Bibliography: leaves 93-106.

COL5A1 encodes the α1 chain of type V collagen, a minor fibrillar collagen that is an important regulator of collagen fibril assembly. A polymorphism (rs12722, C/T) within the 3'-untranslated region (UTR) of COL5A1 is associated with chronic Achilles tendinopathy (TEN) and other soft tissue injuries as well as exercise-related phenotypes. These phenotypes are directly or indirectly associated with the mechanical properties of musculoskeletal soft tissue. It has therefore been hypothesised that variants in the COL5A1 gene, specifically the 3'-UTR, regulate synthesis of the α1(V) chain and type V collagen production. Type V collagen levels in turn regulate fibril architecture and structure and, thereby, mechanical properties of musculoskeletal soft tissues. Although the 3'-UTR of many eukaryotic genes have been shown to play an important regulatory role, the function of the COL5A1 3'-UTR is currently unknown. Aim. The primary aim of this thesis was therefore to determine whether the COL5A1 3'-UTR was functional and to identify functional differences between the COL5A1 3'-UTR cloned from participants with TEN and healthy asymptomatic control individuals. The secondary aim was to start mapping the functional regions within the 3'-UTR, focusing on regions which are potentially responsible for contributing to the tendinopathic phenotype.

INTRODUCTION: Chronic diseases of lifestyle (CDL) are a major cause of global morbidity and mortality. Although CDL are largely preventable and treatable through adopting and maintaining healthy lifestyle behaviours, CDL rehabilitation programmes remain an underutilised resource. Behaviour modification is thus complex, and requires a collaborative approach between psychologists and medical clinicians involved in the management of CDL. This thesis examined the role of psychological factors in the management of patients with CDL who participated in a comprehensive lifestyle intervention (CLI) programme. METHODS: An explanatory mixed methods design was used to describe the CLI experience. These included an initial clinical audit of 308 patients commencing and completing a twelve week CLI programme to test associations of psychological, demographic, medical and diagnostic factors with physical outcomes. Two qualitative studies were subsequently conducted to further understand patient experiences of CDL and CLI programmes. The first involved interviews of 14 patients at programme commencement and completion. The second consisted of a case study of a patient participating in the programme using human centred design principles as well as ethnography.

Glycogen depletion has frequently been shown to result in a decrease in respiratory exchange ratio (RER). However, the metabolic response to glycogen depletion has generally been studied in overnight fasted subjects or in subjects who were already fatigued, or hypoglycaemic, or both, raising the question of whether the differences seen were due to general "carbohydrate deficiency" or due specifically to muscle or liver glycogen depletion. If euglycaemia and especially hyperglycaemia is maintained, the " carbohydrate deficiency" is overcome. In addition, because insulin stimulates muscle glucose uptake and not liver glucose uptake during euglycaemia (except at very high concentrations), insulin infusion would differentiate between liver and muscle glycogen depletion, since if the decrease in RER previously observed is abolished with insulin infusion while euglycaemia is maintained, this would indicate that the decrease is specifically due to muscle glycogen depletion. Thus, the aim of this study was to investigate the metabolic effect of glycogen content while an adequate amount or an excess of carbohydrate was provided in the form of an intravenous glucose infusion and when plasma insulin concentrations are raised.

