Phylo-epidemiological and pathogenic diversity of Mycobacterium tuberculosis strains in London with implications for vaccine develpoment

PhDApproximately one-third of the global population is infected with tuberculosis causing approximately 1.7 million deaths. Currently, the BCG vaccine is used to protect against TB, but it cannot prevent primary infection or reactivation of latent infection. Ideally a vaccine should protect against a diverse array of Mycobacterium tuberculosis strains and promote a strong, long-lasting TH1 cell-mediated immune response. Whilst evaluating the efficiency of novel vaccines using laboratory control strains (M. tuberculosis H37Rv, H37Ra and M. bovis-BCG), it is important to test efficacy against a representative panel of wild-type circulating strains. In England 42.2% of TB cases are reported in London and the diversity of nationalities generates a diverse pool of strains consisting of globally representative TB strains. The aim of the study was to construct a representative panel of strains for vaccine evaluation studies and general TB research. Common M. tuberculosis strains were identified by performing molecular MIRUVNTR and spoligotyping on 2363 isolates from TB cases reported in London during a one-year period. Epidemiological analysis demonstrated there were representatives from 13 global regions, including high TB burden countries. An algorithm was designed to select strains for a preliminary panel based on associations between MTBC families in clusters of more common strains, the country of birth and VNTR sub-clusters. The preliminary panel contained 42 MTBC strains belonging to 10 MTBC families from patients born in 17 countries. Results of phylogenetic analysis of all 2363 isolates was used to select a smaller panel of strains from the preliminary panel to represent MTBC lineages to investigate if wild-type strains were phenotypically similar. The final panel included five strains from each of the Baker et al., 2004 M. tuberculosis lineages (M. tuberculosis Beijing, LAM10, two CAS, EAI5 strains representing lineage I, II, III, IV, respectively) and an M. africanum strain. In vitro tissue culture experiments demonstrated significantly higher growth of the Beijing strain compared to the other wild-type and laboratory strains. Higher growth rates of this strain were also observed in a cell-free culture system. Aerosol challenge of guinea pigs with wild-type strains showed a quicker dissemination of the EAI5 strain from the lung to the spleen 16 days post-challenge, but significantly higher c.f.u. count of the Beijing strain in the spleen 56 days post-challenge. Collectively, the data demonstrated that there are phenotypic differences between wild-type circulating MTBC strains

Public Attitudes Toward Collective Action: Three Social Psychological Investigations in Malaysia, the United States and Israel-Palestine

Collective action often aims to elicit a response from the broader public. This dissertation presents three distinct but interrelated investigations on the societal outcomes of collective action among both high- and low- status groups in society, grounded in a range of social and political contexts. Chapter 1 provides an integrative literature review that identifies the motivation for the present research. Chapter 2 examined whether and how collective action organized by a social movement can shape the public’s subsequent attitudes toward the movement and its goals, in the context of the electoral reform Bersih movement in Malaysia. Chapter 3 investigated when and how public reactions to movements for social change can promote the rise of reactionary counter-movements to defend the status quo in the context of race relations in Malaysia and the United States. Chapter 4 examines whether distinct modes of ingroup identification and preferences for justice can shape public support for normative and non-normative collective action in the context of the ongoing Israel-Palestinian conflict. Chapter 5 concludes by discussing the overarching theoretical contributions and applied implications of studying the societal impact of social movements, as well as considering the limitations of the present research and future directions

Quantitative Multimodal Mapping Of Seizure Networks In Drug-Resistant Epilepsy

Over 15 million people worldwide suffer from localization-related drug-resistant epilepsy. These patients are candidates for targeted surgical therapies such as surgical resection, laser thermal ablation, and neurostimulation. While seizure localization is needed prior to surgical intervention, this process is challenging, invasive, and often inconclusive. In this work, I aim to exploit the power of multimodal high-resolution imaging and intracranial electroencephalography (iEEG) data to map seizure networks in drug-resistant epilepsy patients, with a focus on minimizing invasiveness. Given compelling evidence that epilepsy is a disease of distorted brain networks as opposed to well-defined focal lesions, I employ a graph-theoretical approach to map structural and functional brain networks and identify putative targets for removal. The first section focuses on mesial temporal lobe epilepsy (TLE), the most common type of localization-related epilepsy. Using high-resolution structural and functional 7T MRI, I demonstrate that noninvasive neuroimaging-based network properties within the medial temporal lobe can serve as useful biomarkers for TLE cases in which conventional imaging and volumetric analysis are insufficient. The second section expands to all forms of localization-related epilepsy. Using iEEG recordings, I provide a framework for the utility of interictal network synchrony in identifying candidate resection zones, with the goal of reducing the need for prolonged invasive implants. In the third section, I generate a pipeline for integrated analysis of iEEG and MRI networks, paving the way for future large-scale studies that can effectively harness synergy between different modalities. This multimodal approach has the potential to provide fundamental insights into the pathology of an epileptic brain, robustly identify areas of seizure onset and spread, and ultimately inform clinical decision making

