Ngoepe and Ventikos have developed one of a growing number of computational models of thrombosis of cerebral aneurysms designed with consideration towards clinical use and research. Their model, amongst many others, utilizes computationally inexpensive steady flow conditions. However, pulsatile flow better characterizes blood flow in-vivo. Steady flow is an acceptable approximation of pulsatile flow from a fluid dynamics perspective, but there is no prior evidence suggesting whether it is an acceptable approximation when considering clot formation within a flowing environment. To this end a pulsatile flow model has been created in ANSYS® Fluent, and a function from Ngoepe and Ventikos’s computational model that simulates the release of thrombin, a chemical responsible for clotting activation, has been implemented. The output of this simulation is compared to the output of an otherwise identical simulation utilizing Particle-Image-Velocimetry (PIV) validated steady flow conditions, to determine whether clotting outcome of Ngoepe and Ventikos’s model, amongst others, differs with pulsatile flow This experiment revealed that the concentration of thrombin required for clotting activation is generated in nearly half the time when utilizing pulsatile flow over steady flow. Pulsatile flow creates unsteady flow patterns within the aneurysm, which create an environment where less thrombin is carried out of the aneurysm and into the regular bloodstream. This indicates that steady flow approximations for realistic clotting in computational models of thrombosis of cerebral aneurysms without strong consideration for the effects of pulsatile flow are inaccurate.

Dyslipidaemia is a commonly encountered clinical condition and is a major risk factor for cardiovascular diseases. Although there are many factors associated with dyslipidaemia, a strong genetic component is evident. Apolipoprotein E (APOE), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cholesteryl ester transfer protein (CETP) are key regulators of plasma cholesterol levels. Thus, genetic variation in the genes coding for these proteins contributes to dyslipidaemia. In this study, a cohort of black South African Type 2 Diabetes Mellitus (T2DM) patients was characterized for mutations in genes coding for APOE, PCSK9, and CETP, and the possible effects of these variants on their lipid profiles was evaluated. Participants (n=417) were recruited from the Chris Hani Baragwaneth Hospital Diabetes Clinic, Johannesburg from whom blood samples were obtained for DNA extraction. The cohort was further stratified into two groups; individuals on statin treatment (Sim+, n=291), and the second that was not on treatment (Sim-, n=87). Lipid profiles were determined by enzymatic methods. DNA was genotyped for APOE, PCSK9, and CETP variants using PCRRFLP and Sanger sequencing. Analysis of the effects of the genetic variants was carried out in two ways. Firstly, for all the participants combined, and then by separating those on statin treatment from those without (Sim+ vs. Sim-). Genotype and allele frequencies were calculated followed by genotype-phenotype correlations with lipid profiles. Univariate analysis showed a significant association between the APOE4 isoform and lower HDL-c levels in the combined cohort (p=0.034). The effects were more pronounced in the Sim- group (p=0.004) but were absent in the Sim+ group. Contrary to above, APOE2 was significantly associated with lower total cholesterol (TC) (p< 0.001) and lower LDL-c (p< 0.001) when compared to APOE3 in the combined cohort. Upon analysing treatment groups, the correlations were observed in the Sim+ group (p=0.027 and p=0.003, respectively), while there were no observed correlations in the Sim- group. The CETP rs34065661C/G and G/G genotypes were significantly associated with increased HDL-c levels (p=0.017; when applying a dominant genetic model) in the combined cohort, as well as in the Sim+ group (p=0.026). Multivariate analysis, using a generalized linear model, confirmed associations between APOE rs429358C and lower HDL-c (OR=0.881, p=1.64e04), and APOE rs7412T and decreased LDL-c (OR=0.759, p=0.012). No significant associations were observed for PCSK9 polymorphisms. We report significant associations between APOE and CETP genetic variations and altered lipid levels in this black South African T2DM population. These genetic variants could be biomarkers for dyslipidaemia among Africans. However, it is imperative that the APOE, PCSK9, and CETP genes are fully characterized for additional polymorphisms in order to come up with a better genetic profile that explains the variance in lipid levels observed in the black South African population. The impact of these genetic variants could be relevant to other black African populations as well.

