study GH responsiveness by estimation of pharmacokinetics and bioavailability of injected recombinant human GH (rhGH), of growth response as gain in heightSDS during childhood and puberty, and IGF-I response as change in circulating IGF-ISDS and IGFBP3SDS. Methods Short children were recruited during 1988–1999 into two national randomized multicentre clinical trials on growth until adult height. A group of 117 GHD patients who had been treated from prepuberty with a single GH dose of 33μg/kg/day for at least 1 year were randomized at onset of puberty either to remain on this dose regimen or to an increased dose, GH67μg/kg/day, administered once daily or divided into two doses, GH33x2μg/kg/day. Data on IGF-ISDS and IGF binding protein 3 (IGFBP3)SDS were available from 111 patients and analysed as stated below. The 151 short prepubertal non-GHD patients were randomized into three groups: untreated controls, GH33 or GH67μg/kg/day. A subpopulation from both trials, 128 patients examined annually in Gothenburg, formed the study sample on GH uptake. They received sc GH injections to obtain 16–24 hour GH curves and the GH pharmacokinetics and bioavailability was calculated. Results: A dose-dependent effect on Cmax was found with great intra- and inter-individual variability. Of the Cmax variability, 43% was explained by the rhGH dose and proxies for injection depth. Median bioavailability of the injected dose was 71%, with great variation, mainly dependent on injection depth. In the IGHD group a dose-dependent difference in pubertal gain in heightSDS was found, with mean of 0.8 for the GH67 group and 0.4 for GH33, p<0.01. The mean total gain in heightSDS during treatment was 1.9 for GH67 and 1.4 for GH33, p<0.01. A dose-dependent pubertal ΔIGF-ISDS was 0.5 vs −0.1, p=0.007, correlating to pubertal gain in heightSDS, p=0.003; and was the most important variable to explain the variation in pubertal gain in heightSDS. In the non-GHD group the ΔIGF-ISDS from baseline to mean study level was dose-dependent 2.07 vs 1.20, p=0.001; and correlated negatively with baseline values of IGF-ISDS, rho= -0.56 for GH67, p=0.001, vs rho= -0.82 for GH33, p=0.0001, and correlated positively with gain in heightSDS in both GH-treated groups, rho= 0.42, p<0.001. In multivariable regression analyses, ΔIGF-ISDS was always an important explanatory variable for long-term growth response from the prepubertal period until adult height, while the IGF-ISDS study level per se was not. Conclusion: Growth response to GH treatment was dose dependent with great variability between patients. More pubertal growth was attained by an increased rhGH dose, mimicking the physiology of healthy children, in whom GH secretion rate increases during puberty. This resulted in a gain in IGF-ISDS closely correlating to pubertal gain in heightSDS in both IGHD and non-GHD patients. A broad range in GH responsiveness was found for both growth and IGF response in both diagnostic groups, but lower in the non-GHD group. Higher uptake of a given GH dose was observed after a deep injection and a higher GH concentration. These results are clinically applicable for individuals who remain short close to onset of puberty; by identifying and deeply injecting a rhGH dose that accounts for individual responsiveness, we can stimulate an increment in IGF-ISDS that correlates to gain in heightSDS during puberty.

Many researchers have investigated ways to improve the separation power of conventional chromatography, most notable is the development of ultra-high performance liquid chromatography (UHPLC). However, only slight improvements in separation efficiency have been achieved up to this point, and unfortunately, modern reversed phase liquid chromatography (RPLC) methods do not have high enough resolving power to analyze complex proteomic mixtures.Uniformly sized silica particles from 10 nm to 1 micron are known to self-assemble into a highly ordered face centered cubic crystal. Silica colloidal crystals have shown recent promise in biological applications such as permselective nanoporous membranes, DNA sieving, reversed phase separation of small molecules on planar substrates, protein sieving, microarrays, total internal reflection fluorescence microscopy of live cells, and 3-D scaffolds for supported lipid films. In this work, silica colloidal crystals packed in capillaries are explored for their potential improvement in the efficiency of reversed phase chromatography.The silica colloidal crystal columns were chemically stabilized by with trichlorosilanes. The trichlorosilanes form chemical bonds between the particles and the particles and the substrate creating an increase in mechanical stability, and at the same time, providing an excellent chromatographic monolayer. After stabilization the fritless columns were able to withstand the pressure limit of the commercial UHPLC. Next, the columns were characterized using a small dye molecule, 1,1' - Didodecyl - 3,3,3',3' - tetramethylindocarbocyanine (DiIC12). The dye was run under capillary electrochromatography (CEC), and sub-micron plate heights were achieved. Further, a van Deemter plot of the dye molecule indicates that the plate height is largely due to the molecule's diffusion. This result suggests that the plate heights for proteins would be even smaller, since proteins have diffusion coefficients an order of magnitude smaller. The analysis of proteins by CEC yielded nanometer plate heights. Finally, pressure driven flow separations coupled with nano-electrospray ionization (n-ESI) MS have also been explored. The Poiseuille flow profile has been shown not to perturb the low plate heights. Gradient elution of peptides was also achieved, and the results demonstrate the highest chromatographic peak capacities for short analysis times to date.

