[Truncated abstract] Asthma is a chronic and complex disorder and despite our increase in the understanding of the genetics, pathology and mechanisms underlying asthma a gold standard definition of asthma does not exist. A criterion for recognising and diagnosing asthma in epidemiological studies is crucial in order to determine risk factors for disease. Prospective longitudinal birth cohort studies have increased our understanding of the natural history and risk factors for asthma, yet we are still not able to accurately predict which children will go on to have asthma as adults. It is during the transition from childhood to adolescence where factors underlying asthma change and the prevalence of asthma shifts between the sexes. There are inconsistencies regarding risk factors for the development and persistence of disease during this transitional period. Risk factors predicting the development and persistence of asthma and intermediate phenotypes (BHR, airway inflammation and atopy) may be influenced by gender and risk factors predicting disease may differ between childhood and adolescence. Aims 1. To identify risk factors for Asthma, BHR and Atopy at 14yrs of age. 2. To determine risk factors for persistence of asthma between 6 and 14 years. 3. To examine the influence of gender on risk factors during adolescence. Method The West Australian Pregnancy Cohort is a longitudinal birth cohort. The cohort initially consisted of 2868 live births with follow-ups at 1, 2, 3, 6, 8, 10 and 14 years of V age. ... Strong associations were seen with BHR and new diagnosis of wheeze and asthma in VI teenagers. Interestingly having either a cat or dog inside was protective for persistence of disease; in particular stronger associations were seen in teenage girls not in boys. During this transitional period the risk factors for asthma and intermediate phenotypes differ between the sexes. Different mechanisms are likely to be involved in determining asthma in boys and girls during adolescence and shed new light on the recognised switch in the gender balance in asthma prevalence from the male predominance in childhood to the female predominance in adult life. Our understanding of the natural course of disease from the prenatal period to adulthood and the identification of the various asthma phenotypes has the potential to change prognosis and planning of therapeutic strategies. Identifying those at high risk for persistence of disease in the early stages of life will allow therapeutic interventions to be more appropriately targeted.

Background. The incidence of starting renal replacement therapy (RRT) among young people (< 20 years of age) in 2013 in Scotland was 7.7 per million (age-related) population. Little knowledge exists about cardiovascular risk factors (CVRFs), long-term survival and cardiovascular disease (CVD) outcomes in patients who initiated RRT in childhood. The main source of routine data for these patients is available from the European Society of Paediatric Nephrology/European Renal Association- European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry. In Scotland nationally comprehensive data on patients receiving RRT is available from the Scottish Renal Registry (SRR). Aim and objectives. The overall aim of the thesis is to review relevant literature and conduct retrospective cohort studies describing CVRF prevalence, all-cause mortality and incidence of CVD outcomes in patients who initiated RRT in childhood. ESPN/ERA-EDTA registry data were used to describe the prevalence of anaemia, hypertension, dyslipidaemia and BMI categories and their association with all-cause and CV mortality. SRR data were used to describe all-cause mortality and CVD incidence and their association with age at start of RRT, sex, primary renal disease (PRD), type of RRT and period of start of RRT. Methods. Systematic searches were performed to identify relevant literature. For the ESPN/ERA-EDTA analyses patients who started RRT between 0 and 20 years of age and who had CVRF data were included. Patients were followed from date of first CVRF measurement until the earliest of death, loss to follow-up, reaching 20 years of age or the end of follow-up (December 31st 2012). Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality, comparing patients with and without each CVRF. For the SRR analyses, patients who started RRT under 18 years of age in the period from 1963 to 2013 were included in the analyses. To describe CVD incidence the SRR data were linked to national registers for death and CVD hospital admissions available from 1981 onwards. These analyses, therefore, included patients who started RRT between 1981 and 2013 with follow-up until first CVD event after start of RRT, end of follow-up period or censoring at death. Cox proportional hazard models were used to examine the association of age at initiation of RRT, sex, PRD, type of RRT and period of initiation of RRT with all-cause mortality and CVD incidence. Results. The systematic reviews revealed a gap in current knowledge about CVD incidence and the association of CVRFs with CVD outcomes in patients who initiated RRT in childhood. In total, 7,845 patients were included in the ESPN/ERA-EDTA registry analysis. The mean age of the patients was 9.5 (SE 0.06) years, 58.9% were male, and the most common PRD was congenital anomalies of kidney and urinary tract (CAKUT). The prevalence of dyslipidaemia, hypertension, anaemia overweight/obesity and underweight was 87.5%, 79.3%, 36.0%, 29.9% and 4.3%, respectively. During median follow-up of 3.7 (IQR 1.7-6.8) years 357 patients died. HRs for anaemia were 2.19 (95% CI 1.64-2.93) and 2.55 (95% CI 1.27-5.12) for all-cause and CVD mortality, respectively. The HR for all-cause mortality for underweight was 1.81 (95% CI 1.30-2.53). No other studied CVRFs were statistically significantly associated with all-cause and CVD mortality. In total, 479 patients were included in the SRR analyses of all-cause mortality. The most common PRD was CAKUT and 55.3% of patients were male. During a median follow-up of 18.3 (IQR 8.7-27.0 years) years 126 patients died. Twenty-year survival among patients initiated RRT in childhood was 77.6% (95% CI 73.8-81.3). Age at start of RRT, PRD and type of RRT were significantly associated with all-cause mortality. HR for all-cause mortality for patients who started RRT under 2 years of age was 2.50 (95% CI 1.19-5.25) compared to patients who started RRT at 12 to 18 years old. HR for all-cause mortality for patients with PRD other than CAKUT or glomerulonephritis (GN) was 1.58 (95% CI 1.05-2.39) compared to patients with CAKUT. HRs for all-cause mortality for patients who only received either HD or PD during follow-up were 19.4 (95% CI 10.4-36.4 and 19.5 (9.65-39.7), respectively, compared to patients who received a renal transplant. In total, 381 patients were included in the SRR analyses of CVD incidence. During a median of 12.9 (IQR 5.6-21.5) years of follow-up after initiation of RRT 134 patients (35.2%) developed CVD. The overall crude CVD incidence was 2.6 (95% CI 2.2-3.0) per 100 person-years. HRs for CVD were 1.69 (95% CI 1.05-2.74) for males compared to females, 1.72 (95% CI 1.02-2.91) for PRD other than CAKUT or GN compared to CAKUT and 8.38 (95% CI 3.31-21.23) and 7.30 (95% CI 2.30-23.16) for patients who only received either HD or PD during follow-up, respectively, compared to patients who received a renal transplant. Conclusions. This thesis has contributed to knowledge about CVRF prevalence, longer-term survival and CVD outcomes in patients who initiated RRT in childhood by identifying high prevalence of CVRFs and that CVD is a common complication. This study did not investigate whether anaemia, hypertension, dyslipidaemia and obesity are associated with a higher risk of developing CVD after start of RRT. Future research is needed to study whether treatment of anaemia, hypertension, dyslipidaemia and controlling body weight will reduce the risk of CVD and mortality in patients who initiated RRT in childhood.

This thesis looks at risk factors for multiple sclerosis (MS), a chronic, degenerative autoimmune disease which is usually diagnosed between the ages of 20 and 50 years. It is estimated to affect over 100,000 people in the UK. The research setting was Orkney and Shetland, two archipelagos situated north of mainland Scotland, and both of which have very high MS prevalence as do other countries at high latitudes. I examine genetic and environmental risk factors in Orkney and Shetland using multiple methods over four studies. I also review the vitamin D and UV exposure literatures as these are risk factors pertinent to MS in Orkney and Shetland. After devoting three chapters to introducing the purpose of the thesis, MS, and Orkney and Shetland, in the fourth chapter, I aim to establish whether the birthplace of cases show any spatial, temporal, or spatiotemporal clustering. Evidence of these kinds of clustering may indicate that there are environmental risk factors present in some areas or that were present over particular periods, which raise risk of developing MS. Although I find statistically significant temporal, spatial, and spatiotemporal clustering in Orkney, and a spatial cluster in Shetland, for