Search

In recent years, Graduate Teaching Assistants (GTAs) have been increasingly employed by higher education institutions to support student learning. As PhD students they find themselves in liminal and precarious positions, balancing conflicting priorities as they forge professional identities. Many institutions offer professional development opportunities to support new GTAs as they embark on teaching. However, in this project I argue that such activity is often based on a deficit model of GTA practice, and can be too narrowly focused on developing their skills and knowledge in a way that socialises them to institutional norms. This research draws on realist social theory to explore how GTAs forge identities as teachers and cultivate spaces for agency despite the structures and cultures that may constrain them. Its contribution to knowledge and practice is twofold. Firstly, while social realism has been applied to academic identities, there has been little exploration of GTA identity and agency through this lens. Secondly, I adopted a collaborative approach of working in depth with three participants to construct fictionalised composite stories from reflections based on observations of their practice. This not only celebrates the messy, complex, emotional and often contradictory nature of GTA practice, but also deploys a methodology rarely applied to educational research in higher education contexts. While the GTAs I worked with tended to maintain rather than challenge prevailing structural and cultural forces, their experiences nonetheless offer unique insights into the spaces for agency they create through the ordinariness of everyday practice. Through this research I hope to raise critical, unsettling questions for those working in academic development, including myself, about the assumptions we make around GTA practice, the ways in which we could honour the diversity of GTA experiences, and our potential role in empowering GTAs to explore where they might enact agency in their individual contexts.

Background: Strong evidence links consumption of the Mediterranean diet (MD) to a reduced risk of Cardiovascular Disease (CVD) and type II diabetes, however, there is uncertainty about whether non-Mediterranean regions will adopt this dietary pattern and how to best measure MD adherence among these populations. To date, interventions that have encouraged individuals to adopt a MD have used intensive dietary change methods that would be expensive and time consuming to roll out. Peer support (PS) is a potential novel and cost effective strategy for achieving dietary change towards a MD. Further research on the effectiveness of PS for encouraging dietary change, however, is needed. Aims: This thesis therefore aimed to assess the feasibility of PS for encouraging adoption and maintenance of a MD in a Northern European population at high CVD risk. Methods: This PhD comprised (i) a systematic review of the effect of PS in encouraging dietary change in adults; (ii) qualitative analysis of barriers to a MD in a Northern European population; (iii) validation of a Mediterranean diet score (MDS) to assess MD adherence in a Northern European population and (iv) development and interim-analysis of a pilot RCT to assess the effectiveness of PS for encouraging MD adoption and maintenance in a Northern European population at high CVD risk (TEAM-MED study). Results: The systematic review (Chapter 2) found that more studies reported a positive effect of PS or mixed results, than studies that did not find an effect of PS for achieving dietary change. However, as evidence was mixed, the effect of PS in encouraging dietary change in adults is not clear and further information is needed. Individuals at high risk of CVD from a Northern European population showed preference towards a group based PS model which was developed for assessment in the TEAM-MED study (Chapter 3). Qualitative research among this population indicated a limited knowledge of, and a number of barriers towards consuming a MD (Chapter 4). These factors were addressed in the TEAM-MED study. Validation of the TEAM-MED study MDS deemed this to be a reliable tool for assessing MD adherence among Northern European populations (Chapter 5). The TEAM-MED study interim-analysis (Chapter 6) demonstrated transferability of the MD to a non- Mediterranean region. No significant difference in MD adherence was found between a PS and a proven intensive intervention and minimal intervention for encouraging dietary change at this early stage of analysis. Conclusion: Findings revealed that evidence for the effect of PS for encouraging dietary change is not yet clear, but interim-analysis of the TEAM-MED study has shown potential for the use of PS to facilitate dietary change. Future PS interventions in non-Mediterranean populations could consider use of the group based PS model and validated MDS developed for this work in a Northern European population. These interventions should define key study characteristics, such as the training and support needs of peer supporters. Interventions to encourage dietary change towards a MD in non-Mediterranean populations should tailor the intervention through addressing awareness, attitudes and barriers towards the MD.

