Includes bibliographical references.

Urban agriculture has been advocated by NGOs and development agencies as being a food security strategy, and an effective poverty alleviation measure. This view is reflected within the City of Cape Town, as the City's 2007 Urban Agriculture Policy illustrates. Since the initiation of the Policy, many urban agriculture projects have been established by the local government in the low income areas of Cape Town. The urban agriculture projects set up in the townships of Du Noon and Joe Slovo Park are two of the projects established by the city. While these projects have provided primary livelihoods for some participants, the City has expressed concern regarding the age demographic of this practice, as a lack of youth involvement is noticed. Academic literature within this discourse highlights a gap in knowledge concerning the urban youth, and this increases the importance of understanding why the younger generation is hesitant to partake in this activity. The main aim of the study is to explore two City established urban agriculture projects, one in which youth involvement is visible, whilst in the other it is not. The study interrogates whether there are any barriers which could prevent the youth from participating within this activity. The City of Cape Town's Urban Agriculture Policy and projects were examined in order to explore how they engage with urban agriculture, and in turn how they understand the youth and their lived experience. In addition, the existing urban farmers' perceptions of the youth were examined in order to explore what role these perceptions play in youth involvement. Lastly, the study narrowed its focus onto the youth themselves in an attempt to understand their own opinions of urban agriculture, and explore what underlies these perceptions.

Small-animal imaging has been widely implemented to study succession of disease, therapeutic treatments and the effects of environmental insults. The gold standard noninvasive technique for following progression of heart failure in small-animal models is magnetic resonance imaging (MRI). The aim of this project was to adapt a clinical MRI system to perform small-animal cardiac MRI. The first part of the thesis describes the adaptations required, which included design and construction of a small-animal radiofrequency (RF) coil, physical support (cradle), a core body temperature regulation system, and optimization of pulse sequences. The system was validated using a phantom and in-vivo in 5 healthy rats. The signal-to-noise ratio (SNR) in the phantom was 91% higher using the small-animal coil compared to the standard head coil. SNRs of 7 ± 2 and 18.9 ± 0.6 were achieved in myocardium and blood, respectively, in healthy rats and MR left ventricular mass (LVM) was highly correlated with (r=0.87) with post-mortem mass. In the second part of the study, left ventricular remodeling (LVR) was investigated in a nonreperfused model of myocardial infarction (MI) in 5 sham and 7 infarcted rats. Rats were scanned at 2 and 4 weeks post surgery to allow for global and regional functional and structural analyses of the heart. Images were of sufficient quality to enable semi-automatic segmentation using Segment. Significant increase in end-systolic volume (ESV) was observed in MI rats at 2 weeks post surgery. At 4 weeks post surgery, end-diastolic volume (EDV) and ESV of MI rats were significantly higher than in sham rats. Ejection fraction (EF) of MI rats dropped significantly at 2 weeks and a further significant drop was observed at 4 weeks indicating contractile dysfunction. Wall thickness (WTh) analyses in MI rats at 4 weeks revealed significant reduction in end-diastolic (ED) wall thickness in the anterior region due to necrosis of myocytes. In the posterior region, WTh was significantly higher due to LV hypertrophy. At end-systole (ES), the MI rats revealed significant decrease in WTh in the anterior and lateral regions. MI rats suffered reduction in systolic wall thickening in all regions of the heart, indicating global contractile dysfunction.

