4. Electronic Theses and Dissertations (ETDs) - Faculties submissions
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Item The Enhancement of the SDLC Methodology utilised in the Delivery of Digital Healthcare Products(University of the Witwatersrand, Johannesburg, 2024) Asamoah-Bekoe, Michael; Sunjka, BernadetteThe digital healthcare industry has experienced significant growth in recent years, resulting in increased competition among companies operating in this market. Company X, a competitor in this industry, utilises a mixed set of methodologies across their teams, where some methodologies may be outdated. With the emergence of new software development lifecycle methodologies (SDLC), it is crucial for Company X to adapt their current approach to remain competitive. As part of a research study, 24 participants from various teams in Company X were interviewed to gain insights into the industry, the current methodology being used, and how management could ensure a smooth transition to a new SDLC methodology. According to the study results, 21% of participants from Team A-D were unwilling to change their current methodology, while 37% were willing to make a switch. The remaining 42% were indifferent, with their decision depending on the reason for the transition. Based on the literature review and the findings from the study, a conceptual framework was developed to guide the process of transitioning to a new SDLC methodology.Item Electrocatalytic detection of biomarkers of tuberculosis and cervical cancer(University of the Witwatersrand, Johannesburg, 2024-07) Peteni, Siwaphiwe; Ozoemena, Kenneth IkechukwuThe need for simpler, low cost and efficient diagnostic methods remains a matter of urgency. This has opened numerous streams of research. Electrochemistry is a simple, cost effective and efficient method that has been used for the detection of several diseases such as tuberculosis (TB) and human papilloma virus (HPV). TB has been ranked amongst the most problematic diseases in HIV/AIDS burdened communities, this alone calls for concern. Biomarkers of TB not only indicate mycobacterium infection but can also assist in the early detection of TB which is highly beneficial for the infected person and the health care system. HPV is the causative agent for cervical cancer. Cervical cancer is ranked as the fourth disease that causes mortality amongst women. With that in mind, HPV-16 L1 early detecting means possible early detection of cervical cancer. In this thesis, methyl nicotinate (MN), which is one of TB’s biomarkers was detected in phosphate buffer solution (PBS, pH 6.0) and commercial human serum using cobalt nanoparticles supported on carbon derived from trimesic acid (TMA) (abbreviated as Co-NPs@CTMA) and biphenyldicarboxylic acid (BPDC) abbreviated as Co-NPs@CBPDC) as electrocatalysts. These electrocatalysts were obtained using microwave-assisted metal-organic framework process with TMA and BPDC as ligands. XRD data showed that these electrocatalysts are cobalt nanoparticles with dominant {111} and {200} phase with traces of cobalt oxide (CoO). XPS and Raman data showed that Co-NPs@CBPDC is defect-rich compared to the Co-NPs@CTMA counterpart. BET showed that CoPs@CBPDC has higher surface area and pore size and volume than the Co-NPs@CTMA catalyst. Both electrocatalysts showed reversible cobalt nanoparticle oxidation and reduction reactions, in the absence and in the presence of the MN, thereby allowing for a facile indirect electrochemical detection of this biomarker. The calibration curves showed low limit of detection (LoD) of 0.47 and 0.147 µM for Co-NPs@CTMA and Co-NPs@CBPDC, respectively. The higher performance of the latter is attributed to its enhanced physico-chemical properties compared to the former. Next, HPV-16 L1, which is the conventional high-risk antigen that is present in cervical cancer, was detected using onion-like carbon (OLC) and polyacrylonitrile fibre integrated with OLC (OLC-PAN) as electrode platforms. Two electrode platforms were used; onion-like carbon (OLC) and its polyacrylonitrile (OLC-PAN) composites. Both platforms led to the detection in a wide linear concentration range (1.95 fg/ml to 50 µg/ml), excellent sensitivity (>5.2 µA/log([HPV-16 L1, fg/mL]) and ultra-low detection of ca. 1.0 and 1.4 fg/ml for OLC-PAN and OLC-based immunosensors, respectively. The high specificity of detection was proven by experimenting with an anti-Ovalbumin antibody (anti-Ova) and native Ovalbumin protein (Ova). An immobilized antigenic HPV-16-L1 peptide showed insignificant interaction with anti-OVA in contrast with the excellent interaction with anti-HPV-16 LI antibody. The immunosensors showed satisfactory stability of ~ 3 days of re-usability. The application of the immunosensor as a potential point-of-care