Includes bibliographical references / The prevalence of childhood overweight and obesity has increased substantially globally with a concurrent decline in both children's physical activity and fitness levels. The socio-ecological model proposes that health behaviour, such as physical activity, is influenced by multiple factors, at an individual, social and environmental level. However, there seems to be a lack of consensus in the current literature on the factors influencing physical activity in different settings (e.g. school, neighbourhood), and across a wide range of socio-economic conditions. To our knowledge, there are no data available on the role of different environmental factors (within the school and the neighbourhood environment) in relation to children's physical activity in a South African setting. Therefore, one of the key aims of this thesis was to assess the effectiveness of a novel intervention on fitness, measures of physical activity and factors that influence physical activity. Specifically, this thesis assessed the effectiveness of a school-based, curriculum-grounded, educator-focused intervention designed to increase physical activity and healthy eating in South African primary school students in low income settings, on fitness levels and physical activity related knowledge, attitudes and behaviour (Chapter 2). Additionally, this thesis examined factors within the school environment associated with observed physical activity in children during in-school break time, self-report activity, and moderate- to -vigorous, in-school objectively-measured activity (Chapter 3-5). Furthermore, this thesis assessed the influences of parental perceptions and the neighbourhood environment on children's physical activity (Chapter 6). The overarching aim of this thesis is to examine the association between environmental constructs (physical spatial and built environment, social environment, and policy environment) and children's physical activity.

Background: Global levels of overweight and obesity in preschool-aged children have increased dramatically in the last two decades, with most overweight and obese children younger than five years living in low- and middle-income countries (LMICs). Statistics from the 2013 South African National Health and Nutrition Examination Survey (SANHANES-1) confirm that levels of overweight and obesity are high in South African preschool-aged children, with prevalence rates of overweight and obesity up to 18.2% and 4.7%, respectively. This increasing problem of overweight and obesity in South African preschoolaged children highlights the need for intervening in this age group. Overweight and obesity interventions in preschool children typically include one or more of the following behaviours: physical activity, sedentary behaviour and screen time. Aim and objectives: The aim of this study was to characterise the preschool environment in rural South Africa, and to explore physical activity, gross motor skill proficiency, sedentary behaviour and screen time in rural South African preschool-aged children. Additionally, aims of this study were to explore the associations between gross motor skills, body composition and physical activity; and to assess compliance with current physical activity and sedentary behaviour guidelines. Methods: Preschool-aged children (3-5 years old, n=131) were recruited from three Preschools and two Grade R (reception year) settings in Agincourt, a rural village in north eastern South Africa. In order to gain an understanding of the Preschool and Grade R settings, an observation of the preschool environments was conducted using a tool adapted from the Outdoor Play Environmental Categories scoring tool, Environmental and Policy Assessment and Observation instrument, and the Early Learning Environments for Physical Activity and Nutrition Environments Telephone Survey. Each child’s height and weight was measured. Physical activity and sedentary behaviour were measured objectively using a hip-worn ActiGraph GT3X+ accelerometer for 7 days (24 hours, only removed for water-based activities). Gross motor skills were assessed using the Test for Gross Motor Development–Version 2 (TGMD-2). Physical activity and sedentary behaviour, including the contextual information for these behaviours, during the preschool day (08h00 until ±12h00) were measured using the Observational System for Recording Physical Activity in Children (Preschool Version). A separate sample of parents/caregivers were recruited (n=143) to complete a questionnaire that was adapted from the Healthy Active Preschool Years questionnaire and Preschool Physical Activity Questionnaire. Parents reported on their child’s screen time, and on factors within the home and community contexts in which physical activity and sedentary behaviours occur. Results: In terms of the environment, the Preschools and Grade R settings differed in that fixed play equipment only featured in the Preschool settings. Grade R settings had more open space in which to play. All Preschool and Grade R settings provided children with limited