multiple reasons these results need to be interpreted with caution. I conclude that the clusters are very likely to be artefacts. Furthermore, there are multiple possible alternative explanations for such clusters that could not be explored by the available data. Chapter 5 examines the heritability of MS in Orkney and Shetland to estimate the proportion of phenotypic variance attributable to additive genetic effects. I also look at the birthplaces of ancestors of cases and controls to see if any locations contribute a greater amount of ancestral DNA to the gene pool of modern MS cases, which I term ‘genetic clustering’. In Orkney I obtained a heritability estimate of 0.36 (95% CI -0.26, 0.98); in Shetland this estimate was 0.20 (95% CI -1.88, 2.28). These modest estimates are consistent with the heritability literature. The genetic clustering analyses highlight two Orkney registration districts, Kirkwall and Westray, which earlier studies identified as areas of MS clustering. I also identify three Shetland registration districts, however these locations had not shown any evidence of clustering in earlier studies. Again, I advise caution in interpreting results, particularly as all the error bars across registration districts overlap. Chapter 6 presents a scoping review to map the literature and identify evidence of an association between vitamin D and UV exposure with MS. In methodically searching the literature, I identify a large and heterogeneous evidence base comprising multiple observational, intervention, and genetic studies. Overall, many studies support an association between vitamin D deficiency and MS. There is also evidence for an association between UV exposure and MS, although UV exposure is considerably less explored than vitamin D. I finally identify gaps in the literature and make suggestions for future research. In Chapter 7 I aim to compare vitamin D levels in Orkney and mainland Scotland, and establish the determinants of vitamin D status in Orkney. I firstly compare mean vitamin D and prevalence of deficiency in cross-sectional data from studies in Orkney and mainland Scotland. I secondly use multivariable regression to identify factors associated with vitamin D levels in Orkney. I find that mean (standard deviation) vitamin D is significantly higher in Orkney compared to mainland Scotland (35.3 (18.0) and 31.7 (21.2), respectively), and prevalence of severe deficiency is lower in Orkney (6.6% to 16.2% p = 1.1 x 10-15). Factors associated with higher vitamin D in Orkney include older age, farming occupations and foreign holidays. I conclude that although mean vitamin D levels are higher in Orkney compared to mainland Scotland, there is substantial variation within the Orkney population which may influence MS risk. Chapter 8 examines the correlates and determinants of UVB exposure in Shetland. I firstly construct correlation matrices to visualise how 1) personal characteristics such as sex, occupation, and skin type, 2) physical activity, and 3) body weight and fat, correlate with UVB exposure. I then use multivariable regression to identify factors associated with UVB exposure in Shetland. I run two multivariable models. The first includes the full sample size where activity data were measured by questionnaires. The second includes both questionnaire physical activity data and step-count data from pedometers, however as only a subset of participants had been supplied with pedometers, this analysis comprises a smaller sample size. I find that the amount of skin exposed was most strongly correlated with UVB exposure. Step count and activity minutes were also moderately positively correlated, and indoor occupations moderately negatively correlated, with UVB exposure. The regression analysis using the full sample with questionnaire activity data found that factors associated with greater UVB exposure were age and ambient UVB, while working indoors was significantly associated with lower UVB exposure. The model including the pedometer data found that found that age, total steps, and the amount of ambient UVB were significantly associated with greater UVB exposure. I conclude that atmospheric conditions, working outdoors and older age are important factors in UVB exposure in Shetland. It remains to be seen how UVB exposure translates to vitamin D levels in Shetland. I found evidence for environmental and genetic risk factors for MS in Orkney and Shetland. The two environmental risk factors, vitamin D deficiency and reduced UV exposure, are more likely to affect the younger population who are still within their lifetime risk of developing MS.

