Molecular Characterisation of Diffuse Large B-cell Lymphoma in South Africa

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous and aggressive disease and is the most common subtype of non-Hodgkin lymphoma (NHL) in adults. Additionally, this subtype of lymphoma is also the most common in people infected with the Human Immunodeficiency virus (HIV), and the incidence has remained high despite the advent of Antiretroviral therapy (ART). About 30-40% of DLBCL patients' relapse, or are refractory to standard first-line therapy, and this is attributed to the high genetic and clinicopathological heterogeneity of the disease. Reports indicate that, among HIV-positive DLBCL patients, the response rate is even poorer. In low resourced settings, this is further aggravated by multiple factors including access to health facilities and gaps in communication. Recent genetic studies of DLBCL tumours allowed for the further subclassification of the ABC- and GCB- subtypes into at least 5 new groups, each with distinct genetic, molecular and clinicopathologic features, revealing potentially novel drivers of the disease. There is therefore a need to further understand the molecular pathology of these distinct subtypes, including within the context of HIV. The latter formed the basis of this study and used multiple approaches and methodologies, including immunophenotyping and mutational analysis of samples from local patient cohorts, as well as gene set enrichment analyses of publicly available DLBCL datasets. An analysis and comparison of immune cell populations in peripheral blood mononuclear cells, of HIV negative and HIV positive DLBCL patients was performed using flow cytometry (Chapter 3). The participants were newly diagnosed, chemotherapy naïve DLBCL patients. Some of the key observations were as follows: HIV-positive patients were diagnosed with DLBCL at significantly younger ages (75% under the age of 50 years), compared to the HIV negative DLBCL group. Furthermore, more extranodal disease and EBV infection were observed in the HIV-infected group, and both these factors are known to be indicative of more aggressive, advanced-stage disease. In general, cytopenias were observed in the DLBCL patient cohort, regardless of HIV status. Since most of the HIV infected patients were not adequately receiving antiretroviral therapy at the time of DLBCL diagnosis, the CD4+ helper T-cell population within this group was significantly reduced, in comparison to the HIVuninfected group. Interestingly, there was a significant difference in monocyte count between the two groups, with lower counts observed among the HIV-infected DLBCL patients. Additionally, increased activation of cytotoxic T-cells (CD8+CD38+), as well as lower mature cytolytic CD56dimCD16+ Natural Killer (NK) cells were observed in the HIV-positive DLBCL group. The prevalence of Myeloid differentiation primary response factor 88 (MYD88) L265P and Cluster of Differentiation 79B (CD79B) Y196 activating mutations were analysed in a cohort of archived ABC-DLBCL tumours (consisting of both HIV positives and negatives) (Chapter 4). Genomic DNA was isolated, the relevant genomic regions amplified by PCR, subjected to Sanger sequencing and then analysed and confirmed. The co-occurrence of both these mutations is characteristic of a newly described subset of DLBCL shown to have an inferior outcome. The prevalence of these mutations within an African population has as yet not been reported. The MYD88L265P mutation was detected in 26% of the amplified ABC-DLBCL tumours, while mutations at CD79BY196 were observed in 12% of the tumours. Co-occurrence of both these MYD88 and CD79B mutations were present in only 3 tumours, all of which were HIVnegative. Analysis of patient survival in relation to the mutations highlighted a trend showing that patients harbouring both mutations had worse overall survival. Interestingly, this pathogenic effect was more prominent for CD79B mutations, and this was comparable to the survival probability observed for HIV-positive patients. For the MYD88L265P mutation, an HIV positive status further decreased the survival probability. The final study presented in this thesis focused on investigating the expression and regulation of the Suppressor of cytokine signalling 1 (SOCS1) gene. SOCS1 has been recently reported to be a frequently altered gene in DLBCL, but molecular pathological studies on the role of SOCS1 in DLBCL are scarce. Using cell line models, basal SOCS1 gene and protein expression levels were assessed. In two DLBCL cell lines (SUDHL-4/GCB-DLBCL subtype and HBL-1/ABC-DLBCL subtype), SOCS1 expression was reduced at both the mRNA and protein levels when compared to control lymphoblastoid cell lines (LCLs), while in a third ABC-DLBCL cell line (U2932), results were varied. In silico analysis using the Cancer Genome Atlas (TCGA) database confirmed that SOCS1 is in the top 20 frequently mutated genes in DLBCL. Furthermore, these frequent mutations, which lead to reduced or low SOCS1 expression, are associated with DLBCL disease in its early stages (stages I and II) and with better survival estimates. In contrast, high expression of SOCS1 was associated with poor overall survival. This was further corroborated by gene set and pathway enrichment analyses, which highlighted factors involved in the enhancement of cancer-promoting processes such as proliferation, migration, invasion, and metastasis. Additionally, a previously reported association between the expression of methylation-related genes and SOCS1 expression was confirmed. Overall, these studies have uncovered novel insights into the pathology of DLBCL, including features unique to HIV-associated DLBCL. The implementation of a differential approach to the management of the disease, based on specific genetic and molecular features, should be explored. These findings support the importance of more studies, incorporating comprehensive genomic and molecular technologies, to continue to unravel the complex disease that is DLBCL

