ResearchSpace

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Influence of drug transporter gene polymorphisms on pharmacokinetics and treatment outcomes in African Mycobacterium tuberculosis Cohorts.
(2025) Tulsi, Sahil.; Ramsuran, Veron.
Background: Tuberculosis (TB) remains a major health challenge in Africa, and achieving the United Nations Sustainable Development Goal of ending TB by 2030 may be hindered by limited understanding of how African populations respond to current therapies. Emerging evidence indicates that African patients metabolize anti-TB drugs differently due to unique genetic variants, particularly in drug-transporter genes. Many variants known to affect drug response in Asian and European populations occur at lower frequencies or are absent in African groups, while numerous African-specific or understudied variants remain unexplored. This study examined the role of drug-transporter genes and genome-wide variants with pharmacodynamics, HIV and TB-associated biomarkers among South African patients receiving anti-TB therapy or HAART. Specifically, this study: (1) reviewed the genetic diversity of transporter-gene variants in African individuals with TB; (2) assessed the effects of specific ABCB1 and SLCO1B1 mutations on moxifloxacin pharmacokinetics (PK); (3) investigated genome-wide markers associated with HIV/TB co-infection and TB recurrence; and (4) identified ATP-Binding Cassette (ABC), Solute Carriers (SC) and genome-wide variants influencing moxifloxacin pharmacokinetics (PK). Materials and Methods: A total of 1,407 black race South African participants from various clinical trials from rural and urban KwaZulu-Natal were included for this study across chapters, namely the TB Recurrence upon treatment with HAART study (TRUTH) n= 427, Improving Retreatment Success (IMPRESS) n=157, University of KwaZulu-Natal cohort (UKZN) n=778, Integrase Strand Trasnfer Inhibitors (INSTIs) for The Management of HIV-associated TB study (INSIGHT) n=32 and Individualized M(X) drug-resistant TB Treatment Strategy Study (InDEX), n= 13. TB diagnoses were confirmed through microscopy, PCR, and culture methods. Moxifloxacin pharmacokinetic measurements were obtained approximately 24 hours post-dose using mass spectrometry. ABCB1 and SLCO1B1 variants were genotyped by real-time PCR, and genome-wide Single Nucleotide Polymorphisms (SNPs) were genotyped by microarray technology.
The ecology, plant functional composition and ecosystem services across a range of the Afromontane and Afroalpine palustrine wetlands in Lesotho.
(2019) Chatanga, Peter.; Sieben, Erwin Jacobus Joannes.; Okello, Tom Were.
Although wetlands are among the most socio-economically and ecologically valuable ecosystems worldwide, global coverage and condition of wetlands is declining, both to the detriment of ecosystem service delivery. Classification and description of wetland vegetation provide an understanding of how wetland vegetation is related to its environment, as well as the associated spatial variation and information for biodiversity conservation and water resource management. Furthermore, understanding the distribution of wetland ecosystem services across landscapes is essential for planning the conservation of the wetlands for a sustainable provision of the services. This study aimed to achieve four main objectives:(1) to classify and describe the Afromontane wetland vegetation in Lesotho, (2) to classify and describe the montane palustrine wetland vegetation of the Maloti-Drakensberg and the surrounding areas, (3) to assess the plant functional composition of the Afromontane palustrine wetlands of Lesotho and link this to environmental variables, and (4) to assess the Afromontane palustrine wetland ecosystem services in Lesotho and link them to environmental factors and functional traits, as well as to assess the level of threat to the delivery of the services. For the first objective, data on vegetation and different environmental variables were collected from the Afromontane wetland vegetation in Lesotho using the Braun-Blanquet method and a recommended protocol developed for environmental information of wetlands in South Africa, respectively. Regarding the second objective, the montane subset of the National Wetland Vegetation Database of South Africa (also collected using the same methods) was selected and coupled with the new data collected from the Lesotho part of the Maloti-Drakensberg. To achieve the third objective, in addition to the data collected for the first objective, plant functional trait data were also collected from the Afromontane wetlands of Lesotho using methods recommended in literature. For the purposes of the fourth objective, the WETEcoServices tool was used to collect data on wetland ecosystem services and this was coupled with the data collected for the first and third objectives. For all the objectives, the data were analysed mainly by means of clustering, indicator species analysis and ordination techniques. The study distinguished 22 Afromontane wetland plant communities in Lesotho and these displayed a high level of diversity in terms of species richness. With respect to species composition and diversity, the communities at higher altitudes were more diverse and were quite different from those at lower altitudes. While the higher-altitude communities mainly exhibited the dominance of C3 plants, those at lower altitudes were mainly dominated by C4 species. As revealed by the ordination, variation in the wetland vegetation in the country was mainly related to altitude, longitude (directly correlated with rainfall in the context of Lesotho), slope, inundation, soil parent material, landscape, potassium content, total organic carbon, soil texture, nitrogen, electrical conductivity and latitude. In terms of distribution, the occurrence of some plant communities was limited to either the Lowlands or Highlands, while others were widely distributed along the altitudinal gradient, occurring in both regions. For the Maloti- Drakensberg montane palustrine wetlands, the classification produced 42 wetland plant communities, which were summarised into 16 major vegetation types. These major vegetation types were rich in species and also displayed remarkable variation along the altitudinal gradient. This variation was mainly attributed to changes in the conditions of the environment that include the amount of precipitation, temperature and the underlying parent material. The ordination indicated that the variation in the vegetation types could more specifically and mainly be ascribed to variation in altitude, longitude, latitude, nitrogen content, soil depth, inundation depth and electrical conductivity. However, slope, pH, total