This thesis presents, discusses and critically evaluates the content and contribution of a selection of research papers published in international peer-reviewed sports science journals. Collectively, these works make a novel contribution to the field of motion analysis of physical performance in official professional soccer competition. Rather than being the result of an initial grand working plan, the programme of research represents the evolution and expression of the author's work over a period of 4 years in a professional soccer club. The research was partly shaped by the author's concomitant experience of the industry and academia but mainly driven by emerging and evolving needs-analyses identified within his work. A total of 1 review (presented in the thesis as an introduction to the field of study) and 9 original peer-reviewed articles are included. This thesis introduces and critically comments on papers within two main streams of work investigating competitive physical performance in the author’s own professional soccer team: a) general characteristics and position-specific demands of play, and; b) factors potentially affecting performance. The original research papers are presented in a conceptual sequence within the two themes, rather than a strictly chronological order so as to demonstrate the coherence and synergy within the two collections. The thesis provides critical reflection on the overall contribution to the current body of scientific knowledge and the collective impact of the papers that has been achieved. Limitations in study designs encountered over the course of the work are discussed as are current and future themes for research.

Community Based Tourism (CBT) emerged during the 1980s as a result of the increasing need to define and implement ways of addressing the challenges of tourism development in the destination through a ‘community approach’. It has since become a popular approach to tourism development that seeks to address the negative environmental and social impacts derived from such development whilst adopting the principles of sustainable development. Unsurprisingly, given its focus on benefiting and engaging local destination communities within tourism development, CBT has also attracted a significant degree of academic attention. However, such attention has been concerned primarily with the planning and management of CBT from a ‘supply’ perspective; conversely, a gap in the literature exists in regards to considering CBT as a tourism product in general, and from the perspectives and experiences of tourists in particular. In other words, limited attention has been paid to the demand for CBT as a tourism ‘product’. Therefore, the purpose of this study is to address this gap by developing an understanding of CBT from not only the perspective of the supply side but also from the perspective of the consumer, more specifically, both international and domestic tourists. Consequently, Pai, a well-known destination in Thailand for both international and domestic tourists was selected as a case study. Given the focus of this study on seeking to identify and appraise the perceptions and experiences of tourists consuming the CBT product, in-depth interviews were conducted to obtain rich and detailed data, the samples comprising 25 domestic and 25 international tourists. In addition, interviews were undertaken with the supply-side stakeholders, including three representatives of the local public sector administration and eight private sector respondents, including entrepreneurs and members of the local community, in order to understand the current situation with regards to CBT development in Pai. Brochure contents analysis was also undertaken in order to identify the contemporary ‘induced’ destination image of Pai as one influence on the destination choice and decision making process made by tourists. The outcomes of the interviews and contents analysis, along with a cross-cultural analysis of the responses of international and domestic tourists, revealed that the destination images held by both groups of tourists matched those portrayed by tour operators in the brochures. However, tourist knowledge and recognition of CBT in general, and Pai as a CBT destination in particular, were found to be limited. Nevertheless, international visitors in particular perceived the authenticity of the destination more so than domestic tourists, reflecting the differing characteristics and motivations based on their own cultures. Furthermore the community itself lacked the participation and unity required for CBT to be effective. Hence, this study concludes that not only does a destination such as Pai, that originally developed within a community based development policy framework, face significant challenges in developing tourism according to the principles of CBT, but also that tourist themselves have difficulty in understanding the concept of CBT. Nevertheless, the study reveals that, despite the differing perceptions and demands of international and domestic tourists, the potential exists to develop tourism in Pai to bring greater benefit to the local community. Therefore, the thesis proposes collaborative plans that are necessary to allow CBT managers to better design and develop strategies that enhance the community’s benefits from tourism, whilst meeting the needs of both international and domestic tourists.

