Background In 2010, 2.2 million adolescents were living with HIV (Human Immunodeficiency Virus) worldwide. This study aimed to describe the socio-demographic and clinical characteristics of the adolescents (10-19 years old) initiating anti-retroviral treatment (ART) and to investigate characteristics that are associated with virological failure in adolescents on ART. Methods This was an analysis of adolescents initiating ART from June 2004-2010 at the Hlabisa Treatment and Care Programme in KwaZulu-Natal, South Africa. Data was collected from two datasets at Africa Centre for Health and Population Studies. Time to outcomes of death and lost to follow up (LTFU) were quantified using Kaplan-Meier estimates. The outcome was virologic response (< 70copies/ml) after at least 6 months on ART and the associations with an unsuppressed viral load were investigated using multivariable logistic regression. Results 543 adolescents, median age 15 years (IQR 12-18), initiated ART; 67.8% (368) were females. Age at treatment initiation showed a bimodal distribution, with a peak at 11 years and another at 17-19 years; 61 females aged 16-19 years initiated ART whilst pregnant. At baseline, median CD4 count was 152 cells/μl (IQR 72-251), 392 (72.2%) had prior TB and 129 (23.8%) a weight-for-age z-score ≤ -2 (i.e. were under-nourished). Numbers of adolescents starting ART increased from 53 in the years 2004-2006 to 196 in 2010. Overall mortality was 36.5 per 1000 person years (95% CI 27.2 - 48.8); LTFU 98.8 per1000 person years (95% CI 82.8-118). Adjusting for age and gender, LTFU was significantly higher in females initiating in late adolescence (15-19 years) (p<0.001) and 24 (39.3%) of those initiating ART whilst pregnant were LTFU. The first viral load after initiation was taken at a median time of 11.25 months (IQR 7.78-16.20). Of the 364 adolescents with a viral load result after at least 6 months of ART, 119 (32.7%) had an unsuppressed viral load (95% CI 27.9- 37.5). Adolescents who initiated in the year 2010 were found to have less odds of an unsuppressed viral load compared to those who initiated between 2004 and 2006 [adjusted Odds Ratio (aOR) 0.29 (95% CI 0.11-0.79)]. Those who had the first viral load test done after > 30 months of ART had higher odds of an unsuppressed viral load compared to those tested after 6-12 months of ART [ aOR 6.88 (95% CI 1.29-36.66)]. Conclusion Despite the yearly increase in adolescents initiating ART, good virological responses can be obtained through increased ART support to both individuals and health care providers. Timely viral load monitoring identifies those in need of increased adherence support on ART and may result in good virological responses. Recommendations Adolescents on ART are a vulnerable group that requires special attention to improve clinical and virological outcomes. Adolescent friendly ART clinics may be useful in providing this service and mitigate the high attrition rates of those on treatment for HIV. Public health awareness campaigns on HIV and its treatment may have a positive impact on virological response to ART and therefore campaigns targeting adolescents must be intensified. Early virological testing after 6 months on ART to monitor treatment responses helps to identify those with sub-optimal response to ART and reduce the progression to virological failure and drug resistance to anti-retroviral drugs.