Imaging the fetal brain in utero is challenging due to the unpredictable motion of the fetus. Although ultra-fast MRI sequences are able to image a 2D slice in under a second, thus limiting the time in which fetal motion can corrupt images, Cartesian sampling makes these sequences sensitive to signal misregistration and motion-corruption. Corruption of a single 2D slice renders it impossible to reconstruct 3D volumes from these slices without complex slice-to-volume registration. There is a need for motion-robust sequences that can produce high-resolution 3D volumes of the fetal brain. The Siemens Cardiovascular sequence was edited to produce a new radial readout that sampled a 3D spherical volume of k-space with successive diametric spokes. The diameter end points map a spiral trajectory on the surface of a sphere. The trajectory was modified so that multiple sub-volumes of data are sampled during a single acquisition where M is the number of sub-spirals and N is the number of diametric spokes per sub-spiral. This allows reconstruction of individual sub-volumes of data to produce a series of low-resolution navigator images that can be co-registered to provide information on motion during the acquisition. In this way, a segmented sequence suited to self-navigation was developed. Imaging parameters for the 3D radial sequence were optimised based on theoretical calculations and scans performed in adult brains and abdomens. Optimum values for M and N needed to be determined. Increasing M for a constant total number of projections improves the temporal accuracy of motion tracking at the expense of decreased signal to noise ratio in the navigator images. The effects of breathing and rigid body motion on image quality were also compared between 3D radial and equivalent 3D Cartesian acquisitions. Custom reconstruction code was written to separate the incoming scan data according to the sub-spiral trajectories described within the sequence such that individual navigator images could be reconstructed. Successive sub-spiral images were co-registered to the first navigator image to quantify motion during the acquisition. The resulting transformation matrices were then applied to each sub-spiral image after reconstruction and co-registered sub-spiral images combined in image space to generate the final 3D volume. To improve the quality of navigator images, a method is presented to perform navigator image reconstruction at a lower base resolution, thus reducing streaking artifacts and improving the accuracy of image co-registrations. Finally, the methods developed were applied to two fetal scans. The radial sequence was shown to be more motion-robust than an equivalent Cartesian sequence. The minimum number of diametric spokes that provided navigator images that could be accurately co-registered when scanning an adult brain was N=256, which could be acquired in 1.25 s. For abdominal scans, the minimum number of spokes was N=1024, which could be acquired in about 6 s when water excitation is applied. However, the latter could potentially be reduced by reconstructing navigator images at a lower base resolution. Although fetal scans demonstrated poor image contrast, navigator images were able to track motion during the acquisition demonstrating the potential use of this method for self-navigation. In conclusion, a motion-robust radial sequence is presented with potential applications for prospective navigation during fetal MRI.

INTRODUCTION: Breast cancer makes up 25% of all cancers diagnosed worldwide. Despite an increasing yearly incidence, there has been a significant decrease in mortality owing to early diagnosis and advances in treatment. Anthracycline-based chemotherapy is a relatively low cost yet highly effective anti-cancer treatment, increasing survival from 30% to >80%, presently. However, treatment efficacy is marred by the increased risk of anthracycline-induced cardiotoxicity (ACT) - estimated at 10-26%. Internationally, there has been evidence of ACT having a genetic basis. Currently in South Africa, there is little information on ACT in cancer patients and survivors, and no information on the genetic basis of this phenomenon. Our recruitment sites in Cape Town - Groote Schuur Hospital (GSH) and Tygerberg Hospital (TBH), routinely treat hundreds of patients, notably with breast cancer, with anthracycline-based therapy every year, and provided the environment to assess ACT, as well as genetic factors which may influence this adverse drug reaction. Left ventricular ejection fraction (LVEF) acts as a surrogate measure of cardiac function in the public health-care setting. OBJECTIVES: To provide insight into the clinical management of breast cancer patients on anthracycline-based treatment with a focus on the prevalence of ACT. To provide an index of genetic susceptibility to ACT and potentially contribute to a personalized medicine approach for a genetically diverse population. METHODOLOGY: In the retrospective part of the study, the clinical records of cancer patients treated with anthracyclines from 2011- 2016 at the Oncology Clinic at GSH were analysed. Clinical co-morbidities such as hypertension, diabetes, pre-existing cardiac disease and smoking as well as type and dose of anthracyclines, cardiac function and patient status were assessed. In the prospective study, breast cancer patients treated with anthracyclines, with a pre and post-treatment LVEF measure were recruited at GSH and TBH from 2013 to 2016. Patients were consented for access to both clinical information and biological material. Demographics, clinical risk factors and chemotherapeutic regimen data were analysed. LVEF, biomarkers and clinical status were also assessed in terms of reflecting ACT. In some instances certain clinical information was not available (i.e. LVEF) and out of necessity, a statistical correlation model or classifier was created in order to use available clinical data to derive missing clinical measures. Patients' DNA were analysed for seven genetic variants in the following six genes ABCC1 (rs246221); ABCC2 (rs17222723; rs8187710); HNMT (rs17583889); NCF4 (rs1883112): RAC2 (rs13058338) and RARG (rs2229774), and tested for correlation with clinical status and cardiac injury. Finally, a corollary study was conducted on a subset of patients in an attempt to determine whether cardiac biomarkers may be more sensitive measures of cardiotoxicity. RESULTS & DISCUSSION: In the retrospective cohort (n=402) 19.7% of patients showed diminished cardiac function. Logistic regression showed that the following predictors: type of first line chemotherapy, and total dose significantly contributed to the ACT phenotype as measured by change in LVEF. In the prospective patients (n=272), 14% were affected with ACT, with an increased likelihood of cardiotoxicity in the Indigenous African population. Logistic regression showed that both total anthracycline dose and change in LVEF were predictive of ACT. In the association study of prospective patients, only the RARG rs2229774 variant was significantly associated with patient ACT status (p=0.049, Chi-Square Test). Forty-two patients were assessed for the β-Natriuretic Peptide (BNP) biomarker and showed limited utility in correlating clinical status and/or LVEF decrease in all patients except Indigenous Africans indicating potential increased susceptibility of population group to ACT. LVEF was found to be unreliable as significant LVEF decreases did not always correlate with cardiac impairment and vice-versa. Changes in routine clinical patient management and overburdening of the nuclear medicine department also translated to only one LVEF measure being obtained in some instances. The statistically derived classifier for missing indicators of heart function was useful, but will require refinement. CONCLUSIONS AND RECOMMENDATIONS: Despite the inability of genotype as a predictor of ACT in this study, the increased susceptibility in the Indigenous African population to ACT as well as increased BNP levels after chemotherapy requires a closer look. The interrogation of lndigenous African patient genomes for novel variants of susceptibility to ACT are recommended; this requires building up of a substantial cohort from this population group, which would likely require collaboration with health care institutions in one of the other provinces of South Africa e.g. Eastern Cape, KwaZulu-Natal and/or Gauteng. Both this study and literature recommend the need for clinical trials for new and existing drugs on local African populations for both safety and efficacy. Furthermore, the BNP biomarker may be better suited to the prediction of irreversible cardiac damage rather than early cardiotoxicity. Troponin, released in response to cardiomyocyte death, may be a more sensitive biomarker in predicting ACT. Similarly, the inherent variability and lack of sensitivity of LVEF as a measure of cardiac function warrants the consideration of alternatives such as echocardiography or tissue-doppler imaging. Findings derived from this study indicate the need for refined patient management of ACT in a South African population to potentially allow for treatment with minimised risk and event-free breast cancer survival.

