Characterization of a novel cell death related gene, DWNN, in cervical cancer

Master of Science - ScienceDWNN-deficient Chinese Hamster Ovary cells have been found to be resistant to staurosporine-induced apoptosis. The human DWNN gene is located on chromosome 16p21, with 18 exons and is 36 kb long. It is alternatively spliced at exon 16 and makes two major mRNA transcripts, 1.1 and 6.1 kb, encoding 13 kDa and 200 kDa proteins respectively. The purpose of the study was to elucidate the possible role of DWNN in cervical cancer and apoptosis, to establish tissue distribution and expression levels of DWNN at protein and mRNA levels in cervical cancer. In situ hybridization studies showed elevated levels of the three mRNA transcripts in cervical cancer as compared to the normal tissues. The transcripts were localized in the nuclei of invaded stroma, moderately differentiated islands of tumours, dysplastic epithelium and some infiltrating lymphocytes. Immunocytochemistry showed that DWNN proteins were highly expressed in the dysplastic epithelium, dysplastic endocervical glands, moderately and well differentiated islands of tumours and the invaded stroma. Image analysis indicated elevated expression levels in the islands of tumours. Apoptosis detection by TUNEL revealed high apoptotic levels in the invaded stroma and moderately differentiated islands of tumours and this significantly correlated with DWNN localization. Proliferation assay using Ki67 antibody was found to be indirectly directly proportional to DWNN expression. Antiapoptotic Bcl-2 expression levels were found to be inversely proportional to the expression levels of DWNN. The up-regulated levels of DWNN in cervical cancers in contrast to normal tissues suggest DWNN to be proapoptotic, as there were elevated levels of apoptosis in the same sites where there were high levels of DWNN expression and Bcl-2 was down-regulated in the same sites. DWNN expression significantly correlated with apoptotic levels and was indirectly proportional to ki67 in human cervical cancers. Real Time PCR also confirmed the up-regulation in levels of DWNN in cervical cancer. This study suggests that the DWNN gene may be involved in apoptosis. Further characterization of this gene could lead to its manipulation as a diagnostic marker and a potential therapeutic target for cancer treatment

A Threat-Vulnerability Based Risk Analysis Model for Cyber Physical System Security

The ability to network machinery and devices that are otherwise isolated is highly attractive to industry. This has led to growth in the use of cyber-physical systems (CPSs) with existing infrastructure. However, coupling physical and cyber processes leaves CPSs vulnerable to security attacks. A threat-vulnerability based risk model is developed through a detailed analysis of CPS security attack structures and threats. The Stuxnet malware attack is used to test the viability of the proposed model. An analysis of the Natanz system shows that, with an actual case security-risk score at Mitigation level 5, the infested facilities barely avoided a situation worse than the one which occurred. The paper concludes with a discussion on the need for risk analysis as part of CPS security and highlights the future work of modelling and comparing existing security solutions using the proposed model so to identify the sectors where CPS security is still lacking

NATIONAL DIGITAL LIBRARY STRATEGIES: A SOUTH AFRICAN PERSPECTIVE

The objects of the National Library of South Africa (NLSA) and the functions it is required to perform are prescribed by the National Libraries Act, Act 92 of 1998. The NLSA is the primary resource of South African published documentary heritage. The NLSA strives to ensure equitable access to its comprehensive collections for all members of South African society. The National Library’s collections contain a wealth of information including South African books, periodicals, newspapers, maps, special collections, government publications and foreign official publications

Automated analysis of digital medical images in cervical cancer screening: A systematic review

