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- This community is for all faculties and schools' research outputs and publications by Wits academics and researchers.
- This community hosts traditional outputs such as published and unpublished research articles, conference papers, book chapters and other research outputs authored by Wits academics and researchers. Items in this collection are also mapped to relevant collections within the Faculties/Schools/Departments communities for more specific browsing and searching.
- This Community hosts a collection of electronic theses and dissertations (ETDs) submitted by doctoral and masters' students of Wits University.
- This community is for all faculties and schools' theses and dissertations by masters and doctoral students.
Recent Submissions
Characterising the Role of Cholesterol in Hypoxia-induced Epithelial- Mesenchymal Transition in Breast Cancer
(University of the Witwatersrand, Johannesburg, 2022) Abdulla, Naaziyah; Kaur, Mandeep
The cellular epithelial-mesenchymal transition (EMT) process is a complex labyrinth dependent on subversion of critical cellular signalling pathways, which crosstalk extensively to confer cancer cells with characteristics that mediate metastasis. Based on the pleotropic role of cholesterol in the cell, it is not surprising that cancer cells have evolved several mechanisms to facilitate cholesterol dyshomeostasis. In addition to meeting the increased metabolic demands of cancer cells, deregulated cholesterol metabolism also facilitates increased cellular cholesterol availability which is crucial to regulating the activity of protein intermediates in EMT-related signalling pathways. Despite evidence indicating that cholesterol directly regulates signalling pathways related to EMT, no publication to date has attempted to address the effect of EMT induction on cellular cholesterol levels in cancer. To shed light on the dynamics of cholesterol in the relationship between hypoxia and EMT, cholesterol content in MCF-7 cells pre- and post-hypoxia induced EMT was assessed. This dissertation presents findings indicating increased levels of free cholesterol, cholesteryl esters as well as lipid raft cholesterol in MCF-7 cells following hypoxia-induced EMT. Interestingly, MCF-7 cells post- EMT induction displayed increased sensitivity to treatment with cholesterol targeting agents and presented with reversion to an epithelial state as evidenced by the increased expression of epithelial markers, decreased expression of mesenchymal markers and also reduced invasive potential. Importantly, treatment with cholesterol targeting agents is also seen to abrogate the drug resistant potential following hypoxia-induced EMT. Based on these observations, it is proposed that targeting cellular cholesterol could be a promising area to invest in the search for novel therapeutics effective in combatting cancer metastasis
An evaluation of the integration of oral pre-exposure prophylaxis (prep) as standard of care for HIV prevention in clinical trials in South Africa
(University of the Witwatersrand, Johannesburg, 2023) Beesham, Ivana; Mansoor, Leila E; Beksinska,Mags
Background: Oral tenofovir-based pre-exposure prophylaxis (PrEP) is an effective biomedical HIV prevention option. In 2015, the World Health Organization (WHO) recommended oral PrEP for those at substantial risk of HIV infection, and several countries have since adopted oral PrEP into their national guidelines. In the context of trials, HIV endpoint-driven trials frequently enrol individuals who are at elevated risk of acquiring HIV. Ethical guidelines recommend that study sponsors and investigators should provide access to a package of HIV prevention methods to trial participants, as recommended by WHO, including adding new prevention methods as these are validated. In 2017, the South African Medical Research Council recommended that oral PrEP be provided in HIV prevention trials. The Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial was ongoing at the time and incorporated oral PrEP into the trial’s HIV prevention package, including the onsite provision of oral PrEP at the South African trial sites during the last eight months of the trial. The ECHO Trial, conducted from 2015 to 2018, enrolled women aged 16-35 years, from 12 research sites in four African countries, and assessed the effect of three contraceptives on HIV incidence. In 2019, when this PhD project was conceptualised, there was a lack of data on the integration of oral PrEP as part of the HIV prevention package in HIV endpoint-driven trials. To address this gap, I evaluated the integration of oral PrEP as standard of care for HIV prevention in clinical trials in South Africa. Objectives: 1. To describe the process of implementing oral PrEP provision, the uptake of oral PrEP and the characteristics of women who initiated (versus those who did not initiate) oral PrEP during the ECHO Trial. 