An exploration of higher education teachers’ experience of decolonising the Bachelor of Education honours curriculum at a South African university

The ongoing 2015/16 student unrest (#RhodesMustFall; #FeesMustFall) has displayed heightened calls for the decolonising of the curriculum in the higher education (HE) sector. Students have highlighted in the recent protests that the curriculum remains largely Eurocentric and continues to reinforce white and Western dominance. In response to the need for a decolonised curriculum, higher education lecturers at a university in South Africa embarked on a Bachelor of Education honours writing exercise workshop with the purpose of decolonising the curriculum. This entailed rethinking ways of knowing and a deconstruction of old epistemologies, with the aim that transformation in the classroom would be reflected in what is taught and how it is taught, as a means to ripple through to grassroots classroom level. This study explores, through using Foucauldian discourse as theoretical frame, the experiences of eight lecturers at a university involved in teacher induction of honours-level education students. This link serves as a fundamental basis between societal change that speaks to creating a space for the African child in challenging teacher conceptions of power and privilege and rethinking the norms of praxis that manifest when teachers enter the classroom. Semi-structured interviews were transcribed and thematically analysed to gain understanding as to the prominent methods used and the dominant conceptualisation of what decolonising the curriculum entails. Findings suggest a need to return to grassroots classroom level as a means to involve stakeholders, such as teachers and tertiary students, in shaping the curriculum. It is further found that lecturers lack the means to engage with a solely Afrocentric theoretical basis and that Western discourse remains a prominent source of knowledge due to the lack of indigenous knowledge systems and research

Trusting code in the wild: A social network-based centrality rating for developers in the Rust ecosystem

As modern software extensively uses open source packages, developers regularly pull in new upstream code through frequent updates. While a manual review of all upstream changes may not be practical, developers may rely on the authors' and reviewers' identities, among other factors, to decide what level of review the new code may require. The goal of this study is to help downstream project developers prioritize review efforts for upstream code by providing a social network-based centrality rating for the authors and reviewers of that code. To that end, we build a social network of 6,949 developers across the collaboration activity from 1,644 Rust packages. Further, we survey the developers in the network to evaluate if code coming from a developer with a higher centrality rating is likely to be accepted with lesser scrutiny by the downstream projects and, therefore, is perceived to be more trusted. Our results show that 97.7\% of the developers from the studied packages are interconnected via collaboration, with each developer separated from another via only four other developers in the network. The interconnection among developers from different Rust packages establishes the ground for identifying the central developers in the ecosystem. Our survey responses ($N=206$) show that the respondents are more likely to not differentiate between developers in deciding how to review upstream changes (60.2\% of the time). However, when they do differentiate, our statistical analysis showed a significant correlation between developers' centrality ratings and the level of scrutiny their code might face from the downstream projects, as indicated by the respondents

The role of human cytomegalovirus encoded viral G protein-coupled receptors in onco-modulatory signalling

Human cytomegalovirus (HCMV) is a ubiquitous virus of the herpes type that infects a high percentage of some populations. One of the most researched genes expressed by HCMV with close homology to human chemokine receptors is the US28 G protein-coupled receptor. Study design: This study was initiated to elucidate the intracellular signalling pathways of an inflammatory factor (IL-6) and an angiogenic factor (STAT3) triggered by the viral US28 oncogene and the presence of US28 in the HCMV viral particle. These pathways were observed by introducing the US28 gene into two human cell lines by infection with a HCMV strain that expresses the US28 gene (wild type), and two HCMV strains where the US28 gene was deleted (ÄUS28 and ÄUS28/UL33). Special attention was directed at the expression of IL-6 after promotion of the US28 gene and subsequent phosphorolation of STAT3. A new US28 antibody was validated and a method developed in an attempt to determine US28 on the viral particle. The following techniques were applied: Cell culture work, two mammalian cell lines were used, HFF’s and U373 MG. Virus stock titre determination to determine the multiplicity of infection. Protein quantitation to determine very small quantities of protein for Western blot analysis. ELISA for the quantitative determination of IL-6. Western blotting for phospho- STAT3 determination and validation of the US28 antibody. Immunocytochemistry was used for back titrations of virally infected cells. Immunofluorescence assay and use of confocal microscopic techniques was used for the location of the US28 gene in the virion and for tSTAT3 translocation to the nucleus. Conclusion: A clear increase in IL-6 secretion (495% ± 1%) was seen, and this was after only an hour in HCMV WT infected cells. From the increase in IL-6 secretion a subsequent increase in STAT3 phosphorylation was detected in the same samples. A clear link has been established between IL-6 and STAT3. A method to determine whether US28 was present in the HCMV viral particle was designed and preliminary results obtained. The results were inclusive.Dissertation (MSc)--University of Pretoria, 2011.Pharmacologyunrestricte