diagnostic (PoC) device was investigated with the screen printed carbon electrode which showed the ability to detect ultra-low (~ 0.7 fg/ml) and high (~ 12 µg/ml) concentrations. This study opens the door of opportunity for further investigation with other electrode platforms and realization of PoC diagnostic devicesfor screening and testing of HPV biomarker for cervical cancer.Item Using a hybrid adsorption-membrane filtration system to produce biologically stable drinking water(University of the Witwatersrand, Johannesburg, 2024) Omalanga, Landry Sendango; Biyela , Precious; Simate, Geoffrey S.The purpose of water treatment is to produce clean and safe drinking water, for consumers. Water quality, both during treatment and distribution, is greatly affected by the presence of natural organic matter (NOM). The presence of NOM affects the effectiveness of water treatment processes and sometimes increases the cost of water treatment and leads to operational problems. Furthermore, the presence of biodegradable organic matter (BOM), which is a fraction of NOM, can degrade water quality during distribution resulting in the loss of biological stability. The excessive presence of BOM can be addressed using advanced water treatment processes or by relying on systems which combine multiple water treatment processes to increase treatment efficiency. The main aim of this study was to evaluate the effectiveness of a hybrid adsorption- membrane filtration system in lowering the bacterial regrowth potential in water. Ready-made multi-walled carbon nanotubes (MWCNTs) were used as adsorbents in this study. MWCNTs were chosen because they exhibit high adsorption properties mainly because of their fibrous shape and external surface accessibility. MWCNTs have hydrophobic characteristics and a propensity to aggregate due to the presence of electrostatic interactions among them, therefore, functionalization of MWCNTs was required to improve their dispersion in the organic and inorganic solvents. A non-covalent functionalization process was employed using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant to ameliorate the stability and dispersibility of MWCNTs in aqueous solution. The non-covalent functionalization was preferred to sustain the functionalities needed for BOM capture enhancement and environmental safety. Polysulfone (PSF) membranes were produced by phase inversion method using N, N- dimethylformamide as solvent for the removal of BOM from water. The phase inversion method was chosen in this study due to its simple processing, flexible production scales, and low cost. The MWCNTs and PSF membranes were characterized using microscopy techniques such as transmission electron microscopy (TEM), scanning electron microscopy (SEM), X ray diffraction (XRD), Raman spectroscopy, tensile strength test, and the hydrophilicity (contact angle) test. These techniques were selected because they enable the evaluation of the morphology, composition, physical characteristics, and dynamic behavior of nanostructured materials. iv Batch adsorption experiments were employed to investigate the adsorption properties of functionalized MWCNTs for BOM removal. Four different concentrations of functionalized MWCNTs were tested to determine the ideal conditions for the adsorption of two forms of BOM; assimilable organic carbon (AOC) and biodegradable dissolved organic carbon (BDOC), from water. The concentrations of functionalized MWCNTs used were 4, 8, 12, and 16 mg in 100 mL of BOM solution. Furthermore, the cross-flow filtration mode, also known as tangential flow filtration, was used to separate the remaining BOM in water by passing water along the surface of the NF membrane using pressure difference. Cross-flow filtration was chosen because it removes the buildup from the surface of the membrane and provides the benefit of an improved membrane lifespan by helping to prevent irreversible fouling. A mathematical model of membrane filtration process in continuous system was also developed to better understand the correlations between the different variables of the membrane filtration process such as the inlet (feed) concentration (Cin) and flow rate (Qin), and the outlet (retentate) concentration (Cout) and flow rate (Qout), and the permeate concentration Cp. Results obtained after the functionalization process of MWCNTs showed an improvement in their stability and dispersibility in aqueous solution. The characterization of both MWCNTs and PSF membranes showed some interesting features. For example, morphological and structural studies show that MWCNTs possess fibrous shapes with a high aspect ratio, and a hollow structure with an inner diameter. The finger-like structures found on the surfaces of PSF membranes play a crucial role in their adsorption capabilities. These