organic carbon, sodium content, soil texture and degree of wetness were also important factors. Furthermore, with respect to species composition, significant variation was also observed between higher-altitude and lower-altitude plant communities. In terms of distribution, the montane wetland vegetation was more concentrated in the Maloti-Drakensberg than the other parts of the region, although some vegetation types also occurred in the lower altitudes of Lesotho and in all of the South Africa provinces. In terms of plant functional composition, eight plant functional types were obtained from the functional classification of the plant species in the Afromontane wetlands in Lesotho. The functional types were dominated by plants with C3 photosynthetic pathway, particularly in the high-altitude wetlands. Plant communities in the Lesotho exhibit the coexistence of species from different plant functional types, which highlights functional differentiation to exploit microhabitat heterogeneity. Both functional traits and functional composition of the communities were mainly and broadly influenced by altitude, longitude and slope, and more finely by edaphic factors that include electrical conductivity, total organic carbon, nitrogen, clay percentage, potassium, magnesium and calcium. Thus, functional differentiation of wetland vegetation along environmental gradients was demonstrated in this study. Furthermore, the study highlights the possibility of alterations in plant functional traits, types and functional composition in the face of environmental alterations, including climate change. Although the wetlands were all important for ecosystem service delivery, higher-altitude wetlands differed distinctively from the lower-altitude wetlands in the services they deliver most. The highest scoring ecosystem services for the higher-altitude wetlands were carbon storage, provision of natural resources, streamflow regulation, maintenance of biodiversity and erosion control, while natural resources, cultivated foods, nitrate removal, phosphate trapping and streamflow regulation scored highest for the lower-altitude wetlands. The most important environmental factors influencing the delivery of wetland ecosystem services in this study were altitude, longitude, landscape, soil parent material, slope and soil depth. The delivery of ecosystem services was also correlated with the functional traits of the dominant plant species in each wetland type where specific leaf area, total dry mass, shoot mass, root mass, rooting depth and plant height were the most important traits influencing ecosystem service delivery. For example, carbon storage and maintenance of biodiversity were positively correlated with plant shoot mass, total plant biomass and rooting depth, while specific leaf area and root/shoot mass ratio had a positive and strong correlation with supply of natural resources, cultivated foods and cultural significance. The ecosystem services provided by a given wetland are thus dependent on the location and environmental characteristics of the wetland within a catchment and the functional characteristics of the dominant wetland plant species. However, the supply of ecosystem services in Lesotho is threatened, with the level of threat higher in the loweraltitude than in higher-altitude wetlands. The threats, which are largely anthropogenic, are mainly associated with crop cultivation, overgrazing and trampling by livestock and economic development. The diversity exhibited by the wetlands in Lesotho and the Maloti-Drakensberg, coupled with their restricted habitat and distribution at high altitudes, capacity to support endemic species, their role in water resources and supply of other ecosystem services, points to the high conservation value of these ecosystems, particularly in the face of biodiversity loss and climate change. Thus, given the reported threats, the conservation of these montane palustrine wetlands is indispensable and should be set as a priority. Based on these findings that can contribute the information needed for biodiversity conservation planning and sustainable provision of wetland ecosystem services in Lesotho and beyond, the study recommends urgent attention and up-scaling of the conservation efforts to protect these Afromontane palustrine wetlands and theservices they provide.
Exploring the efficacy of employee motivation on municipal performance: a case study of eThekwini Metropolitan Municipality.
(2025) Maseko, Thembelihle Patience.; Nzimakwe, Thokozani Ian.
Employee motivation has been identified as one of the most critical organizational phenomena in today's competitive business environment, particularly within public sector institutions where service delivery directly impacts community development. The eThekwini Municipal Academy plays a vital role in providing training to young people through trade programs and apprenticeships aimed at enhancing participants' socio-economic status. This study examined the relationship between employee motivation, managerial perceptions, and municipal performance within the eThekwini Municipal Academy. The study aimed to ascertain the role of managerial perceptions in shaping employee behavior and motivation, understand motivation's impact on eThekwini Municipal Academy performance, and determine current motivational strategies' effectiveness on employee performance and satisfaction. A qualitative research approach utilizing correlational research design was adopted to explore relationships between variables. The target population comprised employees including training coordinators, facilitators, administrative staff, and management personnel. A purposive sample of 10 participants was selected. Primary data collection employed semi-structured interviews and observational methods, with interviews conducted across hierarchical levels to elicit experiences, perceptions, and understanding of employee motivation and management practices. Data analysis was conducted using NVivo software, employing thematic analysis grounded in Performance Management System theory. The research revealed significant correlations between managerial perceptions and employee motivation levels. Participants commonly reported moderate motivation levels, with recognition and rewards identified as primary motivational factors. Key challenges identified included insufficient training opportunities, poor communication from management, and limited career advancement prospects. Participants unanimously agreed that improved employee motivation would enhance service delivery quality. The study contributed valuable insights to existing literature on motivation theory within public sector contexts while providing recommendations.