2. To evaluate oral PrEP adherence and factors associated with adherence by conducting plasma tenofovir (TFV) drug level testing using stored blood samples among a subset of women from South Africa who reported current oral PrEP use at the final ECHO Trial visit. 3. To describe the experiences of women who initiated oral PrEP at the Durban, South Africa, ECHO Trial site. 4. To explore post-trial access to oral PrEP, and barriers and enablers to post-trial oral PrEP access, among a subset of women from the Durban, South Africa, ECHO Trial site. 5. To review the current status of oral PrEP as standard of care for HIV prevention in clinical trials in South Africa. Methods: This was a mixed methodology study, conducted from 2019 to 2022, and both qualitative and quantitative methods were utilized. I describe the process undertaken by the ECHO Trial team to incorporate oral PrEP delivery into the trial’s HIV prevention package, including the onsite provision of oral PrEP by ECHO Trial staff at the South African trial sites. Characteristics between women who ever initiated oral PrEP versus those who had access to but did not initiate oral PrEP, were assessed using Chi-squared/Fisher’s exact tests for categorical variables and t-tests for continuous variables. HIV seroincidence comparisons between participants who never versus ever initiated oral PrEP were modelled using exact Poisson regression. To objectively measure adherence to oral PrEP, plasma samples collected at the final ECHO Trial visit, from a subset of women enrolled at the South African ECHO Trial sites, who reported ongoing PrEP use, were tested for TFV. Bivariate logistical regression was used to evaluate participant characteristics associated with quantifiable TFV at the final ECHO Trial visit. 10 | P a g e To understand experiences of women who used oral PrEP and patterns of oral PrEP use, we conducted questionnaires with women who initiated oral PrEP onsite at the Durban, South Africa, ECHO Trial site. Face-to-face questionnaires were conducted approximately three months following oral PrEP initiation, and explored reasons for using and discontinuing oral PrEP, side effects experienced, oral PrEP adherence and disclosure of oral PrEP use. I also evaluated factors associated with oral PrEP continuation at the final ECHO Trial visit using univariate and multivariate logistical regression. Among women continuing oral PrEP at ECHO Trial exit, telephonic follow-up was conducted 4-6 months later, to briefly explore oral PrEP access and ongoing use following study exit. Additional face-to-face, participant in-depth interviews were conducted in 2021 with a subset of women from the Durban, South Africa, ECHO Trial site, who reported ongoing oral PrEP use at ECHO Trial exit and who were given a 3-month PrEP supply at study exit. The interviews explored barriers and enablers to post-trial oral PrEP access. Finally, telephonic in-depth interviews were held with key stakeholders from research sites across South Africa known to conduct HIV endpoint-driven clinical trials to explore their perspectives on providing oral PrEP as HIV prevention standard of care in clinical trials in South Africa. Participant and stakeholder interviews were audio-recorded and transcribed, and thematic analysis was facilitated using NVivo. Results: Our key findings indicate that it was feasible to integrate oral PrEP as standard of care for HIV prevention in the ECHO Trial. PrEP uptake was 17.2% (622/3626) among those eligible for oral PrEP when it became available. Women who initiated oral PrEP were more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p<0.05). There were 37 HIV seroconversions among women who had access to oral PrEP but did not initiate oral PrEP, and 2 seroconversions among women who initiated oral PrEP (HIV incidence 2.4 versus 1.0 per 100 person-years; Incidence Risk Ratio = 0.35; 95% confidence interval (CI) = 0.04 to 1.38). Among the 260 plasma samples from the eight South African ECHO Trial sites that were available for TFV testing, plasma TFV was quantified in 36% of samples (94/260). Women >24 years old had twice the odds of having TFV quantified compared to younger women (Odds Ratio (OR) = 2.12; 95% CI = 1.27 to 3.56). Women who reported inconsistent/no use of condoms had lower odds of TFV quantification (age-adjusted OR = 0.47; 95% CI = 0.26 to 0.83). The ancillary study conducted at the Durban, South Africa ECHO Trial site found that onsite oral PrEP uptake was high (43%, 138/324). Almost all women who initiated oral PrEP at the trial site agreed to participate in the ancillary study (96%, 132/138). Of these, 88% reported feeling at risk of acquiring HIV. Most women (>90%) heard of oral PrEP for the first time from trial staff. Oral PrEP continuation via self- report was 87% at month-1, 80% at month-3, and 75% elected to continue using oral PrEP at trial exit and were referred to off-site facilities for ongoing access. Disclosure of oral PrEP use was associated with five-fold increased odds of continuing oral PrEP at trial exit (adjusted OR = 4.98; 95% CI = 1.45 to 17.13; p=0.01). At