Background Cervical cancer is the second highest cause of mortalities in women living in resource-constrained countries compared to those living in high income countries, due to lack of organized population screening. Cervical cancer screening is the best way to detect lesions and remove them before they advance into malignancy. In South Africa, the current standard cervical cancer screening protocol begins with cytology examination then a referral for colposcopy follows if the cytology screening test is abnormal. Thereafter, histopathology examination is conducted on biopsy specimen collected during colposcopy. Biopsy specimen are only collected when suspicious lesions are observed during colposcopy. These screening procedures need to be performed by qualified specialist clinicians because accuracy of diagnosis is highly dependent on the skill level and experience of the clinician making the diagnostic decision. In South Africa, colposcopy and cytology are constrained by a shortage of specialists and expensive diagnostic infrastructure. Consequently, public health interventions such as population screening programs for cervical cancer are poorly implemented. Researchers have been developing low-cost portable devices, some of which are incorporated with automated image analysis to enhance diagnostic decision-making. The methods for incorporating automation within each domain of the cervical cancer screening protocol are becoming numerous as researchers continue to advance the field. As the knowledge base is growing rapidly, progress on the implementation status of novel imaging devices and novel algorithms in cervical cancer screening has become unclear. Thus, there is a need to identify all relevant technologies, i.e. devices and algorithms, currently being researched in the field, and to understand their unique strengths and challenges toward clinical adoption. The aim of this project was to provide a systematic review summarizing the full range of automated technology systems used in cervical cancer screening. Method A systematic search on five main academic databases (PubMed, Scopus, EBSCOhost, Web of Science and Google Scholar) was conducted to identify articles on automated technology systems applied in cervical cancer screening. The search results were screened by two independent reviewers to assess eligibility in meeting Population, Intervention, Comparator, and Outcome (PICO) criteria. The screening of articles was a two-step approach: firstly, screening for eligibility by only reading the title and abstract of articles; then secondly, screening by reading full texts. A data extraction form was developed and used to systematically summarize information contained in 70 studies that were included for analysis. Bias in each study was assessed using a risk of bias template adapted from established checklists, namely the Cincinnati Children's LEGEND guideline and the Joanna Briggs Institute critical appraisal checklist for diagnostic test accuracy studies. A conceptual map of common computer aided diagnostics (CAD) tasks that make up the automation pipeline was developed as a narrative tool to synthesize the specific functions that proposed CAD algorithms in multiple screening domains were performing. Results This systematic review found 16 studies which reported application of algorithms paired with novel image acquisition devices, and 52 studies reporting on standalone image analysis algorithms. CAD algorithms associated with acquisition devices (both novel and conventional) revealed that automated analysis achieved superior performance than manual expert analysis; thus, improving diagnostic decisions made by clinicians performing colposcopy, cytology and histopathology. The pertinent algorithms were those developed for devices designed with a mobile phone or tablet, which were the Pocket Colposcope, MobileODT EVA Colpo, Smartphone Camera, Smartphone-based Endoscope System, Smartscope, Mobile high resolution micro-endoscopy (mHRME), and Pi high resolution micro-endoscopy (PiHRME). These mobile-based systems in particular could be applied more widely in low- to middle-income countries than bulky devices because of their anticipated low purchase cost. Most interventions were in the feasibility stage of development, undergoing initial clinical validations. Conclusion This review found that cervical cancer screening researchers have proven the positive clinical impact that CAD algorithms might have in reaching outstanding prediction performance. This accomplishment is a significant step toward minimizing reliance on experts to provide cervical cancer screening services. Furthermore, the systematic review summarized evidence of the algorithms which are being created utilizing portable devices, to circumvent constraints prohibiting wider implementation in LMICs (such as expensive diagnostic infrastructure). These advances can make the decentralization of colposcopy services more feasible if unsupervised community health workers are trained to effectively utilize portable imaging devices with automated functionality for interpreting results. However clinical validation of promising novel systems is not yet implemented adequately in LMICs, because most studies did not include nurses who are a crucial segment of the target population. Additionally, it is not clear whether the proposed portable interventions are economically feasible when hidden costs are also taken into account

Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch.

BACKGROUND: High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification. METHODS: Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression. RESULTS: One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77-263) and 4.3 log10 copies/mL (IQR, 3.8-4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥ 1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL. CONCLUSIONS: Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure

Poverty and Rural Policy in South Africa

Poverty in South Africa is a rural and urban problem. It is endemic to the rural environment where the majority of the people live. It is transferred to the urban areas through labor migration. Rural people depend on agriculture for subsistence. Apart from subsistence farming there are no employment opportunities. The choice for a rural young man is to be a subsistence farmer or a migrant laborer. The industrial sector is unable to offer a job for everyone. Thus, the rural migrant’s dream of a city job often becomes an unemployment nightmare. I argue, therefore, that poverty can best be treated through development programs targeted at the rural area. Most writers on poverty in the developing countries support this hypothesis. A vibrant rural environment will have the effect of improving the living standards of the rural people. Some of the labor force will be retained in the area provided there is hope for a better life. As the standard of living rises in the rural area the benefits will spill over to the cities through backward and forward linkages. Economic theorists for the alleviation of poverty emphasize growth as a prerequisite for poverty reduction. They argue that no country can achieve poverty reduction without economic growth. However, critics call this trickle-down economics. The argument of the theorists is extended to encompass other societal values such as efficiency, security, freedom and equity. To achieve growth countries mobilize savings for investment. The productivity of investment promotes growth and overall development. To test whether a rural development program will not slow down economic growth, I used a cross-section study of 33 developing countries. The result showed that a country can achieve economic growth while having a rural development program. Therefore, all other things the same, on average a rural development program will not slow down economic growth. I conclude, therefore, that by developing the rural area South Africa can reduce poverty and promote growth

The in-situ faecal decomposition in a vermicomposting toilet

Dry sanitation approach, where there is no need for water-flush, is a low-cost technology that has gained interest in recent years, and the focus in this study is vermicomposting as an on-site toilet system that can be used to reduce the wastewater released into the environment. A toilet design outline was used to illustrate and create a functioning vermicompost unit, whereby faeces was added into the vermicomposting unit on a daily-basis, to simulate an on-site urine diverting toilet. The earthworms used were Esenia fetida and the average feeding rate per adult worm of 0.02g/day and this system had a continuous (daily) faecal feeding that began at 80g/day for 3 weeks to 120g/day for 8 weeks. The indicator micro-organisms Enterococcus spp. and Escherichia spp. and pathogen Salmonella spp. were monitored and reduced in terms of concentration from 9 log10, 7 log10, 6.5 log10 respectively to 5 log10, 2.5 log10 and 3 log10. The bacteriophages MS2 and ΦX174 were also evaluated to no significant reduction within the vermicompost unit. A total material added into the vermicompost on a VS basis was 2.5 kg with an output material being that of 0.9 kg which gave a material mass balance reduction of 63 % (VS basis). The continuous faecal loading preceded in a gradual faecal build-up that did not affect the system from achieving this material reduction. Therefore, the vermicomposting system with its material reduction was seen as a viable dry sanitation approach for faecal decomposition

Outcome of the antiretroviral treatment intervention in Mankweng

Thesis presented in partial fulfilment for the degree of Master of Management (in the field of Public Sector Monitoring and Evaluation) to the Faculty of Commerce, Law, and Management, University of the Witwatersrand 2016The purpose of this research was to assess outcomes of the antiretroviral treatment intervention in Mankweng. The antiretroviral treatment intervention was conceived with the aim to reduce HIV transmission through viral load suppression. Literature has shown that viral load is used as a tool to measure the performance of the intervention and studies on viral load outcomes in rural settings of Limpopo are limited. For this reason, the research was focused on viral load suppression with the aim of (1) determining the proportion of adults with viral load suppression among people taking antiretroviral treatment for 12 months, and (2) identifying factors associated with failure to achieve viral load suppression among people on antiretroviral treatment for 12 months. Binomial logistic regression model was used to identify factors associated with failure to suppress viral load. This study used the theory of change to interpret its findings as well as theories of behavioural planning and self-regulation models to understand the logic that underpins the theory of change. The findings revealed that the majority (78%) of adults achieved viral load suppression, and a quarter of the individuals failed to suppress the viral load. There was no significant difference in baseline characteristics between people who achieved viral load suppression and those who did not. In addition, males, with a low CD4 and opportunistic illnesses when in the primary disease stages were more likely to fail to suppress the viral load. Moreover, people who were initiated on a 3-pill containing treatment and do not have social support were also likely to fail to achieve viral load suppression. Although the study showed a trend of likelihood towards failure to achieve viral load suppression, the estimates were not statistically significant. Theoretical arguments from this study suggest that failure to achieve viral load was attributed to poor adherence to treatment. This is supported by the logic that underpins the theory of change, in which the assumption of adherence was possibly violated. However, the results chain framework highlighted that the implementation of the intervention was effective as it led to good outcomes and an effective intervention. Drawing all this together, the study highlights the need for intensified adherence counseling during treatment in order to improve the performance of the intervention. Author: Ramatsobane Johanna Ledwaba, Thesis Title: Outcomes of the antiretroviral treatment intervention in Mankweng, Johannesburg, March 2016GR201