Memoria para optar al Título Profesional de Médico Veterinario / Las poblaciones naturales de Trypanosoma cruzi, agente etiológico de la enfermedad de Chagas, presentan propiedades biológicas diferentes y es posible diferenciar dentro del taxón dos sublinajes, TcI y TcII, así como subgrupos de parásitos dentro de cada uno. El objetivo del presente estudio fue describir la diversidad molecular de las poblaciones de T. cruzi circulando en territorio chileno a partir de vectores silvestres de Mepraia spinolai y Mepraia gajardoi obtenidos de diferentes áreas de Chile. Para dicho objetivo se utilizaron dos partidores, p18 y p20, diseñados en base a la secuencia de la cepa Tulahuén de T. cruzi. 516 pb del gen mitocondrial para citocromo b fueron secuenciados de 17 muestras biológicas, y comparadas filogenéticamente con otras 50 secuencias Sudamericanas. La caracterización molecular de estas 67 secuencias en un filograma de máxima verosimilitud permitió la identificación de tres clados previamente conocidos (TcI, TcII, y TcV junto con TcVI). TcI y TcII son genotípicamente heterogéneos. Por su parte TcV y TcVI son genotípicamente homogéneos y no diferenciados por secuenciación del gen para citocromo b

M.Sc.(Med.), Faculty of Health Sciences, University of the Witwatersrand, 2011 / Hepatitis B virus (HBV) and human immunodeficiency virus (Thakur et al.) are endemic in South Africa. There no data on the HBV genotypes prevailing in HIV-infected South Africans. The aim this study was to determine the HBV genotypes in HIV-infected patients and to identify mutations occurring in the basic core promoter/preccore (BCP/PC) and complete S regions. Twenty six HBV isolates from HBV-HIV co-infected individuals from Helen Joseph urban hospital prior to and at six month after initiation of HAART were analyzed. Three hundred HBV isolates from the rural Shongwe Hospital were recruited prior to treatment. Restriction fragment length polymorphism (RFLP) together with sequencing of the BCP/PC and complete surface region amplicons were employed for genotyping and analysis. There was no significant difference in the HBV genotypes from both cohorts. Subgenotype A1 was the predominant genotype. HBV DNA was detected in 13/26 (50 %) Helen Joseph patients and 72/300 (24%) HBV DNA was detected in patients from Shongwe cohort: 28/300 (9.3%) HBsAg-positive and 44/300 (14.7%) HBsAg-negative. The BCP/PC region of HBV isolates from both cohorts showed mutations that could account for the HBeAg negativity, although in the case of the Helen Joseph cohort the HBeAg status was unknown because of depletion of serum. The HBeAg negativity in 44/49 Shongwe patients (89,7%) could be accounted for by the following mutations: 1) the basic core promoter mutations T1753C A1762T G1764A, which down regulate transcription of precore mRNA; 2) the Kozak sequence mutants that affect HBeAg translation, 3) the G1862T mutation, which interferes with post-translational modification of the HBeAg-precursor, and 4) the classical G1896A stop codon mutation with C1858T. The G1862T mutation occurred in HBV from 24.1% HBsAg-positive Shongwe patients but in none of the HBsAg-negative patients (p<0.05). PreS deletion mutants were found in isolates from both cohorts. These have previously been described in hepatocellular carcinoma patients. The Helen Joseph HBV isolates had the “a” determinant and immune/vaccine escape mutants. In addition to these, Shongwe isolates had HBV reactivation markers mutations V168A + S174N in 23.8% of the HBsAg-negative and in none of the HBsAg-positive infections. Drug resistant mutations were found in three Shongwe HBV isolates from ART naïve individuals and in none Helen Joseph HBV isolates. In conclusion, South African HIV-infected individuals were predominantly infected with subgenotype A1 of HBV. Mutations in the BCP and precore region of HBV isolates could account for the HBeAg negativity in the majority of patients. A number of HBV isolates displayed both immune escape and drug resistance mutations that were responsible of the HBsAg-negativity in patients from which they were isolated.