Gender representation in four SADC high school Business Studies textbooks.

Doctor of Philosophy in Social Science Education. University of KwaZulu-Natal, Durban 2017.This study assumes that text – the printed word and visual representations – is never neutral; it is always embedded with ideological representations. Textbooks, which are the dominant defining authorities of the curriculum in schools, can therefore be regarded as a key contributor to the curriculum as a site of ideological struggle. Significantly, there may be limited understanding among educators and educational authorities of the ideological nature of the contents of textbooks. As instruments of socialisation, textbooks are important vehicles in the construction of beliefs and attitudes about gender that may not be immediately apparent to the untrained eye. The purpose of this study is to understand the way in which gender is represented in four Business Studies textbooks selected from countries in the Southern African Development Community (SADC), and to theorise their particular representation. More specifically, the focus of this study is to understand how gender is represented in the four SADC textbooks and to develop a theoretical explanation for how the phenomenon presents. This qualitative study is located in the critical paradigm and engages the tenets of feminist critical discourse analysis as the key analytical frame. The purposive sample comprised four contemporary Business Studies textbooks from the last phase of schooling preceding tertiary education. Feminist poststructuralist theory was used in order to examine gender representation in the selected textbooks. Both semiotic and textual representations were examined. The findings reveal that the representations of women and men in these textbooks are indeed ideologically invested and contribute to the perpetuation of patriarchal constructions. At a semantic level, the mention of the male pronoun first in sentences and conversation and not the female pronoun endorses the principle of the firstness and superiority of the masculine. In terms of representation, intersectionality of race, gender and disability is pervasive in the four textbooks. This reinforces the ideology of the able-bodied, heterosexually masculine and white person as the norm for entrepreneurial success. Management, leadership and entrepreneurial knowledge are scripted almost exclusively in favour of the male gender. Representations related to sexual diversity are also absent, thereby endorsing a construct of the idealised businessperson as a white, heterosexual, able-bodied male, excluding females, those of another race or gender, and the disabled. In terms of ‘ideal’ business personality traits, women and others are constructed as relatively incompetent and dependant, while men are portrayed as assertive and forthright. Gender and race bias in occupational roles and careers is also evident in the texts, with women and ‘others’ shown in low-paid occupations or domestic settings, whereas white men are shown in high-paying, high-status, technological occupations, and are mostly absent from domestic settings. The four textbooks promoted Western ideals in which the Western male white canons were reinforced as the norm for business success. These Western ideals are responsible for the different manifestations of marginalisation stereotyping, silencing and limited representation of women and minorities in exceptional roles. This may not be done intentionally – textbook knowledge appears to be constructed ‘unconsciously’ or in ways that reflect oblivion to institutionalised prejudice. The implication of these findings is that development of a more gender-inclusive curriculum is needed, where there is not only representation of the idealised businessperson as a white, heterosexual male. This research suggests that teachers, pre-service teachers and learners may need to engage with the textbooks critically and examine how particular texts are written and why they are written in particular ways. Teachers, pre-service teachers and learners are encouraged to interrogate textbook content. There is also a need for textbook writers to question their own ideological assumptions of gender. This demands a robust introspection of possible stereotypes and uncritical assimilation of regressive gender ideologies that may be perpetuated. It is only by reflecting on and reworking oppressive gender norms, that a gender-inclusive curriculum might be contemplated

Gender representation in contemporary Grade 10 Business Studies textbooks.

