MSc (Med) Epidemiology and Biostatistics, Faculty of Health Sciences, University of the Witwatersrand, 2009 / Focus in public health research is shifting to the role of socio-economic factors in the promotion of health. Hence, an understanding of the roles socio-economic factors plays in improving health and health-seeking behaviour is important for public health policy. This study examined the relationship between socio-economic factors and HIV infection in rural Limpopo Province South Africa, an area characterized by poverty differentials and migration. Various possible social and economic risk factors (such as nationality, education status, marital status, employment status, migration status and socio-economic status) for HIV infection are analysed and discussed. This is secondary data analysis was carried out during the period June 2001 to March 2005 among 2345 14-35 year old residents in eight (8) villages in rural Limpopo. Married participants (OR 0.53 [95%CI 0.28 – 1.00]), those from poor (OR 0.49 [95%CI 0.28-0.85]) and less poor households (0.38 [95%CI 0.21-0.70]) are less likely to contract HIV infection. Noteworthy from these analyses also is the increased risk for HIV infection seen among female participants, those not currently schooling (OR 1.9 [95%CI 1.2 – 3.3]) and non-South African citizens (OR 5.18 [95%CI 1.04-25.8]). Conclusion: Women, out-of school youths and non South African citizens are shown to be high-risk population groups for HIV infection. HIV prevention programs that target identified vulnerable population groups and increased social support for the family may contribute to mitigating the spread of HIV in rural South Africa.

This research survey was carried out to investigate three areas of concern which are commonly associated with the implementation of government development projects: namely: (i) cost overrun causal factors, (ii) effective remedial cost control measures and (iii) apportionment of professional responsibility for either cost overrun causal factors or costs control remedial measures’ implementation. The ultimate aim was to identify major causes of cost overruns, generate and recommend possible solutions to the problem of cost overruns in the Botswana public construction industry. The research strategy adopted, involved the circulation of questionnaires and subsequent statistical data analysis. Initially, an expert group questionnaire test survey was conducted among ten (10) professionals (expert group), in order to solicit professional opinion and contributory input on the research. The purpose of the expert group questionnaire test survey was to refine the research questionnaires, make necessary questionnaire structure amendments, eliminate possible ambiguities, and finally, to make data collection an easy exercise. Through the expert group questionnaire test survey, the research questionnaires were assessed for validity and reliability. Thus, the questionnaire content validity (Saunders et al. 2003) was established by soliciting comments from the expert group, on the representativeness and suitability of the research questionnaires. Lists of causes of cost overruns factors and effective cost control measures were, developed for each of the three major project development cycle phases; namely: the conception/planning/designing, implementation, and completion/commissioning phases. The research questionnaires which were formulated through expert group questionnaire test survey lists of cost overruns causal factors and cost control remedial measures were circulated to a wide range of practicing professionals. In addition, a representative number of case study projects, with specific reference to cost overruns and cost control, were selected for detailed investigation. Three statistical data analytical methods; the respondents ‘s cost overrun factor/cost control measures ranking order, the Kendell’s Correlation Coefficient and the case study analysis, were simultaneously (triangulation analysis), employed in order to draw conclusive results of the research findings. Hence, the result of the survey identified: i) the most frequent cost overrun causal factors; as inadequate project brief, insufficient/inadequate project design, lack of project coordination and contractual claims and ii) the most effective cost control measures; as appointment of competent project personnel, improved project monitoring, awarding contracts to reputable/competent contractors and monitoring teams and providing time and financial management facilities. The third objective, which was to identify and apportion professional personnel responsibility for causal factors and remedial cost control implementation measures; within each of the three-project development cycle phases; yielded the following results: Clients and project managers were found to play a major contributory role in activities that lead to project cost overruns at conception/planning/designing phase. The project implementation phase allocated blame to contractors, architects and quantity surveyors for cost overruns, while quantity surveyors and contractors were found to be responsible for cost overruns at the completion/commissioning phase. On the implementation of effective remedial cost control measures, the professional responsibility scenario was found to be as follows: clients and project managers play a major role at conception/planning/designing phase, whereas quantity surveyors are key players at implementation phase and project managers; at completion /commissioning phase.

South Africa is passing through a phase of transition and children living in the country are still subject to many social and financial problems. They face high levels of social adversity, socio-economic deprivation, migration, displacement and morbidity. Rural South African children’s right to education and physical and mental health remains unfulfilled because of exposure to on-going adversity including poverty, family disruption through labour migration, malnutrition, inter-personal violence, chronic illness and death of family members due to HIV/AIDS. Although numerous studies highlight psychosocial problems amongst these children in South Africa and even document risk factors, there is paucity of studies that have focused on rural children’s mental health with consideration to both protective and risk factors. The study is focused on primary school children aged 8-12 in grades 5 and 6. It examines the prevalence of psychosocial problems among these children and determines the socio-demographic factors which can serve as predictors of psychological outcomes in these children. The study looks at both risk factors and protective factors as predictors of said psychological outcomes.