Members of the family Hepadnaviridae have been detected in both avian and mammalian species. They have a very limited host range, and among the nonhuman primates, have been found to occur naturally in chimpanzees, gorillas, gibbons, orang-utans and woolly monkeys. The human hepatitis B virus (HBV) has been shown to infect chimpanzees, Barbary macaques and tree shrews. During the course of a previous study, to determine the susceptibility of baboons (Papio ursinus orientalis) to HBV infection, HBV DNA was detected in the serum of 2 baboons prior to their inoculation with HBV-positive human serum, raising the possibility that baboons are naturally infected with a hepadnavirus. Therefore the aim of this study was to determine the prevalence of HBV in wildcaught baboons and to molecularly and functionally characterise the virus isolated from these baboons. DNA was extracted from the sera of wild-caught baboons and four separate regions of the HBV genome amplified by nested polymerase chain reaction (PCR). Samples were only considered to be positive for HBV if at least three of these regions amplified. DNA was extracted from the liver tissue of one of the HBV DNA-positive baboons using a proteinase K digestion followed by a phenolchloroform extraction and ethanol precipitation. From this extract, the complete HBV genome was amplified by nested PCR of eight overlapping subgenomic fragments, and sequenced. This sequence was analysed phylogenetically using both the PHYLIP and Simmonic software packages. A selective real time PCR using SYBR®-green detection was used to detect covalently closed circular (ccc) DNA. RNA was extracted from the baboon liver tissue using a guanidinium-acidphenol extraction method, reverse transcribed and portions of the HBV genome amplified by nested PCR. Transmissibility of the virus was tested by injecting four experimentally naïve baboons individually with serum from four HBV DNApositive baboons and followed for 26 weeks. HBV was detected in the serum of 5/69 (7,2%) wild-caught baboons by Southern hybridization and in 11/49 (22,4%) adult and 4/20 (20,0%) juvenile wild caught baboons. This gave an overall prevalence of 21,7% in the baboon population surveyed. Serologically, the baboon sera were negative for all markers of HBV infection and alanine aminotransferse (ALT) levels were normal. In the one baboon liver tissue available, HBcAg was detected by immunohistochemical staining in some of the hepatocyte nuclei, but HBsAg was not detected. Phylogenetic analysis of the complete genome of the HBV isolate found it to cluster with subgenotype A2, a surprising result considering that subgenotype A1 predominates in South Africa. However, unlike other subgenotype A2 isolates, the basic core promoter had the G1809T / C1812T double mutation characteristic of subgenotypes A1 and A3 and the precore region had the G1888A mutation unique to subgenotype A1. These mutations in the basic core promoter and precore regions have previously been shown to reduce the expression of the precore and core proteins. Four additional mutations in the polymerase, surface, X and core open reading frames (ORFs) further differentiated the baboon HBV strain form the majority of previously sequenced subgenotype A2 isolates. cccDNA was detected at low levels in the baboon liver tissue. Regions of the precore/core and surface ORFs were amplified off reverse transcribed cDNA. These results demonstrate HBV replication in the baboon liver. Transmission of the virus was shown by the detection of HBV DNA in the sera of the four inoculated baboons at various times throughout the 26 week follow-up period. These baboons also showed transient seroconversion for HBsAg and HBeAg during this period with intermittent fluctuations in ALT levels. Moreover, using DNA extracted from liver tissue obtained at necropsy from one of the injected baboons, the sequence of the HBV surface gene amplified was found to be identical to the sequence of the isolate from inoculum. The finding of subgenotype A2 in the baboon is paradoxical because subgenotypes A1 and A3 as well as genotypes D and E predominate in Africa. The possibility exists that subgenotype A2 is an older strain that has been overtaken by these other strains. There is however a scarcity of subgenotype A2 sequencing data from Africa and a higher circulation of this subgenotype could be uncovered with more extensive molecular epidemiological studies in more remote areas. Alternatively, a recent discovery of alternative compartmentalization of subgenotype A2 infections in the peripheral blood lymphocyte population of individuals from India, where subgenotype A1 also predominates, could explain the lack of detection of this subgenotype in Africa. Occult hepatitis B infection is defined as the presence of HBV DNA in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg by currently available assays. The detection of HBV DNA in the baboon liver and serum in the absence of serological markers therefore classifies this infection as occult. To our knowledge, this is the first study to demonstrate a naturally occurring occult HBV infection in non-human primates.