portable play equipment, and none of the schools had access to screens. Although all children recruited for the study were preschool-aged, the Grade R children were significantly older than the Preschool children (5.6±0.3years vs. 4.4±0.4 years, p <0.05). According to IOTF cut-offs, the prevalence of overweight/obesity was low (5.0%) in the sample, and 68.1% of children were classified as normal weight. On average, children spent 477.2±77.3 minutes in light- to vigorous-intensity physical activity (LMVPA) per day, and 93.7±52.3 minutes in moderate- to vigorous-intensity physical activity (MVPA). In terms of the new current guidelines (180min/day LMVPA, including 60min of MVPA, described as ‘energetic play’), and using average daily average of LMVPA and MVPA, 78.2% met current guidelines. Observed and objectively measured sedentary behaviour results revealed that children were more sedentary during preschool time (between 08:00 to 12:00) compared to the afternoons. Overall, boys were significantly more physically active than girls; and Preschool children did more physical activity during preschool time than Grade R children (all p< 0.05). Over 90% of the sample achieved an ‘average’ or better ranking for gross motor skill proficiency. The Grade R children were significantly more proficient than the Preschool children for all gross motor skill components (raw scores and standardised scores). Overall, boys achieved significantly better object control raw scores than the girls, and displayed greater proficiency than the girls in the strike (p=0.003), stationary dribble (p< 0.001) and kick (p< 0.001). None of the preschool or Grade R settings had access to screens such as televisions or iPads, and parent-reported screen time was low for the total sample (0.5±0.3hr/day). The majority of the sample (97.9%) met current screen time guidelines (<1 hour per day). Parents (82.5%) reported that they believed that their child did sufficient PA for their health, but 81.8% also reported believing that television time would not affect their child’s health. Parent responses revealed neighbourhood safety as a potential barrier to being physically active in the community. Conclusions: Rural preschool-aged children in South Africa appear to be engaged in adequate amounts of physical activity, particularly LMVPA, and are adequately proficient in gross motor skills. The children did not engage in excessive amounts of screen time. Overweight and obesity were not prevalent in this sample of rural preschool-aged children, and therefore it would appear that an intervention to reduce or prevent obesity by increasing physical activity, improving gross motor skills and reducing screen time is unnecessary. Rather, interventions that facilitate the increase in levels of MVPA in order to meet current physical activity guidelines are warranted. Additionally, it is essential that the high levels of physical activity (LMVPA) and good foundation of gross motor skills observed in this sample are promoted in an effort to maintain them throughout childhood. Future research may want to determine whether these activities (high levels of LMVPA, low levels of screen time) track throughout childhood and into adolescence.

Includes abstract. / Includes bibliographical references. / The HIMS test, which consists of controlled exercise at increasing workloads, has been developed to monitor changes in training status and accumulative fatigue in athletes. As the workload can influence the day-to-day variation in heart rate, the exercise intensity which is associated with the highest sensitivity needs to be established with the goal of refining the interpretability of these heart rate measurements. The aim of the study was to determine the within subject day-to-day variation of submaximal and recovery heart rate in subjects who reached different exercise intensities.

Obesity treatment requires approaches that target the reduction of body weight and fat mass. The improvement of cardiorespiratory fitness (CRF), metabolic flexibility and insulin sensitivity also contribute towards reducing obesity-associated risk factors. While energy restriction alone results in significant weight loss, exercise-only interventions provide small amounts of weight loss and prevent weight gain, while also improving many of the other variables targeted in obesity treatment. Once achieved however, successful weight-loss maintenance is challenging, with many individuals subsequently experiencing weight regain. The main objectives of this thesis were to explore the role of metabolic rate and substrate utilization in influencing body weight, body composition and insulin sensitivity. This twopart thesis hypothesised that: 1) exercise training, without dietary intervention, will improve metabolic rate and substrate utilization in a sedentary obese population, and that this would be associated with improved body composition, insulin sensitivity and CRF; and 2) metabolic rate, substrate utilization and insulin sensitivity are altered through weight loss/regain, predisposing these individuals to weight regain and