Stroke is the main cause of disability worldwide. With over 110,000 first strokes occurring in the UK every year, the individual and societal burden of stroke will continue to increase. Consequently, there is a pressing need to develop therapies to both reduce the burden of stroke and the risk of stroke recurrence. Hyperglycaemia, dyslipidaemia, hypertension, reduced cardiorespiratory fitness and obesity are metabolic irregularities closely linked to stroke risk and represent possible therapeutic targets. In healthy individuals, a physically active lifestyle and structured exercise have been found to improve metabolic control. Research reporting the impact of physical activity and exercise on metabolic control, stroke risk and wellbeing is lacking in the study of stroke. This thesis aims to define and explore physical activity, exercise and metabolic control following stroke with a view to improving clinical care. A cross-sectional longitudinal study (n=31) demonstrates physical activity levels are low immediately following stroke and do not return to levels comparable to healthy individuals after six months, despite individuals having only mild impairment. A randomised controlled trial (n=40) of a community based exercise intervention post stroke investigated the impact of exercise primarily on metabolic risk factors. Significant improvements occurred in cardiorespiratory fitness (p<0.01); high density lipoprotein cholesterol (p<0.01); and diastolic blood pressure (p<0.04). The intervention also resulted in improvements in cognition, overall stroke recovery and mood, with the most marked changes occurring in walking endurance, walking speed and balance. This thesis delivers two clear messages: physical activity is reduced following stroke and does not fully recover after time; and the reversal of low levels of physical activity with a community based exercise therapy programme provides significant benefit to individuals after stroke. This information suggests that clinicians should consider both the importance of physical activity and the therapeutic potential of structured exercise therapy post stroke.

Ribbon-Wearing: A Sociocultural Investigation explores the sociological significance of 'awareness' ribbons, such as those worn for AIDS or breast cancer, in contemporary British society. The thesis discusses the ribbon's place in the culture, examines the meanings that ribbon-wearers attach to the symbol, considers the social and cultural context out of which awareness campaigns emerged, and integrates these analyses into a critique of the project of 'showing awareness'. The work is based upon primary data collected from in-depth interviews, participant observation and questionnaires, as well as a wide range of secondary data, including political speeches, newspaper and magazine articles, films, and novels. Using the work of sociologists such as Giddens, Goffman, Sennett, and Beck and Beck-Gernsheim, Ribbon-Wearing provides a wide-ranging analysis and includes discussions on, among other topics, the lived-experience of risk, the nature of contemporary mourning practices, the sociology of compassion, the marketing discourse of charities, and the relationship between 'awareness' and consumerism. These various points of discussion also work toward a more general assessment of contemporary British society and culture. In particular, my work points to a two-way social trend in which a heightened interest in personal authenticity is coupled with a widespread distrust and repudiation of social institutions. This social current is traced back to the counter-cultural period of the 1960s and 1970s, a time during which a desire for self-fulfilment and cynicism about social authorities became particularly marked.

In the South American and Southeast Asian forests, the Anopheles mosquito malaria vectors bite outdoors early in the evening, and rest outdoors. These behaviours preclude complete control by insecticides and bednets. Personal protection is necessary to protect from drug-resistant malaria. The thesis investigates the development of novel, plant-based mosquito control and personal protection: 1) discovery of new, culturally acceptable plants, 2) laboratory testing of those plants and 3) field testing of efficacious candidates as revealed by laboratory testing. Focus is upon on development of robust methodologies for the laboratory and field that carefully consider Anopheles behaviour to minimise bias. In Phase 1, an ethnobotanical survey in Yunnan, China, investigating knowledge, attitudes and practise about malaria and personal protection, several potentially insecticidal plants traditionally used against insects were identified. Knowledge of malaria was low, but everyone used personal protection at home, but not outdoors, to prevent nuisance biting. The expense of personal protection precluded use and the incorporation of plants into a low-cost insect repellent or mosquito coil would be acceptable for Yunnan. In Phase 2, a laboratory evaluation of neem (Azadirachta indica) as a larvicide, oviposition kairomone and bednet treatment, several assay methods were compared. WHO methodologies proved robust, and should be used as gold standards. When testing oviposition kairomones, choice tests should be run parallel with no-choice tests, as Anopheles mosquitoes oviposit in sub-optimal substrates in the absence of choice. A novel laboratory assay representing a normal exposure of bednet treatment to host-seeking mosquitoes was developed. In Phase 3, a field evaluation of plant based repellents in Bolivia, focus groups and novel repellents were investigated. Volatilisation of repellents proved unsuitable for use in open housing. 20%, of mosquitoes, are diverted from deet repellent-protected to unprotected individuals. The implications for repellent-testing methodology, and repellents as a means of disease control, are discussed.