Includes bibliographical references (leaves 61-69). / Community participation has become a key concept in research on the development and governance of underprivileged communities. It is on these grounds that the post-apartheid South African government has encouraged meaningful participation between local communities and the state, particularly through structures of local government. However, the role that street committees can play in the realisation of this ideal has received little attention from either government or academic scholars. For this reason, this study examines the role that the street committee in Waterworks, Grabouw, in the Western Cape plays in community governance. It analyses data from a qualitative study which took place between 2007 and 2008. In this thesis I argue that while the street committee has a role to play in the governance of the community, that role is limited by their lack of power. The street committee is not a statutory body and this hinders their ability to participate in local government issues. Despite these restrictions, the street committee in Waterworks was largely perceived by the local residents as doing their best in addressing pertinent issues. However, there were some who accused members of the street committee of nepotism and seeking political patronage.

Includes bibliographical references (leaves 106-116). / Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by the expansion of a CAG repeat within the ataxin-7 gene. The South African SCA7 population has been shown to have arisen due to a founder effect, and a single nucleotide polymorphism (SNP) within ataxin-7 has been linked to the SCA7 mutation in all South African patients genotyped to date. Recently, this SNP has been exploited in a potential allele-specific RNA interference (RNAi) based therapy, in order to knock down the expression of the mutant transcript in heterozygous patients. Although this approach has been tested in an artificial cellbased model of SCA7, focus has shifted towards testing the therapy in SCA7 patient-derived transformed lymphoblast cell lines