impairing successful weight-loss maintenance. In Part 1 of this thesis a 12 week exercise intervention in sedentary, obese (BMI 30-40kg.m-2 ) black South African (SA) women (aged 22, IQR 21-24 years) was completed. Previous studies have shown that black SA women present with very low CRF, a key indicator of increased risk for non-communicable disease (NCD), and have a high prevalence of obesity and insulin resistance (IR). They are thus at increased risk for developing type 2 diabetes (T2DM). Furthermore, physiologically black SA women have also been shown to have less visceral adipose tissue (VAT) and more peripheral gluteal fat mass (FM) compared to their white counterparts, but are paradoxically more IR. Despite this presentation, to date there has been no supervised exercise intervention studies undertaken in this very high risk population group. The first study of this thesis (chapter 2) aimed to assess the effects of the exercise intervention on changes in CRF, energy expenditure (EE) and substrate utilization, both at rest and during steady-state exercise compared to non-exercising controls. It also assessed baseline and changes in these measurements in relation to changes in body composition. Black SA women (BMI 30-40 kg.m-2 , 20-35 y) were recruited and randomized into control (CTL, n=15), or exercise (EXE, n=20) groups. The CTL was instructed to maintain usual activity while the EXE completed 12 weeks of combined resistance and aerobic exercise training (4d.wk-1 , 40-60min.d-1 @ >70% peak heart rate (HRpeak)). At pre-intervention, a treadmill-based CRF test, measuring peak volume of oxygen consumption (VO2peak), was carried out. Thereafter resting and steady state exercise (50% VO2peak) energy expenditure (EE) and respiratory exchange (RER) were measured along with body composition (dualenergy X-ray absorptiometry (DXA)). A frequently sampled intravenous glucose tolerance test (FSIGT) was also carried out to determine changes in insulin sensitivity. These tests were repeated at post-intervention testing with steady state testing being carried out both at the same relative intensity (50% post-testing VO2peak) and the same workload (treadmill speed and gradient) as used for pre-testing. Dietary intake (4d diary) and daily step-count (ActivPAL) data was collected at pre-testing, 4, 8 &amp; 12 weeks. Results showed that all participants had very low baseline CRF, falling below the 20th percentile previously shown in African American women. In response to exercise training, CRF increased by ≈11% and rates of fat oxidation during steady-state exercise were improved, while in controls these remained unchanged. Compared to CTL, EXE also showed small but significant reductions, in weight, as well as BMI, waist (WC) and hip (HC) circumferences. In contrast weight, BMI and WC increased in non-exercising controls. Gynoid FM (absolute FM and as a proportion of total FM), rather than visceral adipose tissue (VAT), was reduced in exercise participants. Within the exercise group higher baseline fat oxidation rates during steady state exercise and lower resting carbohydrate oxidation rates explained 61.6% (p< 0.001) of the variability in changes in gynoid FM in response to 12 weeks of exercise training in this group. In conclusion, exercise training improved CRF and fat oxidation rates during submaximal exercise in sedentary, obese black SA women. Higher fat oxidation rates during steady state exercise and lower resting carbohydrate oxidation rates at baseline were associated with the mobilization of gynoid FM in response to exercise training, rather than VAT as is typically shown in exercise interventions. This novel finding potentially represents an ethnic/gender specific response to exercise training. Further studies are needed to confirm this. Similar exercise training programs, that are sustainable over the long term, would therefore be beneficial in achieving meaningful increases in CRF while also supporting weight management and body composition improvements in this high risk population group. Using data from the exercise intervention in obese black SA women, the second study of this thesis (chapter 3) investigated inter-individual variability in the CRF response (∆VO2peak) to exercise training. The study specifically aimed to compare changes in EE and substrate utilization at rest and during steady state exercise, body weight and composition and insulin sensitivity between high and low CRF responders to the 12 week intervention. Furthermore it aimed to explore associations between baseline metabolic rate, EE and substrate utilization and subsequent changes in CRF in response to exercise training, to determine if baseline variability in these measures contributed to inter-individual variability in the CRF outcome. Within the exercise group, high inter-individual variability in CRF response to exercise training was identified. Based on a median split in ∆VO2peak, high responders (HRS, n=10) increased CRF by 21.7 ±10.0% (p< 0.001) compared to no change in both low responders (LRS, n=10; +0.6 ±6.3%, p=0.748) and CTL (-3.2 ±10.8%, p=0.195). This occurred despite all groups having similar baseline VO2peak and the exercise group receiving the same exercise dose (number of exercise sessions attended and average intensity of the exercise sessions). At baseline, HRS derived ≈62% of energy expenditure from fat oxidation during steady-state exercise compared to just 41% in LRS, who relied to a greater extent on carbohydrate oxidation. Furthermore, HRS were ≈11 kg lighter than LRS. There was also a positive association between BMI and RER such that individuals with higher BMI showed lower fat utilization (i.e., higher RER). HRS reduced gynoid FM whereas in LRS this remained unchanged. This is in line with the findings of the previous chapter which showed that exercise-related reduction in gynoid FM was associated with greater baseline fat oxidation. LRS showed improvements in insulin sensitivity compared to CTL and HRS. Using regression analysis including the exercising participants, greater baseline carbohydrate oxidation rates both at rest and during steady state exercise predicted a poorer CRF to exercise training, explaining 37.5% of the variability in ∆VO2peak. To the best of my knowledge, this is the first study to show that baseline variability in substrate utilization among sedentary obese individuals contributes towards explaining the variability in the CRF response to exercise training. However, further studies are required to confirm these results. Together, these studies show that higher fat oxidation rates are necessary for FM mobilization, while correspondingly reduced reliance on carbohydrate oxidation both at rest and during exercise supports improvements in CRF in response to exercise training. These findings add to a growing body of research aimed at explaining inter-individual variability in exercise intervention outcomes and may contribute to individualizing the exercise prescription. Part 2 of this thesis used a cross-sectional approach and investigated firstly whether there was evidence for metabolic adaptation to weight loss/regain in response to long term weight maintenance, potentially predisposing individuals to future weight gain/regain. Secondly, I investigated whether insulin sensitivity is altered as a result of prior weight loss history, or whether successful weight loss restores insulin sensitivity to levels that are comparable to phenotypically similar controls with no weight loss history. Weight stable, BMI-matched South African women aged 20-45 years with or without a history of prior weight loss were screened and recruited. Four groups were defined as follows: Weight Reduced (RED, n=15) - lost at least 15% of body weight &amp; maintained a reduced weight (BMI ≤ 27kg.m-2 ) for over 12 months (15% of body weight), but relapsed back to overweight or obese (BMI ≤ 27kg.m-2 ); and overweight or obese (BMI ≤ 27kg.m-2 ) stable-weight controls (OSW, n=11) - no history of significant weight loss. The first study in Part 2 (Chapter 4) compared metabolic rate and substrate utilization in RED and REL to their respective BMI-matched controls with no weight loss history, both at rest and in response to a high fat meal challenge. Metabolic rate and substrate utilization were measured both at rest, immediately after consumption of the high fat test-meal and every hour thereafter for three hours. Dietary intake (3 x 24h recalls) and physical activity (ACTi Graph GT3X accelerometer worn for 7 days) data was collected and body composition was measured (bioelectrical impedance, BIA). Questionnaires were also completed covering weight history, socio-economic status and eating behaviour. Results showed that there was no difference in either resting EE or substrate utilization between the RED and REL compared to the respective BMI-matched controls, after accounting for fat free mass (FFM). The TEF, postprandial EE (absolute and per kg FFM), post-prandial energy balance, RER, fat oxidation rate and post-prandial fat balance were similar between RED and REL compared to their respective controls, indicating that there was no evidence of metabolic adaption to weight loss. However, successful weight-loss maintainers did show behavioural strategies that may have counteracted weight-loss associated adaptive thermogenesis and supported weight-loss maintenance. These individuals had manipulated macronutrient intake (increasing protein and reducing carbohydrate intake), were more physically active, exhibiting less sedentary behaviour and increased moderate and vigorous activity, and had greater fat free soft tissue mass (FFSTM). While the presence of adaptive thermogenesis is not disputed in these results, the distinct physiological and behavioural differences together observed in the RED may have been instrumental in attenuating weight-loss associated declines in EE, shown to persist into weight-loss maintenance. Together with these lifestyle strategies, weight reduced individuals also reported greater dietary restraint in comparison to controls. This is surprising after such a significant period of weight-loss maintenance (median weight-loss maintenance: 30 