Mémoire de master 2e année : Histoire : Evry Val d' Essonne : 2008. / Titre provenant de l'écran-titre. Notes bibliogr. Bibliogr. p. 283-395.

Thesis (doctoral)--Universität zu Köln, 1982. / Added thesis t.p. Includes bibliographical references (p. [i]-xxvi).

Despite the medical advances in recent decades, cardiovascular disease (CVD) remains one of the leading causes of mortality in most developing countries. Ongoing efforts have been focused on evaluating new strategies targeting on novel risk factors. Vitamin D deficiency, a previously neglected condition, has recently attracted much attention from the scientific community with its potential extra-skeletal effects. There is accumulating evidence from epidemiological studies that a suboptimal 25-hydroxyvitamin D [25(OH)D] level is associated with all-cause and cardiovascular mortality, increased risk of coronary heart disease, stroke and peripheral vascular disease, and various traditional CVD risk factors including hypertension, diabetes mellitus (DM) and metabolic syndrome. Several theories have been proposed to explain these relationships but none receive universal recognition. There is recent laboratory evidence that vitamin D may exert specific effects in patients with DM. However, relationships between vitamin D deficiency and supplementation on vascular function in this group of patients are unclear. In this dissertation, I sought to explore the effects of vitamin D deficiency on vascular function in patients with type II DM in a cross-sectional study. In the later part, the results of a randomized controlled trial investigating the effects of daily vitamin D supplementation in type II DM patients are presented and discussed. The cross-sectional study (Chapter 3) investigated the association of vitamin D status with endothelial function as measured by brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in 280 patients with type II DM. The results showed that suboptimal vitamin D status was more common among patients with DM. Furthermore, patients with vitamin D deficiency had significantly lower brachial FMD (mean difference = -1.43%, 95% CI: -2.31 to -0.55, P = 0.001) and CD133/KDR+ EPC counts (mean difference = -0.12%, 95% CI: -0.21 to -0.02, P = 0.022) than those with sufficient vitamin D after adjustment for age, sex and cardiovascular risk factors, including HbA1c levels. Based on these positive results, the objectives of the randomized controlled trial (Chapter 4) were to study and confirm the effects of daily oral vitamin D supplementation on the vascular function in this group of patients. Over a 12-week period, 100 DM patients with suboptimal vitamin D status were randomized to receive 5,000 IU/day vitamin D or placebo. There were no reported adverse events including hypercalcemia, although a slight increase in serum ionized calcium (treatment effect 0.037 mmol/L, P = 0.018) was recorded in the vitamin D group. Despite a significant improvement in serum 25(OH)D in the treatment group, supplementation of vitamin D did not result in any significant improvement in vascular function as determined by FMD, circulating EPC count or arterial stiffness (all P > 0.05). Furthermore, the serum level of high-sensitivity C-reactive protein, oxidative stress markers, low- and high-density lipoprotein and glycated haemoglobin were also similar between two groups (all P > 0.05). The results of this study did not support a therapeutic role of supplementation with vitamin D for cardiovascular benefits. In conclusion, the results of these studies demonstrated that deficiency of vitamin D was associated with worse vascular function in patients with type II DM. However, vitamin D supplementation did not result in any significant benefits on vascular function or improvement in traditional CVD risk factors in DM patients. Further large clinical trials on vitamin D supplementation in patients with DM using clinical outcomes rather than surrogate CVD markers are necessary to confirm its benefits. / published_or_final_version / Medicine / Master / Master of Research in Medicine

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For any technology to become widely-used and accepted, it must support end-user authoring and customisation. This means making the technology accessible by enabling understanding of its design issues and reducing its technical barriers. Our interest is in enabling end-users to author dynamic virtual environments (VEs), specifically their interactions: player interactions with objects and the environment; and object interactions with each other and the environment. This thesis describes a method to create tools and design aids which enable end-users to design and implement interactions in a VE and assist them in building the requisite domain knowledge, while reducing the costs of learning a new set of skills. Our design method is based in constructivism, which is a theory that examines the acquisition and use of knowledge. It provides principles for managing complexity in knowledge acquisition: multiplicity of representations and perspectives; simplicity of basic components; encouragement of exploration; support for deep reflection; and providing users with control of their process as much as possible. We derived two main design aids from these principles: multiple, interactive and synchronised domain-specific representations of the design; and multiple forms of non-invasive and user-adaptable scaffolding. The method began with extensive research into representations and scaffolding, followed by investigation of the design strategies of experts, the needs of novices and how best to support them with software, and the requirements of the VR domain. We also conducted a classroom observation of the practices of non-programmers in VR design, to discover their specific problems with effectively conceptualising and communicating interactions in VR. Based on our findings in this research and our constructivist guidelines, we developed VRBridge, an interaction authoring tool. This contained a simple event-action interface for creating interactions using trigger-condition-action triads or Triggersets. We conducted two experimental evaluations during the design of VRBridge, to test the effectiveness of our design aids and the basic tool. The first tested the effectiveness of the Triggersets and additional representations: a Floorplan, a Sequence Diagram and Timelines. We used observation, interviews and task success to evaluate how effectively end-users could analyse and debug interactions created with VRBridge. We found that the Triggersets were effective and usable by novices to analyse an interaction design, and that the representations significantly improved end-user work and experience. The second experiment was large-scale (124 participants) and conducted over two weeks. Participants worked on authoring tasks which embodied typical interactions and complexities in the domain. We used a task exploration metric, questionnaires and computer logging to evaluate aspects of task performance: how effectively end-users could create interactions with VRBridge; how effectively they worked in the domain of VR authoring; how much enjoyment or satisfaction they experienced during the process; and how well they learned over time. This experiment tested the entire system and the effects of the scaffolding and representations. We found that all users were able to complete authoring tasks using VRBridge after very little experience with the system and domain; all users improved and felt more satisfaction over time; users with representations or scaffolding as a design aid completed the task more expertly, explored more effectively, felt more satisfaction and learned better than those without design aids; users with representations explored more effectively and felt more satisfaction than those with scaffolding; and users with both design aids learned better but did not improve in any other way over users with a single design aid. We also gained evidence about how the scaffolding, representations and basic tool were used during the evaluation. The contributions of this thesis are: an effective and efficient theory-based design method; a case study in the use of constructivism to structure a design process and deliver effective tools; a proof-of-concept prototype with which novices can create interactions in VR without traditional programming; evidence about the problems that novices face when designing interactions and dealing with unfamiliar programming concepts; empirical evidence about the relative effectiveness of additional representations and scaffolding as support for designing interactions; guidelines for supporting end-user authoring in general; and guidelines for the design of effective interaction authoring systems in general.

