The dissertation consists of four separate studies that have focused on different aspects of the relationship between the management of sports related injuries and utilisation of best practices before sports, during sports and after sports-related injuries. Background: Participation in sports has an associated risk of injury which is defined by the type of sport and level of participation. Any injury affects the athletes‘ health status. To mitigate this risk, international sporting organizations provide guidelines, and mandates the proper evaluation and care for athletes before, during and after training or participation in competition. Despite the availability of guidelines describing best medical care practices for managing athletes, inappropriate management practices are reported globally. The barriers to best medical practice vary. While these barriers have been investigated in a variety of sports in developed countries, similar investigations have not been extensively conducted in developing countries, where the demands are different. Therefore, the overall aim of this thesis was to explore barriers to best medical practices in a variety of sports in Uganda. Methodology: The research was conducted as four studies. The first study used a descriptive case study approach. The data were collected on a sample of injured athletes (n=75) from four sports in Uganda (football/soccer, athletics, basketball and rugby) to describe the medical care practices of the sports resource providers. The current prevention, emergency care, intermediate treatment, rehabilitation services and return-to-sports strategies were all documented in a period of six months. The gaps in best practices were observed, and further investigated in the next three studies. Firstly, a validated questionnaire was used to establish the level of knowledge and practices of various components/themes of athletes‘ well-being and best practices among the stakeholders. Secondly, the current standards of the sports arenas and medical and high-performance facilities were examined using a validated checklist. The last study was a semi-structured interview which assessed the available national health care policies to support sports best practice strategies in Uganda Findings: The overall results of the first study showed there was a significant lack of compliance to best medical care practices in all the phases of athletes‘ health care. The barriers to best practice were confirmed as: (i) the lack of adequate knowledge and awareness on various best practice strategies, (ii) the sports and health facilities were below the required standards and, (iii) there were no national health sports care policies to support and facilitate the implementation of best practices in Uganda. Conclusion: (i) A holistic approach may be required to address the best medical care practice barriers in Uganda to improve on the health and safety of athletes. (ii) The knowledge of stakeholders should be improved and awareness created about best medical practices in sports in Uganda. (iii) There is a critical need to develop a national sports health care policy. (iv) The facilities for sports and health care of athletes urgently need improvement and supported.

TBX3, a member of the developmentally important T-box transcription factor family, has been shown to be overexpressed and to behave as an oncogene in several cancers. Much of this work has, however, been performed in carcinomas of epithelial origin and little is known about the role ofTBX3 in sarcomas of mesenchymal origin. This study provides novel evidence to show that TBX3protein, but not mRNA, is upregulated in a number of transformed fibroblast and fibrosarcoma cell lines of mesenchymal origin. Fibro sarcoma is an aggressive soft-tissue sarcoma derived from fibroblasts and, while it occurs very rarely, there are no targeted therapy approaches and survival rates remain low. More work is clearly needed to characterise the molecular mechanisms involved infibrosarcoma development, to allow for more effective treatments to be identified. This study, therefore, aimed firstly to determine the role of TBX3 in transformed fibroblast and fibrosarcoma cells; secondly to investigate the signalling pathways responsible for the upregulation of TBX3; and lastly to identify target genes which mediate the role of TBX3 in these cells. To determine the function of TBX3 in transformed fibroblast and fibro sarcoma cells, cell culture models were generated in which TBX3 was stably knocked down in transformed CT-1 cells, as well as the naturally occurring aggressive HT1080 cell line, and the effect on key features of oncogenesis determined. In both cell lines, a substantial decrease in in vitro cell proliferation, measured using growth curve and BrdU incorporation assays, anchorage independence, measured using soft-agar assays, and migration, measured using scratch and transwell migration assays, was observed. Importantly, the knockdown of TBX3 was also able to significantly increase the in vivo tumour forming ability of HT1080 cells in a mouse model. A TBX3 overexpression cell culture model was also generated in the HT1080 cells and, despite their aggressive nature, increased TBX3 expression resulted in a reduced oncogenic phenotype, including markedly decreased in vivo tumour formation. These results were unexpected and demonstrate for the first time that TBX3 behaves as a tumour suppressor in transformed fibroblast and fibro sarcoma cells, suggesting it may function as either oncoprotein or tumour suppressor depending on cellular context. [Please note: the thesis file has been deferred until June 2018]