MSc (Med), Biostatistics and Epidemiology, Faculty of Health Sciences, University of the Witwatersrand, 2009 / Introduction: Endometrial cancer is a gynaecological cancer that mostly affects women in their sixth and seventh decades of life. It is the fourth most common malignancy in women and ranks eighth among all causes of female cancer in terms of age-adjusted mortality. In developed and numerous developing countries endometrial cancer, as well as other types of cancer in women, is an ever-increasing threat that may be explained, among other reasons, by increased life expectancy and a reduction in fertility or birth rates. Conversely, in South Africa and most other African countries, the previous reasons do not exist, because there is a decline in life expectancy due to increased HIV, low income, and a high fertility rate. International epidemiological studies have established significant relationships between endometrial cancer and risk factors such as the woman’s age, race, early menarche and late menopause, parity, a history of breast or ovarian cancer, the use of endogenous estrogens, concomitant diabetes, family history of breast and ovarian cancer, estrogen therapy, obesity, and the use of tamoxifen. The aim of the study was to identify risk factors associated with endometrial cancer among black South African women. Method: The present case control study comprised black South African women diagnosed with a cancer in Johannesburg, between 1995 and 2005. The study included 592 women aged 27 to 90 years who were admitted to three main public hospitals in the city of Johannesburg with histologically confirmed cancers. 148 cases with endometrial cancer and 444 women with other forms of cancer were analysed. Only newly occurring cases (incident) were included. Women in the control group consisted of those with V cancers not associated with reproductive or hormonal factors, i.e. not cancers of the breast or the female reproductive system. Data handling, cleaning and analysis were done using Stata 9 (STATA). Results: Univariate analysis showed that the risk for endometrial cancer was significantly (P<0.05) affected by: miscarriages, the place of former residence, place of current residence, the use of snuff, wine consumption, age of the youngest child, diabetes, age of menarche, age of menopause, and menstrual status. Smoking was found to be a protective factor for endometrial cancer compared to other cancers. After multivariate adjustment, endometrial cancer risk was significantly (P<0, 05) associated with miscarriages, age at menarche, and earlier completion of childbearing. Smoking remained a protective factor against endometrial cancer. Conclusion: The current study reports similar results to those observed in other international investigations. The risk of endometrial cancer was higher among women who were older, women who experienced miscarriages, and those who fell pregnant early in their reproductive lives. Smoking was a protective factor against endometrial cancer compared to other cancers. However, comparing the cases of endometrial cancer with smoking-associated cancer controls (i.e. lung cancer, oesophageal cancer, and mouth cancer) might have distorted the results. A more appropriate control group for confirming the relationship between smoking and endometrial cancer would be subjects with no cancer. Also, it will be important to evaluate the risk factors for cancer among the other race groups in South Africa.

MSc (Med), Population-Based Field Epidemiology, Faculty of Health Sciences, University of the Witwatersrand / Background Complications of childbirth and pregnancy are leading causes of death among women of reproductive age. Worldwide, developing countries account for ninety-nine percent of maternal deaths. The United Nations’ fifth millennium development goal (MDG-5) is to reduce maternal mortality ratio by three fourths by 2015. Aim The aim of this study is to explore the levels, trends, causes and risk factors associated with maternal mortality as put forward by World Health Organization (WHO) in rural settings of Tanzania. Specific objectives To establish the trend of maternal mortality ratios in Rufiji health and demographic surveillance system (RHDSS) during the period 2002-2006. To determine the main causes of maternal deaths in RHDSS during the period 2002-2006. To determine the risk factors associated with maternal mortality RHDSS during the period 2002-2006. Method Secondary data analysis based on the longitudinal database from Rufiji Health and Demographic Surveillance System was used to study the risk factors and causes of maternal death. Data for a period of 5 years between 2002-2006 was used. A total of 26 427 women v aged 15-49 years were included in the study; 64 died and there were 15 548 live births. Cox proportional hazards regression was used to assess the risk factors associated with maternal deaths. Results Maternal mortality ratio was 412 per 100 000 live births. The main causes of death were haemorrhage (28%), eclampsia (19%) and puerperal sepsis (8%). Maternal age and marital status were associated with maternal mortality. An increased risk of 154% for maternal death was found for women aged 30-39 versus 15-19 years (HR=2.54, 95% CI=1.001- 6.445). Married women had a protective effect of 62% over unmarried ones (HR=0.38, 95% CI=0.176-0.839). These findings were statistically significant at the 5% level. Conclusion This analysis reinforced previous findings pointing to the fact that haemorrhage and eclampsia are the leading causes of maternal mortality in Tanzania and other developing countries. This indicates the need for better antenatal and obstetric care, particularly for women over thirty years of age, as well as implementing health care delivery strategies according to the regional specific risk factors of maternal deaths and not the global factors.