The plasma vitamin D binding protein (DBP) is an a-glycoprotein, synthesised and secreted by the liver, which binds specifically vitamin D and its metabolites. The DBP molecule, has a single high affinity binding site for its ligands, and is present in blood in concentrations about 1000-fold greater than the sum of all its vitamin D ligands. Previous studies have not found any change in the concentration of DBP related to various derangements in mineral homeostasis. Therefore the general view is that DBP has a passive role in the physiology of vitamin D and its metabolites, and simply acts to solubilise and transport these hydrophobic ligands in the aqueous extracellular fluid. However, differences which have been described in its affinity for various vitamin D metabolites suggest that there have been evolutionary influences on the properties of this protein. Furthermore, plasma DBP concentration has been found to change in response to a number of physiological factors, such as changing sex steroid hormone secretion. The aim of the studies presented in this thesis was to investigate variation in the plasma concentration of the DBP in a range of vertebrate species, and in response to a variety of physiological factors. The results suggest that DBP may have an active role in regulating the bioavailability, and hence the utilisation and metabolism of its ligands. DBP concentration has traditionally been measured using immunological techniques. These techniques, although fast and simple, have a number of draw-backs which can be overcome by the use of assays which rely upon functional aspects of the DBP. A saturation binding assay was modified from those described previously. Using this technique, it was found that both the circulating concentration of the DBP and its affinity for 25-hydroxyvitamin D3 (25(OH)D3) varied significantly among a wide range of species of reptiles and birds. This variation did not reflect phylogenetic relationships among the study species, suggesting that the variation was more likely to be the result of selective pressure in response to individual ecological or physiological circumstance, rather than to random mutation. In support of this, both the plasma concentration of DBP, and its affinity for 25(OH)D3 were significantly associated with a number of ecological factors which might be considered to have some significance to vitamin D and calcium homeostasis. In addition, comparative binding data suggests that the ability of the DBP to bind 25-hydroxyvitamin D2 with equal affinity to 25(OH)D3 is an evolutionary innovation of mammalian vertebrates. In order to extend the idea of genetic variation in the concentration and affinity of plasma DBP, two strains of broiler (meat-type) chickens were studied. It was found that both the concentration and the affinity of plasma DBP for 25(OH)D3 was characteristic for each strain, emphasising the sensitivity of DBP to genetic variation. A number of factors have been found to modulate the genetically determined plasma concentration of DBP. Deficiencies of dietary protein and dietary energy, and variation in concentrations of sex steroids were found to affect the circulating concentration of DBP. However, species differences were still apparent, suggesting that the sensitivity of DBP to these physiological modifiers may have developed independently in different species, and may be secondary to genetic determinants of DBP properties. The plasma DBP concentration and specific binding affinity both determine the availability of its ligands for cellular uptake. It is likely that this process is complex, and involves a combination of protein mediated and non-mediated uptake events. This makes DBP a potentially important determinant of the biological actions of its ligands. The studies in this thesis have produced two main lines of argument supporting an active role for DBP in the regulation of vitamin D metabolism and utilisation. The first is that genetic variation in the properties of plasma DBP appears to be genetically determined, and is selected for, both at the between-species, and the within-species level, than it is to random mutation. Secondly, the ability of physiological and environmental factors to modify the circulating concentration of DBP suggests that this protein is responsive to homeostatic processes. It is proposed that DBP is an active regulator of the physiological economy of vitamin D and its metabolites by being itself regulated by a number of genetic and non-genetic factors.

Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2003? / Includes bibliographical references (leaves 226-273.). Also available in an electronic version.

Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2002. / Includes bibliographical references. Also available in a print form.

Thèse (de maîtrise)--Université Laval, 2007. / Bibliogr.: f. 69-70. Publié aussi en version électronique dans la Collection Mémoires et thèses électroniques.