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The tsetse transmitted fatal disease of humans, sleeping sickness, is caused by two morphologically identical subspecies of the parasite T. brucei; T. b. rhodesiense and T. b. gambiense. Current distributions of the two forms of disease are not known to overlap in any area, and Uganda is the only country with transmission of both. The distribution of Rhodesian sleeping sickness in Uganda has expanded in recent years, with five districts newly affected since 1998. This movement has narrowed the gap between Rhodesian and Gambian sleeping sickness endemic areas, heightening concerns over a potential future overlap which would greatly complicate the diagnosis and treatment of the two diseases. An improved understanding of the social, environmental and climatic determinants of the distribution of Rhodesian sleeping sickness is required to allow more effective targeting of control measures and to prevent further spread and possible concurrence with Gambian sleeping sickness. The work presented in this thesis investigates the drivers of the distribution and spread of Rhodesian sleeping sickness in districts of central and eastern Uganda which form part of the recent disease focus extension. The spatial distribution of Rhodesian sleeping sickness was examined in Kaberamaido and Dokolo districts where the disease was first reported in 2004, using three different methodologies. A traditional one-step logistic regression analysis of disease prevalence was compared with a two-step hierarchical logistic regression analysis. The two-step method included the analysis of disease occurrence followed by the analysis of disease prevalence in areas with a high predicted probability of occurrence. These two methods were compared in terms of their predictive accuracy. The incorporation of a stochastic spatial effect to model the residual spatial autocorrelation was carried out using a Bayesian geostatistical approach. The geostatistical analysis was compared with the non-spatial models to assess the importance of spatial autocorrelation, to establish which method had the highest predictive accuracy and to establish which factors were the most significant in terms of the disease’s distribution. Links between Rhodesian sleeping sickness and landcover in Soroti district were also assessed using a matched case-control study design. Temporal trends in these relationships were observed using an annually stratified analysis to allow an exploration of the disease’s dispersion following its introduction to a previously unaffected area. This work expands on previous research that demonstrated the source of infection in this area to be the movement of untreated livestock from endemic areas through a local livestock market. With regards to the comparison of regression frameworks, the two-step regression compared favourably with the traditional one-step regression, but the Bayesian geostatistical analysis outperformed both in terms of predictive accuracy. Each of these regression methods highlighted the importance of distance to the closest livestock market on the distribution of Rhodesian sleeping sickness, indicating that the disease may have been introduced to this area via the movement of untreated cattle from endemic areas, despite the introduction of regulations requiring the treatment of livestock prior to sale. In addition, several other environmental and climatic variables were significantly associated with sleeping sickness occurrence and prevalence within the study area. The temporal stratification of the matched case-control analysis highlights the dispersion of sleeping sickness away from the point of introduction (livestock market) into more suitable areas; areas with higher proportions of seasonally flooding grassland, lower proportions of woodland and dense savannah and lower elevations. These findings relate to the habitat preferences of the predominant vector species in the study area; Glossina fuscipes fuscipes, which prefers riverine vegetation. The findings presented highlight the importance of the livestock reservoir as well as the climatic and environmental preferences of the tsetse fly vector for the introduction of Rhodesian sleeping sickness into previously unaffected areas, the subsequent spread of infection following an introduction and the equilibrium spatial distribution of the disease. By enhancing the knowledge base regarding the spatial determinants of the distribution of Rhodesian sleeping sickness within newly affected areas, future control efforts within Uganda may be better targeted to decrease prevalence and to prevent further spread of the disease.

C. imicola has been described as a species complex in South Africa on the basis of taxonomy, with at least seven species world-wide. Phylogenetic validity of five taxa within the Imicola group, namely C. imicola s.s., C. loxodontis, C. bolitinos and two currently unconfirmed species - Culicoides Sp. 30 (tuttifruitti) and Culicoides Sp. 107 (kwagga), were established using mtDNA COI sequence data, which confirmed their identity, not only as separate genetic entities, but also in exact correlation with the sibling species based on morphological and ecological parameters. In addition, the separate species status was reinforced for C. kwagga and C. tuttifrutti, which showed BCL of 100 with respect to C. imicola, using sequence data from the ITS-2 nuclear rRNA gene spacer region, and the mtDMA 16S gene respectively. Phylogeographical studies were undertaken using all three genomic regions, and revealed that C. imicola is present in Europe as C. imicola in sensu stricto, which acts as the vector for AHSV and BTV in this region. Intra-specific variation was highest in the COI amplicon, and extremely low in both ITS-2 and 16S regions. Phylogenetic resolution of internal clades was poorly supported for each gene region, and haplotype sharing suggests that the C. imicola populations across this wide geographical range are highly heterogeneous, with a high degree of haplotype mixing. Ecological field studies were carried out in farmyards in Spain and Portugal. When population composition of C. imicola was determined alongside host preference, it was found that although C. imicola are present in farms around cows, domestic fowl and pigs, they are present in higher numbers, comprise a higher total % of Culicoides caught and are present in a more stable population around horses. These results have serious implications for the spread of AHSV in these regions of Iberia where equestrian stud farms, producing quality polo and racing horses, play a significant part in the economy of the area.