Submitted in partial fulfilment of the requirements for the degree of Master of Public Health, in the field of Maternal and Child Health, to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, September 2014 / Introduction: Nevirapine (NVP) is used in combination antiretroviral treatment especially for pregnant HIV infected women. NVP has been shown to be inferior and more toxic than other similar drugs, but continues to be used in developing countries due to cost. Aim: This study aimed to determine the prevalence of NVP toxicity and associated factors among 478 pregnant women from three public health facilities in inner city Johannesburg. Materials and methods: We employed a cross-sectional retrospective record review study design to analyse the records of 478 pregnant women in the above mentioned public health facilities. Variables including demographic (age, weight, gestational age) and clinical (CD4 cell count, WHO HIV clinical stage, prior ART experience) characteristics were extracted and the association between these characteristics and the development of toxicity post NVP exposure was explored. Results: The study found that approximately nine out of ten women (89.5%) were ART naïve at the time of NVP initiation. When compared with ART naïve women, ART experienced women had a slightly higher mean CD4 cell count, however, for both groups of women, mean CD4 cell count was less than 250 cells/mm3. Overall, 85.1% of women had a CD4 cell count less than 250 cells/mm3. More than half (55.3%) of the women were in the third trimester of pregnancy and the majority (82%) classified as WHO HIV clinical stage one. At least one adverse event was reported in 63 (13.2%) women. Mild skin rash was the most prevalent adverse event, occurring in 9.6% of women. Hepatotoxicity occurred in 5.3% of women and severe skin rash occurred in 1.5% of women. Almost 85% of adverse events occurred in women with CD4 cell counts <250 cells/mm3. WHO HIV clinical stage II and IV were significantly associated with the overall development of toxicity (ρ <0.01). Conclusions: Whilst the overall prevalence of mild and severe skin rash in this sample was less than that demonstrated in earlier studies, a higher overall prevalence of hepatotoxicity was found. When compared with ART naïve women, ART experienced women were found to have a higher prevalence of mild skin rash. Hepatotoxicity and severe skin rash only occurred in ART naïve women. In this sample, CD4 cell count ≥250 cells/mm3 was not associated with the development of NVP adverse events. Recommendations: Our findings support the continued use of NVP as part of combination ART regimens in women of African descent. In contrast with previously published data, our study showed a significant association between WHO HIV clinical stage and NVP toxicity, our study also included relatively few women with higher CD4 cell counts. Further research including predominantly healthy HIV infected pregnant African women as well as women with higher CD4 cell counts is required in order to fully explore the association between these variables and the development of NVP post-exposure toxicity.

A Dissertation Submitted to the Department of Physiology, University of the Witwatersrand, Johannesburg for the Degree of Master of Science. / Extensive disruption of muscle fibres has been shown to occur after short term eccentric exercise where high mechanical forces are generated. This study tested whether downhill running acts as a stimulus for inducing eccentric damage, and results in greater muscle damage and deterioration in muscular performance than an equal workload of uphill running. The study aimed at determining whether an adaptation or training eflect takes place such that the muscle is more resistant to the damaging effects of a repeated bout of the same exercise. In addition, the study aimed at determining whether the lower muscle volumes and forces of muscular contractions in females compared to males, makes females less susceptible to the damaging effects of eccentric contraction. / IT2018

Despite the improved survival of human immunodeficiency virus (HIV) infected individuals with the introduction of highly active anti-retroviral therapy (HAART) in the South African public sector in 2004, new challenges have been brought to the fore. These include drug-related toxicities, particular those of stavudine, which remains in common use within developing countries. A prospective analysis of 9040 HIV-1-infected adults initiated on HAART from 2004 to 2007 at the Themba Lethu Clinic, Helen Joseph Hospital in Johannesburg, confirmed the ability to roll out a successful HAART programme in a resource limited environment with a high retention rate of 70%. Nearly 30% of patients switched to non-stavudine based regimens due to side effects - predominantly peripheral neuropathy, symptomatic hyperlactataemia and lipoatrophy. In an attempt to look for safer options, a prospective randomized controlled trial comparing standard and low dose stavudine with tenofovir was undertaken in 2009. Sixty patients were randomized 1:1:1 to either standard (30-40 mg), low (20-30 mg) dose stavudine or tenofovir (300 mg) each combined with lamivudine and efavirenz. Adipocyte mitochondrial DNA (mtDNA) levels, gene expression, anthropometry, markers of inflammation, lipid and glucose metabolism were assessed at various time intervals. Results demonstrate early mitochondrial depletion among black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared to patients on tenofovir. Mitochondrial toxicities occurred in both the stavudine arms. Immunological and virological outcomes were similar for all three arms. Both drugs caused lipid changes, but tenofovir had a more favourable effect on anthropometry and adipokines. Both stavudine regimens increased fasting insulin and C-peptide levels, with the higher stavudine dose also causing increased fasting glucose and HOMA levels. This study demonstrates an early association between mitochondrial depletion and stavudine therapy in the black South African population and shows that tenofovir has a minimal effect on mitochondrial numbers. Only two of eight adipocyte genes were significantly affected by stavudine therapy when compared with tenofovir, but this was only seen with the standard dose. This study highlights the occurrence of significant metabolic abnormalities with both drugs. Therefore, awareness of the potential increased cardiovascular risk should be of concern with tenofovir and stavudine, although toxicity is lower in the low dose compared to the standard dose stavudine regimen with no attenuation of anti-retroviral effectivity.

