Mutagenic predisposition in genes implicated in Alzheimer's Disease

Alzheimer’s disease is the most common cause of late-life dementia and the fourth leading cause of death in the developed world. The aetiology of AD has not yet been resolved. It has been suggested that AD could result from multifactorial process involving both a genetic predisposition and an exposure to environmental factors modulated by the biological aging process. To date, epidemiological and molecular genetic data have led to the identification of three genes, amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) genes, which, when mutated, can cause an early onset form of AD. Genetic linkage studies and association studies have also shown that the ε4 allele of the apolipoprotein E gene increases risk for AD in a dose dependent manner in both early onset and late onset AD. Recently, it has also been suggested that environmental factors may interact with a genetic predisposition to modify the risk of AD. Extensive research is underway to identify environmental and genetic risk factors for this complex disease. Over 40 genes have been tested as AD candidates yet none has been clearly established as an AD risk factor. Currently scientists are investigating the interrelationship between various gene loci and how environmental factors could affect an individual’s susceptibility to AD. This study evaluated the genotoxicity of environmental agents such as hydrogen peroxide, cadmium chloride and γ radiation induced oxidative DNA damage in lymphocytes and within specific DNA sequences of APP (exon 15-18) and PS1 (exon 3-12) genes of AD patients and age-matched control subjects. As indicators of oxidative DNA damage, the frequencies of DNA strand breaks, oxidized pyrimidines and altered purines was assessed using the alkaline Comet assay modified with lesion-specific endonucleases, endo-III and fpg; and fluorescence in situ hybridisation. The number of APP and PS1 hybridisation spots per comet were used as an indicator of the extent of damage. The location of the hybridisation spots in the head or tail of the comet were recorded to further determine whether the gene of interest lies within or in the vicinity of a damaged region of DNA. With the alkaline Comet assay modified with endo-III and fpg, it was demonstrated that patients with AD had significantly increased levels of DNA strand breaks, oxidized pyrimidines and altered purines induced by hydrogen peroxide, cadmium chloride and γ radiation compared with control subjects (p<0.05). This was further confirmed by the fluorescence in situ hybridisation modification of the alkaline Comet assay by demonstrating a significant increase in the mean number of APP and PS1 gene hybridisation spots per comet in AD patients compared with control subjects. Moreover, the gene sensitivity index of APP and PS1 to hydrogen peroxide, cadmium chloride and γ radiation were found to be higher in AD patients than in control subjects. Taken together, our results suggest (i) that lymphocytes from patients with AD are sensitive to these environmental genotoxic agents and (ii) there was an overall increase in the mean number and sensitivity index of APP and PS1 genes to environmental genotoxic agents which might link a genetic cause to oxidative stress in peripheral cells of AD patients than in control subjects. Although the mechanisms by which these environmental agents induced oxidative DNA damage remained to be elucidated, our data suggest that increased oxidative stress is an inherent property of cells carrying genes associated with AD.Dr. H. Abrahamse Mrs. J. V. Hin

Like father, like son?

Dissertation submitted in partial fulfilment of the requirements for the Degree of Masters in Community Based-Counselling Psychology in the Faculty of Humanities at the University of the Witwatersrand, 2016This investigation explored how fathers and sons perceive what it means to be a father. A review of current literature revealed that there has been extensive work on the theme of fatherhood. Though extensive, the literature has not included both fathers and sons within a single investigation. Thus, this study has included both fathers and their sons in order to explore their perceptions of fatherhood. The findings revealed that both fathers and sons believed that being a father meant that one had to be the moral guide and primary breadwinner of the family. Some sons experienced their fathers as being emotionally absent and demonstrated a desire to have more present father figures. This desire, along with the notion that “the father is the primary role model of the son” is in line with ideas pertaining to “New Fatherhood”. With these definitions of fatherhood in mind, it was noted that all fathers believed that they still had some work to do before they could consider themselves the ‘perfect’ father. Despite this, the main findings of this investigation indicated that many sons continued to aspire to be like their fathers. While aspiring to be more like their fathers, the men in this investigation also felt that they needed to perform certain paternal functions better than their own fathers

Assessment of spatial and temporal variation in water quality of the Pienaars River, Limpopo water management area.