Although virtual reality (VR) head-mounted displays (HMD) have been in use since the mid-1960s, the surge in public awareness and access to VR had spurred an increased interest in all industries to investigate the potential of VR as an interaction modality associated with high subjective presence. Many challenges need to be addressed through the disciplined application of research methods, especially combating VR sickness, if this potential is to be realised. This Engineering Doctorate thesis reports a series of investigations within the context of real-world development with a partner company (BMT Defence Service, a naval engineering consultant). The primary interest of the thesis is in the potential of VR for developing cases and uses for this technology in training. The target modality of training was a portable set-up, i.e. sitting down with a laptop, HMD and a game controller. This set up would prove beneficial for providing axillary training to personnel who are not always able to receive regular on-board training. It would also prepare people for situations which are difficult to simulate in real-world conditions. Example cases included familiarisation, line of sight tests, hazard recognition and evacuation procedures. An initial study of VR HMD experience in training scenario highlighted VR sickness as a key limiting factor for usability thus focusing the research on identifying and reducing the factors which induce VR sickness. Prior research suggest that static field of view restrictions could help but only at the cost of loss of presence. There were no reported studies of the effects of restricting the field of view dynamically thus this thesis presents two investigations of dynamic Field of View (FOV) constriction triggered by movement in a virtual space. It was hypothesised that a reduction in FOV reduced the induction of VR sickness. The problem with doing so however was that it may negatively influence presence as the change in FOV could distract the user. This thesis reports the development of a method for adjusting FOV to reduce simulator VR without loss of presence. Two dynamic FOV constriction studies are reported. The first failed to demonstrate a clear effect but subjective user reports suggested methodological and experiential issues in its design. Meanwhile, research into a similar method was published at the 3DUI Symposium at IEEE VR 2016. Fernandes \& Feiner (2016) \cite{DynamicFOV_Feiner16}, who demonstrated that dynamic FOV constriction can reduce VR sickness without compromising presence. However, their work used interaction scenarios with normal walking in an unchallenging virtual environment. Users were not subject to the types of motion which literature suggests are most likely to induce sickness. Consequently, the second DFOV constriction study tested VR sickness reduction in more discomforting situations via involuntary movements and animations on the virtual character and camera. Many of these animations and movements are typical in first-person applications and yet are absent from VR applications. These include for example head-bobbing, falling animations, stumbling, and forward rolls. The aim was to test whether DFOV constriction could allow VR developers to include such facets in future development. It showed that extreme movements still generate VR sickness, despite the use of DFOV constriction, but subjective reports suggest some users appear to benefit. Further research is recommended on introducing user control to the extent of DFOV manipulation. The thesis concludes with an evaluation of the state-of-the-art in DFOV constriction as a general approach to immersive VR interactions, including how the human vestibular system may limit DFOV effectiveness as a means of controlling VR sickness.

This study offers a close, interdisciplinary reading of several specific instances in which health and sickness were discussed or considered by Locke and his contemporaries. Medical historians have long known that Locke was a medical adviser and practitioner of sorts, and his medical 'cases' have traditionally been scrutinised for details of his medical career and for details of past illnesses and treatments, read against a context of specifically medical thought. In a departure from that tradition, this study presents several of Locke's health-related interactions in their contemporary social contexts, These contexts are not exclusively medical, and it is shown how health issues overlapped with and permeated discussions of land, literature, gender, politics and religion. Focussing on specific micro-historical scenes, this study explores the myriad ways in which health was configured in Locke's world. In this study, we see Locke engaged in presenting the health of a colony in Carolina in America; employed in the management of Anthony Ashley Cooper's festering abscess; writing to the Fletchers of Saltoun about nature-hastening medicines and ignorant practitioners; subduing rumours about Matthew Slade, a mentally unstable scholarly friend; helping Elizabeth Northumberland to describe her searing pains, and more. In this thesis, stories of health from Locke's world are interwoven with similar short scenes of health from his published works to show the reader how Locke himself considered health-related scenes stimulating and illuminating.