structures, which vary in pore size, contribute to the overall capacity of the membranes to absorb BOM from water. During adsorption experiments, it was observed that the removal of BOM from water increased with an increase in the adsorbent (functionalized MWCNTs) concentration. This is likely due to high concentration gradient which acts as a driving force to overcome resistances to mass transfer of dye ions between the aqueous phase and the solid phase. However, the maximum removal of both AOC and BDOC was recorded at a concentration of functionalized MWCNTs of 12 mg, at a contact time of 4 hours and at an agitation speed of 180 rpm. The PSF membrane produced by phase inversion method demonstrated the highest flux of 0.0091 ml/cm2.min at room temperature (25°C) and after a filtration time of 90 minutes. The selectivity and permeate flux were increased with forward flushing and backwashing processes of the PSF membranes because it flushes out accumulated debris and particles on the surface and inside the pores of the membranes. After using the hybrid adsorption-membrane v filtration system, BDOC concentrations dropped to an average of 65% of the initial raw water BDOC and the AOC concentrations dropped to approximately 80% of the initial raw water AOC. Outputs from the mathematical model demonstrated that the change in initial conditions (Cin and Qin) is responsible for the transient response (changes from one steady state to another) in these membranes. The adsorption and membrane nanofiltration hybrid system adopted in this study, effectively removed both AOC and BDOC from water, and can therefore be used to produce biologically stable drinking water. The outcome of this study could be the application of the combination of BOM targeting strategies and residual disinfection to better control bacterial regrowth in drinking water distribution systems (DWDSs). This in turn could help water utilities with meeting distribution systems, water quality guidelines, and protect public healthItem Spirit of place: demystifying the significance of sangoma practices in our communities, education, and well-being, while looking at how they can exist in modern spaces(University of the Witwatersrand, Johannesburg, 2024) Pitse, DikelediWith the evolution of technology and the modern man, sacred spiritual practice and African tradition has become lost amongst our people. Ancient communities took pride in preserving ancestral teachings and rituals that kept us connected and grounded before the rise of modern medicine as we know it. The role of the sangoma/traditional healer in these communities was seem as extremely significant, in that they can communicate with our forefathers. These modes of communication provide clarity on where we come from, as well as where we should go. Therefore, I will be looking at ways in which this sacred practice can be preserved and have a legacy in the modern environment. Additionally, I will show that indigenous knowledge can form part of higher education. Lastly, through research and interviews, I will show the types of spaces that are required in urban the environment for traditional spiritual practices to remain part of everyday life.Item Healing from the Past, into the Future: Socio-Cultural & Health Remediation for a Holistic Wellness Facility in Riverlea Township (Extension)(University of the Witwatersrand, Johannesburg, 2024) McCulloch, Claude Martin; Jivan, SundeepThe Witwatersrand Mining Basin has been in existence since 1852, which is astonishingly more than a century old. It is the world’s largest gold and uranium basin and has created extraction from over 120 mines stretching from the East to the West of Johannesburg. It is an integral part and the backbone of Johannesburg’s economy. However, regardless of how much mining has boosted the economy, it has not played a sustainable role with the health of the citizens of Johannesburg. This is largely because of radioactive chemicals within the pyrite basin, holding 600 000 tons of uranium, amongst other chemicals as well (Liefferink, 2022). These radioactive chemicals are spread from the mining basin into the surrounding environment via windblown dust (Coetzee et al., 2008). Monitoring of these occurrences have shown that this dust is inhalable due to its structure and particle size, that being either PM 2,5 or PM 10. These happen at residential settings and have exceeded the levels of occupational health standards. A link is suggested from (Nkosi et al., 2015) between the respiratory issues amongst residents that live in communities next to mine tailings & waste facilities. These communities are exposed and have an increased prevalence of ‘chronic respiratory symptoms’ compared to other communities (Van Wyk, 2013). There are currently 585600 people living in