Thesis (M.Ed.)-University of KwaZulu-Natal, Durban, 2013.Since 2009 the textbook has emerged as a key educational resource in South African classrooms. This has been a direct response to rapid curriculum change, and real and perceived inadequacies in teacher content and pedagogic knowledge. Of significance though is that there is limited understanding of the nature of content selections that textbook authors invoke and the subtext thereof. The purpose of this study therefore is to understand how gender is represented in Business Studies textbooks available to teachers and pupils in the Further Education and Training (FET) band in South African classrooms. This qualitative study is located in the critical paradigm and engaged the tenets of Critical Discourse Analysis as the key analytical frame. A purposive sample of two contemporary Business Studies textbooks was selected to investigate the phenomenon of gender representation. Findings reveal that stereotypes of women and men are reinforced in the selected textbooks under study. Women were shown more frequently in home settings than were men. Men were shown in a wider variety of occupational roles than women. Textbooks portrayed men in a wide range of highly-paid, high-status occupations such as managing directors, doctors, lawyers etc. In both texts more males have been represented in leadership positions in government, economic and corporate institutions. The textbooks further represented women as being disabled and destitute. Males were portrayed as confident and educated in the usage of technology while women were portrayed as illiterate. Additionally men were portrayed as assertive and forthright business individuals, while women were also portrayed as emotional and as more reliant on, or needing, the advice of men to deal with business-related issues. Finally, the portrayal of firstness presented the male pronoun first in sentences and conversation as opposed to the female pronoun. The findings indicate that representations in the textbooks are gender-biased and gender-insensitive. Of concern is that these representations may be transmitted to school learners. A critical approach to the selection and use of textbooks is thus necessary. Much work needs to be done by key role players in the educational sectors to ensure that gender inclusivity becomes a feature of South African Business Studies textbooks

Prevalence and Resistance Pattern of Acinetobacter Species in a Tertiary Care hospital in Kanyakumari District

BACKGROUND: Acinetobacter infection has emerged as a serious threat to the healthcare system owing to the emergence of pan resistance from multi resistance. AIM OF THE STUDY: To Study the prevalence and resistance pattern of Acinetobacter species in a tertiary care hospital. MATERIALS AND METHODS: A total of 3832 samples received for culture and sensitivity during 2017 january to 2018 december (1 year) were analysed. Identification of isolates was done by colony characteristics and biochemical reactions. The resistance patterns of these isolates were studied using various antibiotics by Kirby-Bauer disc diffusion test as per CLSI (Clinical Laboratory Standard Institute) guidelines. RESULTS: Out of the total 3832 samples 1332 were culture positive samples. In that 1332 culture positive samples 89 (6.68%) isolates were identified as Acinetobacter species. Multidrug resistance was observed for 32 (35.96%), extensively Drug Resistant were 14 (15.73%) and Pan drug resistant were 11(12.36%). CONCLUSION: Prevalence of Acinetobacter species from our study was 6.68%. Most of the isolates were sensitive to Cotrimoxazole (53.9%), Amikacin (52.8), piperacillin/ tazobactum (48.3 %). Among cephalosporins more sensitivity is for fourth generation cephalosporins (Cefipime 40.4%) . Polymixin is more sensitive than colistin. The emergence of increasingly resistant strains causing such infections has become a public health problem. Early detection is necessary for timely implementation of strict infection control practices and judicious treatment with susceptible antimicrobials

The ‘firstness’ of male as automatic ordering: Gendered discourse in Southern African Business Studies school textbooks

There is little contention that gender equity continues to be a challenge in many societies across the Southern African region. Dominant discourses that perpetuate inequality are often reflected in school materials such as textbooks, which have the potential to socialise girls and boys into particular gender performances. The aim of the study being reported on was to examine representations of gender in a sample of Business Studies school textbooks. The textbooks were selected from four Southern African countries: Swaziland, Lesotho, Zimbabwe and South Africa. The study employed a sociolinguistic analytical framework, namely critical discourse analysis and was guided by the tenets of feminist poststructuralism in the analysis of this phenomenon. The findings of the study reveal superficial content changes in the texts under study. Gendered ideologies continue to prevail in a remarkably overt fashion. One key finding was at a semantic level, namely the mention of the male pronoun first in sentences and conversation and not the female pronoun, having the likely effect of endorsing the principle of the ‘firstness’ and superiority of the masculine. In the order of two words paired for sex such as ‘Mr and Mrs’, ‘brother and sister’ and ‘husband and wife’, the masculine word came first. This automatic ordering is likely to reinforce the second-place status of women. The article concludes with a discussion on the implications of these findings for pedagogy and the textbook publishing industry. The findings also have the potential to ignite debate, as it relates to re-imagining the programmatic curriculum (school textbooks) as a contested genre