Masters Degree. University of KwaZulu-Natal, Pietermaritzburg.Abstract available in pdf

Modelling hepatotoxicity in HIV/TB co-infected patients: extensions of the Cox Proportional Hazards Model

Hepatotoxicity which is also known as liver damage is mainly caused by intake of medicine. It is common among patients who are co-administering Tuberculosis (TB) treatment and the antiretroviral therapy (ART) for the Human Immunodeficiency Viruses (HIV). If severe, hepatotoxicity sometimes necessitates cessation or interruption of treatment. Therefore, understanding, monitoring and managing hepatotoxicity in patients co-infected with TB and HIV is crucial for optimal treatment outcomes. Hepatotoxicity has been investigated in patients coinfected with TB and HIV, however, most studies have analyzed only the first occurrence of hepatotoxicity and discarded information relating to the resolution and recurrence of hepatotoxicity. Data from the ‘Starting Antiretroviral therapy at three Points in Tuberculosis' (SAPiT) trial is used in this project. This was a trial that was instrumental in finalizing treatment guidelines for patients co-infected with HIV and TB in South Africa. The clinical objectives of this project are to estimate incidence rates and determine risk factors associated with hepatotoxicity. The statistical objectives are to fit a Cox regression model, the resolution model of hepatotoxicity, and the extended Cox models for recurring events, including the Andersen Gill (AG) model, the Shared frailty model, the Prentice, Williams and Peterson (PWP) total time (TT) model, the PWP gap time (GT) model, as well as a Cox based recurrent model, that models only the second occurrence of hepatotoxicity. There were 593 patients assessed for hepatotoxicity in the study, 30% (179/593) developed the first occurrence of hepatotoxicity (grade >=1) and 2% (13/593) developed severe hepatotoxicity (grade >=3). Resolved cases (grade = 0) are 76% (136/179) and recurring cases (grade >=1) 24% (32/136). In the Cox multivariable analyses: time-varying treatment arm, older patients, alcohol consumption, low baseline total bilirubin and a positive baseline Hepatitis B surface antigen status, were associated with a higher risk of developing the first occurrence of hepatotoxicity. The extended Cox models (AG model, Shared frailty model, PWP TT model and PWP GT model) in combination identified that: time-varying treatment arm, older patients, alcohol consumption, baseline CD4 count that is greater than 50 cells per mm3 , low baseline total bilirubin, and a positive baseline Hepatitis B surface antigen status were associated with an increased risk of developing recurrent hepatotoxicity. In the resolution model multivariable analyses; non-consumers of alcohol and an abnormal liver function tests at baseline, were associated with an increased chance of resolving the first occurrence of hepatotoxicity. In the multivariable analyses of the recurrent model: younger patients and the time-varying treatment arm were associated with the development of the second occurrence hepatotoxicity. Since the Cox regression model utilized data up to the first occurrence of hepatotoxicity, in some instances, the time-varying treatment effect based on the Cox regression model was closer to unity and marginally significant. And the corresponding effect based on the recurrent event models (AG model, Shared frailty model, PWP TT model, PWP GT model and the recurrent model), that utilized data of the first and second occurrence of hepatotoxicity, generally produced a time-varying treatment effect slightly far from unity with a strong statistical significance. This trend was similar for other predictors of hepatotoxicity, like CD4 count and alcohol consumption. In conclusion, hepatotoxicity is common in this study, however, it is often transient or mild and did not necessitate treatment interruption. However, close monitoring of patients especially in the first 5 months of TB-treatment is recommended. The PWP TT model seemed to be the best model for modelling recurring hepatotoxicity, since the identified risk factors that were associated with hepatotoxicity, changed from the first occurrence of hepatotoxicity to the second occurrence of hepatotoxicity

Voices from the village: local perspectives on the empowerment of women through CBNRM in Tsholotsho District, Zimbabwe

A symposium paper on gender participation in rural development through the programme CBNRM in one of Zimbabwe's rural areas of Tsholotsho.Tsholotsho has 20 wards, 20 Councillors composed of one woman, one white man and 18 black men. The woman is the Councillor for Ward 7, which is the focus of the paper. The Ward has a population of 8 191 with 650 San Khois and the rest of them are Ndebeles. The San Khois are the minority ethnic group in Tsholotsho and are marginalised. There have been certain projects targeted at these people. When the Ndebele came to the District in 1953, the San Khois were already settled in area. These Ndebele people were moved from Matopo during the colonial era when the land that they occupied was gazetted for commercial fanning purposes. These San Khois were hunters and gatherers, meaning that they relied on the forest for livelihood, whereas the Ndebele were pastoralists/ agriculturists. There was a lot of vegetation in the areas that they lived in because they did not use trees. The problem that was encountered when the Ndebele moved to Tsholotsho is that it took time for the two groups to integrate because they were both afraid to meet each other and relate closely.The success of this conference and the publication of these proceedings has been possible through support from the US Agency for International Development (USAID