A research report submitted to, the Faculty of Health Sciences, University of Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Science in Population based field epidemiology March, 2013 / Introduction: Access to highly active antiretroviral therapy has dramatically increased worldwide since 2004. However, the emergence of HIV drug resistance presents huge obstacle in ART scale up as it contributes to treatment failure and poses a greater risk of disease progression and loss of treatment options. The study therefore investigated the risk factors and the association of HIV drug resistance, virological failure and CD4 cell count changes in patients on ART at Aurum Institute for Health Research in South Africa. Methods: A cohort of HIV infected patients who developed virological failure of their first HAART regimen was assessed. A genotypic resistance testing was performed using stored plasma on a subset of patients at first detection of virological failure. Data were collected prospectively on all registered patients using standardised forms. Clinical data was obtained from laboratory and pharmacy electronic records. Logistic regression and Cox proportional hazard models were used to assess factors associated with HIV drug resistance and virological failure respectively. Linear mixed-effects regression models were used to assess the changes in the CD4 cell count among patients who developed HIVDR. Results: Between January 2003 and December 2010, a total of 146 ART-treated patients who experienced virological failure were assessed. Of these, 108 (74%) developed HIVDR, of whom 80 (74%) were males; the median CD4 cell count at ART initiation was 121 cells/mm3 (interquartile range, 61-210). The most frequent NNRTI mutations patterns found were mutations leading to resistance to NNRTI agents with 33% having NNRTI resistance. The second most common resistance v pattern was resistance to lamivudine conferred by the M184V mutation (30%). The multivariable analysis showed that higher CD4 cell count at HIVDR detection was significantly associated with the reduced odds of developing HIV drug resistant mutation after adjusting for gender and age(adjusted OR=0.37, 95% CI 0.15–0.94). Similarly, there was significant association between age at ART initiation (adjusted HR=0.71, 95% CI 0.52–0.97) and CD4 cell count during follow-up (adjusted HR= 0.54 95% CI 0.36–0.81) with virological failure in those patients who developed HIVDR. The CD4 cell count slope on average increased by 10 cells per mL per year for the patients without any resistance (average annual change 9.89 cells per mL, 95% CI -6.90-26.69) and decreased by 10 cells per mL per year for patients who had any resistance (average annual change -9.61 cells per mL, 95% CI -19.41- 0.17). Conclusion and recommendation: HIV drug resistant virus was found in 74% of the South African patients who were accessing HIV care at Aurum Heath Institute and developed virological failure of first HAART regimen. Higher CD4 count at detection of HIVDR was significantly associated with lower risk of developing HIV drug resistant virus. Lower CD4 count and male gender were significantly associated with the development of virological failure. Patients with virological failure had significantly great CD4 count declines when any mutation and thymidine analog mutation (TAM) mutation were present. There is a great need therefore for multifaceted approach to target interventions that aim to increase patients CD4 cell counts. Patients should be either screened, possibly with HIVDR testing, prior to reinitiation of a first-line regimen