telephonic follow-up 4-6 months after women exited the ECHO Trial, >50% reported discontinuing PrEP. Qualitative interviews conducted with a subset of women from the Durban, South Africa ECHO Trial site identified several barriers to post-trial oral PrEP access at facilities such as long queues, facilities being located far from women’s homes, unsuitable clinic operating hours, negative attitudes from providers, and oral PrEP being unavailable at some clinics. Interviews with key stakeholders from research sites in South Africa found that most stakeholders reported incorporating oral PrEP provision as part of the HIV prevention package offered to participants in HIV endpoint-driven trials. Stakeholders identified barriers to oral PrEP 11 | P a g e uptake, adherence, persistence, and post-trial access. Demand creation, and education and counselling about oral PrEP were reported as factors that facilitated uptake. Conclusion: The ECHO Trial provides evidence that it was feasible to successfully integrate oral PrEP provision as part of the trial’s HIV prevention package offered to study participants. Other HIV endpoint-driven trials can utilize our findings as a model to integrate oral PrEP provision into the HIV prevention package offered in a trial. The ancillary study findings on PrEP uptake, adherence and persistence can be utilized to guide oral PrEP trials and implementation programs. While post-trial oral PrEP access was concerning and several barriers were identified, it is possible that with the scale-up of oral PrEP in the public sector in South Africa after the ECHO Trial was completed, participants exiting trials and desiring to continue oral PrEP could have better access
Influence of polyploidy on morphology, genetic differentiation and reproductive strategy amongst varieties of Rhodohypoxis baurii (Hypoxidaceae)
(University of the Witwatersrand, Johannesburg, 2023) Ferreira, Bianca Tasha; Goodman-Cron, Glynis V.; Glennon, Kelsey L.
Evolutionary mechanisms, such polyploidy (increase in chromosome sets), alters plant morphology, gene flow and reproductive strategies, which can facilitate the generation or loss of species. Rhodohypoxis L. (Hypoxidaceae) is a small near-endemic Drakensberg genus comprising six species, one of which is Rhodohypoxis baurii. Rhodohypoxis baurii contains three morphologically distinct varieties, with varying ploidy-levels: R. baurii var. baurii (2×, 4×), R. baurii var. platypetala (2× 3× , 4×), and R. baurii var. confecta (2×). Therefore, R. baurii is an ideal system to evaluate whether polyploidy leads to lineage divergence or homogenization and contributes to biodiversity in this lineage. The aim of the study was to assess the influence of ploidy on morphology, genetic differentiation and reproductive strategy among varieties of Rhodohypoxis baurii (Hypoxidaceae), as well as to better recognise the three varieties. Thirty vegetative, floral, and reproductive traits were measured across 124 herbarium specimens and 43 individuals housed in the greenhouse. A matrix containing 20 quantitative and 12 qualitative characters was constructed and a Principal Coordinates Analysis (PCoA) and Non-Metric Multidimensional Scaling analysis (NMDS) were conducted. Important distinguishing morphological features that had a high eigenvalue (shown via a PCA) were selected for direct comparison using box and whisker box plots to compare means ± standard errors (SE). Certain morphological traits such as anther length, peduncle length and tepal sizes differed significantly among the varieties and ploidy levels, with polyploid individuals exhibiting the gigas effect. This was especially evident in R. baurii var. platypetala, which contained many polyploid individuals and exhibited larger flowers (longer and wider tepals) and larger anthers compared to other varieties. Rhodohypoxis baurii var. confecta and R. baurii var. platypetala are genetically, geographically and morphologically similar, differing only in flower colour, flower size and peduncle length. However, most of these differences can be attributed to differences in ploidy and /or altitude with R. baurii var. confecta occurring at higher altitudes and R. baurii var. platypetala containing multiple ploidy-levels. It is therefore evident that ecological differences and polyploidy have shaped the morphological differences in these two taxa. In addition, R. baurii var. baurii populations in the 7 Eastern Cape Drakensberg were morphologically, geographically and genetically distinct from all other populations and varieties, and may be a new/ undescribed taxon; however, this warrants further investigation. Out of 231 experimental crosses, 113 intra-varietal and inter-varietal crosses produced seeds. Rhodohypoxis baurii polyploid individuals show a shift away from sexual reproduction to asexual reproduction as they all showed higher rates of clonal reproduction than the diploid individuals. Moreover, crosses between polyploids yielded lower seed sets and lower germination rates than diploid-diploid