communities next to mine tailings according to the 2011 census. (Kneen et al., 2015). The community I will be conducting my research will be in the Township of Riverlea, located in the South-West of Johannesburg. Riverlea is in close proximity to industrial areas and mine dumps. Research has shown that harmful pollutants can from these areas can have negative effects such on the respiratory system, as the particles are airbourne (Makene, 2007). Built in 1963 during Apartheid, ‘coloured’ residents were forcibly removed from other parts of the city and given new homes by the government. The township is conveniently located 500m away from the mine dumps, thus making it a high exposure zone to airborne dust pollution (Kneen et al., 2015). The respiratory diseases in Riverlea are caused from environmental problems. To relate this Architecturally, I research that social and cultural problems may be a symptom towards the residents being unhappy about their environment. This unhappiness and deals with the ‘Sense of Place’ for the resident’s and I believe, alters their social and cultural behaviour, hence many of these communities suffer from poverty, drugs, and crime (Najafi et al., 2011). This can be done using the design methods of Salutogenic design, which promotes healthy living and creates better places that can reduce stress, encourage physical activity, and afford opportunities for socializing, enhancing the general daily health and wellbeing of people (Cushing et al., 2020). I aim to design a holistic wellness facility that remediates the social, cultural and environmental problems which contests the current narrative of the context - that being poverty and respiratory disease.Item Factors influencing innovation in public healthcare in South Africa: A critical analysis(University of the Witwatersrand, Johannesburg, 2024) Nkosi, Mbali Rosemary; Siriram, RajenlallHealthcare innovation has proven to reduce morbidity and mortality rates by enhancing healthcare delivery. Most of the South African population depends on the public healthcare system for health needs. The morbidity and mortality rates in South Africa are much higher compared to other middle-income countries in the world. To enhance healthcare delivery in South Africa, understanding the factors that influence innovation in public healthcare is important. Therefore, this research aims to provide a comprehensive understanding of the factors influencing innovation in public healthcare in South Africa and the potential impact of innovation on the country's healthcare system. The main objectives of this study are to determine the level of successfully implemented innovation in public healthcare and the factors influencing it. Existing literature identifies several factors that influence innovation in public healthcare, including design empathy, technological infrastructure, decision-makers, human capital, and organisational culture. This study also investigates the readiness of the public health sector to embrace innovation and the strategies in place for implementing innovation in public healthcare. A gap was identified in the existing literature. There is evidence in literature is that healthcare innovation centres in South Africa and their impact on the adoption of innovation in public healthcare were only covered marginally by existing literature. To bridge this gap, this study provides results on the status of suitable research and development hubs for testing healthcare innovation prototypes in South Africa and their impact on the adoption of innovation in public healthcare. Currently, there are limited health innovation centres in South Africa. This study posits that an increase in the number of healthcare innovation centres would increase evidence-based innovation which would increase the uptake of innovation in public healthcare. A qualitative research approach was used to acquire descriptive information on the factors that influence innovation in healthcare through interviewing participants. Semi-structured interviews were used as the primary instruments of data collection. The interviews were then subjected to a thematic analysis. One of the significant findings of this research is that the lack of funding in public healthcare hinders innovation in the public healthcare system. Also, the rigorous regulatory requirements pertaining to healthcare innovation tend to cause uncertainty and delays, which in turn reduces the funding available for innovative projeItem The effect of cholesterol depletion on TGF-ß-induced epithelial-mesenchymal transition in pancreatic cancer cells(University of the Witwatersrand, Johannesburg, 2024-06) Breytenbach, Andrea; Kaur, MandeepPancreatic ductal adenocarcinoma (PDAC) is a highly metastatic cancer that relies on the epithelial to mesenchymal