Thesis (MTech (Internal Auditing))--Cape Peninsula University of Technology, 2015. / Social media has undoubtedly emerged as one of the greatest developments in this technology driven generation. Despite its existence from years back, social media popularity has recently surged drastically, with billions of users worldwide reported to be on at least one social media platform. This increase in users of social media has further been necessitated by governmental and private-sector initiatives to boost Internet connectivity to bridge the digital divide globally. Mobile Internet access has also fuelled the use of social media as it allows easy and economical connectivity anytime, anywhere. The availability of hundreds of social media platforms has presented businesses with several opportunities to conduct business activities using social media. The use of social media has been reported to avail businesses with plenty of benefits when this use is strategically aligned to business objectives. On the flipside of the coin, these social media platforms have also emerged as new hunting grounds for fraudsters and other information-technology related criminals. As with any invention, engaging social media for business has its own inherent risks; this further complicates existing information-technology risks and also presents businesses with new risks. Despite blossoming into a global phenomenon, social media has no universally accepted frameworks or approaches (thus no safeguards) when engaging with it, resulting in almost unlimited risk exposures. The uncertainly, i.e. risks surrounding social media platforms, proves problematic in determining the optimum social media platform to use in business. Furthermore, organisations are facing challenges in deciding whether to formally adopt it or totally ignore it, with the latter emerging not to be a viable option. The complex nature of social media has made it difficult for enterprises to place a monetary value and determine a return on investment on these platforms. From a governance perspective, it remains a challenge for most enterprises to identify and appoint individuals responsible for social media management within businesses, although recently social media strategist positions have been surfacing. Due to their nature, the social media trigger matters relating to governance, risk and compliance, which imply that internal auditors therefore are expected to champion the adoption of social media in enterprises. As a relatively new concept, the role that internal auditors should play towards social media appears not to be well defined. Through examination of existing guidelines, an attempt is made to define the role of internal auditors towards social media.

Thesis (Ph. D. (Medical Sciences)) -- University of Limpopo, 2016 / Refer to document / The Belgium Development Co-operation through VLIR-UOS, The University of Limpopo,and The Flemish Universities

by Choi Ka Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 113-128). / Abstract and appendix in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Abstract (Chinese version) --- p.iv / Table of Contents --- p.vi / List of Tables --- p.xi / List of Figures --- p.xiv / List of Abbreviations --- p.xv / Chapter CHAPTER ONE: --- BACKGROUND AND LITERATURE REVIEW / Chapter 1.1 --- Coronary Heart Disease: a global health problem --- p.1 / Chapter 1.2 --- Risk Factors of Coronary Heart Disease --- p.3 / Chapter 1.2.1 --- Age --- p.3 / Chapter 1.2.2 --- Gender --- p.4 / Chapter 1.2.3 --- Family History of Cardiovascular Disease --- p.5 / Chapter 1.2.4 --- Hypercholesterolemia --- p.7 / Chapter 1.2.5 --- Unhealthy Dietary Habits --- p.11 / Chapter 1.2.6 --- Obesity --- p.14 / Chapter 1.2.7 --- Physical Inactivity --- p.20 / Chapter 1.3 --- Clustering of Risk Factors --- p.24 / Chapter 1.4 --- Risk Factors in Children: Atherosclerosis Begins Early in Life --- p.26 / Chapter CHAPTER TWO: --- RESEARCH IN HONG KONG AND PURPOSES OF THIS STUDY / Chapter 2.1 --- Nutrition Transition --- p.27 / Chapter 2.2 --- CHD Mortality Trends in Hong Kong --- p.28 / Chapter 2.3 --- Serum Total Cholesterol and Obesity in Hong Kong Adults --- p.29 / Chapter 2.4 --- "Obesity, Serum Total Cholesterol, Dietary Habits and Physical Activity of Hong Kong Children and Adolescents" --- p.31 / Chapter 2.5 --- Study Purpose and Objectives --- p.35 / Chapter CHAPTER THREE: --- SURVEY DESIGN / Chapter 3.1 --- Sample Selection --- p.39 / Chapter 3.2 --- "Blood Total Blood Cholesterol, Triglyceride and Anthropometric Measurements" --- p.40 / Chapter 3.2.1 --- Total Blood Cholesterol and Triglyceride --- p.40 / Chapter 3.2.2 --- Anthropometry Measures --- p.42 / Chapter 3.3 --- Questionnaire --- p.45 / Chapter 3.3.1 --- Questionnaire Design and Pre-testing --- p.45 / Chapter 3.3.2 --- General Health and Socio-demographic Questionnaire --- p.47 / Chapter 3.3.3 --- Physical Activity Questionnaire --- p.47 / Chapter 3.3.4 --- Dietary Questionnaire --- p.48 / Chapter 3.4 --- Data Management --- p.49 / Chapter 3.5 --- Statistics --- p.49 / Chapter 