In this thesis it is shown that PI 3-kinase is constitutively activated in SCLC cell lines (H69, H345 and H510). Inhibition of PI 3-kinase activity using the selective inhibitors wortmannin and LY294002 markedly inhibits cell proliferation and stimulates apoptosis in liquid media. This inhibition of proliferation is shown to occur via both ribosomal protein s6 kinase (p70s6kinase) dependent and independent mechanisms. Furthermore, PI 3-kinase inhibition reduced basal SCLC cell growth in agarose semi-solid media which could not be rescued by the addition of neuropeptides. This is the first description of a constitutively activated PI 3-kinase in any human cancer. It is proposed that this constitutive activity plays an important role in promoting growth, anchorage-independence and tumorigenicity in SCLC, and may account for the non-adherent phenotype and highly metastatic nature of this cancer. Resistance to chemotherapy is a major problem in the treatment of SCLC. Adhesion to extracellular matrix (ECM) proteins can protect cells from undergoing detachment-induced apoptosis. SCLC cells in vivo are surrounded by a specialized micro-environment rich in ECM containing in part laminin, fibronectin and collagen IV. It is shown that SCLC cells adhere to the ECM proteins in vitro in a β1 integrin-dependent manner, enhancing tumourigenicity and conferring resistance to standard chemotherapeutic agents. This adhesion to ECM proteins increases SCLC cell growth and protects cells from the pro-apoptotic effects of the chemotherapy agents via a β1-integrin-dependent mechanism requiring tyrosine kinase activation. Thus ECM proteins in vivo may provide a signal resulting in resistance to chemotherapy. These findings may begin to proivde us with novel targets for the therapeutic intervention of SCLC.

This t~esis is concerned with the synthesis of phosphonate analogues of carbohydrates as stable lsosteres of the corresponding phosphates. Analogues of glucose-6-phosphate (Part A) and mannose-6-phosphate (Part B) were prepared. Part A Glucose-6-phosphatase plays a central role in the homeostatic regulation of blood glucose, by catalysing the conversion of glucose-6-phosphate to glucose in the terminal steps of both gluconeogenesis and glycogenolysis. Abnormally high glucose-6- phosphatase activity has been noted in some cases of diabetes mellitus. Phosphonate analogues of glucose-6-phosphate (which contain a P-C linkage in place of the P-O-C moiety of the corresponding phosphate) are potential inhibitors of glucose-6-phosphatase and therefore could have an application in the treatment of diabetes. Here, the syntheses of three phosphonate analogues of glucose-6-phosphate are described. A non-isosteric phosphonate analogue (in which the phosphate bridging oxygen of glucose-6-phosphate has been removed) was prepared in seven steps from D-glucose, the key step being an Arbuzov reaction between triethyl phosphite and a benzyl protected glucose-6-bromide. Isosteric and isoelectronic phosphonate analogues (in which the bridging oxygen of glucose-6-phosphate has been replaced by a methylene [CH2] and a difluoromethylene [CF2] group, respectively) were also synthesised in seven steps from D-glucose, the key step being the nucleophilic attack of anion (EtO)2P(O)CX2- (X = H, F) on the C-6 triflate of a benzyl protected glucose derivative. PartB Transforming growth factor-~l (TGF-~l) is one of several cytokines implicated in scarring during adult wound healing. TGF-~l is stored in an inert form and activation is due, in part, to the binding of mannose-6-phosphate residues on latent TGF-~l to the mannose-6-phosphate/insulin-like growth factor-II (M-6-PIIGF-II) receptor. Phosphonate analogues of mannose-6-phosphate could inhibit TGF-~l activation by competitive inhibition of binding of latent TGF-~l to the M-6-PIIGF-II receptor and therefore have antiscarring potential. A non-isosteric phosphonate analogue of mannose-6-phosphate was prepared in eight steps from D-mannose utilising Arbuzov chemistry. Initial evaluation in a rat model indicated an anti-scarring effect. An a-hydroxy phosphonate analogue of mannose-6-phosphate was prepared utilising a Pudovic reaction between the anion of dibenzyl phosphite and the C-6 aldehyde of a benzyl protected mannose derivative. The Pudovic reaction proceeded with a diastereoisomeric excess of -80 % and various attempts were made to determine the absolute configuration of the major diastereoisomer. Several esterified derivatives were prepared in an attempt to obtain crystals suitable for X-ray analysis, however only oils or fine powders were formed. Reactions designed to synthesise conformationally restricted analogues in order to determine the conformation by NOE NMR spectroscopy are also described, however these were not successful. Phosphorylated a-I,2-linked mannobiosides are known to bind strongly to the M- 6-P/IGF-II receptor, and therefore an a-I,2-linked mannose disaccharide with a nonisosteric phosphonate at the non-reducing terminus was prepared. The coupling of a thioglycoside donor bearing a 6-phosphonate with the 1,3,4,6-tetra-O-acetyl-~-Dmannopyranoside acceptor was achieved with the use of the mild activator, Niodosuccinimide. Finally, methodology towards the synthesis of a bidentate ligand incorporating two mannose-6-phosphate groups, together with. the a-I ,2-mannosi~ic linkage is described. A cyclohexane-I,2-diacetal protected a-I ,2-hnked mannose dlsacchande _ beanng a 6- phosphonate moiety at the non-reducing terminus was prepared from protected monosaccharides, again using a mild activation procedure.