MSc (Med), Popualtion-Based Field Epidemiology, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand / Background Improving the health of the poor and reducing health inequalities between the poor and non-poor has become central goals of international organizations like the World Bank and WHO as well as, national governments in the contexts of their domestic policies and development assistance programmes. There are also unquantified and poorly understood inequalities in access to health services within and between various population groups. Little is known about the factors that determine these inequalities and the mechanisms through which they operate in various sub-groups. Objectives The aim of the study was first to describe under-five mortality trend according to wealth index; second to describe risk factors for under five mortality; and finally to investigate the relationship between socio-economic and demographic factors and under five mortality during the period 2001 to 2006. Methods The study involved all children born in 2001-2006. A total of 22,422 children younger than 5 years were found in 21,494 households yielding 36603.13 Person-Years Observed (PYOs) up to 31st December 2006. Household wealth index was constructed by use of Principal Component Analysis (PCA), as a proxy measure of each household SES. From this index households were categorized into five quintiles (i.e., poorest, poorer, poor, less poor and least poor). Life table estimates were used to estimate mortality rates per 1000 PYO for infants (0-1), childhood (1-5) and underfives children. Health inequality was measured by poorest to least poor mortality rate ratio and by computing mortality concentration indices. Trend test chi-square was used to determine significance in gradient of mortality rates across wealth index quintiles. Risk factors of child mortality were assessed by the use of Cox proportional hazard regression taking into account potential confounders. v Results The result indicates unexpected low mortality rate for infant (33.4 per 1,000 PYO, 95% CI (30.4 – 35.6)) and childhood (15.0 per 1,000 PYO, 95% CI (13.9 – 16.3)). Under-five mortality rate was 18.2 per 1,000 PYO (95% CI (75.6 – 108.0)). The poorest to least poor ratios were 1.1, 1.5 and 1.5 for infants, childhood, and under-five year olds respectively, indicating that children in the poorest quintile were more likely to die as compared to those in the least poor household. Computed values for concentration indices were negative (infant C= -0.02, children C= -0.09 and underfive C= -0.04) indicating a disproportionate concentration of under-five mortality among the poor. The mortality rates trend test chi-square across wealth index quintiles were significant for both childhood (P=0.004) and under-five year old children (P<0.005) but not for infants (P=0.134). In univariate Cox proportional hazard regression, children in the least poor households were shown to have a 35% reduced risks of dying as compared to children in the poorest category [crude H.R =0.65, P=0.001, 95% C.I (0.50 – 0.84)]. The results showed that for under five children, a boy is 1.15 times more likely to die as compared to a girl [crude H.R =1.14, P=0.038, 95% C.I (1.00 - 1.31)]. Second born had a 18% reduced risk of dying as compared to first born [crude H.R =0.82, P=0.048, 95% C.I (0.67 – 0.99)]. After controlling for potential confounders, the adjusted hazard ratio for wealth index decreased slightly. The estimated hazard for wealth index in the univariate was 0.65 while in the multivariate modeling the estimated hazard ratio is 0.60 in the first model. Conclusion The study shows that household socio-economic inequality is associated with underfive mortality in the Navrongo DSS area. The findings suggest that reductions in infant, childhood, and under five mortalities are mainly conditional in health and education interventions as well as socioeconomic position of households. The findings further call for more pragmatic strategies or approaches for reducing health inequalities. These could include reforms in the health sector to provide more equitable resource allocation. Improvement in the quality of the health services offered to the poor and redesigning interventions and their delivery to ensure they are more inclined to the poor.