MSc (Med) Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, 2009 / The underlying mechanism and determinants of inhibitor formation in approximately 30% haemophilia A and 5% haemophilia B patients are not fully understood. A large amount of the data on immune responses against FVIII and FIX is from animal models. Studies investigating cytokines in haemophilia are very limited and fragmentary, and the classification of hemophilia patients according to their factor activity levels has been observed to be inconsistent. The current study aims to find the associations between factor levels, clinical phenotype, cytokine profiles and polymorphisms in the IL-10 gene promoter of haemophilia A and B patients with and without inhibitors. This may give more insight into the pathophysiology of haemophilia, help improve the understanding of the pathogenic mechanisms that underlie inhibitor development, and facilitate new diagnostic and therapeutic strategies for haemophilia. Haemophilia A and B patients with and without inhibitors were enrolled in the current study. Forty (40) patients from the Charlotte Maxeke Johannesburg Academic Hospital Haemophilia Comprehensive Care Centre (CMJAH-HCCC) were randomly selected. An equal number of frequent bleeders and infrequent bleeders were recruited. Frequent bleeders were defined as those patients with 2 or more bleeding episodes per month on three consecutive months. Bleeding frequency was evaluated on the patient’s bleeding charts. FVIII and FIX activity levels of all patients were measured using the Dade Behring Sysmex CA-7000 coagulation analyzer, and information on each patient’s bleeding episodes was obtained from the haemophilia bleeding charts. The inhibitor status of all patients was evaluated using the Bethesda inhibitor assay. IL-1β, IL-6 and TNF-α were analyzed using an ELISA kit method. IL-2, IL-4, IL-10 and IFN-γ were analyzed using the CBA Human TH1/TH2 Cytokine Kit. DNA was extracted using the Nucleon BACC3 from Amersham Biosciences. Polymorphisms in the IL-10 gene promoter region were analyzed using PCR. The Statistica Release 8 statistics package was used for statistical analysis. The present study population showed significant discrepancies in the theoretic classification of haemophilia patients. Severe haemophilia patients had significantly higher levels of IL-6 than the mild/moderate group and biochemical classification correlated positively with IL-6. IL-6 was also the only significant predictor of biochemical classification. IL-1β and IL-4 was found to be significantly higher in the mild/moderate group than in the severe group. There were no significant differences in the levels of IL-2, IL-10, and IFNγ between the mild/moderate and severe groups and between patients with inhibitors and without inhibitors. There were also no differences in the cytokine profiles of low and high responders. No significant differences were found between cytokine profiles of frequent and infrequent bleeders. IL-6 and TNF-α were found to be significantly higher in patients with inhibitors than in haemophilia patients without inhibitors. IL-6 and IL-1β were the only significant predictors of the inhibitor status of haemophilia patients. Haemophilia severity and race were found to be significant risk factors for inhibitor development. A 150 bp allele of the IL-10 promoter region with the microsattelite marker was observed in patients with and without inhibitors as well as the healthy controls. The 150 bp allele was also observed in both black and white subjects. Large phenotypic heterogeneity exists in haemophilia patients. The pro-inflammatory cytokines IL-6 and IL-1β together with IL-4 may be involved in determining the biochemical severity of haemophilia. IL-6 was the only cytokine in this study found to be a significant predictor of bleeding frequency. The study results also suggest that IL-6 and IL-1β may be involved in the production of antibodies against infused factor in patients with inhibitors. The presence of a 150 bp allele of the highly polymorphic IL-10 promoter region in patients with and without inhibitors as well as the healthy controls suggests that, polymorphisms in this gene do not influence inhibitor development in this population.