Bibliography: p. 400-445. / The aim of this thesis was to investigate the relationship between chronic exercise activity, aging, the neuromuscular system and the symptom of fatigue in a series of studies. The hypothesis of the thesis was that in contrast to the accepted dogma that exercise is beneficial to an individual, increasing longevity and improving quality of life, excessive or chronic exercise activity may accelerate the aging process, lead to neuromuscular damage, and cause the development of pathological symptoms or levels of fatigue.

The Optional Protocol to the International Covenant on Economic, Social and Cultural Rights (the 'Optional Protocol' or the 'OP-ICESCR') has recently been adopted by the General Assembly of the United Nations. This document establishes a new complaints procedure for economic, social and cultural rights ('ESCR') within the United Nations human rights system. Hence, those rights ' as it is already the case for civil and political rights (CPR) ' will become quasi-justiciable at international level. Once the Optional Protocol will enter into force, individuals and groups victims of violations of any right contained in the International Covenant on Economic, Social and Cultural Rights (the 'Covenant' or the 'ICESCR') will have the possibility to submit communications to the United Nations Committee on Economic, Social and Cultural Rights (the 'Committee' or the 'CESCR'), as long as the state concerned is party to the OP-ICESCR.

Includes bibliographical references.

Includes abstract. / Includes bibliographical references. / A patriarchal reading of the Qur'ānic verse 4:34 implies the subordination of wives to their husband within their families. The fundamental duty of the husband to support his wife materially has led to the entrenched notion of male protection of women. In exchange for such protection, the wife has the reciprocal duty of obedience to her husband, which may lead to the restriction of her right to work, amongst other rights. In contemporary societies where women are increasingly participating in the maintenance of the family, different interpretations of the verse are now becoming more influential than the patriarchal view. Allowing women access to equal opportunities on the labour market and to receive equal remuneration will not only contribute to the overall improvement of society but could also lead to the effective implementation of gender equality as required by international legal standards and religious doctrines.

Includes abstract. / Includes bibliographical references. / Host genetic variation is an important determinant of HIV infection, disease progression and HIV-associated neurocognitive deficits. However, there is no sufficient knowledge on the role of genetic variants especially among African populations. This study is focused on investigating variation in HIV/AIDS restriction genes; CCR2, CX3CR1, SDF1, RANTES, APOBEC3G and MBL2 and their possible role in HIV infection and neurocognitive function among children born to HIV infected mothers, recruited in Harare, Zimbabwe. A total of 116 children comprising of 73 perinatally exposed to HIV (34 who were born infected and 39 who were uninfected) and 43 unexposed controls were recruited in 2011(at ages 7-9 years) from a cohort of mother-baby pairs that has been followed up since 2002. The demographic characteristics of the recruited children were captured from their medical records. A McCarthy Scale of Children‟s Abilities (MSCA) was administered to determine each child‟s neurocognitive status. Genotyping for allelic variants was done using PCR-RFLP, SNaPshot® and Sanger DNA sequencing. Statistical analysis was carried out to determine association between genotypes, HIV status and neurocognitive function. The observation of different genetic variants or combinations of genotypes between the HIV-exposed and infected group and that of the HIV-exposed but uninfected group may be a pointer to critical pathways in differential HIV susceptibility. Exposure and infection with HIV is controlled by a multitude of genes/processes, thus, SNPs are unlikely to show statistically significant effects individually and may be more useful in a multifactorial model, as observed from comparisons of genotype combinations and haplotypes. The role of host genetic variation on neurocognitive function remains disputed but our observations suggest innate immune factors such as MBL2 may have a pronounced effect. Therefore, it may be possible to genotype for a suite of genes and use them as markers of either HIV susceptibility or neuro-developmental patterns.

Includes bibliographical references (p. 141-166).

Bibliography: leaves 161-191. / Cancer of the colon and rectum is the third-most common cause of death due to neoplasia in Western countries. Colorectal cancer (CRC) can broadly be divided into the hereditary, non-hereditary and sporadic forms. Hereditary cancers account for approximately 10% of the CRCs. Familial cancers can be divided into thos types in which polyps are a dominant feature (e.g. familal adenomatous polyposis-FAP) and the non-polypotic forms (e.g. hereditary nonpolyposis colorectal cancers-HNPCC).

Includes bibliographical references.