Thesis advisor: Katherine L. McNeill / Reform movements in science education have repeatedly called for more dialogic and student-centered discussions during science lessons. The approach secondary science teachers take towards talk during whole-class discussions continues to be predominantly teacher-centered even when curriculum materials are designed to support a shift in discourse. This dissertation explores what factors may be influencing the approach that both teachers and students take towards whole-class discussions in order to understand why the type of talk that occurs in high school science lessons is not changing. In order to achieve a more comprehensive understanding of this issue, this dissertation made use of mixed methodology. To explore secondary science teachers' beliefs in general, responses to a statewide survey of science teachers (N=185) were analyzed statistically to investigate factors that were related to their efficacy beliefs about whole-class discussions, as well as their beliefs about the effectiveness of dialogic and authoritative approaches to bring about learning in students. Acknowledging that discursive interactions are context dependent, a case study of a high school chemistry teacher and her students (N=45) was also included which examined both the teacher's and her students' beliefs as well as how those beliefs manifested themselves during instruction. Findings suggest that although teachers believe that a dialogic approach to whole-class discussions is more important for student learning than an authoritative approach, lower self-efficacy for engaging in dialogic talk is related to limited opportunities teachers have to learn and recognize alternative strategies that can be used to shift talk during whole-class discussions. Furthermore, school and student characteristics may play a role in teachers' beliefs about the effectiveness of dialogic talk as an approach to learning science. The teachers' role is only one part of the interaction, however. This dissertation also shows that secondary students have beliefs and expectations about whole-class discussions that also influence the type of discourse that can occur. Changing the type of talk that occurs in high school science classes will require not only professional development about talk strategies for teachers, but also a shift in how students frame their role in discussions and the purpose of talk in learning science. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Lynch School of Education. / Discipline: Teacher Education, Special Education, Curriculum and Instruction.

The types of intrusion errors (Prior List, Semantically Related, and Unrelated) made on the LASSI-L verbal memory task were compared across three diagnostic groups (N = 160, 61 % female), Cognitively Normal (CN), amnestic Mild Cognitive Impairment (aMCI), and Alzheimer’s disease (AD). Errors related to Proactive, Recovery from Proactive, and Retroactive Interference were also analyzed, as well as the relationship of errors to Amyloid load, a biomarker of AD. Results suggest that the types of error made indicated the level of cognitive decline. It appears that as deficits increase, impaired semantic networks result in the simultaneous activation of items that are semantically related to LASSI-L words. In the aMCI group, providing a semantic cue resulted in an increased production of Semantically Related intrusions. Unrelated intrusions occurred rarely, although, a small number occurred even in the CN group, warranting further investigation. Amyloid load correlated with all intrusion errors. / Includes bibliography. / Thesis (M.A.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

The pioneering work of Ödegaard (1932) was the first to link migration and schizophrenia by reporting rates in Norwegian immigrants in Minnesota as twice that of native Minnesotans and of Norwegians in Norway. However, only in recent decades has an interest in migration and schizophrenia been rekindled as a result of reports of elevated rates of schizophrenia in Afro-Caribbean immigrants in the United Kingdom in the mid- 1960s (Hutchinson & Haasen, 2004). Later studies reported elevated rates in secondgeneration Afro-Caribbean immigrants compared to first-generation (Harrison, Owens, Holton, Neilson, & Boot, 1988). In the United States, Blacks were diagnosed with schizophrenia 2.4 times more often than Whites (Olbert, Nagendra, & Buck, 2018). However, mental health researchers in the United States generally combine all individuals of African descent as African- Americans. This practice obscures the nuances of culture and ethnicity within the Black subgroups as well as the immigrant status of Afro-Caribbeans. This research focused on the Afro-Caribbean immigrants and factors that predict risk for schizophrenia within this population. The process of migration is a complex enterprise that produces stressors and challenges, the effects of which are multifaceted. The social and environmental forces that parallel the process of migration may predispose individuals to severe psychiatric disorders such as schizophrenia. Socio-political dynamics in the host country that marginalize others of different cultural and/or racial persuasions can compound the negative effects of post-migration. Therefore, migration is considered a social determinant of health. Empirical evidence has substantiated that socio-environmental factors such as urbanicity, discrimination or socio-economic deprivation, social support, and goal striving stress are potential contributing factors to the development of psychotic disorders in immigrants. Moreover, evidence has supported that the darker the skin color of the immigrant the greater the risk (Cantor-Graae, 2007). The findings of this study confirmed that for Afro-Caribbean immigrants stressors in the post-migration phase such as discrimination, limited social support, and economic hardship that can be compounded by the number of dependent children were identified as possible predictors of risk for schizophrenia. This risk increased with length of residency and continued into the second-generation. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

