4. Electronic Theses and Dissertations (ETDs) - Faculties submissions
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Item Characterising skeletopathy in an animal model of type 2 diabetes(University of the Witwatersrand, Johannesburg, 2022-11) Dlamini, Gcwalisile Frances; Ndou, RobertType two diabetes (T2D) is a chronic, progressive heterogonous syndrome with a genetic and environmental origin. It is now recognized as an epidemic with a high morbidity and mortality rate. The endocrinology of type 2 diabetes (T2D) and its predisposing factors have been studied extensively, while diabetic skeletopathy has received negligible research. Previous studies report that fractures in T2D vary with specific sub regions in bones, therefore prompting our study to focus mainly on the femoral head and neck as well as the humerus head. Femoral neck fractures are the commonest, followed by the proximal femur, distal radius and proximal humerus. Susceptibility to fracture is a sequelae of poor bone remodeling. Poor bone remodeling is established at molecular and cellular levels. It depends on the activity of osteoblasts, osteocytes and osteoclasts, which are under the influence of TGF-β1, a pro-osteogenic cytokine, together with BMP3, an anti-osteogenic cytokine. T2D induced bone marrow adipocity and the accumulation of AGEs in cortical bone have also been implicated in increasing susceptibility to fracture. It is still unclear how T2D affects molecular and cellular elements that culminate in weaker bones observed in diabetic patients. In addition, it is debatable if T2D affects the skeleton at disease onset or later in the disease. Therefore, this study aimed to characterize T2D induced skeletopathy and related it to age, in the Zucker Diabetic Sprague Dawley (ZDSD) rat, using the femur and humerus. This study initially confirmed the diabetic state by monitoring animal weights, fasting blood glucose levels, and fasting oral glucose tolerance tests (OGTTs) every fortnight. Then triglyceride levels and quantified serum levels of osteoregulatory hormones such as insulin and osteocalcin were monitored. To assess oxidative stress, Malondialdehyde (MDA) serum levels were also determined by ELISA. Once diabetes was successfully induced, rats were grouped according to strain and age at termination. Termination age was at 20 weeks and 28 weeks . The Sprague Dawley (SD) rats were the controls, while the Zucker Diabetic Sprague Dawley rats (ZDSD) were the experimental groups. These were designated as SD20WK (n=8) and ZDSD20WK (n=7) respectively. Another batch was designated as SD28WK (n=8), and ZDSD (n=15) that were terminated at 28 weeks of age. The latter were further divided into moderate diabetes (ZDSD28WK-MOD) (n=9) and severe diabetes (ZDSD28WK-SVD) groups (n=6). Bilateral humeri and femora were harvested then fixed in 10% buffered formalin. Right proximal femora and humeri were scanned using a 3D-μCT scanner (Nikon XTH 225L) to analyse trabecular morphometric parameters, cortical bone area and medullary canal area. Biomechanical strength was analyzed by three point bending tests using a universal tensile tester. Left proximal femora and humeri were processed for histology. Some sections were stained with Haematoxylin and Eosin (H&E) to assess normal histologic morphology and adipocyte quantification. Remnant sections were immunolabelled using the anti-TRAP and anti-ALP antibodies for osteocyte and osteoblast quantification respectively, to assess osteolysis and osteogenesis. Immunolocalization of AGEs, TGF-β1 and BMP3 was also conducted to investigate their role in diabetic skeletopathy. We found that diabetes affected osteoblastogenesis as measured by ALP positive cells and bone marrow adipocytes. TRAP positive osteocytes numbers were increased in the presence of T2D, suggesting an increased osteolysis. There was reduced TGFB1 expression with increased BMP3 expression. The number of AGEs immuno-positive cells as well as its extracellular expression was increased. Our finding suggest that osteoblast and osteocyte numbers are regulated by TGFβ1 and BMP3 in both bones, under the influence of AGEs. Our findings from osteometry, 3-point bending tests and Micro CT support that diabetes weakens bone. The diabetic effect results in lighter, shorter hollow bones that perform poorly under loading, as well as exhibit unfavourable trabeculae microarchitecture. Our findings confirm that T2D causes increased fragility in the proximal femur and humerus as well the mid-diaphysis. These perturbations occur early and late in the disease, and they are also exacerbated by the presence of hyperglycemia. We conclude that the ZDSD rat can be used as a translational model for diabetic skeletopathy at cellular and molecular level, and it can be extrapolated to humans after consideration of other factors like, basal metabolism, age, sex and skeletal loading patterns. We recommend optimal control of blood glucose levels at all stages of the disease to reduce the incidence of fractures in diabetic patients.Item The