Trypanosome alternative oxidase (TAO) is the sole terminal oxidase responsible for the aerobic respiration of the parasite T. b. brucei. Specific strains of this parasite cause the neglected tropical disease Human African trypanosomiasis (HAT), and thus TAO is an interesting target for the potential treatment of this disease. Inhibition of TAO with the natural product inhibitors colletochlorin B or ascofuranone has been shown to clear infections of T. b. brucei in mice at high concentrations. However, these natural product inhibitors contain undesirable chemical functionality and have poor physicochemical properties, preventing adequate drug exposure to effectively treat HAT. Robust protocols for the expression and purification of recombinant TAO were developed, which enabled the development of biochemical assays to identify inhibitors of TAO function. Single point inhibition screening of the Medicines Malaria Venture 'kinetoplastid collection' of 400 compounds identified a range of micro-molar inhibitors of TAO. A program of chemical optimisation was carried out around the natural product inhibitor colletochlorin B, with the aim to improve the physicochemical properties and retain inhibitory potency against TAO. The structure activity relationships generated over the course of this exploration identified a dependency on high lipophilicity to retain potent TAO inhibition. The TAO inhibitors synthesised were also assessed for parasite growth inhibition and mammalian cell cytotoxicity to correlate inhibition data with cellular efficacy, in collaboration with Novartis. The physicochemical properties of these novel compounds showed improvement over the natural product colletochlorin B and prompted further assessment of leading compounds in advanced parasite kill kinetic and parasite clearance assays at Novartis. The data generated in these assays for compounds synthesised in this thesis determined that TAO inhibition results in a trypanostatic response, and not a preferred trypanocidal response in T. b. brucei.

This thesis is the main product of a Masters degree in Health Science, written by a student at the Department of Social Work and Health Science at Norwegian University of Science and Technology. The thesis discusses sickness presenteeism in general and sickness presenteeism among nurses in particular. Nursing is one of the occupations that are more exposed to sickness presenteeism. Despite this, very little research has yet been done on this correlation – in Norway, almost none. The thesis consists of two articles. The first article presents the concept of sickness presenteeism along with existing theories and research in general and concerning nurses. This is a theoretical article, in which the purpose is to identify why sickness presenteeism is not an ideal situation for nurses and which work-related factors that influence sickness presenteeism among nurses. The research question for this article is “What work-environmental factors have an influence on nurses sickness presenteeisem?” The second article is an empirical article and is done in connection with a survey of nurses’ sickness presenteeism within a Norwegian hospital. The survey examines the connection between sickness presenteeism and the use of substitutes, different working time arrangements and the influence of teamwork. The purpose of this article is to assess how the three work-environmental factors influences nurses’ sickness presenteeism, conducted with the help of three hypotheses. These are: H1: Working-time arrangements have an influence on sickness presenteeism H2: Low extent of using substitutes is related to higher level of sickness presenteeism H3: Good working relationship between co-workers is related to higher level of sickness presenteeism The empirical work for this master’s thesis has been conducted using a quantitative method. This method was chosen based on a desire to investigate the extent, distribution and differences within sickness presenteeism among nurses. A quantitative method gives an opportunity to investigate a larger group of nurses, and obtain results that can also be valid for other nurses. If a qualitative method were to be used, it would not have been possible to collect information from the same number of nurses and the results would most likely not represent nurses in general because of assumed differences between nurses. By using a qualitative method I was also able to compare the results with results from similar studies done in other countries. Still, the quantitative method has little room for a flexible approach to theory, and does not provide information about what might cause the sickness presenteeism. I still found this method to be the most suitable for what I wanted to achieve in this master’s thesis. A survey based on questions used by other researchers with an interest in the same field, was used to collect data. Using questions that others had already used made the results easier to compare, and also acted as some kind of quality control to the questions I first developed. The choices made concerning the survey, items and analysis is further described in chapter 2.0 Method of my empirical article. The strength and limitations of the method is discussed in chapter 4.1 Strengths and limitations of that same article.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 95-104).