3.6 --- Data Analysis --- p.50 / Chapter 3.6.1 --- Blood Total Cholesterol and Triglyceride --- p.50 / Chapter 3.6.2 --- Obesity and Fat Distribution --- p.50 / Chapter 3.6.3 --- Diet --- p.51 / Chapter 3.6.4 --- Physical Activity Patterns --- p.51 / Chapter 3.6.5 --- Body Mass Index of Parent and Family History of Diseases --- p.52 / Chapter CHAPTER FOUR: --- RESULTS / Chapter 4.1 --- Sample Size and the Characteristics of the Students in the Two Schools --- p.54 / Chapter 4.2 --- Gender and Age Distribution --- p.55 / Chapter 4.3 --- Blood Total Cholesterol and Triglyceride --- p.56 / Chapter 4.4 --- Anthropometry Measures --- p.58 / Chapter 4.5 --- Dietary Habits --- p.60 / Chapter 4.5.1 --- Dietary Composition of 3-day Dietary Record --- p.60 / Chapter 4.5.2 --- Eating Behaviors --- p.65 / Chapter 4.6 --- Physical Activity --- p.68 / Chapter 4.7 --- Family History of Diseases --- p.70 / Chapter 4.8 --- Parents' Anthropometry --- p.71 / Chapter 4.9 --- Demographic Data --- p.71 / Chapter 4.10 --- Inter-relationships --- p.75 / Chapter 4.10.1 --- Blood Total Cholesterol and Triglyceride --- p.75 / Chapter a. --- "Blood Total Cholesterol, Triglyceride and Body Fatness" --- p.75 / Chapter b. --- "Blood Total Cholesterol, Triglyceride and Diet" --- p.75 / Chapter c. --- "Blood Total Cholesterol, Triglyceride and Physical Activity Patterns" --- p.77 / Chapter d. --- Blood Total Cholesterol，Triglyceride and Family History of Hypercholesterolemia --- p.78 / Chapter e. --- Relative Importance of the Key Factors in Predicting Blood Total Cholesterol levels --- p.79 / Chapter 4.10.2 --- Obesity and Body Fatness --- p.79 / Chapter a. --- "Obesity, Body Fatness and Physical Activity Patterns" --- p.79 / Chapter b. --- "Obesity, Body Fatness and Diets" --- p.82 / Chapter c. --- Body Fatness and Genetics --- p.84 / Chapter 4.10.3 --- Diet and Physical Activity --- p.86 / Chapter 4.10.4 --- "Blood Total Cholesterol, Triglyceride, Obesity and Other Demographic or Economic Characteristics" --- p.87 / Chapter 4.11 --- Clustering of Risk Factors among Obese children --- p.87 / Chapter CHAPTER FIVE: --- DISCUSSION / Chapter 5.1 --- Implication of Research Findings --- p.89 / Chapter 5.2 --- Limitations --- p.108 / Chapter CHAPTER SIX: --- CONCLUSIONS AND RECOMMENDATIONS --- p.111 / References --- p.113 / Appendices / Chapter I --- Questionnaire (English version) --- p.129 / Chapter II --- Questionnaire (Chinese version) --- p.139 / Chapter III --- Introductory letter (English version) --- p.152 / Chapter V --- Introductory letter (Chinese version) --- p.153 / Chapter V --- Consent form (English version) --- p.154 / Chapter VI --- Consent form (Chinese version) --- p.155 / Chapter VII --- Photos of the standard household measures given to children for estimation of portion size (English version) --- p.156 / Chapter VIII --- Photos of the standard household measures given to children for estimation of portion size (Chinese version) --- p.157 / Chapter IX --- Responses from the children to the food frequency questionnaire --- p.158 / Chapter X --- The frequency of the reported food items liked or disliked by the children --- p.160

Congenital Heart Disease (CHD) is one of the most common birth defects. It is the single most modifiable cause of infant mortality under one year of age. Therefore, the causes of CHD have been extensively researched in the past but the etiology remains largely unknown. Environmental risks, particularly maternal risk factors for congenital cardiac malformation have been evaluated in the original BWIS previously. However, in this research we examined one of the additional risk factors. We sought to determine whether maternal headache during six months prior to conception and throughout gestation until birth is a risk factor for CHD in the BWIS dataset. Among 3274 singleton cases and 3519 controls, a maternal report of headache was found to be associated with a nearly 20% increase in the risk of a congenital heart defect (OR= 1.2 p=0.001). Moreover, any medications use for headache 1-6 months prior to conception increased the risk of abnormal cardiac development by 1.3 fold (OR = 1.3, p=0.0004). Aspirin or aspirin containing analgesics were found to increase the risk for CHD at the defined risk period. According to subgroup analysis, aspirin or aspirin containing analgesics and acetaminophen or acetaminophen containing analgesics were found to be the risk factor for CTD i.e. Conotruncal defects. Furthermore, aspirin or aspirin containing analgesics increased the risk for PVSD i.e. Peri-membranous Ventricular Defect in offspring when the mother uses these drugs 1-6 months prior to conception. Additionally, the risk for CVD i.e. critical valve disease were found to be increased when women were exposed to aspirin or aspirin containing analgesics during third trimester after pregnancy. In conclusion, maternal headache increased the risk for CHD by 20% and the use of headache medications specifically pain relievers during 1-6 months prior to conception modulated type of defect was observed.