role of the 20-hydroxyecdysone (20E) signaling pathway in modulating Anopheles arabiensis reproduction, gut microbiome and anti-bacterial immunity(University of the Witwatersrand, Johannesburg, 2023-05) Ekoka, Elodie; Dahan-Moss, Yael; Koekemoer, LizetteThe 20-hydroxyecdysone (20E) signaling pathway, which is activated when 20E binds to its ecdysone receptor, EcR, is a promising target to reduce Anopheles mosquitoes’ ability to transmit malaria. The function of this pathway is typically assessed by altering the pathway and assessing how this manipulation affects a phenotype of interest. Two ways to alter this pathway include injecting mosquitoes with 20E or reducing EcR transcript levels with RNA interference (RNAi). Whether the 20E signaling pathway regulates An. arabiensis fecundity, fertility, gut bacteria, and immunity has never been investigated. These questions were addressed in this study by using a South African An. arabiensis strain. First, RNAi was used to investigate whether EcR silencing affects An. arabiensis reproductive output. While EcR depletion did not affect the mosquito fecundity, both vitellogenesis and egg fertility were impaired, as indicated by adecrease in the expression of some yolk genes and the number of eggs that hatched into larvae. Next, a link between the gut bacteria and EcR expression was established, by showing that antibiotic-fed (i.e., with less gut bacteria) mosquitoes displayed fewer EcR transcripts. To investigate whether the relationship between An. arabiensis gut microbiome and EcR expression was mediated by the mosquito innate immune defenses, the expression of ten selected anti-bacterial immune genes was measured in the gut and the whole mosquito after disturbing the 20E signaling pathway. This experiment uncovered that the 20E signaling pathway down-regulates the mosquito anti-bacterial immune defenses, which may favour bacterial proliferation post feeding. Finally, the effect of Gram-negative and Gram-positive bacteria on EcR expression was assessed by injecting mosquitoes with each type of bacteria and quantifying EcR transcripts. The results suggested that only Gram-negative bacteria influenced EcR expression. Altogether, these results demonstrated that An. arabiensis reproduction, gut microbiome, and antimicrobial peptides are regulated by 20E.Item Bisexuality in Democratic South Africa: Experiences of Women in Johannesburg(University of the Witwatersrand, Johannesburg, 2024) Khuzwayo, Zuziwe; Roy, SrilaThe field of gender and sexuality studies has been growing in academic institutions since the 1970’s. One of the reasons for its growth is that women across the globe are challenging conservative ideas and norms on how they should engage in romance, sexuality and heteronormativity which has implications for broader society. There has also been an increase in LGBTQI+ rights globally including in parts of the world where historically these identities were viewed as illegal and foreign to the indigenous people. In recent years though, there has also been a growing anti-gender backlash across the globe that has resulted in hard-won legal rights being reversed, or new legislation being imposed that is homophobic and transphobic. When it comes to research on sexuality, studies on bisexuality, however, and specifically research stemming from Global South contexts, is limited. This research contributes to the field of sexuality studies by looking at how bisexual women construct and express their sexuality, looking at multiple factors such as race, class, age and space in the city of Johannesburg. Using qualitative methods of life-history and in-depth interviews conducted during the six years of the PhD, this study shows how each of these factors shapes and influence an individual’s sexuality in a democracy where LGBTQI+ rights exist but are inadequately materialised. Drawing on feminist and queer theory, the study delves into how bisexuality is expressed and performed by women living in Johannesburg, and how challenges in claiming their sexuality exist outside but also within LGBTQI+ spaces. The study shows how queer women continue to carve out public and private spaces for themselves amid high levels of violence against women. Lastly, the research shows the continued regulation of women’s sexuality through heteronormativity in public and private spaces, and what this says about how women living on the African continent claim their sexuality in different waItem Cultural Diplomacy and Soft Power: The Impact of South Korea’s Pop Culture on China and the World(University of the Witwatersrand, Johannesburg, 2024) Jiang, ZhiqiThis research paper, titled "Cultural Diplomacy and Soft Power: The Impact of South Korea’s Pop Culture on China and the World" is submitted by Zhiqi Jiang on August 16, 2024, as a Master’s Research Report in International Relations. It examines the extent to which South Korea’s pop cultural diplomacy has challenged China’s cultural dominance in East Asia and contributed to South Korea’s rise in global soft power