Background Chronic Kidney Disease (CKD), has a high and increasing burden in sub-Saharan Africa. Environmental factors that have been associated to CKD are associated with multiple co-morbidities such as hypertension, diabetes, and HIV. Some genetics factors such APOL1 have been associated with the highest burden of CKD among population of African ancestries. Other emerging genetic factors such as Sickle Cell trait (SCT) have been investigated mostly among African Americans. Sickle Cell trait (SCT) has the highest burden in sub-Saharan Africans, because of a natural selection, attributed to its protective advantages against the severest form of Malaria, caused by Plasmodium falciparum. Many studies showed that SCT has an impact on the normal functioning of the kidneys among African Americans with some studies indicating significant association between SCT and CKD. However, no study has been reported from Sub-Saharan Africa, where most SCT carrier reside. Moreover, there are multiple other loci and variants in the genome that have been associated with CKD in many populations, and that are used for Polygenic Risk Score (PRS) models but have not been explored in populations living in Africa. Aims This project aimed to study in a sub-Saharan African cohort, the association between 1) Sickle cell trait (SCT) with Chronic Kidney disease (CKD), and 2) the association of CKD with 29 targeted single nucleotide polymorphisms (SNPs) identified in multiple Genome-Wide Association studies (GWAS). Methods Patients and controls: 300 Cameroonian adult participants were included: 150 CKD cases and 150 non-CKD age, sex, and comorbidities matched controls. Molecular methods: SCT heterozygosity was determined by RFLP-PCR using the restriction enzyme DdeI. A total of 29 targeted SNPs was genotyped using MassArray and TaqMan techniques, followed by Sanger sequencing in a subset of samples. 11 Statistical Analysis: Descriptive statistics and logistic regression, and Fisher exact test were used. Functional pathway analysis: following the identification SNPs with significant association with CKD, we performed functional pathway test using the Linux programme Cytoscape. Results The mean age of cases was 53 years (range 46-55 years), with 43% that were female; there were no age and sex significant differences with controls. We identified, an expected, association between CKD and various co-morbidities, demographic and anthropometric variables: hypertension (p value = 5.16X10-9 ), HIV (p value = 2.68x10- 9 ), diabetes (p value = 7.12X10-7 ), BMI (p value = 4.58X10-8 ) and age (p value = 4.5X10-8 ). HbAS carrier status was significantly associated CKD (p value= 4.3X10-9 ; Odds Ratio:7.05). Only three targeted SNPs (3/29) previously associated with CKD in GWAS among African Americans, European and Asian population, were significantly associated with CKD among this group of Cameroonians (KBTBD2 rs3750082, PTPRO rs7956634 and LPR2 rs4667594 with p values of 0.02335, 0.0408 and 0.0398). Genes protein-protein interactions analysis identified the two key functional pathways and one network cluster that could play a crucial role in kidney dysfunctions. Lastly, we distinguished that HbS carrier state doesn’t influence the relationship between APOL1 G1/G2 risk alleles and CKD (p value = 0.5725) in this group from subSaharan Africans. Conclusion and perspectives Our study illustrates a strong association between SCT and CKD, an important discovery that will have a major implication in preventative medicine policies and practices in both sub-Saharan African where there is a very high prevalence of SCT. The data also has global resonance, with the projected increase in the prevalence of 12 individual with SCT, due to migration and the improve life expectancy and genetic fitness of people living with both SCT and SCD. We identified a relatively low proportion of (3/29) of target SNPs positively associated with CKD among this group of Cameroonians. The study illustrates that the vast majority of targeted SNPs associated with CKD in GWAS studies in multiple populations including African American, Europeans, and Asians, are not relevant for sub-Saharan Africans, indicating the urgent need to include diverse populations, specifically those living in Africa. Therefore, the data support the possible bias in currently available Polygenic Risk Score generated from GWAS data, where population from sub-Saharan Africa are largely underrepresented. The data further indicate that there is potential to discover new loci associated with CKD when investigating populations of African ancestry living in Africa.

This dissertation examines the plight of children in street situations in Tanzania. It also examines the obligations the State owes to children in street situations, what it has done to fulfil those obligations. It analyses the effectiveness and impact of the steps and actions undertaken to fulfil the obligations towards children in street situations.

Includes bibliographical references (leaves 118-132). / Spinocerebellar ataxia 1 (SCA1) is part of a broader group of dominant neurodegenerative disorders caused by an unstable CAG trinucleotide repeat. There is no known cure for this disease and symptoms worsen progressively culminating in death. The disease-causing mutation in SCA1 occurs in the ATXN1 gene. The function of the gene product (the ataxin-1 protein) is unknown, however; the protein has been linked to RNA processing in the cell. The first part of this study followed on a 1997 report of two founder haplotypes in the Mixed Ancestry SCA1 families in the Western Cape of South Africa, using microsatellites. The aim was to narrow the region investigated in the previous study, and confirm the existence of founder haplotypes using a SNP-based haplotype. The SNPbased haplotype was constructed using 4 SNPs in individuals from 5 different families of Mixed Ancestry origin from the Western Cape and the two founder events were confirmed. The SNP-based haplotype also shows the existence of a minimum common interval and indicates regions of possible break-points which may be useful in determining the extent and origins of the two haplotypes. The second aim of the study was to preferentially silence the mutant transcript of the ATXN1 gene by targeting a single nucleotide difference. Two of the SNPs genotyped for the SNP-based haplotype were found to be heterozygous in over half of the patient cohort. Eight shRNA effector molecules were screened against short target sequences incorporating one of these SNPs. Results are promising, with significant discrimination achieved between the wild-type and mutant alleles by targeting this SNP. This study has shown that RNAi may be developed as a beneficial therapeutic technique for a subset of SCA1 patients in South Africa.