Thesis (MTech (Environmental Health))--Cape Peninsula University of Technology, 2016. / Environmental remediation of organic and inorganic contaminants such as hydrocarbons has been a research focus area of interest. Chemical surfactants have been extensively used for the remediation of contaminated sites for immobilisation of hydrocarbons from environmental matrices. The focus has been on the impact of chemical surfactants on the environment. These petroleum-based chemical surfactants have raised serious environmental concerns as: 1) they are toxic, 2) they deteriorate the environment owing to their non-biodegradability, 3) they are costly, and 4) most are not intended for environmental applications. As such, alternatives had to be found to mitigate concerns associated with the application of such synthetic surfactants in bioremediation. Biosurfactants produced by microorganisms are a potential alternative to these synthetic surfactants. They have minimal environmental impact, are biodegradable and can withstand extreme conditions. However, biosurfactants are associated with high production costs and low production yield. Currently, large-scale production of biosurfactants cannot be achieved. Most research focuses on improving production yield which will contribute to the reduction in production costs. A lichenysin lipopeptide biosurfactant producing Bacillus sp., which grew exclusively on Beta vulgaris agrowaste, was identified. The microorganism was found to be an effective emulsifier for high molecular weight hydrocarbons such as, lubricant oil and diesel. The aim of this study was to improve biosurfactant production yield from this Bacillus sp., including emulsification efficacy by optimising fermentation conditions by supplementing the broth with biocompatible nanoparticles synthesised using a green chemistry approach with B. vulgaris (B. vulgaris) extracts. This study also aimed at reducing production costs by using B. vulgaris agrowaste exclusively as the production medium, both for the biosurfactant and the nanoparticles.

The growth of bacterial colonies is a very ubiquitous phenomenon occurring in nature and observed in the laboratories. However, there is a limited knowledge on how at the microscopic level these colonies develop and the individual cells spatially organize. In this thesis, we experimentally investigate the physics of growing microcolonies at the level of the individual Escherichia coli (E. coli ) cells, focussing on the order-disorder evolution and the understanding of it in the context of active matter. Bacterial cells are indeed constantly transducing energy from the environment to move and grow, therefore they behave as active microscopic units, defining an inherently far from equilibrium system. In Part I, we present a brief summary of passive liquid crystals that provide us with some basic concepts and tools for investigating the bacterial microcolony evolution. Then an overview of the biology of E. coli cell is given, both as part of multicellular structures (biofilm) and as individuals. Active matter is then discussed along with some examples of active nematics. This first part ends with the materials and methods used in the experiments and analysis. In Part II, we provide our experimental results on the study of growing bacterial microcolonies as active nematics. We describe the way a bacterial microcolony evolves from the first mother cell into a layer of hundreds of cells, and we study the global and local orientational order. We find that a transition from an anisotropic to an isotropic phase occurs as the colony increases and that instabilities and topological defects develop, in analogy to the case of an active nematic. We also compare the real system with simulated ones by investigating (i ) the case of equilibrated configurations with respect to experimental nonequilibrium ones, and (ii ) long-time behaviour of nonequilibrium analogues. In Part III, we discuss the buckling of bacterial microcolonies, that is, the transition from a 2D layer of cells to a 3D structure. We investigate the link between the buckling event and the presence of topological defects in the nematic map of the bacterial microcolony, finding that the buckling sites tend to be closer to topological defects with a negative charge. Later, we present some results of buckling in microcolonies composed of mutants lacking some appendages that play a role in the motion in and attachment to the surrounding environment, finding that buckling occurs at earlier times in the case of these mutants than the wild type. The aim of this work is to show that a growing bacterial microcolony is an interesting model of active matter to experiment on, and that the investigation tools developed for the study of liquid crystals can be useful for describing the evolution of these living systems in mechanistic terms, and for improving the current understanding of nonequilibrium phenomena.

Esse estudo tem como tese que o comportamento de recém nascidos e bebês é ativo, ou seja, guiado a uma meta específica e baseado no conhecimento a respeito do ambiente ao seu redor. Também é assumido que essa capacidade de adaptação se fortaleça ao longo dos 4 primeiros meses após o nascimento. Foram investigadas as atividades manuais de recém nascidos e bebês, tendo em vista que as mãos são uma importante ferramenta de percepção e interação com o ambiente. Assim, os objetivos do estudo foram: a) descrever o comportamento de apertar ao longo dos 4 primeiros meses após o nascimento; e b) identificar acoplamentos entre apertos manuais e o contexto ambiental durante os quatro primeiro meses após o nascimento. Os resultados mostraram que os bebês alteraram a organização temporal dos apertos diferentemente nas situações de contingência e não contingência, um indicativo inicial do comportamento ativo nos apertos manuais / This thesis searched for evidences that newborns and infants behaviour are active, in the other words, intentional, guide by a goal and based in environment knowledge. Also, it is suggested that the adaptation capacity improve around the first 4 months of age Thereunto, the manual activities were investigate, because the hand is an important font of perception and interaction with the environment. So, the goals of the study were: a) to describe neonate and infant clutches around four first months after birth; and b) to verify the coupling between clutches and environmental outcomes during the first four months after birth. The results showed that infants could alter the temporal organization of clutches differently in contingent and no contingent conditions, an initial indicative of active clutch behaviour in young infants