Regulation of gene expression in a spatiotemporal manner specifies cellular identity. Transcription factors (TFs) bind to DNA regulatory elements to remodel chromosome structure, to recruit transcription machinery to initiate gene transcription or to prevent the assembly of such machinery to repress gene transcription, thus they lie at the heart of gene regulation. Given important roles of TFs in gene regulation, numerous attentions have been attracted for engineered transcription factors (eTFs). The recent advance of generating customized DNA-sequence specific binding domains, including transcription activator-like effectors (TALEs) and RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) gene Cas9, has greatly accelerated the study and application of eTFs. The eTFs with these new binding domains offer a powerful and precise approach for modulating gene expression. / Oct4 is an important TF and it plays essential roles in the formation of inner cell mass during embryogenesis, and the maintenance of embryonic stem cells in culture as well as the reinstatement of cellular pluripotency from somatic cells. / In this study, we systematically investigated the potential of TALE-TFs and CRISPR/Cas9-TFs in activating Oct4. We designed a number of TALEs and small guide RNAs (sgRNAs) targeting various regions in the mouse and human Oct4 promoters. Using luciferase assays, we found that the most efficient TALE-VP64s bound on the region −120 to −80 bp upstream of transcription start site (TSS), while highly effective sgRNAs targeted −147 to −89 bp upstream of TSS to induce high activity of luciferase reporters. This positional effect can serve as a simple guideline for designing eTFs for activating transcription from a reporter system. Next, we examined the potential of TALE-VP64 and sgRNAs to activate endogenous Oct4 transcription. We found that the positional effect was less obvious as individual eTFs exhibited marginal activity to up-regulate endogenous gene expression. Interestingly, we found that when multiple eTFs were applied simultaneously, Oct4 could be induced significantly and synergistically. This phenomenon was well supported by activation of human SOX2, KLF4, cMYC, CDH1 and NANOG by TALE-VP64s. / Using optimized combinations of TALE-VP64s, we successfully enhanced endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64- and sgRNA/dCas9-VP64-induced transcription of endogenous OCT4. Taken together, this study demonstrated that engineered TALE-TFs and dCas9-TFs are useful tools for modulating gene expression in mammalian cells. / 基因表達調控是決定細胞命運的關鍵。轉錄因子可以結合到DNA調控序列上，以重塑染色體的結構；而且可以募集轉錄機器，以起始轉錄, 或者幹擾轉錄機器的組裝，從而抑制基因轉錄；因此，在基因表達調控過程中轉錄因子處於核心地位。由于轉錄因子在基因調控方面的重要作用，研究者們越來越多的關注人工轉錄因子的研究。DNA 序列特異性結合域的發現與發展很大程度上促進了人工轉錄因子的研究與應用。最近從TALE和CRISPR/Cas9衍生而來的人工轉錄因子給我們提供了一個強大而且精確的調控基因表達的方法。Oct4是一個重要的轉錄因子，對胚胎發育過程中內細胞團的形成，和體外培養的胚胎幹細胞的維持，以及細胞多能性的重塑等多方面都至關重要。 / 在本研究中，我們系統性地探討了TALE和CRISPR/Cas9衍生而來的人工轉錄因子在激活Oct4基因方面的潛能。我們針對小鼠和人的Oct4的啓動子設計了一序列的TALEs和sgRNAs。通過熒光素酶實驗，我們發現結合到轉錄起始位點上遊120‐80bp位置的TALE‐VP64s，或者結合到147‐89bp位置的sgRNAs可以最有效地誘導熒光素酶報告基因的表達。在激活報告基因方面，這種位置效應可以作爲一條設計人工轉錄因子的簡單原則。然後，我們進一步檢測了這些人工轉錄因子在激活內源性Oct4轉錄方面的效果。結果顯示上述觀察到的位置效應並不明顯，因爲每一單個的人工轉錄因子都幾乎不能上調內源性基因的表達。但是，當同時導入多個人工轉錄因子時，我們可以顯著地激活Oct4的表達，而且可以觀察到明顯的疊加效應。利用人工轉錄因子激活SOX2, KLF4, cMYC, CDH1和NANOG,我們進一步證明了這種疊加效應。 / 通過篩查不同的人工轉錄因子組合，我們在小鼠NIH3T3細胞系把Oct4基因的表達提供到了原來水平的30多倍，而在人的HEK293T中，提高了20多倍。更重要的是，我們可以檢測到蛋白質表達水平的提高。通過檢測不同的表觀調控因子，我們發現組蛋白乙酰化轉移酶p300可以進一步提升這些人工轉錄因子誘導的Oct4基因表達。因此，本研究表明這些人工轉錄因子是調節哺乳動物細胞內基因表達的有效工具。 / Hu, Jiabiao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014.y066 / Includes bibliographical references (leaves 132-157). / Abstracts also in Chinese. / Title from PDF title page (viewed on 13, December, 2016). / Hu, Jiabiao. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.