After anterior cruciate ligament reconstruction (ACL-R), persistent strength and biomechanical deviations remain. Reducing these by training may reduce risk of re-injury or osteoarthritis for these patients. A cross-sectional study investigated biomechanics of ACL-R male patients long-term (~5 years) post surgery. Fifteen ACL-R and fifteen healthy controls were tested in walking and running using motion capture. Devi- ations were found, primarily between-limbs, and also between groups. Largest deviations were lower knee angles and moments in the affected limb during running. However, these were not found during walking; thus, differences were highlighted by the higher-intensity task. During running, knee abduction moment was lower (more valgus) for the affected compared to unaffected and control limbs. The larger effects in moment show greater clinical potential than knee valgus angle. The ACL-R patients had lower impact foot strike during running than controls. The above results indicate chronic, clinical changes in joint loading. A randomised controlled intervention trial evaluated progressive eccentric cycling for ACL-R males, compared to concentric controls. This is one of the first trials of eccentric vs. concentric training for ACL-R, matched by rating of perceived exertion. Twenty-six adult males, 12 weeks post hamstring-graft ACL-R trained three times/week for 8 weeks under supervision. During training the eccentric group limb powers absorbed were higher than those produced by the concentric group, with a lower heart rate. For both groups, pain scores were low, and one of the patient-reported outcomes (IKDC) improved. Hamstring strength increased in the eccentric group by 15%, but this was not seen in the concentric group. For both groups, 60°/s quadriceps strength increased by a similar amount, approximately 28%. Biomechanically, eccentric training was more effective than matched concen- tric training at resolving knee (P=0.022, walk) and hip (P =0.010, run) flexion angle deviations in the affected limb. In both groups, knee extension moments increased, reducing asymmetries. Large knee abduction moment deviations at baseline were not reduced by either programme (P >0.05). At follow-up (~6 months), both groups showed similar return-to-sports progress; several patients passed using one criterion (IKDC), and none passed using a stricter four-criteria method (Univ. Delaware). Thus it can be concluded that for adult ACL-R males, eccentric cycle training is clinically acceptable, with similar or in some cases better outcomes than concentric cycle training. It improves patient-reported outcomes, strength recovery, biomechanical deviations, and return-to-sports measures.

In population groups where subjects do not lie still during Magnetic Resonance Spectroscopy (MRS) scans, real-time volume of interest (VOI), frequency, and main magnetic field (B0) shim correction may be necessary. This work demonstrates firstly that head movement causes significant B0 disruption in both single voxel spectroscopy and spectroscopic imaging.

Includes abstract.~Includes bibliographical references. / The first part of this thesis examines issues in the processing and analysis of continuous wave functional linear infrared spectroscopy (fNIRS) of the brain usung the DYNOT system. In the second part, the same sensorimotor experiment is carried out using functional magnetic resonance imaging (fMRI) and near infrared spectroscopy in eleven of the same subjects, to establish whether similar results can be obtained at the group level with each modality. Various techniques for motion artefact removal in fNIRS are compared. Imaging channels with negligible distance between source and detector are used to detect subject motion, and in data sets containing deliberate motion artefacts, independent component analysis and multiple-channel regression are found to improve the signal-to-noise ratio.

Executive function (EF), that shows rapid development in the preschool years, is foundational for cognitive development. Previous research has found aspects of physical development including gross motor skills and physical activity to be related to EF. However, evidence for these relationships in the preschool years, as well as in low- and middle-income countries is lacking. Therefore, this study aimed to investigate the relationships between EF (and related components of cognitive development) with physical activity and gross motor skills (GMS) in a sample of preschool children from urban and rural low-income settings in South Africa. Cognitive and physical outcomes were measured in a sample of preschool children (N=129; Mage = 50.7±8.3 months; 52.7% girls) from urban (Soweto) and rural (Bushbuckridge) low-income settings in South Africa. Cognitive components included EF, self-regulation (Early Years Toolbox, EYT), attention (adapted visual search task) and school readiness (Early Childhood Development Criteria Test). Physical outcomes included objectively measured physical activity (accelerometry), gross motor skills (Test for Gross Motor Development 2) and anthropometric measurements (height and weight). On average, children from both settings showed higher than expected scores for EF and self-regulation (based on Australian norms for the EYT), adequate gross motor proficiency and high volumes of physical activity (M total physical = 476 minutes per day). In contrast, a high proportion of children, particularly in the rural setting, demonstrated below average scores for school readiness. Investigations into the relationships revealed that EF was positively associated with self-regulation, attention and school readiness. Positive associations were also found between GMS and physical activity and, and physical activity and body mass index (BMI). And finally, that GMS, but not physical activity, was positively associated with all components of cognitive development. This study is the first to provide evidence for the importance of EF and the link between motor and cognitive development in preschool children from South African, low-income settings. Another key finding was that there may be factors promoting early EF skills in these settings but that these skills, although associated, are not transferring to school readiness. The lack of (or negative) associations between physical activity and cognition presents another key finding, further research is needed to identify whether there are specific amounts and types of physical activity that specifically benefit cognitive development.