Hepatitis B virus (HBV) has been found to be highly endemic in Africa and south east Asia. In southern Africa, subgenotype A1 and genotype D prevail while in south east Asia genotype B and C predominate. Infection with HBV can lead to a wide spectrum of clinical presentations ranging from an asymptomatic carrier state to self-limited acute or fulminant hepatitis to chronic hepatitis with progression to cirrhosis and hepatocellular carcinoma (HCC). It has been shown that viral factors as well as a number of host and environmental factors can influence the course of HBV infection. Development and progression of various liver diseases are associated with either an increase or decrease in hepatocyte apoptosis. Dysregulated apoptosis itself may be a fundamental feature of most acute and chronic human liver diseases. The purpose of this study was to characterise the subgenotype A1 and genotype D HBV infection, prevailing in South Africa. To control for the influence of host factors on HBV infection as well as to avoid the use of in vitro cell lines, such as Huh-7, that have defective apoptotic pathways, the in vivo urokinase plasminogen activator severe combined immunodeficient (uPA-SCID) transgenic mouse model was utilised. The HBV infection of the transgenic mice infected with HBV positive sera containing either subgenotype A1 wildtype, subgenotype A1 with the G1862T mutation, subgenotype A2 or genotype D, was compared. For the first time, we were able to demonstrate the successful infection of the uPA-SCID transgenic mouse model with subgenotype A1 of HBV. The successful establishment of the in vivo HBV infection with different genotypes or subgenotypes in the uPA-SCID transgenic mice was demonstrated by the increase of HBV DNA levels, the presence of cccDNA and HBV transcripts as well as the detection of the core and/or surface HBV antigens in the liver tissue of the chimeric mice. Differences between the HBV infections with the various genotype/subgenotypes were observed. Subgenotype A1 with the G1862T mutation showed the earliest detection and therefore highest levels of cccDNA as well as the highest HBV DNA levels when compared to the other strains. The highest HBV DNA levels were recorded for the subgenotype A1 G1862T infected transgenic mouse followed by genotype D, subgenotype A2 and the lowest levels observed in the subgenotype A1 wild-type infected transgenic mouse. HBsAg was also only detected in the livers of mice infected with subgenotype A1 with the G1862T mutation. HBcAg staining in the chimeric liver was positive when the mice were infected with genotype D, which concurs with previous observations that genotype D is characterised by high HBcAg expression. Subgenotype A1 with the 1862 mutant showed the highest levels of apoptosis as a result of the abnormal precore precursor protein accumulation shown to be associated with this 1862 missense mutation. Thus different genotypes and subgenotypes as well as variations within genotypes can influence HBV infection. Moreover, the results of these experiments in the immunocompromised chimeric mice, grafted with liver cells from a single donor, suggests that even when host and environmental risk factors are controlled for, the subgenotype or genotype can influence the course of infection. The limitations of the uPA-SCID transgenic mouse model include the lack of an immune system and the short life-span of the animal; therefore a population based study was carried out to investigate the influence of host factors on HBV infection in various disease groups. The study cohort comprised 635 serum samples from South Africa, China and Japan. Of these samples, 564 were HBsAg-positive and the remaining 71 HBsAg-negative, HBV DNA negative controls. The study cohort included asymptomatic carriers; chronically infected HBV patients as well as patients with HBV associated HCC. Possible associations were determined between HBV genotype, HBV viral load, apoptosis levels, disease group and the age and gender of the patient where available. Apoptosis levels were quantified by the measurement of cleaved cytokeratin 18 (M30) in serum. Patients infected with genotype C or subgenotype A1 were shown to possess a higher odds ratios of developing HCC compared to subgenotype B2 or genotype D, respectively. Significantly higher HBV viral loads were observed in genotype C compared to subgenotype B2. Among the Asian cohort, it was also shown that the male gender was positively associated with high viral loads in HCC patients. Moreover, a positive association between higher HBV viral load levels and HCC in the South African cohort was observed. Male gender, older age, HBV viral load, subgenotype A1 and the presence of the G1862T mutation were shown to be positively and significantly associated with higher levels of apoptosis. In this study it was discovered that the levels of cleaved cytokeratin 18 could potentially be used as a biomarker for the severity of HBV infection because a significant difference was observed with the apoptosis levels between the asymptomatic and HCC patient disease groups. We conclude that even when the influence of host and environmental factors is controlled for, as is the case in the chimeric mouse model, the HBV genotype can affect the progression of infection. Moreover, it was shown in the population based study that the effect of HBV genotype on the outcome of HBV infection can be influenced by host factors. The subgenotype A1 G1862T mutation was shown in both studies to affect both HBV infection and apoptosis. This suggests that HBV variants should be investigated to ascertain their potential impact on the course of HBV infection as it may differ from the wild-type. Apoptosis was shown to be associated with HBV infection in both studies and could possibly be an ideal marker of the progression of HBV infection. These findings are important in helping us to understand factors influencing the course of HBV infection. We have therefore shown in both the studies that differences do exist between the South African subgenotype A1 and genotype D, and that these differences should be taken into consideration for the future evaluation of HBV infection and treatment of South African HBV infected patients. Moreover, cleaved cytokeratin 18 may provide an ideal surrogate marker for HBV disease progression and monitoring.

