Hearing impairment is a chronic condition for which limited screening and diagnostic services are available in low-and-middle income countries (LMICs). In addition to the conventional medical devices existing to screen for the condition, several smartphone- and tablet-based applications have been introduced as mobile health (mHealth) solutions. This study was aimed at reviewing the set of mobile health tools available for screening for hearing loss in both developed countries and LMICs. Furthermore, to consider the suitability of the screening tools identified in the first objective for use in developing countries. The research approach adopted for this study was that of a state-of-the-art review. Relevant literature on mobile technology solutions to assess hearing loss were identified in electronic databases and reviewed. The mHealth solutions were reviewed with a focus on: countries of origin and evaluation; devices, software platforms and hardware considerations; hearing loss characteristics of recruited populations; features of the tests conducted and of the testing environment; reference methods to which the mobile application was compared; application performance; feedback from users; and cost. Eighteen available smartphone- and tablet-based applications for hearing loss screening were reviewed. Studies on these applications included participants from a variety of ages and, with and without hearing loss. A variety of testing environments were used. Studies on the applications found 11 of them to have acceptable functionality for use in screening for hearing loss. These 11 applications are also potentially suitable for use in LMICs, although they have some limitations. While these applications are not able to replace the conventional audiometer, they have potential as a first point of access for referral to conventional audiometry, and to help increase access to hearing loss tests in resource-constrained health systems.

Mseleni Joint Disease (MJD) is a crippling osteoarthropathy of unknown aetiology endemic to southern African Bantu-language speakers in a remote region of Northern KwaZulu-Natal, South Africa. Effective management of MJD has been hindered by limited insight into risk factors, explanatory models or treatment-seeking behaviours in those affected. Until MJD is better understood, disability, unemployment and dependence on social assistance grants and family income for subsistence will remain a reality for those affected. A mixed methods study was conducted with the aims of examining risk factors, explanatory models and treatment-seeking behaviours associated with MJD. The distribution, differential diagnosis and treatment of MJD were statistically analysed using medical records (n=723), MJD-patient surveys (n=37) and a meta-analysis. Socio-economic and cultural risk factors were assessed from surveys (n=99) and census publications. Interviews with MJD patients (n=6), nurses (n=7) and doctors (n=9) were qualitatively analysed for themes pertaining to perceptions, experiences and treatment-seeking for MJD. A point prevalence of 9% was estimated. Women were nearly twice as likely to have MJD than men (OR= 1.89; p=0.03) and the likelihood of MJD increased almost three-fold in those older than 50 years (OR= 2.83; p<0.01). Age was a confounder of the association between gender and MJD, as the sample was skewed in the representation of elderly women. MJD was only detected in patients older than 35 years, indicative of a later onset age than previously reported. The prevalence of MJD in settlements along tar and concrete roads, with access to public transport but limited piped water was suggestive of environmental risk factors or differential access to hospital-based care. Explanatory models of MJD were supernatural (witchcraft or ancestral displeasure); natural (nutritional deficiencies, 'genetics' and/or environmental); and/or social (gender-based practices and lifestyle). MJD patients described supernatural and natural aetiologies, and conceptualised disability as an inevitable reality. Consequently, patients reported taking few measures to prevent joint immobility, focussing instead on immediate symptomatic relief. Psychosocial and systemic barriers to treatment were suggestive of a disconnect between traditional African healing and Western biomedicine. This work demonstrates the value of the biocultural approach in identifying spatial, ecological, social and cultural processes that shape population patterns of health and disease.

Includes abstract. / Includes bibliographical references (p. 203-244). / The aetiology of obesity is complex, and in addition to intrinsic factors such as the biology of individuals (presented as genetics, age, gender) that contribute to the high obesity epidemic, there are behavioural determinants, along with economic, socio-cultural and environmental factors which are largely extrinsic, that either directly or indirectly influence the development of obesity, therefore are called “obesogenic” (Swinburn et al., 2005; Egger and Swinburn, 1997). In South Africa, these “obesogenic” factors have been only partially explored, and as such, there are gaps in our knowledge. We are also not certain of the extent to which the language, culture and age influence these afore-mentioned factors. As such, this dissertation focused on finding and adapting culturallysensitive and age-appropriate instruments to better understand these obesogenic factors in South African women and girls.

Bibliography: leaves 170-187. / Osteological, dental, and molecular analyses were conducted on remains from seven historical archaeological sites within South Africa. The emphasis was on the collection of lifestyle data for the purpose of adding to the unwritten history of indigenous South African peoples and to give voice to a once forgotten group of peoples. The demographic distribution reveals three different community dynamics: the Griqua sample are a pastoralist group incorporating some agricultural activities, the Colesberg individuals are an indigenous group resembling a migrant workers population living on the margins of society, and the Wolmaransstad demographics are suggestive of a Zabantu labouring community. All individuals are relatively healthy with low rates of dental disease and trauma and share similar growth patterns to living populations. However all of these individuals display high frequencies of porotic hyperostosis and cribra orbitalia, skeletal manifestations of iron deficiency anaemia. Many theories about the occurrence of anaemia are discussed and the hypothesis that, in these individuals, it is related to infection by the smallpox virus is investigated through the analysis of ancient DNA.