In distribution networks, the traditional way to eliminate network stresses caused by increasing generation and demand is to reinforce the primary network assets. A cheaper alternative is active network management (ANM) which refers to real-time network control to resolve power flow, voltage, fault current and security issues. However, there are two limitations in ANM. First, previous ANM strategies investigated generation side and demand side management separately. The generation side management evaluates the value from ANM in terms of economic generation curtailment. It does not consider the potential benefits from integrating demand side response such as economically shifting flexible load over time. Second, enhancing generation side management with load shifting requires the prediction of network stress whose accuracy will decrease as the lead time increases. The uncertain prediction implies the potential failure of reaching expected operational benefits. However, there is very limited investigation into the trade-offs between operational benefit and its potential risk. In order to tackle the challenges, there are two aspects of research work in this thesis. 1) Enhanced ANM. It proposes the use of electric vehicles (EVs) as responsive demand to complement generation curtailment strategies in relieving network stress. This is achieved by shifting flexible EV charging demand over time to absorb excessive wind generation when they cannot be exported to the supply network. 2) Uncertainty management. It adopts Sharpe Ratio and Risk Adjust Return On Capital concepts from financial risk management to help the enhanced ANM make operational decisions when both operational benefit and its associated risk are considered. Copula theory is applied to further integrate correlations of forecasting errors between nodal power injections (caused by wind and load forecasting) into uncertainty management. The enhanced ANM can further improve network efficiency of the existing distribution networks to accommodate increasing renewable generation. The cost-benefit assessment informs distribution network operators of the trade-off between investment in ANM strategy and in the primary network assets, thus helping them to make cost-effective investment decisions. The uncertainty management allows the impact of risks that arise from network stress prediction on the expected operational benefits to be properly assessed, thus extending the traditional deterministic cost-benefit assessment to cost-benefit-risk assessment. Moreover, it is scalable to other systems in any size with low computational burden, which is the major contribution of this thesis.

Fluid-borne noise is one of the main components of hydraulic noise. Its attenuation may have a significant effect on the cost of hydraulic systems. Standard passive silencers and dampers can be useful in reducing it in certain frequency ranges; however, these tend to be heavy, bulky and expensive. Active control algorithms, which are a comparatively recent means of reducing fluid-borne noise, can be applied to overcome this compromise. The work presented in this thesis is the development of some active control algorithms utilized in a simple hydraulic system to cancel a number of harmonic orders of fluid-borne noise generated by a servo valve or a real pump. To realize cancellation the filtered reference least mean square (FXLMS) adaptive control method is mainly presented. Furthermore, a fast response servo valve is applied as an actuator to generate a proper anti-noise flow signal in real-time. For simplicity, an off-line identification method for the secondary path is applied in the time invariant working condition. Moreover, ripple reflection from both ends of the hydraulic circuit can produce different effects under different working conditions. In order to execute the cancellation without any prior information about the dynamics of hydraulic systems, the on-line secondary path identification method is discussed. However, in this algorithm an auxiliary white-noise signal applied to an on-line method may contribute to residual noise and an extra computation burden may be added to the whole control system. The performance of these control algorithms is firstly investigated via simulation in a hydraulic pipe model and the real-time application on a test rig using a servo valve as a noise source. Finally, these schemes are realized in a simple hydraulic system with a real pump noise source. The fluid-borne noise can be attenuated by about 20 dB in normal working conditions.