months) and highlights the ongoing challenges to maintain reduced weight. These findings contribute to the relatively smaller body of research into the longer-term persistence of weight-loss associated adaptive responses in comparison to that covering the acute weight loss phase. It also highlights strategies that may be effective in counteracting metabolic adaption to weight loss. As such, these strategies may warrant inclusion as part of weight-loss maintenance programs as they potentially help to reduce the risk for weight regain as a result of weight-loss associated adaptive thermogenesis. The next study in Part 2 of the thesis (Chapter 5) aimed to examine the impact of successfully maintained weight loss and weight-loss relapse on insulin sensitivity compared to BMImatched controls without a weight loss history. Predictors of variability in insulin sensitivity were also explored. Following the measurement of resting metabolic rate and substrate utilization a 75g oral glucose tolerance test was used to determine fasting and 2hr plasma glucose and insulin. The Homeostatic Model Assessment (HOMA-IR) and insulin sensitivity index (ISI(0,120)) were used to assess insulin sensitivity. A novel finding of this study was that successfully maintained, weight-reduced individuals displayed enhanced measures of insulin sensitivity (lower HOMA-IR and higher ISI(0,120) measurements), compared to all other groups, including BMI-matched controls with no weight loss history. Previously studies have investigated changes in insulin sensitivity in response to weight loss and in weight-loss maintenance, but not necessarily in comparison to individuals without a weight loss history as defined by this study protocol. With weight regain however, insulin sensitivity measures for REL were not different compared to either LSW or OSW, showing that enhanced insulin sensitivity accompanying weight loss is likely reversed with weight regain. Prior weight history, fasting substrate utilization, measures of body weight and composition, protein intake per kilogram, physical activity and CRF were all associated with measures of insulin sensitivity. Using these variables in regression models, ≈60% of the variability in insulin sensitivity in both HOMA-IR and ISI(0,120). Weight loss and weight regain history followed by fasting RER were the most significant independent predictors of insulin sensitivity. In conclusion, a novel finding was that successfully weight-reduced individuals are more insulin sensitive than their BMI-matched controls with no weight loss history, independent of dietary intake and physical activity. This remains evident even after significant periods of maintaining the reduced weight. Weight loss maintenance programs are essential to retaining metabolic benefits acquired through weight loss. Remaining physically active by reducing sedentary behaviour and in particular including small amounts of vigorous physical activity significantly predicts improved insulin sensitivity. This thesis includes a number of novel findings. In Part 1, we showed that in response to exercise training gynoid FM, rather than VAT, was reduced in sedentary obese black SA women undergoing a 12 week exercise intervention, which may represent an important ethnic/gender specific response. We also showed that substrate utilization plays an important role in altering body composition and CRF in response to an exercise intervention. Greater fat oxidative capacity at the outset resulted in an enhanced ability to reduce gynoid FM in response to exercise training. Furthermore, a greater reliance on carbohydrate rather than fat oxidation during baseline testing predicted a poorer CRF response. Identification of individuals with a lower capacity for fat oxidation at the outset of an exercise intervention may therefore allow for a more targeted exercise prescription, which may in turn improve outcomes of exercise interventions. The lack of clinically significant weight loss suggests that future exercise interventions should prescribe exercise EE of sufficient magnitude to achieve weight loss and emphasize adherence to this prescription or include some dietary restriction. Education around the possible adaptive responses to increased EE and the imposed energy deficit, highlighting the strategies employed by weight reduced individuals from Part 2 of this thesis, may help to attenuate potential metabolic adaption to increased EE and further improve the weight loss outcomes of exercise-only interventions. It may also help to inform weight-loss maintenance programs to assist individuals to maintain the reduced weight following weight loss. The enhanced insulin sensitivity in weight reduced individuals as shown in Part 2, may potentially represent an ongoing and persistent adaptive response to weight loss that may in itself increase the risk for weight-loss relapse. Education around the physiological adaption to significant weight loss and emphasizing strategies that may counteract this metabolic adaptation may improve the efficacy of both weight-loss and weight-loss maintenance programs.