Protecting our wildlife for life: a discussion on how we have failed to protect our rhino populations in the past and what our future options really are

The poaching of the rhino of southern Africa is not a new debate. In fact, it has been a key area of environmental concern for a number of years. Today, it falls under the rubric of ecological criminology which shall be addressed in this dissertation. I intend to deal with the impact poaching and the illegal trade has had on this endangered species and, in addition, to give an overview of the current measures of the criminal justice system in force to combat it. I shall discuss the international perspective and propose some solutions to prevent the further elimination of the species. Approximately 350 million wild animals and plants are traded each year world-wide, estimated to be worth US $20 billion per year. It is argued that up to a quarter of this trade may be illegal .and, thus after drugs and weapons it is the third most significant trade internationally. This illegal activity continues despite the operation of an international convention aimed to prevent it, the Convention on International Trade in · Endangered Species of Wild Fauna and Flora, (CITES). I shall address many of the attributes of CITES, but also consider its numerous flaws which have failed to protect · the rhino adequately

The effect of cooling on brewer's yeast quality

The primary concern of a brewer is to produce beer of a desired flavour and quality, in an economic and efficient manner. In large scale brewing operations, process efficiency and beer quality rely on consistent fermentation. Stewart (1977) reports that improper handling of yeast in the brewing process may result in beer of sub-standard quality

The requirements and consequences of sections 17 (5) and 23 (5) of the Matrimonial Property Act 88 of 1984: a comparative scrutiny for the South African legal system

This thesis is a comparative scrutiny of sections 17 (5) and 23 (5) of the Matrimonial Property Act 88 of 1984. The comparison centres on the legal situation in South Africa, Germany and Switzerland. References, however, will also be made to other countries such as England, Scotland, France, Belgium, Spain, Sweden, Austria and Poland. Sections 17 (5) and 23 (5) of the Matrimonial Property Act 88 of 1984 provide that for legal transactions in respect of household necessaries both spouses are, respectively, jointly and severally liable [section 23 (5)] or may be sued jointly and severally [section 17 (5)]. As regards the question of liability for the debts arising from transactions in respect of household necessaries, the statutory provisions are relatively clear. However these statutory provisions give rise to many important questions other than the issue of liability such as the historical background, the ratio legis and the legal nature of sections 17 (5) and 23 (5) of the Matrimonial Property Act 88 of 1984, the requirements and the effects of sections 17 (5) and 23 (5) in respect of the contractual position of the spouses and the acquisition of ownership. Furthermore the question arises as to how the effects of sections 17 (5) and 23 (5) of the Matrimonial Property Act 88 of 1984 can be excluded. Unfortunately it would appear that the South African authorities have not yet grappled with many of these questions, in spite of the importance thereof. The author therefore attempts to submit his own answers. Furthermore the legal situation in Germany and Switzerland is presented. No attempt is made to answer questions which arise in these countries, since the primary object of the present thesis is the legal situation in South Africa. The author thus merely describes the legal situation in Germany and Switzerland and concentrates on the majority opinion in these countries. Only where, from the South African point of view it appears to be necessary, a short criticism is submitted. Finally the author compares the different legal systems, highlights weaknesses of the South African law and the advantages of the Swiss and German law in order to submit a proposal which could improve the current legal situation in South Africa