A Phenomenological Study on Entrepreneurial Identity of Female Entrepreneurs in South Africa

Objective: To understand the entrepreneurial identity, through the lived experience of female entrepreneurs who are familiar with the phenomenon. This objective was premised on understanding that entrepreneurial identity is a product of context which shapes the social-cultural norms and environment within which individuals, operate and construct their identity. This is captured in entrepreneurship scholarship where the discipline is still struggling to build a reliable definition of female entrepreneurship applicable to both developed and developing countries and its effect on their respective economies. Research Design &amp; Methods: This study used a qualitative research design that followed a phenomenological approach with thirty five female entrepreneurs, utilising semi structured in depth individual meetings. Findings: Female entrepreneurs build, balance, and manage a wide range of entrepreneurial ventures of varying sizes across sectors while maintain both role and social identities. Female entrepreneurs also express strong views on earning returns and income to not only grow their business but support their employees, communities, themselves, and their families. Implications &amp; Recommendations: This study generated five themes that should be researched quantitatively to determine further understanding of entrepreneurship and developing other entrepreneurs in developing countries. Contribution &amp; Value Added: The study contributes to the existing body of knowledge on entrepreneurship in entrepreneurial identity, by exploring the female entrepreneur as both a role and identity. It examines this through the perspective of role identity and learn how female entrepreneurs consider their role as an entrepreneur

Integration of MOODLE into the classroom for better conceptual understanding of functions in Mathematics

Many South African educational institutions are adopting learning management systems (LMS) into their daily teaching and learning practice. The Western Cape Education Department piloted Modular Object-Oriented Dynamic Learning Environment (Moodle), an LMS for improving teaching and learning. The objective of the research reported on here was to determine whether Moodle improved Grade 10 learners’ conceptual understanding of the topic, functions, in mathematics. The research investigated two classes; one dependent upon a traditional chalk-and-talk teaching method (control), and another exposed to Moodle (experimental). It was found that learners constructed their own knowledge by drawing on resources embedded in Moodle and framed within a Social Constructivist theory. A hybrid e-learning framework was deployed; learners acquired knowledge by interacting with computers. Interaction was monitored and results were recorded using online surveys and tests. A quasi-experimental design was employed to compare the groups. The comparisons were statistically analysed. Results showed that the functionalities within the Moodle LMS were instrumental in improving conceptual understanding of mathematical functions. Keywords: constructivism; digital technologies; functions; mathematics; Moodl

Inconsistencies in the adjudication of rights: an examination of three South African Constitutional Court decisions.

Masters Degree. University of KwaZulu-Natal, Pietermaritzburg.The Republic of South Africa has a constitution that is often lauded as among the best in the world. This can be attributed, at least partly, to the fact that at the heart of it lies transformative constitutionalism, which has the objective of addressing the injustices of the past with the entrenchment of fundamental human rights. Last but not least, the Constitutional Court has to give teeth, metaphorically, to all the human rights in the Bill of Rights. The question this project seeks to answer is whether or not the Constitutional Court does a good job – is consistent - in applying the Bill of Rights to the facts of particular cases. The cases examined in this research project demonstrate that there are inconsistencies in the approach that the Constitutional Court adopts in the adjudication of rights. This study, therefore, attempts to explain why these inconsistencies arise, why they are a problem, and to some degree, how they can be avoided. In an effort to satisfy the above research question and aim of this study, this dissertation is divided into five chapters followed by the requisite bibliography. Chapter 1 introduces the project and gives a historical background to the South African Constitutions with a view to putting the current constitutional position in context. As the inconsistencies seem to play themselves out in the adjudication of rights, the focus of Chapter 2 shifts to the concept of transformative constitutionalism in the hopes of shedding light on why there are inconsistencies in the adjudication of rights. Chapter 3 details the theoretical framework within which judicial decision-making takes place, referring specifically to the work of Ronald Dworkin. This chapter is inextricably linked to Chapter 4 which is an examination of actual applications of judicial decision-making. Finally, Chapter 5 concludes the study and offers some suggestions for the way forward. To briefly note, all the authorities that were consulted for the research are acknowledged in the bibliography