Thesis (PhD)--Stellenbosch University, 2013. / Bibliography / ENGLISH ABSTRACT: Introduction: Lipoatrophy is a common adverse effect of stavudine and this effect is strongly dose-dependent. Stavudine remains the most commonly used paediatric antiretroviral drug in sub-Saharan Africa, yet when the current study began in 2009, the prevalence and severity of lipoatrophy in children on antiretroviral therapy in sub-Saharan Africa had never been studied. The development of lipoatrophy may have serious and far-reaching consequences for patients and their families. The off-label stavudine dosing method, prescribed to children whose caregivers do not have access to a refrigerator, in which the contents of an adult capsule is mixed into tap water, has potential for over-dosing or under-dosing. In addition, children on stavudine continue to be exposed to a disproportionately high dose out of line with the reduced adult dose. Aims: 1. a) To investigate the prevalence and risk factors for lipoatrophy in HIV-infected children in Southern Africa b) To identify a simple anthropometric screening tool to detect early lipoatrophy in children 2. To validate the off-label stavudine dosing method prescribed to children whose caregivers do not have access to a refrigerator, with a view to reducing the recommended dose and thereby the side-effects. Methods: 1. a) We recruited pre-pubertal children on antiretroviral therapy from a family HIV clinic in our facility. Lipoatrophy was identified by two experienced paediatric HIV clinicians using a standardized grading scale. A dietician performed dietary assessment and anthropometric measurements. Previous antiretroviral exposures were recorded. A subset of recruits received Dual-Energy X-ray Absorbtiometry scanning. b) Anthropometric measurements in children with and without lipoatrophy were compared using multivariate linear regression adjusting for age and gender. The most discerning anthropometric variables underwent Receiver Operating Characteristic curve analysis to identify the most appropriate diagnostic cut-off. 2. a) Accuracy of the standard off-label stavudine dosing method was investigated using high-performance liquid chromatography to recover active drug from solutions made up using the prescribed method. This was compared to the stated drug content of the capsules. b) Bioavailability was investigated by performing a randomized crossover pharmacokinetic study wherein healthy HIV-seronegative adult volunteers received one of two generic stavudine capsule formulations, either intact or mixed in water using the prescribed method. Plasma stavudine concentrations were assayed by liquid chromatography tandem mass spectrometry. Results: 1. a) Prevalence of lipoatrophy was 36%, and incidence was 12% per person-year. Adjusted odds ratio for developing lipoatrophy was 1.9 (CI: 1.3–2.9) for each additional year of accumulated exposure to standard-dose stavudine. b) Baseline biceps skin-fold thickness correlated well with maximum lipoatrophy grading score at any site, giving a partial correlation coefficient of 0.33 (p=0.0006), and a receiver operating characteristic area-under-curve value of 0.75 (CI: 0.64 – 0.84). Biceps skin-fold thickness <5mm at baseline had a sensitivity of 89% (CI: 67–100%) and a negative predictive value of 97% (CI: 91–100%) for predicting which children would go on to develop lipoatrophy by 15 month follow-up. Specificity was 60% (CI: 46–75%) and positive predictive value was 32% (CI: 14–50%). 2. a) Recovery of active drug from solution was 97.1%, 97.4% and 93.8% for the proprietary and two generic formulations respectively. b) Pharmacokinetic parameters of the off-label dosing method were well within the target range of intact capsule dosing for both generics. Conclusions: 1. a) The prevalence and incidence of lipoatrophy in pre-pubertal children on antiretroviral therapy in South Africa is high. Cumulative exposure to standard-dose stavudine was the greatest risk factor for lipoatrophy. b) Biceps skin-fold thickness provided reasonable sensitivity and specificity to detect and predict lipoatrophy in pre-pubertal children on antiretroviral therapy. 