Bibliography: p. 141-166.

Historically, cricketing literature has explored the disciplines of bowling and batting, with fielding receiving little attention until its importance was highlighted by the introduction of T20 matches. The novelty of this research lies in its clinically meaningful contribution to understanding shoulder injury aetiology in cricketers as overhead throwing athletes. The studies included in this thesis investigate the musculoskeletal profile of a cricketer’s shoulder, as well as the intrinsic factors associated with shoulder injury risk. Further, the influence of some of these risk factors on the cricketers’ overhead throwing biomechanics is explored and intend to improve the development of cricket-specific shoulder injury prevention programmes. An overview of the literature (Chapter 2) includes the epidemiology of shoulder injuries in cricketers; as well as a description of overhead throwing kinematics and the musculoskeletal adaptations associated with overhead throwing in cricket, compared to baseball, which has the greatest volume of throwing related studies. Based on previous outdated definitions of injury and not the current consensus definitions, shoulder injuries in cricket have been reported to occur infrequently. Various injury surveillance studies have identified time-loss shoulder injuries in cricketers, yet none have considered non-time-loss shoulder injuries. Although a limited number of studies have proposed potential intrinsic risk factors to shoulder injury in cricketers, no associations have been found. However, the cricketer’s shoulder is prone to injury due to the high forces generated while repeatedly throwing overhead during fielding. While overhead throwing biomechanics has been well investigated in baseball, minimal research exists for cricket. In addition, the understanding of throwing biomechanics in cricket has relied on two-dimensional motion analysis that is known to be insufficient for the analysis of rotational kinematics and kinetics. Elite (senior national and franchise) cricketers were recruited for this study. This study consisted of two parts. During the first part of the thesis demographic, training, competition and injury history data were obtained; and a shoulder-specific functional questionnaire and pre-season shoulder screening protocol were performed, prior to annual musculoskeletal screening. The incidence of all shoulder injuries were recorded throughout a six month cricket season. A profile of pertinent risk factors was assessed. The second part of the thesis evaluated throwing biomechanics of cricketers. Upper quarter, spinal, pelvic and hip kinematics, as well as shoulder and elbow kinetics were measured during the execution of overhead throwing from a stationary position, and with a run-up. This thesis includes three original papers and two experimental Chapters. The first paper (Chapter 3) documents the incidence of non-time-loss shoulder injuries in elite South African cricketers. Overall, the incidence of shoulder injury in cricketers during the 2016/2017 season was 18%, described as 5% time-loss and 13% non-time-loss injuries. Primary skill and fielding were negatively impacted in 100% and 80% of cricketers who sustained non-time-loss shoulder injuries, respectively. The entire cricket cohort recorded low scores on the shoulderspecific questionnaire, completed pre- and post-season, irrespective of injury history or injury sustained during the 2016/2017 season indicating a generalised reduction in the level of function in overhead activity. Paper 2 (Chapter 4) provides a description of the musculoskeletal profile of a cricketer’s shoulder which is atypical to the “thrower’s paradox” described in baseball. Specifically, cricketers present with a loss in total glenohumeral (GH) rotational range of motion (ROM), GH internal rotation deficit (GIRD) in the absence of external rotation gain (ERG); and global weakness of the rotator cuff and scapula stabilising muscles. Further, dominant shoulder supraspinatus tendon (SsT) thickness ≥5.85mm (sensitivity: 72%, specificity: 63%) and nondominant pectoralis minor length (PML) ≤12.85cm (sensitivity: 83%, specificity: 55%) predicted seasonal dominant shoulder injury (p< 0.05). From the findings indicated in Papers 1 and 2 (Chapters 3 and 4) it can be postulated that cricketers are