Includes bibliographical references (p. 228-241). / The present thesis examined the hypothesis that self-paced exercise performance and pacing strategies are regulated by a complex intelligent system in advance of a failure to maintain homeostasis in one or more physiological systems. In the first study, ten trained cyclists performed 20 km cycling time-trials in hot (35°C) and cool (15°C) conditions. The power output was reduced in the heat despite core temperatures that were sub-maximal and not different from those measured in the cool condition. Significantly, the reduction in power output was associated with a lower IEMG activity in the active muscle, suggesting that the brain recruited less muscle even at sub-maximal body temperatures. Thus, self-paced exercise in the heat was regulated in advance of thermoregulatory failure. This model was then applied to conditions where the oxygen content of the air was elevated (yperoxia). Eleven subjects performed 20km time-trails, and it was found that a higher power output was maintained throughput hyperoxic (F₁O₂0.21), and that the IEMG activity was elevated in hyperoxia. The subjective rating of perceived exertion (RPE), measured using the Borg scale, was similar in both this and the first study, despite differences in power output. It was suggested that the RPE may play a mediatory role.

Includes bibliographical references (p. 216-249). / The temperature responses to exercise have been a much investigated topic of intense research interest over the past 50 years. More recently, the effects of fluid ingestion on temperature regulation have been the focus of this area. The aim of this thesis is to undertake research to evaluate what has become the established dogma in this field and to determine whether a new model might better explain thermoregulation in humans during endurance exercise.

Includes bibliographical references (leaves 115-128). / Generally, the factors contributing to success or failure of axon regeneration lie in the intrinsic properties of the injured neurons, as well as the surrounding microenvironment of the transected axon. Mammalian neurons may lack the intrinsic ability to survive after trauma, or to re-express genes required for axonal regrowth. Moreover, several proteins inhibitory to neurite growth, such as Tenascin-R (TN-R) and Nogo-A, have been identified in mammals. These proteins are associated with oligodendrocytes and myelin and are considered major inhibitory components of the CNS environment.

Genome-wide association study (GWAS) has emerged as an effective method for detecting genetic polymorphisms associated with expressed phenotypes. Over the past decade, GWAS of human traits and diseases has revolutionized the field of complex disease genetics, identifying hundreds of genetic variants associated with several different phenotypes, ranging from metabolic diseases to cardiovascular and neuropsychiatric conditions. These associations have provided fundamental insights into the genetic architecture of disease susceptibility and led to initial forays into clinical applications, particularly in creation of genetic risk scores for improved disease risk prediction and identification of new drug targets for novel drug development. Despite this gratifying success, however, for almost all complex traits, the identified genetic loci explain only a small proportion, generally less than half, of the estimated heritability. A number of alternative explanations have been offered for this, including undetected genetic effects, unaccounted-for environmental factors, and gene–gene and gene–environment interaction effects. Although there is no consensus on these explanations, it is universally acknowledged that a substantial proportion of the trait heritability is attributable to existence of a large number of undetected genetic variants distributed across the entire allele frequency spectrum, each of which has very small to modest effect on the phenotype, and non host-DNA factors that contribute to phenotypic variation. In parallel to host GWAS, the advent of next-generation sequencing technologies (NGS) that enable culture-independent profiling of microbial communities has led to the rediscovery of the microbiome - the collective genome of the microorganisms that inhabit the body - and the emergence of microbiome-wide association studies. These studies have linked the gut microbiome to a variety of human conditions, ranging from neurological conditions, such as Parkinson's disease and autism, to metabolic diseases, such as obesity, diabetes, and cardiovascular disease. Given the critical importance of the microbiome in host phenotype, it is clear that in order to more comprehensively understand the basis of host phenotypic status, both the host's genotype and microbiome information have to be examined. This thesis explores the dissection of microbial taxa and host genetic polymorphisms associated with human complex traits and diseases, and the interaction of human host genetic polymorphisms with the microbiome. Then, a Bayesian statistical framework, based on the Dirichlet process random effects model, is proposed for identifying microbial species associated with host phenotype. The proposed method uses a weighted combination of phylogenetic and radial basis function kernels to model microbial taxa effects, and a non-parametrically defined latent variable to model latent heterogeneity among samples. Philosophically, the non-parametric specification amounts to the addition of an infinite amount of prior information about all fine details of the parameters being modelled; thus represents an attractive strategy. The utility of the method is demonstrated through simulation experiments and application to real microbiome datasets for schizophrenia, HIV/AIDS, and atherosclerosis diseases, where it is shown that the method is not only robust but also has high statistical power for association inference, resulting in a framework that can contribute to our understanding of the link between the microbiome and human diseases. Understanding the human genetic predisposing factors in concert with this link will make human GWAS fulfil its translational potential, from patient stratifcation and disease risk prediction to identification of new biology and drug discovery.

Includes bibliographical references. / Musculotendinous stiffness or elasticity is difficult to measure in vivo. Therefore, various procedures have been used in an attempt to quantify the contribution of the elastic properties of muscle and tendon to stretch shortening cycle performance. The results are variable, perhaps as a result of the different techniques utilised. Although several studies have suggested an association between a more compliant muscle-tendon complex, and enhanced stretch shortening cycle performance, this interpretation is not conclusive and needs further testing with particular attention being focused on the non-invasive, in vivo measurement of musculotendinous stiffness. Accordingly, the primary goal of this dissertation was to identify the relationship between the mechanical characteristics of the muscle-tendon complex, in particular tendon stiffness, and stretch shortening cycle muscle function.

Includes bibliographical references (p. 177-213). / The aim of this thesis was to examine the effect of various antecedent exposures and physiological pertubations on the relationship between the perceptual (perceived exertion), the physiological (metabolic milieu), and the performance (overall exercise performance) during both open and closed loop exercise at either a self-placed or constant workload.