Minorities are significantly overrepresented in America's prison population, and many studies have been conducted to determine possible causes for such a disparity. Few of these studies, however, have examined small stature as a potential contributor to criminal behavior. This study examines the relationship between criminal behavior and stature among American males. The heights, weights, stature scores (a function of the product of height and weight) and the body mass indices of criminals are examined as a whole, as well as by subgroup based on race, locality, and nature of the crime committed. The average weight of the male criminal population is substantially lower than that of the general male population. The center of the height distribution for urban criminals is found to be lower than men who commit crimes in suburban or rural areas, as is the center of the weight distribution for index criminals when compared to non-index criminals. Murderers demonstrate the smallest mean and median heights and weights when compared to the rest of the criminal population. Although small stature can be associated with certain crimes and localities, size cannot be associated with the racial disparity in today's prisons.

Title: Selected parameters of gait and foot in consideration of the individual's body height Objectives: This thesis deals with a dependence of the selected gait and foot characteristics on a person's body height. These parameters are compared between a group of men and a group of women. In addition, a validity of selected formulas used for a determination of body height is evaluated. Methods: Mutual relation among the gait and foot characteristics and the individual's body height is observed. The thesis is a descriptive - association research, the comparative method is chosen in the practical part of the thesis. For an objectification of the research, the Plantograph and the 3D kinematic gait analysis performed by Qualysis system was used. Results: It was found out that the selected formulas used for a determination of body height are valid. The best results are brought by the formulas which count with a length of a bare foot, the length of a step and a double-step. On the contrary, the worse results are achieved by using the formulas which count with the dimension of shoe print. A tight dependence of the foot length and the length of the step / double-step on the body height was proven. A minimum dependence of the foot width on the body height was proven. Nevertheless the foot width is verifiably...

Vehicular Ad hoc NETworks (VANETs), an emerging technology, use vehicles as nodes to form a mobile ad hoc network for the dissemination of safety and entertainment messages. The thesis provides a scheme for the fast propagation of messages in VANETs and evaluates the impact of vehicles as obstacles on signal propagation. An improved scheme for intermediate node selection in DBA-MAC (Dynamic Backbone Assisted MAC) is proposed, which consists of a CW (Contention Window) constraint scheme and an updated criterion of suitability. A performance comparison shows that messages in the proposed scheme propagate faster than in DBA-MAC. The CW constraint scheme is also applicable in VANET protocols which adapt the CW mechanism to communicate the suitability of vehicles for acting as intermediate nodes. Additionally, the mathematical models for DBAMAC and the proposal are established, which indicate the probability of candidates to be chosen over alternatives in the intermediate node selection. A novel metric - delay taking into account the effect of formation time(DEFT) - is proposed. DEFT combines the network formation time and propagation delay. It shows the impact of network formation on propagation latency. The configuration for optimal performance can be acquired using the proposed DEFT. In order to evaluate the proposals, a novel distribution of vehicle location is proposed. In the proposed distribution, the security distances between adjacent vehicles in the same lane are considered. The estimation of vehicles’ location can be more practical and accurate using the proposed distribution. In the wide body of the VANET literature, it is assumed that all the vehicles within the radio range of a transmitter are able to receive the signal. Yet, in practice, the vehicles as obstacles between the transmitter and the receiver affect the signal propagation significantly. This thesis presents the impact of these obstacles on the network connectivity and system performance of the protocols. The results and the analysis show that neglecting obstacles in practice leads to a significant degree of error in the estimation of system performance. In practice, tall vehicles forward messages in a more efficient way than do lower vehicles since they are free from the obstacle effect. An improved scheme is proposed, in which the height of vehicles is used as a factor to determine their suitability for message forwarding.