Investigating the Optical Link Performance of the End-of Substructure Card and Susceptibility to SEUs

Particle physics experiments carried out by CERN attempt to investigate the fundamental forces of matter. One of these experiments is the ATLAS experiment, which studies the proton-proton collisions in the LHC. A series of upgrades are planned to increase the luminosity by a factor of five, leading to the high-luminosity LHC (HL-LHC). This upgrade will increase the potential for new discoveries but brings with it design challenges in relation to the harsh radiation environment and significant data throughput required. The ATLAS experiment is building a new detector to cope with these challenges, titled the Inner Tracker (ITk). A crucial part of this new detector is the End-of-Substructure (EoS) card, which constitutes the interface between the ondetector electronics and the off-detector systems. In addition to the operational challenges, the HL-LHC does not allow for repairs or replacing of EoS cards once operation commences, emphasizing the need for thorough testing and qualification of this component. This thesis focuses on characterizing the performance of the EoS card in the presence of radiation, under non-ideal operating conditions and the impact of optical link parameters. The first set of tests is centered on qualifying the radiation tolerance of the EoS card. The radiation environment within the ITk poses a threat to the stable operation of electronics as energetic particles have the potential to cause erroneous changes in device logic, known as Single Event Upsets (SEU). The SEU susceptibility of the EoS card, with a focus on the Versatile Link Plus Transceiver (VTRx+) component, is studied by irradiating the EoS card with a neutron source with a distributed energy spectrum and a peak energy of 11MeV while performing a bit error rate (BER) test to monitor for radiation induced errors. The second set of tests deals with characterizing the impact of an irregular power supply on the EoS card's performance through simulating noise on the supply lines and monitoring the response in BER. The final set of tests investigates the impact the VTRx+ configuration parameters have on the quality of the optical signal. These tests were carried out at the University of Cape Town (UCT) with the support of DESY, a national research institute in Germany, responsible for the production of the EoS cards. A number of new firmware, software and hardware modules were developed as part of this work in order to carry out the tests required. The most significant of which comprised a novel firmware addition allowing for the evaluation of the optical signal quality with an FPGA. This contribution is now being integrated into the quality control proceedings at DESY, to be used in assessing optical signal quality of the entire set of approximately 1552 EoS cards being produced

Natural and anthropogenic influences on recent sediment characteristics in the Knysna Estuary, South Africa and Yangtze River Estuary, China