crosses. Genetic differentiation and gene flow were quantified for 280 individuals among the varieties and ploidy-levels across 11 populations using 12 microsatellite markers labelled with the FAM NED dyes. Leaf material was collected from 237 individuals of Rhodohypoxis baurii (R. baurii var. confecta n = 88, R. baurii var. baurii n = 87, R. baurii var. platypetala n = 62) and flow cytometry conducted to estimate ploidy. A latitudinal ploidy gradient was evident across sampled populations that corresponds with shifts in reproductive strategy, and changes in the extent of gene flow. Population genetic structure coincided primarily with geographic localities, with diploid Northern Drakensberg populations having similar allelic diversity to one another. The Central and Southern Drakensberg mixed ploidy populations also showed similar allelic diversity but differed from the tetraploid Eastern Cape Drakensberg populations. Furthermore, gene flow was higher between geographically close populations irrespective of ploidy-level, with geographically isolated regions (such as the Eastern Cape Drakensberg) and outlying populations (i.e. Karkloof) showing unique genotypes, indicating little gene flow and allele sharing. Consequently, shifts in reproductive strategy and geographic isolation are likely changing gene flow patterns among varieties and ploidy levels which appears to be facilitating both lineage diversification and homogenization in this species
A study into the identification of human factors in digital transformation in a South African rail logistics company
(University of the Witwatersrand, Johannesburg, 2024) Chikirwa, Lloyd Michael
As world industries rapidly move towards digital transformation (DT), organisations are making concerted efforts to become more sustainable in the face of technological revolution. DT has become a compelling necessity for organisations looking for a competitive edge. However, understanding how human elements affect DT’s adoption in South Africa's freight logistics industry remains largely unexplored. The investigation aimed to close this gap by inquiring into the human elements of DT, emphasising digital leadership, digital culture, digital talent, and DT relationships. Over 180 senior management employees of Company X were surveyed. The responses were analysed, and the validity of the hypotheses was assessed utilising Statistical Package for Social Science (SPSS) Amos version 28 structural equation modelling (SEM). The results confirmed that digital leadership significantly impacted digital culture and talent. As such, digital leadership plays a central part in ensuring favourable outcomes for DT. While digital culture positively influenced DT, the same was not established for the impact of digital talent on DT. The result contradicted previous research findings and justified further study. Overall, the outcomes emphasise the value of human elements in successful DT. Consequently, organisations commencing with DT should prioritise digital leadership, culture, and talent as strategic levers for DT's success
The effects of COVID 19 on consumer mobile and online purchase behaviour
(University of the Witwatersrand, Johannesburg, 2023) Chanetsa, Edphan Peter; Saini, Yvonne K.
There obtains an acute paucity of research on the how Covid-19 impacted consumer online and mobile application purchase behaviour in South Africa. Much of the work done on the impact of the pandemic on consumer behaviour has primarily focused on one aspect: online purchase behaviour. This study sought to assess the effects of the restrictions of the novel Covid-19 virus on consumer mobile and online purchase behaviour. The main objective was to understand the impact of Covid-19 related restrictions on mobile application purchase intention in grocery shopping. Similarly, the study also sought to understand the impact of Covid-19 related restrictions on online (desktop/laptop) purchase intention in grocery shopping. An online survey was conducted wherein 345 responses were obtained. The study employed a mixed methodology approach with the primary analysis being done quantitatively employing path analysis to establish the existence of causal links between Covid-19 restrictions and consumer behaviour in terms of both direction and magnitude. Regression analysis was further carried out to corroborate the findings of the path analysis. The qualitative aspect of the analysis was primarily employed to buttress the results of the quantitative analysis. The results showed that Covid-19 had a significant and positive impact on mobile and online consumer behaviour in South Africa. The advent of the pandemic caused an increase in the uptake of alternative means of making grocery purchases. Specifically, the institution of Covid-19 restrictions produced a substitution effect wherein digital purchase platforms were preferred to in-store purchases of groceries. Consequently, all the hypotheses developed by the study proved to be robust as they were confirmed by the results