A avaliação nutricional e o acompanhamento do estado nutricional dos pacientes de uma instituição são fundamentais para o planejamento e avaliação do serviço nutricional oferecido. Dentre os métodos de avaliação, a antropometria é recomendada por ser fácil, rápida e segura para ser empregada. Dentre os dados mais comuns o peso e a altura costumam fundamentar a avaliação do estado nutricional, e fundamentam os cálculos da terapia nutricional e doses farmacológicas. Visto que, tais medidas são difíceis de serem realizadas em pacientes acamados, e que na literatura, as equações sugeridas para estimativa de altura e peso são baseadas em amostras de idosos. O objetivo deste trabalho foi de verificar a adequação destas fórmulas, e desenvolver equações apropriadas, para a população hospitalizada local. A metodologia utilizada para elaboração das equações preditivas foram a antropometria, dobras cutâneas, circunferências, comprimentos; e bioimpedância. Considerando que as formas de estimativa de peso e altura sugeridas na literatura apresentaram diferença significativa das medidas nesta amostra; e visando facilitar a metodologia de estimativa de peso, foram desenvolvidas quatro equações para peso e duas para altura. As novas equações parecem ser apropriadas, sendo a mais simples delas, para estimativa de peso, a equação: Peso (kg) = 0,8956 (circunferência do braço, cm) + 0,3858 (circunferência abdominal, cm) + 1,1180 (circunferência da panturrilha, cm) - 31,759 (r = 0,88 e p> 0,05); e Altura (m) = 83,8750 - 4,3810 (masculino = 2 e feminino = 1) - 0,0872 (idade ,anos) + 1,0840 (meia envergadura, cm), (r = 0,86 e p > 0,05). Sugerimos que estas equações possam ser utilizadas para estimar peso e altura de pacientes acamados. / Anthropometry, including weight and height, is considered as an easy, a fast and a safe procedure for nutritional status evaluation. Body weight (W) and height (H) are both indicators of nutritional status changes and together with others body measurement, is a tool for nutritional therapy and medicine doses prescription. Regarding the impossibility to obtain these measurements from those individuals who cannot stand, formulas to estimate weight and height, based on elderly subjects, have been used for all adults patients. The aim of the current protocol was search, for easily acquired anthropometric measurements and bioimpedance, formulas to estimate weight and height from hospitalized patients. For the construction of predictive equations, anthropometry (skinfold thickness, circumferences, lengths) and bioelectrical impedance analysis were applied. Four equations suggested to estimate body weight, and two for body height the simplest are: W (Kg) = 0,8956 (arm circumference, cm) + 0,3858 (abdominal circumference, cm) + 1,1180 (calf circumference, cm) - 31,759 ( r = 0,88, p > 0,05); and H (m) = 83,8750 - 4,3810 (male = 1 e female = 2) - 0,0872 (age ,year) + 1,0840 (half spread ,cm) (r = 0,86 e p > 0,05). Residuals analysis showed that the error from both formulas was less than 5% (95% range variation). Therefore, when is impossible to get weight or height we suggested the use of those formulas.

Este estudo teve por hipótese que o manejo de pastos de Tifton 85 baseado em parâmetros ingestivos dos animais (pastoreio Rotatínuo – RN), resulta em colheita do pasto mais eficiente que no manejo tradicional. Foram estudadas três estratégias de manejo de pastoreio rotativo em pastos de Tifton 85 pastejados por novilhas leiteiras no Sul do Brasil. Os tratamentos consistiam em variações de critério de altura de pasto para entrada e retirada dos animais. O primeiro tratamento foi o método de pastoreio rotativo “clássico” (máximo aproveitamento do pasto) com metas de altura de manejo pré-pastejo de 30 cm e pós-pastejo de 5 cm (30-05). O segundo tratamento foi o Rotatínuo (RN) que permite a máxima taxa de ingestão de forragem, com altura pré-pastejo de 19,2 cm e pós-pastejo de 11,5 cm. No terceiro tratamento foi utilizada uma proposição de rebaixamento de apenas 40% da altura pré-pastejo tradicionalmente recomendada no país, 30 cm de altura pré-pastejo e 18 cm de altura pós-pastejo (30-18). Foram utilizados animais da raça Holandês, com idade de 20±2 meses e peso médio de 496±22 kg. O delineamento experimental foi em blocos completos casualizados com três repetições. O período experimental foi de 67 dias, entre 14 de janeiro a 22 de março de 2014. Os número de pastejos chegaram a 7 para o RN, 2 para o RT e 5 para o 30-18. A taxa de ingestão de forragem foi semelhante entre os tratamentos. Para manter a taxa de ingestão constante os animais utilizaram diferentes componentes do comportamento. No tratamento 30-05 os animais apresentaram maior massa do bocado, e no RN maior taxa de bocado (P<0,05). O RN obteve maior taxa de acúmulo diária de forragem frente aos demais tratamentos, maior massa de forragem colhida e maior eficiência de colheita do pasto (P<0,05). A adoção de metas de manejo do pasto via alturas pré e pós-pastejo definidas por parâmetros ingestivos, conforme previsto no Rotatínuo, possibilitou obter adequada eficiência de colheita de pasto, sem comprometer o potencial de regeneração dos pastos. / This study hypothesized that the grazing management of Tifton 85 based on animal ingestive behavior parameters (Rotatinuous grazing - RN), results in higher harvesting efficiency than traditional management. Three rotational grazing management strategies were tested on Tifton 85 pastures grazed by dairy heifers in southern Brazil. The treatments were different sward height targets to put and take the animals from the strip. The first treatment was the traditional rotational grazing method named "Classic" (maximum pasture harvest) with pre-grazing height of 30 cm and post-grazing of 5 cm (30-05). The second treatment was named Rotatinuous (RN), aimed to maximize the animal herbage intake rate, where the pre-grazing height was 19.2 cm and post-grazing of 11.5 cm. In the third treatment it was proposed the grazing down of 40% of pre-grazing height traditionally recommended in Brazil (30 cm), resulting in 30 cm and 18 cm of pre and post-grazing height, respectively (30-18). Holstein animals, aged 20 ± 2 months, were used with an average weight of 496 ± 22 kg. The experimental design was a randomized complete block design with three replicates. The experimental period was 67 days, from 14 January to 22 March 2014. The numbers of grazing cycles were 7 on RN, 2 on 30-05 and 5 on 30-18 treatments. Herbage intake rate did not differ among treatments (P>0.05). The animals behaved differently using distinct grazing behavior strategies during the grazing down in order to reach the same level of intake rate. In the treatment 30-05 animals presented higher bite mass, whist RN higher bite rate (P <0.05). The RN had higher daily herbage accumulation rate, amount of forage harvested and pasture harvest efficiency (P <0.05). The grazing management goals defined by ingestive parameters (Rotatínuous) provided adequate pasture harvest efficiency without compromising pasture regrowth potential.