Introduction: The prevalence of overweight and obesity is increasing worldwide. It has been estimated that every kilogram of weight gain during adulthood represents a 3% to 6% risk increased of cardiovascular disease. There are some studies showing an inverse relationship between calcium intake and body weight. Overweight and obese women are advised to lose weight before conception, however the evidence on how to achieve this is scarce. No studies have investigated the effect of calcium supplementation on weight management before conception or during pregnancy. Aims and objectives: The overarching purpose of this project was to provide information and enrich the body of evidence of the effect of calcium intake on body weight. The first aim was to evaluate the effect of calcium intake on body weight of fertile or pregnant women; secondly to investigate the pre-pregnancy weight status, weight gain during pregnancy and adequacy of dietary intake of pregnant women participating in the Calcium and Pre-eclampsia (CAP) trial. The third aim was to perform a systematic review of studies evaluating the effect of calcium intake on body weight. I was part of the core research team throughout the CAP trial duration and also lead the nutritional component. The trial sample size included 540 pregnant women recruited between 2012 and 2017 in South Africa, Zimbabwe and Argentina. Women were randomized pre-pregnancy to receive 500 mg of elemental calcium or placebo until 20 weeks´ gestation, whereafter they received 1500 mg. Weight was measured pre-pregnancy and at 8, 20 and 32 weeks’ gestation. Diet was assessed at 20 weeks´ gestation. Ethical approval was obtained from appropriate national and institutional ethical review bodies as applicable for each study site. Results: There was a high proportion of women who started their pregnancy overweight or obese (73.7% in South Africa and 60.2% in Zimbabwe). Most women had an inadequate intake of micronutrients at 20 weeks pregnancy. For the most basic micronutrients like iron, calcium, folate and zinc, the percentage of women with intakes below requirements was above 90%. Although there was no effect of calcium supplementation on body weight in the sample of the CAP trial, the calcium group had a no statistically significant smaller increase in body weight during pregnancy especially in those who were obese at the start of the trial. The systematic review shows a small but statistical effect of calcium supplementation in body weight (Mean Difference (MD) -0.33 kg, 95% CI -0.57 to -0.09); (p=0.007); 819 participants; 15 studies) and in BMI (MD -0.17, 95% CI -0.21 to -0.13); p < 0.00001; 695 participants; 10 studies). Conclusion: We found a high prevalence of obesity found together with the micronutrient inadequacy which show a very poor nutritional status of women who have the possibility of getting pregnant again. This needs to be addressed so that maternal and perinatal outcomes are improved. There is a need to implement nutritional counselling preconceptionally to these women before they fall pregnant. The results of this thesis show a no statistically significant smaller increase in body weight in women supplemented with calcium, opening a promising area of research for weight management including the study of the mechanisms involved. Before making clinical recommendations further studies are needed with higher sample size to have the power to detect clinically significant effects.

Bibliography: leaves 175-194.

Includes abstract. / Includes bibliographical references. / Several methods have been used to quantify the internal training load of a bout of exercise. However, arecent novel approach to quantify the internal training load has been to investigate the dynamic returntowards resting homeostasis at the cessation of exercise. Objective and non-invasive methods ofmonitoring the return towards resting homeostasis include measures of heart rate recovery (HRR) andexcess post-exercise oxygen consumption (EPOC). However, the relative potential of autonomic- vs. metabolic-type recovery measurements to represent the internal training load or homeostatic stress of the preceding exercise bout has not been established. Therefore, the broad aim of this thesis was to investigate the magnitude of EPOC (EPOCMAG), the time constant of the EPOC recovery curve (EPOCτ),HRR within the first minute post-exercise (HRR60s) and the time constant of the HRR curve (HRRτ) as measures which might reflect the homeostatic stress of an exercise bout. It was hypothesized that a measure representing the homeostatic stress of an exercise bout could have the following possible applications; - to identify inter-individual variation in the homeostatic stress of a standardized exercise bout - to detect intra-individual variation in the homeostatic stress of different exercise bouts- to detect intra-individual variation in “readiness to train”, based on the response to a standardized exercise bout. Therefore, the investigations of this thesis aimed to assess the relative potential of EPOCMAG, EPOCτ,HRR60s and HRRτ in these different roles. The experimental work was divided into 4 studies.

Includes abstract. / Includes bibliographical references) / The primary aim of this thesis was to identify additional genetic elements predisposing individuals to risk of AT using a candidate gene, case-control genetic association approach, and to propose the biological mechanisms underlying this genetic risk. Candidate genes (COMP, THBS2, COL27A1, TNC, COL3A1, COL5A2 and COL5A3) were selected based on their chromosomal location and/or the biological function of their encoded proteins within the extracellular matrix (ECM) of the tendon.