since the 1990s. By contrasting the cultural diplomacy strategies of China and South Korea and investigating the achievements of South Korea’s pop cultural diplomacy in economics, international organizations, and foreign policies, the study argues that South Korea’s strategic promotion of its pop culture, including K-pop, K-dramas, and films, has significantly enhanced its soft power. This influence manifests in South Korea’s ability to shape public opinion and influence economic and foreign policies in and with China. Additionally, South Korea has leveraged global economic gains and diplomatic influence through celebrity youth diplomacy to further strengthen its international soft power. The findings highlight the critical role of pop cultural diplomacy in international relations, providing insights for nations seeking to improve their global standing.Item Synthetic cytology image generation to augment teaching and quality assurance in pathology(University of the Witwatersrand, Johannesburg, 2023-05) McAlpine, Ewen David; Michelow, Pamela; Celik, TurgayINTRODUCTION: Urine cytology offers rapid and relatively inexpensive screening for the detection of high-grade urothelial neoplasia in patients with haematuria. In our setting of a public sector laboratory in South Africa, however, there is a paucity of such specimens with which to train cytotechnologists and cytopathologists. Advancements in Generative Adversarial Networks present a potential solution to this problem by allowing for the generation of synthetic urine cytology images to supplement teaching and training. We illustrate an end-to-end machine learning model – from dataset creation to testing synthetic images in pathology personnel – to assess this technology in a real-world setting. METHODS: Two hundred and fourteen urine cytology slides were digitised and processed to construct a morphologically balanced dataset containing examples of benign, atypical and malignant urine cytology images. This dataset was used to train a StyleGAN3 model to generate synthetic urine cytology images. These synthetically generated images were then tested in a group of pathology personnel – both pathologists and trainees – to assess whether a difference between real and synthetic urine cytology images exists. Diagnostic error rate and subject image assessment were tested. RESULTS: StyleGAN3 was able to generate a wide morphological diversity of realistically appearing benign, atypical and malignant urine cytology images. When testing how these synthetic images were perceived by pathology personnel, there was no significant difference in diagnostic error rate, subjective image quality or inclusion of synthetic images in a cytology teaching set. DISCUSSION: This work presents a proof-of-concept illustration of the feasibility of the use of synthetic cytology images to supplement pathology teaching when real examples may be difficult to obtain. Furthermore, this work presents important insights into the dynamics of pathology dataset creation and discusses the use of synthetic data in health education and the ethical and legal issues that arise with the use of synthetic patient data. CONCLUSION: Our work demonstrates that realistic, morphologically diverse urine cytology images can be generated using existing GANs technology and that human observers find such synthetic data visually acceptable. Additionally, our data indicate that there is no significant difference in synthetic data in terms of subjective image quality or diagnostic classification as determined by pathology personnel.Item Understanding the requirements and barriers to providing Post-Trial Access (PTA): A review of continued access to effective medicine(University of the Witwatersrand, Johannesburg, 2024) Mthembu, XoliswaClinical trials are essential in establishing the safety and efficacy of investigational products and are a mandatory requirement for the registration of a new medicine. Additionally, clinical studies offer access to new therapies, innovative treatments or more effective treatments which may not be readily accessible to the general population. Clinical trial participants receive investigational medicine during the study conduct phase as a study benefit and as compensation for their voluntary participation. In resource-limited countries, this may be the only option available to access new and effective medicine. Therefore, continued treatment access becomes of greater value. However, providing PTA presents ethical considerations which need to be addressed. The provision of PTA to effective medicine can be viewed as an inducement to join a study and creates inequalities between diseased patients, as it excludes other diseased patients who did not participate in the study or patients who were excluded from participation in the study. However, prior to addressing these controversies, it is necessary to establish first whether clinical trial participants have a moral claim to PTA provision. This report seeks to establish the moral requirement for PTA provision to