generally a high-risk population for shoulder injury, amongst overhead throwing athletes, due to the lack of shoulder-specific musculoskeletal adaptation frequently observed in other overhead throwing populations. Paper 3 (Chapter 5) and experimental Chapters 6 and 7 investigate the kinematics and kinetics of overhead throwing from a stationary position, with a run-up and the consequence of GIRD in these two throwing approaches. A kinematic description of overhead throwing in cricket is provided and compared to baseball overhead pitching, in Paper 3 (Chapter 5). Maximum external rotation (MER) was regarded as the most critical point for potential shoulder injury in cricketers when throwing overhead from a stationary position. Further, a comparison between playing levels highlighted that amateur cricketers may display an increased risk for shoulder injury at MER as these cricketers were found to have decreased elbow flexion ROM in 2-14% of the throwing cycle (p=0.01), as well as greater shoulder (p=0.021) and elbow (p=0.043) compression and increased superior shoulder force (p=0.022) at MER, when compared to elite cricketers. Findings from experimental Chapter 6 indicate that when throwing with a run-up (dynamic) increased lumbo-pelvic (p=0.02) and hip flexion (p=0.01) occur sporadically in the throwing cycle, compared to throwing from a stationary position (static). In addition, increased shoulder compression (p=0.02) and posterior force (p=0.009) occur at MER, while reduced superior shoulder force (p=0.005) and elbow compression (p=0.03), superior (p=0.002) and medial (p=0.03) forces occur at ball release (BR), when throwing dynamically versus statically. These two Chapters highlight MER as the most critical point for potential shoulder injury in cricketers, which may further be attenuated by the absence of ERG, level of play and throwing from a stationary position while fielding. Experimental Chapter 7 investigated and highlights the potential correlations between GIRD, a frequently described risk factor for overhead athletes, and the other musculoskeletal variables measured, as well as overhead throwing biomechanics from a stationary and runup approach. Greater GIRD was associated with reduced passive hip external rotation ROM on the dominant side (p< 0.03), measured by inclinometer. In addition, increased GIRD was associated with reduced dominant hip abduction ROM during 0-23% of the throwing cycle (p=0.002), and superior shoulder force (p< 0.004) and elbow compression (p< 0.009), when throwing from a stationary position. Finally, greater GIRD was associated with increased posterior shoulder force at maximum internal rotation (MIR), when throwing from a stationary position (p< 0.013) and with a run-up (p< 0.03). These findings suggest that GIRD may negatively influence ball velocity specifically when cricketers attempt to throw overhead from a stationary position. Further, it is postulated that when throwing overhead (irrespective of approach) cricketers may overcome the mechanical insufficiency of GIRD by actively engaging the dominant hip internal rotators, to prematurely rotate the pelvis forward, in order to generate sufficient ball velocity. This may result in cricketers employing a throw across the body, which when repeatedly performed may cause hypertrophy of the dominant hip internal rotators, thereby reducing passive hip external rotation ROM. This biomechanical adaptation to GIRD may contribute to the cricketer’s predisposition for shoulder injury when throwing overhead, or may occur in an attempt to protect the shoulder against further injury. In conclusion, the inherent musculoskeletal profile of this elite cricketing cohort’s shoulder increases injury risk, particularly when throwing overhead. There is a need to investigate the influence of throwing volume, duration of season and player speciality on the musculoskeletal profile of the shoulder and concomitant injury in cricket. It is suggested that modifiable intrinsic factors found to be associated with shoulder injury and the performance of overhead throwing should be appropriately incorporated into injury prevention or pre-season conditioning programmes, to reduce the occurrence of injury. Further research should determine the efficacy of these programmes on shoulder injury prevention and throwing performance, in cricketers.