Employee views on organisational effectiveness of Chinese organisations operating in Kenya

Over the years there has been a growing interest in the relations between Africa and Asia. This is attributed to what is perceived as increasing Chinese influence and presence in Africa. During the past decades, China has experienced rapid economic growth and expansion which has contributed to its need for additional resources and expanding its geographic footprint into Africa and especially Kenya. The growing presence of Chinese organisations in Africa has also faced challenges. Chinese organisations operating in Kenya have been cited as facing cultural challenges, human resource management issues and external pressures which affect Chinese organisations thus impacting organisational effectiveness and performance. While there has been an abundance of research conducted at a macro level, mainly anecdotal knowledge on Chinese organisational values and management, little information exists at the organisation and community level. This study aimed to contribute an in-depth understanding of Chinese and Kenyan employee relationships in organisations at a micro level. Furthermore, this study assesses employees’ views on organisational effectiveness in a cross-cultural research setting of selected Chinese organisations operating in Kenya using the Burke-Litwin model (1992) of organisational effectiveness. This study is qualitative in nature within the interpretivistic research paradigm and used a case study approach to generate detailed comprehensive understanding of the phenomenon under investigation. Two Chinese organisations specialising in importing and exporting of diverse products, which had expanded its operations to Kenya in order to reach Africa’s growing consumer markets were selected for this study. The selected organisations were chosen under the premises that they had been operating in Kenya for more than 20 years, they are reputable organisations in their industries and were international role players. Non-probability convenience sampling was used to select the two organisations who were willing to participate. Purposive sampling was used to identify employees from different job levels and types of work in the selected organisations who were willing to participate in this study. Data was collected by means of face-to-face open-ended semi-structured interviews, with five Chinese and 12 Kenyan employees. The findings of this study were guided by the dimensions of the Burke-Litwin model, comprising the external environment, transformational dimensions (including mission and strategy, leadership and organisational culture) and transactional dimensions (including management practices, organisational structure, systems [policies and procedures], motivation, work climate, task requirements and individual skills and abilities). Based on the findings, organisational culture was the dominant theme that had a large influence on the organisational performance. Within the context of organisational culture, the main challenges faced by employees were religious, work ethic and communication barriers. Leadership and the organisational structure set by senior managers was also impacted by culture. It is evident that the Chinese organisations are dominated by Chinese employees at senior managerial levels – except for one Indian Kenyan manager – and non-managerial levels are dominated by Kenyan employees. Between these two managerial levels there is lack of trust as well as trade union interference favouring Kenyan employees. Leadership of the selected organisations aimed at recruiting candidates who have the necessary skills to contribute toward organisational effectiveness and performance. However, recruited Kenyan employees indicated that they require strategy visibility, effective communication, and structured processes in order to be effective. Despite challenges faced, Chinese and Kenyan employees both strongly agree with and support the efforts of management for providing training and development and creating an environment that accommodates personal growth. The external environment has exerted pressure on the said Chinese organisations. The Kenyan trade unions favour Kenyan employees and place huge pressure on Chinese management. In addition the trade unions bribe locals while making it difficult for Chinese organisations operating in Kenya to conduct business. Through the empirical development of organisational-level research on the case of Chinese organisations operating in Kenya, insightful management knowledge was gathered and shared to assist Chinese and Kenyan employees in their individual and organisational performance.Thesis (MCom) -- Faculty of Commerce, Management, 202

Cauchy Loss Function: Robustness Under Gaussian and Cauchy Noise

In supervised machine learning, the choice of loss function implicitly assumes a particular noise distribution over the data. For example, the frequently used mean squared error (MSE) loss assumes a Gaussian noise distribution. The choice of loss function during training and testing affects the performance of artificial neural networks (ANNs). It is known that MSE may yield substandard performance in the presence of outliers. The Cauchy loss function (CLF) assumes a Cauchy noise distribution, and is therefore potentially better suited for data with outliers. This papers aims to determine the extent of robustness and generalisability of the CLF as compared to MSE. CLF and MSE are assessed on a few handcrafted regression problems, and a real-world regression problem with artificially simulated outliers, in the context of ANN training. CLF yielded results that were either comparable to or better than the results yielded by MSE, with a few notable exceptions.Comment: A version of this paper was accepted for publication in SACAIR'2