2. The off-label dosing method for stavudine prescribed to children whose caregivers do not have access to a refrigerator is reasonably accurate and is bioequivalent to intact capsule administration. / AFRIKAANSE OPSOMMING: Inleiding: Lipoatrofie is 'n algemene nadelige uitwerking van stavudien en hierdie effek is sterk dosis-afhanklike. Stavudien bly die mees algemeen gebruikte paediatriese antiretrovirale medikasie in sub-Sahara Afrika, maar toe ons studie begin het, was lipoatrofie in kinders op antiretrovirale terapie in sub-Sahara Afrika nog nooit voorheen bestudeer nie. Die ontwikkeling van lipoatrofie kan ernstige en verreikende gevolge vir die pasiënt en hul familie hê. Die af-etiket stavudien dosering metode voorgeskryf aan kinders wie se versorgers nie toegang tot 'n yskas het nie het 'n aansienlike potensiäal vir oor-dosering of onder-dosering. Daarbenewens, is kinders op stavudien blootgestel aan 'n disproporsionele hoë dosis uit-pas met die verminderde volwasse dosis. Doelwitte: 1. a) Om ondersoek in te stel na die voorkoms en risiko faktore vir lipoatrofie in MIV-geïnfekteerde kinders in Suid Afrika b) Om 'n eenvoudige antropometriese instrument te identifiseer om vroeë lipoatrofie op te spoor in kinders op antiretrovirale medikasie 2. Om die af-etiket stavudien dosering metode wat voorgeskryf is aan kinders wie se versorgers nie toegang tot 'n yskas het nie te valideer, met 'n oog op die vermindering van die aanbevole dosis Metodes: 1. a) Ons het 'n groep van onder-puberteitsjarige kinders op antiretrovirale terapie gewerf uit 'n familie MIV kliniek in ons fasiliteit. Lipoatrofie is geïdentifiseer deur twee ervare MIV pediaters deur gebruik van 'n gestandaardiseerde gradering skaal. 'n Diëetkundige het diëet assessering en antropometriese metings uitgevoer. Vorige antiretrovirale blootstellings is aangeteken. In 'n subset was Dual-energie X-straal Absorbtiometry (DXA) skandering uitgevoer. b) Antropometriese metings in kinders met en sonder lipoatrofie is vergelyk met behulp van meerveranderlike lineêre regressie aangepas vir ouderdom en geslag. Die mees kieskeurige antropometriese veranderlikes het Receiver Operating Curve analise ondergaan om die mees geskikte diagnostiese afgesnypunt te identifiseer. 2. a) Akkuraatheid is ondersoek deur gebruik te maak van hoë werkverrigting vloeistofchromatografie om aktiewe medikasie vanuit oplossings te herstel, wat gemeng is soos aangedui deur die voorgeskrewe af-etiket dosering metode. b) Biobeskikbaarheid is ondersoek deur die uitvoering van 'n ewekansige oorgesteekde farmakokinetiese studie waarin gesonde MIV- negatiewe volwasse vrywilligers een van twee generiese stavudien kapsule formulerings ontvang het, óf heel of in water gemeng soos aangedui deur die voorgeskrewe af-etiket dosering metode. Plasma stavudien konsentrasies is gemeet deur vloeistofchromatografie tandem massaspektrometrie. Uitslae: 1. a) Voorkoms van lipoatrofie was 36%, en insidensie was 12% per persoon-jaar. Aangepaste Odds ratio vir die ontwikkeling van lipoatrofie was 1,9 (CI: 1,3-2,9) vir elke addisionele jaar van opgehoopte blootstelling aan standaard dosis stavudien. b) Biceps vel-vou dikte <5mm het 'n sensitiwiteit van 89% (CI: 83-96%) en 'n negatiewe voorspellende waarde van 90% (CI: 84-96%) vir die opsporing en voorspelling van lipoatrofie. 