Estuaries and tidal wetlands situated at the nexus of fluvial, marine and terrestrial conditions is highly dynamic and complex system. Despite strong hydrodynamics, estuarine tidal flats are preferential sites for the accumulation of fine-grained sediment, organic matter and metals from various marine and terrestrial sources including those of natural and anthropogenic origin. The coastal zone performs many key ecosystem service functions for sustainable development, thus making them valuable ecological entities. In this study, the Chongming Island tidal flats of the Yangtze River Estuary in China and the Knysna Estuary in South Africa are selected as case studies. The objective of this study is to investigate the recent distribution and abundance of sediment characteristics, organic matter, and modern major and trace elements in sediments through space and time. Physically speaking, the two estuaries are very different. Three sediment cores taken from the Knysna Estuary and two sediment cores taken from the Chongming Island of the Yangtze River Estuary in 2019 were analysed to document grain size distribution using Malvern Mastersizer, geochemical signatures including major elements (Al, Fe, K, Ti, and Ca) and trace elements (Ni, Cr, Mn, Sr, Rb, Cu, Pb, Zn and Zr) via XRF, loss-on-ignition and magnetic susceptibility. The cores were divided into three zones based on the approximated time periods. Our results show that the introduction of European land-use and human impacts in the Knysna Estuary resulted in an increase in SARs to be at least three times higher than pre-European SAR values. The widespread deforestation coupled with intense farming exerted significant controls on the quantity of sediment transported downstream and increased erosion within the Knysna Estuary. Agriculture intensification increased the terrigenous input of Al, K, Ca, Ti and Cu levels. In Unit I (ca. 1960s-Present), the heavy metals Fe, Mn, Pb, Zn and Cu escalated in concentration indicating anthropogenic input due to urbanization and infrastructure development in the Knysna Estuary. In Chongming Island, Mg, Al, K, Ti, Mn, Fe, Cu, Zn, Rb, Pb and magnetic susceptibility values in the cores all show increasing trends relative to the pre-1950s and post 2002 units. This is consistent with the significantly increasing trends in the total energy consumption for the industrial development in China and the heavy metal input from the Yangtze River. Post 2002 (Unit I), the same elements exhibited a decreasing trend and their mean concentrations (mg kg-1) is the lowest of all the three units. This is attributed to the improvement in environmental protections and regulatory control of atmospheric pollution and a shift in the consumption of energy from the industrial period in the 1950s to 2000s. Coastal zone research tend to view estuaries and tidal wetlands as an independent and isolated system from any global estuary. A benchmarking case study would provide the opportunity to examine coherence, differences and similarity of coastal behavior across two different biographic regions

The role of Muslim identity on perceived workplace religious discrimination of Muslim women working in Kwa-Zulu Natal

The South African Constitution provides a comprehensive list of rights, many of which are important, directly or indirectly, to meet the needs of religious minorities in the country. However, due to South Africa being a secular state and also having particular needs, many workplaces tend to adopt this approach which leads to a conflict between Muslims' religious obligations and the rules of the workplace. As a result, Muslim employees may perceive that their employers are religiously discriminating against them. Muslim women may face more discrimination than Muslim men as their stigma is less concealable due to their modest dressing and the hijab (religious identity marker). Surprisingly, there has been an increase in cases of religious discrimination against Muslim women. To elucidate, these Muslim women employees were asked to remove their hijab on their job as it somewhat violated the company policies. Therefore, presenting a challenge for Muslim women as their religious identity is part of their self-concept and they are required to follow their religious obligations. Informed by theories such as Social Identity Theory and Intergroup Threat Theory, the present study utilised a cross-sectional design to examine the role of Muslim identity in perceived religious discrimination in the workplace. To gain insight about the hijab in various contexts, the current study also examined the comfortability of wearing the hijab in different contexts. The participants were 75 Muslim women living and working in organisations in KwaZulu-Natal, South Africa. The findings of this research indicate that the dimensions of Muslim identity are not significant predictors of perceived religious discrimination; however, psychological identity can lead Muslim women to perceive less or no discrimination. Furthermore, the ANOVA showed that Muslim women did not feel significantly more comfortable wearing the hijab in certain contexts. This study offered implications for both research and practice and made significant recommendations for future research

soMLier: A South African Wine Recommender System

Though several commercial wine recommender systems exist, they are largely tailored to consumers outside of South Africa (SA). Consequently, these systems are of limited use to novice wine consumers in SA. To address this, the aim of this research is to develop a system for South African consumers that yields high-quality wine recommendations, maximises the accuracy of predicted ratings for those recommendations and provides insights into why those suggestions were made. To achieve this, a hybrid system “soMLier” (pronounced “sommelier”) is built in this thesis that makes use of two datasets. Firstly, a database containing several attributes of South African wines such as the chemical composition, style, aroma, price and description was supplied by wine.co.za (a SA wine retailer). Secondly, for each wine in that database, the numeric 5-star ratings and textual reviews made by users worldwide were further scraped from Vivino.com to serve as a dataset of user preferences. Together, these are used to develop and compare several systems, the most optimal of which are combined in the final system. Item-based collaborative filtering methods are investigated first along with model-based techniques (such as matrix factorisation and neural networks) when applied to the user rating dataset to generate wine recommendations through the ranking of rating predictions. Respectively, these methods are determined to excel at generating lists of relevant wine recommendations and producing accurate corresponding predicted ratings. Next, the wine attribute data is used to explore the efficacy of content-based systems. Numeric features (such as price) are compared along with categorical features (such as style) using various distance measures and the relationships between the textual descriptions of the wines are determined using natural language processing methods. These methods are found to be most appropriate for explaining wine recommendations. Hence, the final hybrid system makes use of collaborative filtering to generate recommendations, matrix factorisation to predict user ratings, and content-based techniques to rationalise the wine suggestions made. This thesis contributes the “soMLier” system that is of specific use to SA wine consumers as it bridges the gap between the technologies used by highly-developed existing systems and the SA wine market. Though this final system would benefit from more explicit user data to establish a richer model of user preferences, it can ultimately assist consumers in exploring unfamiliar wines, discovering wines they will likely enjoy, and understanding their preferences of SA wine