transition (EMT) program for its spread. EMT is a cell plasticity program that involves the reorganization of cell structure as cells transition from an epithelial to a mesenchymal phenotype. The dysregulated cholesterol metabolism resulting from metabolic reprogramming in PDAC is thought to play a role in EMT by affecting EMT-related signalling pathways. However, no publication has yet investigated the impact of EMT on cholesterol content in PDAC. To shed light on these dynamics, EMT was induced in PANC-1 cells using TGF-β1, thereafter the effect of cholesterol-depleting agents (KS-01 and methyl-β-cyclodextrin) alone or in combination with chemotherapeutic agents (Gemcitabine (GEM) and 5-Fluorouracil (5-FU)) on cholesterol content, EMT state, drug resistance, and invasion were investigated. Our results showed that mesenchymal cells rely on reduced membrane cholesterol levels, synthesis, and uptake, while storing more cholesterol and promoting efflux. EMT also promoted drug resistance via upregulation of ABCB1 expression and reduced hENT1 expression. Targeting cholesterol using cyclodextrins promoted a cholesterol compensatory mechanism, leading to a hybrid EMT state, drug resistance, and metastatic potential. Treating mesenchymal PANC-1 cells with GEM or 5-FU monotherapies were seen to promote EMT-transcription factors, as well as promote cholesterol efflux, synthesis, and import, an unexpected result as these chemotherapeutic agents are not known to affect cholesterol. When GEM was combined with KS-01, drug resistance, invasion, EMT-transcription factors, vimentin, and E-cadherin was promoted indicating the promotion of a hybrid EMT state. Interestingly however, combining KS-01 with 5-FU resulted in an interplay that was seen to mitigate the EMT-promoting effects typically associated with cholesterol depletion alone. The exact mechanism linking the cholesterol compensatory mechanism to EMT remains complex and unknown. Based on work presented in this dissertation, it is proposed that targeting cellular cholesterol should be continued to be investigated, particularly in understanding the repercussions of the use of cholesterol depleting agents for the treatment of other disorders in patients with PDAC.Item Modelling and analysis of COVID-19 outspread at micro-levels using spatial autocorrelation: Case of eThekwini(University of the Witwatersrand, Johannesburg, 2024-09) Ngubane, Samukelisiwe; Chimhamhiwa, Dorman; Adam, ElhadiThe alarming effects of the COVID-19 pandemic on different socio-economic spheres have been felt across the globe. These destructive effects have prompted plenty of research to understand and control the coronavirus pandemic. Notably, one strategic method of mitigating the effects of the coronavirus epidemic has been the utilisation of spatial and geostatistical models to gain insights into the potential predictors of the prevalence of the coronavirus. Considering the above, it was the aim of this study to explore the use of advanced geospatial modelling and analysis techniques, including Moran’s I, spatial error models, spatial lag models, MGWR, and GWR for analysing and modelling the settlement level determining factors of COVID-19 incidence within the eThekwini Metro to inform effectual micro-level planning. Notably, the lack of micro-level modelling of COVID-19 prevalence predictors also motivated the undertaking of this study. To the above aim, the objectives of the research were to utilise spatial autocorrelation to map the granular level COVID-19 spatial distribution over the 3rd wave in the eThekwini Metro, compare the applicability of global and local models in analysing and modelling micro-level COVID-19 incidence, analyse the spatial dependence of the occurrence of COVID-19 on local level variables through Moran’s I and to spatially model the effects of significant local-level determinants on COVID-19. The incidence of COVID-19 cases for the 3rd wave, which was from the 2nd of May 2021 to the 11th of September 2021, was analysed and modelled. The Moran’s I result illustrated that COVID-19 incidence within the eThekwini settlement places had a positive spatial autocorrelation, with a Moran’s I value of 0.14 and a p-value of 0.00. Also, the MGWR model's local R2 value was greater (72.5%) as compared to the other models. Moreover, economic wellness score, the sum of TB cases and population density came out as the significant determining factors of settlement level incidence of COVID-19. This research report offers a great foundation for gaining insights into the applicability of advanced geospatial models in guiding targeted COVID-19 interventions at lower levels.Item Investigating the DNA methylation status of the PXDN and PXDNL promoter regions in OSCC cell lines(University of the Witwatersrand, Johannesburg, 