address the ethical issues around providing continued access to effective medicines outside clinical trial settings. The first two chapters will focus on discussing the evolution of clinical trials, highlighting the ethical issues surrounding continued access to effective investigational products. The principles of bioethics will be discussed in detail in Chapter 2 to draw out the moral claims which mandate the requirement to provide PTA to efficacious medical therapy offered during the study. In Chapter 3, I will argue for the moral requirement for providing PTA using the principles of bioethics as a framework. In Chapter 4, I will discuss the challenges and PTA solutions. In my conclusion, I will reiterate my support for the mandatory requirement and implementation of PTA until the Investigational Product is commercially available and accessible to all trial participants, emphasising the importance of this stance.Item Contesting Heritage: A Political Analysis of Freedom Park and Voortrekker Monument in South Africa(University of the Witwatersrand, Johannesburg, 2024) Ndlovu, Xolane; Veriava, AhmedThis study critically examines the political and social dimensions of heritage preservation in South Africa, with a specific focus on the contested sites of Freedom Park and Voortrekker Monument. The study is underpinned by a social constructionist framework, which acknowledges the multiplicity of realities and narratives in relation to public memory and heritage politics in South Africa. The research methodology encompasses a qualitative approach, including site visits, archival work, and qualitative content analysis. The theoretical framework draws on Anderson's concept of ‘imagined communities’ to understand the emergence of national identities championed by various political actors in relation to heritage sites. The dissertation explores the role of public monuments in post-apartheid South Africa, the controversies surrounding the Voortrekker Monument, and the creation of counter-structures such as Freedom Park to challenge dominant colonial narratives. It also examines the political symbolism of Freedom Park in nation-building and its influence on visitor perceptions. Ethical considerations were paramount throughout the research process, particularly in conducting site visits and ensuring the integrity and reliability of the data collected. The findings of the study offer recommendations for further exploration of the articulation of heritage sites and the debate by other political actors, such as the Democratic Alliance (DA) and Inkatha Freedom Party (IFP), to potentially illuminate the emergence of an imagined community. Overall, this dissertation provides a comprehensive and nuanced exploration of the political, social, and cultural dimensions of heritage preservation in South Africa, shedding light on the complex interplay of historical narratives, political ideologies, and social values within the country’s heritage landscape.Item Operating under the Radar: Forestry Plantation Workers Everyday Resistance in Chimanimani District, Zimbabwe(University of the Witwatersrand, Johannesburg, 2024) Mvundura, Wellington; Pillay, DevanThis thesis explores and analyses the everyday forms and practices of labour resistance that rural commercial forestry plantation labour crafts to navigate a highly insecure post-colonial capitalist plantation labour process. It attends to the scholarly puzzle that in Zimbabwe, Africa, and elsewhere quotidian forms and practices of resistance are in a much less or barely empirically demonstrated and theoretically elaborated state in both resistance and labour resistance studies. This is even more pronounced in agrarian labour politics studies, yet agriculture labour constitutes a significant proportion of the overall industrial labour-force in xii Africa and elsewhere and is arguably the most easily exploitable form of wage labour. This motivated my empirical focus on commercial plantation labour. In light of evidence from Barura plantation estate, I argue that the workers may have to accept the fact of post-colonial capitalist plantation wage employment, the plantation-specific modalities of statist ethno-national citizenship, and state-sanctioned partisan national politics while contesting the terms and conditions under which these mutual systems of domination and exploitation occur. The practices do not seek to radically decompose the historical material- cum-symbolic bases of these systems of power. The everyday practices of defiance mediate the workers’ realisation of piecemeal de facto material and status gains more than the de jure recognition of those gains. My major empirical contribution is the discovery and foregrounding of the quotidian practices of subaltern groups as an integral part of politics. In a specialised and methodical manner, I re- centre the mundane everyday acts of plantation labour as workplace politics namely labour resistance. Theoretically I deploy and test the conceptual-cum-theoretical positions of seminal scholars on (everyday) resistance and modify some of these positions in light of empirical evidence. Methodologically, I break from the intention-oriented and foreground the practice- oriented approach to everyday resistance. This study is based on a continuous fourteen-month long on-site ethnography at a state-owned commercial forestry plantation. Ethnography was instrumental for the contextualised in-depth discovery and thick description of the workers’ forms, practices, and dynamics of subterranean labour resistance. It also enabled the cultivation of high levels of trust and rapport required to discover a sensitive, incriminating, and largely backstage (hidden) social phenomenon like quotidian labour resistance. For data collection I used three levels of participant observation, unstructured in-depth interviews, casual conversations, and deep hangouts.Item Personhood and Gender in a Traditional African Community(University of the Witwatersrand, Johannesburg, 2024) Nyirenda, Vitumbiko; Etieyibo, EdwinThere is a common assumption that traditional African societies were gender-neutral and lacked hierarchical gender ordering. Proponents of this view argue that women in these societies held significant positions, challenging notions of subordination and oppression. They contend that women have historically been leaders, advisors to kings, queens, soldiers, and landowners. However, some scholars argue that this assumption does not reflect the lived experiences of many African women, who face discrimination and oppression by men and society. This perspective suggests a distinct conception of personhood, indicating that African communities are inherently gendered, which in turn shapes their concept of personhood. The primary claim is that personhood has often been presented in non-gendered terms, based on the general assumption of gender neutrality in traditional African communities. However, this does not align with the realities of these communities. This dissertation thoroughly explores the intellectual divergence surrounding various understandings of gender in African society and its relation to discussions on personhood. Regarding gender, I argue that in the African context, it is viewed as complementary, fluid, and relational, indicating healthy and positive gender relationships within the community. Concerning personhood, I argue that it is often presented in non-gendered ways. Those who fail to recognize this perspective often conflate modern social issues with the dominant values of traditional African communities.Item Access to the Township Economy A comparative study of the spaza shop sector in the City of Ekurhuleni Townships Tsakane and Duduza(University of the Witwatersrand, Johannesburg, 2024) Mongwe, Veli; Quirk, Joel2024 marks 11 years since the Duduza community forced out Somali spaza shop traders from Duduza and it is exactly 11 years of continued gatekeeping from a collaborative informal relationship between the business community, township associations and some state actors. While the state actors and non-state actors may not take the credit for chasing Somalis out of Duduza they take pride in their informal governance systems and agreements they have kept Somalis out of Duduza. This research questions the role and power of state and non-state actors in Township informal governance. The concepts of “informal governance systems” and “gatekeeping” were used to guide this research to respond to the question of access. The study employed a qualitative approach as it is interested in understanding the cause for the variations in on the two townships. Data was collected using semi-structured interviews and participant observation. In the initial stages of the research, the snowball sampling was used to identify participants with leads. These two participants were able to refer the researcher to key state and non-state actors in Duduza and Tsakane. The findings of the study reveal the existence of two cartels, a cartel that facilitates gatekeeping in Duduza and a cartel that runs Somali spaza shops in Tsakane. The Duduza business community, associations and some state actors have created informal rules of trade that prohibit Somali spaza shop traders from trading in Duduza, on this other side, Tsakane appears to have a more relaxed approach to trading rules. Access into the Duduza township economy is controlled and protected through informal systems of governance. Through the informal systems of governance, the business community, associations and some state actors in Duduza exercise the power to agree on trading rules and other rules to govern the township. While the trading rules are said to be binding to all who wish to trade in Duduza, they also appear to be stricter on limiting access to Somali and Bangladesh spaza shop traders because of their history in the township. Lastly, the Somali spaza shop cartel that runs the Somali spaza shops in Tsakane is sustained by various pillars i.e. strategic placing of spaza shops which enables its expansion and prevalence in Tsakane.