Barriers and facilitators to health care access for children in a low-income are in Cape Town

Background In Cape Town the under-5 mortality rate has plateaued to 20 per 1000 live births. The southern subdistrict has the largest paediatric population in Metro West and accounts for 31% of deaths in Metro West. Across the metropole 60% of child deaths are out of hospital. We investigated barriers to accessing health care for children in the False Bay Hospital drainage area. Methods Quantitative and qualitative methods were used: community survey (n=62), qualitative interviews (n=11) with caregivers of children who presented critically ill or deceased (January 2017 - Dec 2020) and a modified nominal group meeting of community based and clinical services managers to identify and achieve consensus on solutions. Results Community members (74%) experienced barriers in accessing care and only 60% knew the correct emergency contact numbers. Knowledge of basic home care for common conditions was limited. Interview themes showed barriers of affordability, acceptability, access, as well as household and facility factors. The nominal group technique suggested that improvement in community-based services, transport access and lengthening service hours would alleviate some of the challenges in accessing care. Conclusions The barriers to accessing care seem insurmountable to those who encounter them, yet solutions and community assets do exist. The optimal utilization of services and community assets have the potential to improve access to care with resultant decreased out-of-hospital deaths and improvement of the under-5 mortality rate. A well-coordinated Community Orientated Primary Care (COPC) program with intersectoral collaboration and government commitment needs to be implemented

Street graphics : thirty-one silkscreen prints, based on South African iconography, with reference to certain characteristics of the street poster

An exploration by graphic means of selected South African iconography is the subject of this thesis. I have produced a collection of thirty-one silkscreen prints, which combine elements of the fine print and the street poster. The screen-prints have been mounted on board and presented in a box, accompanied by an illustrated dissertation. During the production of the printer I displayed a number of individual screen-prints, and later complete series, at various public locations (e.g. bus shelters, fences and walls of buildings) on the U.C.T. campus, in order to relate my working process to a direct public response. The whole collection of prints is ultimately envisaged as an exhibition on simple screens in a public place . The imagery in these prints is drawn from magazines and other mass publications, as well as from personal observation. My themes are based on aspects of South African popular culture and have been developed under eight different titles. The first five prints: OBSERVATIONS, can be seen as the visual parallel to a preface. Series One: ARTEFACTS, asserts the associative values of a well-known object when it is taken out of its context. Series Two: PROTOTYPES, links the quest for individuation with identification by means of uniform or dress. Series Three: INTERIORS, depicts environments that represent the concerns of the people who inhabit them. Series Four: MERE FACADES, portrays selected buildings which reveal aspects of the nature of the society they shelter. Series Five: AHEAD OF OUR TIME, focuses on outward appearance as a denominator of identity and on the resulting loss of individuality. Series Six: SUNNY SKIES, is a personal interpretation of some typical South African images (icons). Series Seven: MEMORABILIA, serves as a conclusion to the collection and is a personal homage to Joseph Cornell. This dissertation comprises a discussion of aspects of the practical work, concentrating on some elements of the historical background to my investigation; notes on my graphic methods and their implications; a documentary report on the display of the prints on the U.C.T. campus and an introduction to the prints