Social work is one of several professions closely associated with caring and femininity, and, as a result, often suggested as a non-traditional occupational choice for a man. Men’s generally poorer educational experience becomes more prominent when studying a subject associated with femininity such as social work (Severiens and ten Dam 2012). Men have more progression issues than women on English university social work courses (Hussein et al. 2008; Schaub 2015), and our understanding of how men experience social work education is limited. This thesis examines in-depth men social work students’ experience and progression, in order to determine the underlying reasons for men’s poorer progression. Twenty-one social work student men from seven English universities were interviewed using qualitative methods. The study found participants described a complex, layered set of experiential and progression challenges that are specific to men. These impediments appear to combine, for some men, with other non-gender specific difficulties, thereby increasing the likelihood of failure or withdrawal. Some men are able to manage these issues, but others find them more challenging, suggesting some men experience a cycle of academic struggle and disengagement closely linked to their identity as men training to become social workers. In order to understand their experience, several theoretical strands were applied. Theories of stigma, masculinities and student retention were used to provide explanations for the challenges found for the men interviewed. In addition to providing a voice for men social work students, this study makes recommendations for social work educators and programmes to support men to more successfully complete social work courses.

Background: Current malaria vector control programmes rely on insecticides with rapid contact toxicity. However, spatial repellents can also be applied to reduce man-vector contact, with the ultimate goal of reducing malaria transmission. Objectives and methods: The overall goal of my PhD thesis was to evaluate existing spatial repellents as potential tools for malaria control. This thesis focused on characterizing the effect of pyrethroid spatial repellents on mosquito behaviour indoors and outdoors. Emphasis was placed on the effect on entomological parameters that influence malaria transmission. Experiments were conducted in experimental huts in a malaria endemic village in rural south eastern Tanzania and in a semi-field system against laboratory reared Anopheles gambiae sensu stricto mosquitoes. Results and conclusions: Transfluthrin and Metofluthrin coils and DDT reduced human vector contact through deterrence, irritancy/excito-repellency and blood-feeding inhibition. Pyrethroid coils were shown to cause excitation and increased activity of mosquitoes in the presence of humans. Transfluthrin coils did not hinder attraction of mosquitoes to humans but prevented mosquitoes from biting and blood feeding. This way coils provided area wide protection for up to 15m and prolonged anti-feeding for 12 hours. There was no evidence of Transfluthrin induced repellency (directional movement of mosquitoes away from humans) under outdoor conditions. Locally developed Transfluthrin hessian strips also prevented mosquitoes from biting. This thesis elucidates the mode of action of spatial repellents: spatial repellents reduce human – vector contact and induce mortality, hence directly affect ma: human biting rate, m: mosquito density and p: mosquito survival which are among the most important parameters of the vectorial capacity of a mosquito population. This information is critical for the development of target product profiles for spatial repellent products. This study shows that spatial repellents may be a suitable complementary option where mosquitoes feed in the early evening and rest outdoors.