The effect of ownership structure on the value of JSE listed firms.
(2018) Adeyanju, Adebiyi Sunday.; Kwenda, Farai.
While numerous studies have drawn attention to the effects of different ownership structures on firm value, previous investigations focused on managerial, state, family and institutional ownership as well as ownership concentration. Few empirical studies have been conducted on the influence of domestic and foreign ownership on firm value. This study adds to the body of knowledge by examining the effect of ownership structure (ownership concentration and the identity of owners) on the firm value of JSE listed companies in South Africa. It also investigates the effect of managerial ownership convergence-of-interest (suboptimal level) and the entrenchment effect (optimal level) on the firm value of JSE listed companies. These objectives were investigated with 187 firms on the JSE from 2004-2016 in static model using Ordinary Least Square, Random Effects and Fixed Effects estimations method and a dynamic model using Generalised Method of Moments estimation method for data analysis. After spotting on corporate governance practices and Black Economic Empowerment in South Africa, we find that managerial ownership and domestic ownership have a positive effect on firm value, and ownership concentration and foreign ownership have a negative influence on firm value. In addition, suboptimal level of managerial ownership has a positive effect on firm value and optimal level have a negative effect on firm value as expected on convergence of interest and entrenchment level. These findings hold after capturing for anomalies of heteroskedastic, unobserved individual effect, simultaneity and all the endogeneity issues, inherent in ownership structure which mark dynamic model in consideration. Our finding is contrary to agency theory and property right theory on the role of large shareholder and foreign investors to half free-riding problem of management that arises from separation of ownership and control. The results obtained suggest that local shareholders in the host country and management shareholding could help to strengthened firm monitoring and corporate governance practices to improve firm value. Local investors and director shareholding could help to reduce agency costs and to ease efficient loss that arise from separation of ownership and control irrespective of diverse institutional framework of the corporate environment. Furthermore, the finding managerial ownership on convergence of interest and entrenchment level findings show that an increase in management shareholding provides efficient monitoring at the low level and a high level of managerial ownership improves firm value while at the intermediate level it reduces firm value. The results obtained show that interaction of manager shareholding reduces agency cost at the low level and higher of managerial ownership and increase monitoring cost at intermediate level.
Geopolitical risk effects on the quality of exchange-traded funds in developed and emerging markets.
(2026) Madlala, Anelisiwe.; Kunjal, Damien.
Exchange-Traded Funds (ETFs) have gained popularity as the demand for low-cost and easily accessible investment vehicles. However, ETFs may be significantly influenced by Geopolitical Risks (GPR). GPR plays an important role in shaping market quality by affecting returns, volatility, and liquidity in both emerging and developed markets, and often lead to heightened uncertainty and market disruptions. Although several studies in the literature have examined the GPR effect on ETF returns, volatility, or liquidity individually, studies that jointly examine the GPR effect on ETF market quality remain scarce. Therefore, this study examines the GPR effect on the quality of ETFs in developed and emerging markets. To achieve the objective of this research, the study makes use of fourteen ETFs that track broad market indices, comprising of seven ETFs from emerging markets and seven from developed markets, and trade in their respective home countries. The sample period spans from each ETF inception date up to 31 December 2024. This study employs a Markov Regime-Switching model to examine the effect of GPR on ETF returns, a GARCH-MIDAS model to examine the effect of GPR on ETF volatility, and NARDL model to investigate the effect of GPR on ETF liquidity. The findings from this study show that GPR has limited effect on ETF returns, with global GPR exhibiting little direct effect, while country-specific GPR shows stronger and more persistent effects on returns, particularly in developed markets. GPR significantly affects ETF volatility, with emerging market ETFs exhibiting greater sensitivity to global GPR, while developed market ETFs show higher volatility persistence following geopolitical shocks. In addition, GPR affects ETF liquidity asymmetrically, with ETFs from emerging markets exhibiting stronger and more unstable long-run and short-run liquidity responses to both global and country-specific GPR, while ETFs from developed markets display muted and stable liquidity reactions. These findings indicate that investors should not assume that holding ETFs from different asset classes will automatically spread-out risk. As a result, investors may need to take proactive adjustments during periods of elevated GPR. Policy makers should ensure market stability because emerging markets are highly volatile and rapidly lose liquidity during geopolitical shocks.