2. a) Herwinning van aktiewe medikasie uit oplossings was 97,1%, 97,4% en 93,8% vir die oorspronklike en twee generiese formulerings onderskeidelik. b) Farmakokinetiese parameters van die af-etiket dosering metode was wel binne die teikenband van ongeskonde kapsule dosering vir beide generiese formulerings. Gevolgtrekkings: 1. a) Die voorkoms van lipoatrofie in onder-puberteitsjarige kinders op antiretrovirale terapie in Suid-Afrika is hoog. Die bedrag stavudien waaraan kinders blootgestel is moet hersien word. Die standaard stavudien dosis vir kinders moet herge-evalueer word. b) Biceps vel-vou dikte het redelike goeie sensitiwiteit en spesifisiteit om lipoatrofie op te spoor en te voorspel. 2. Die af-etiket dosering metode vir stavudien voorgeskryf aan kinders wie se versorgers nie toegang tot 'n yskas het nie is redelik akkuraat en is bio-ekwivalent aan ongeskonde kapsule administrasie.

Submitted in partial compliance with the requirements for a Master’s Degree in Technology, Department of Chiropractic and Somatology, Durban University of Technology, Durban, South Africa, 2016. / Background: Mixed martial arts (MMA) is a contact sport that has grown in popularity worldwide. MMA has been shown to be an activity that generates a high volume of injuries in its participants, especially when subjected to particular factors that are known to carry high risk in contact sports. Limited research has been conducted concerning the risk for injury development in MMA, with no South African statistics being produced to date. This study aims to bridge this gap. Aim: The aim of this study was to determine the prevalence of and risk factors associated with musculoskeletal injuries in Mixed Martial Arts athletes in the greater Durban area of KwaZulu-Natal. Method: This study was a prospective, quantitative survey that sampled 105 MMA athletes from 16 accredited gyms in the greater Durban area. The information captured from the questionnaires enabled compilation of a fighter profile, training profile and injury profile assessing injuries present at the time of data collection and a history of injuries over a 12 month period. Data was analysed with SPSS version 23.0. Inferential techniques included the use of correlations and chi square test values, displayed as p-values and Eta scores. Relationships were considered significant with a p-value of <0.05 and an effect size of >0.23. Results: A 91% response rate was achieved with 83.3% male and 16.2% female participation. Overall, the most commonly injured areas were the upper extremity (36.5%), followed by the lower extremity (34.3%), spine (14.2%), head (8.6%) and trunk (6.5%) regions. In terms of single areas, the most common injuries were to the shoulder (30.9%), knee (29.2%) and elbow (14.4%). The most common injury types were joint sprains (31.1%), muscle strains (20.7%) and ligament tears (18.6%). The most common injury mechanisms were being struck (16.1%), falling (15.7%) and striking an opponent (13.6%). Participants were unsure of the mechanism of their injuries in 7.5% of the injury reports. The number of days missed from training due to injury ranged from zero to 270 days of incapacitation. Risk factors for injury were significant for favoring the dominant hand while fighting (p = 0.011), flexibility training/ stretching (p = 0.019), ground arm-bars (p = 0.014), ground strangles (p = 0.028), groundwork holds/pins (p = 0.028), falling (p = 0.006), increased age (η = 0,619) and increased body weight (η = 0.706). Participation in CrossFit as an additional sport/ conditioning program was a protective factor against injuries (p = 0.007). Conclusion and recommendations: Favouring one side, falling, stretching, arm-bars, strangles, pins and increasing weight are some of the largely modifiable risk factors that play an important role in the development of injuries in MMA athletes. Coaches and their athletes will benefit from adapting training strategies to reduce injury rates from over-exposure to activities that present a high risk of injury as well as by furthering the extent of exposure to conditioning. / M

published_or_final_version / Geography / Master / Master of Philosophy