This thesis explores the social construction and performance of Technological Human Enhancement Advocacy through multi-sited ethnographically inspired participant observation across a range of sites. It argues that advocacy efforts surrounding the ideal of technological human enhancement share the ideational feature of Techno-centrism - an object-level belief embedded in the material present while simultaneously future-oriented and thus principally immaterial. This purposive neo-dualism blurs 'real' and 'imagined' futures to satiate the materialist ontological grounding associated with the scientific worldview, while granting extended licence to more indulgent, compelling visions for technology as an enabler of affirmative, forward-facing action - including revivifying pursuit of humanist ideals associated with the modernisation project. The thesis makes contributions to three areas. Firstly, in substantive terms, it contributes towards sociological knowledge by detailing the intersubjective values, semiotic framing mechanisms and narrative tropes evoked to both justify and promote the notion of Technological Human Enhancement Advocacy (THEA), an area which remains under-researched. Secondly, the thesis makes a theoretical contribution through its modelling of a non- spatially determined constant which recurs across sites associated with THEA: The Techno-centred Imagination (TCI). Finally, the thesis offers a methodological contribution through its novel and creative application of multi-sited research strategy for the study of non-spatially determined cultures of extreme support for science and technology. A 24-month programme of fieldwork was undertaken, comprising multi-locational participant-observation, interviews and surveys. The thesis concludes that far from being new, the emerging social forms associated with THEA capture ambivalences which have long cast a shadow over late-modern society and culture. Although TCI appears most pronounced in the practice of transhumanism - where it is acted out in extreme, almost hyperbolic ways - the phenomena mirrors broader concerns around the future of science, technology and human self-identity in the new millennium. As such, it is deserving of further study.

This thesis is a study of the role of the phenomenon of death in Heidegger's philosophy. The central argument is twofold. First, death is the fulcrum of Heidegger's philosophy. As such, second, death is a crucial key to Heidegger's thought in its entirety. Thus I claim is that a response to the question of being can be given, if one takes death into account. This thesis, therefore, investigates the four main blocks of Heidegger's philosophy and the role of death in them. I identify the four main blocks of Heidegger's philosophy as follows. First, Heidegger's early transcendental analysis of Dasein's existence. Second, the thinking of being as event. Third, Heidegger's critique of technology. Fourth, Heidegger's engagement with language. The thesis is divided into four topical parts according to these blocks. In the first part I argue that death serves as Dasein's utmost limit and as such death is constitutive of Dasein's existential possibilities. The analysis of Dasein's horizons of understanding is what leads Heidegger to turn to being itself. In the second part I identify the place of death in the thinking of the event and in Heidegger's theory of history as the history of being. I argue that death becomes an interest of being as such and is testimony to its epochs. Third, I argue that death continues to play a significant role in Heidegger's philosophy of technology. This is because the essence of technology is a mode of being itself in the sense that being allows for a certain understanding of the current technological age. Thus, technology is an interest of being itself, too, and the essence of technology is sheer availability. Heidegger begins to call death the refuge of being at this time, which indicates that death is as the utterly unavailable, the resting place of being. As such, I argue in parts III and IV, death coenables the fourfold, which is Heidegger's response to the technological world. In the fourfold things are not manipulated but form the bedrock of a shared communal world. In part IV I develop Heidegger's claim that there is an essential relation between death and language. In the information age language is reduced to a transmitter of information. Thanks to its relation with death as the utterly unavailable language retains other dimensions that elude the demands of technology.

by Chan Lik-yuen, Henry. / Thesis (M.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 192-217). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.