A síntese de imagens é uma ferramenta valiosa na compreensão de diversos fenômenos da natureza. Nos últimos anos várias abordagens têm sido propostas para sintetizar tais fenômenos. A grande maioria de tais abordagens têm se centralizado no desenvolvimento de modelos procedurais. Porém, cada uma destas técnicas simula exclusivamente um fenômeno natural. Um dos métodos de síntese de imagens fotorealísticas mais proeminente é denominado de Traçado de Raios (Ray Tracing). Contudo, apesar de produzir imagens de excelente qualidade, este método é computacionalmente muito oneroso. A síntese de fenômenos naturais utilizando-se o traçado de raios é um desafio. É importante que este problema seja abordado, apesar da sua complexidade, pois a simulaçao fotorealista da natureza é muito importante para os cientistas e pesquisadores desde o surgimento dos computadores. Um algoritmo versátil e rápido para a síntese de fenômenos da natureza através do traçado de raios utilizando campos de altitude é proposto. O algoritmo utiliza uma modificação do algoritmo do Analisador Diferencial Digital de Bresenham para atravesar uma matriz bidimensional de valores de altitude. A determinação das primitivas geométricas a serem interseccionadas por um raio é obtida num tempo ( N ) , sendo N o número de altitudes no campo de altitude. Este trabalho faz uma comparação em termos de velocidade e realismo deste método com outras abordagens convencionais; e discute as implicações que a implementação deste método traz. Finalmente, destaca-se a simplicidade e versatilidade que este método proporciona devido à pequena quantidade de parâmetros necessária para a síntese de fenômenos naturais utilizando o traçado de raios. Para a criação de animações basta a especificação de novos parâmetros num intervalo de tempo diferente. / Visualization is a powerful tool for better undestanding of several natural phenomena. In recent years, several techniques have been proposed. Considerable interest in natural scene synthesis has focused on procedural models. However, these techniques produce synthetic scenes of only one natural phenomenon. Ray tracing is one of the most photorealistic methods of image syntesis. While providing images of excellent quality, ray tracing is a computationally intensive task. Natural scene synthesis is a challenging problem within the realm of ray tracing. It is important to tackle this problem, despite of its complexity, because photorealistic simulation have been important to scientific community since the appearance of computers. A fast and versatile algorithm for ray tracing natural scenes through height fields is presented. The algorithm employs a modified Bresenham DDA to traverse a two dimensional array of values. The objects tested for intersection are located in ( N ) time where N is the number of values in the field. This work compares the speed-up and photorealism achieved in natural scene synthesis using this method with other algorithms and discusses the implications of implementing this approach. As a final point, the simplicity and versatility of synthesizing complex natural scenes from a few parameters and data is especially attractive. Animated sequences require only the additional specifications of time modified parameters or data.