2024-06) Sebastian, Mistral; Mavri-Damelin, DemetraBackground: Oesophageal squamous cell carcinoma (OSCC) is the most prevalent form of oesophageal cancer in South Africa. Aberrant DNA methylation is a well-established epigenetic mechanism involved in various cancers, including OSCC. This study focuses on the DNA methylation status of the peroxidasin (PXDN) and perodixasin like (PXDNL) promoter regions and the expression of PXDN and PXDNL in OSCC cell lines. PXDN consolidates the basement membrane through collagen IV unit oligomerization, influences epithelial-mesenchymal transition and correlates with poor prognosis in various cancers. PXDNL modulates the extracellular matrix (ECM) by antagonising PXDN. Since PXDNL shares domains with PXDN, that allow PXDN to interact with the ECM, it is speculated that PXDNL may possess other ECM modulation roles that require further elucidation. Dysregulated PXDNL expression also correlates with poor cancer prognosis. To date, within the context of South African derived OSCC cell lines, no studies pertaining to the DNA methylation status of the PXDN and PXDNL promoter regions and the expression of PXDN and PXDNL have been carried out. Aim: The aim of this project was to investigate the DNA methylation status of the PXDN and PXDNL promoter regions and observe PXDN and PXDNL expression in the SNO and WHCO5 OSCC cell lines. Methods: PXDN and PXDNL localisation was observed using immunofluorescence microscopy; expression of PXDN and PXDNL was quantified using western blotting and the DNA methylation status of the PXDN and PXDNL promoters was assessed using methylation specific PCR and bisulfite sequencing, respectively. Results: Immunofluorescence microscopy results indicated that both cell lines show varying degrees of PXDN and PXDNL expression. In addition, these results also showed that PXDN and PXDNL localise in the ECM. The western blotting results established that these cell lines express the canonical version of PXDN and possibly a PXDNL isoform (146kDa). Methylation specific PCR has shown that the promoter region of PXDN is differentially methylated across both cell lines. The sequencing results of the bisulfite converted PXDNL promoter region were unsuccessful. Hence, bisulfite sequencing requires further optimisation before the DNA methylation status of the PXDNL promoter region can be determined. Conclusion: This study is the first to show the novel finding that PXDN and PXDNL are expressed in South African derived OSCC cell lines. Within the context of OSCC, further investigation is warranted in order to elucidate the underlying mechanisms that these proteins play a role in. In addition, further study may determine whether a correlation exists between PXDN and PXDNL promoter methylation, protein expression as well as prognosis and whether these aspects should serve as novel markers for diagnosis and therapy. This may subsequently lead to increased OSCC patient survival rates by contributing to early diagnosis of OSCC and efficacious targeted therapeutic intervention.Item Birth Freedom: Healing Architecture’s Impact on the Experience of Childbirth and Healthcare Through a Community Maternity Centre in Alberton(University of the Witwatersrand, Johannesburg, 2024) Grobler, Leonie; Szentesi, AnitaThis research explores the topic of childbirth and maternal health care in a community context where such facilities are lacking in focus and accessibility. The study explores the narratives of pregnancy, childbirth, and the postnatal period through the lenses of phenomenological experience, feminist theory, and healing. Its focus lies in how these concepts can shape the design of maternal healthcare architecture. The aim is to research and design a community health care centre that focusses primarily on aspects surrounding childbirth, and secondarily, aspects of female reproductive healthcare and family planning. The intervention aims to challenge the clinical nature of healthcare, improve accessibility to quality and affordable healthcare, and give women freedom over their reproductive healthcare choices. The site of the study is within the town of Alberton, located South of Johannesburg, in the Ekurhuleni Metropolitan Municipality. The goal of the research study is the development of a birthing centre model that serves as an alternative option to existing clinical birth settings which are part of larger hospitals. Research will be conducted through site analysis, contextual analysis, data analysis, theoretical and architectural research and precedent studies. This information will be used to guide the design process and develop a resolved building. This research project consists of two parts, a research report, and a set of design drawings, which will be combined into a single thesis document.