This thesis explores the nature and extent of medical autonomy and dominance of government-employed doctors in Zimbabwe, specifically focusing on the profession's control over the technical aspects of medical work (clinical autonomy); determination of the terms and conditions of work (economic autonomy); and regulation of medical education, licensing and discipline (collective regulation). Data was collected through in-depth interviews with different grades of doctors employed on a full-time basis at the Parirenyatwa Group of Hospitals, key informants and other respondents from the Ministry of Health and Child Welfare and other health-related organisations. Additional information was obtained through extensive document analysis and non-participant observation. The findings of the thesis show that all grades of government-employed doctors in Zimbabwe exercise considerable clinical autonomy. There is minimal administrative regulation of their work, although their clinical autonomy is constrained by severe breakdowns of essential equipment and shortages of all types of resources. They also enjoy a high degree of economic autonomy, largely by default. The findings further indicate that medical education and discipline are inadequately regulated by the various regulatory structures, most of which are dominated by the medical profession, leaving doctors with more autonomy in their work than is desirable for good patient care. The thesis reveals that the factors which erode or maintain medical autonomy in Western developed countries and post-colonial states are very distinct and that current theoretical conceptualisations of medical autonomy, comprising medical dominance theory, deprofessionalisation as well as proletarianisation hypotheses, which are largely based on analyses of medical practice in the United States and Britain, are inadequate for analysing medical autonomy in Zimbabwe and other post-colonial states. In this respect, Johnson (1973) is alone in realising the uniqueness of professions in post-colonial states arising from their different historical, cultural, social, political and economic circumstances, although his analysis is somewhat out of date.

This study explores the pre-travel consultation between nurses and people who plan to travel abroad from the UK. Travel health services have developed ad hoc in response to rising public demand, and are mainly nurse-led in UK general practice. There is little research evidence to describe or evaluate pre-travel healthcare provision. Using a mainly qualitative bricolage design of six methods, the research traces the ‘journey’ of health recommendations made to travellers. Starting with guidance documents produced by experts, it then tracks the fulfilment of these recommendations through consultations conducted by nurses and captures the ways in which travellers use or discard the recommendations while travelling. It explores the clinical reasoning behind activities in pre-travel consultations, and generates ideas for practice development. The key findings are that pre-travel healthcare is medicine-centric and issues of time, organisation, and the model adopted by nurses affects the quality of consultations. Two styles of consultation were identified: the Kitchen Sink style was comprehensive and verbose; the Medical and Minimal style focused on vaccinations. Travellers recalled or used very little of what was imparted during their consultations, but far from being ‘blank slates’, travellers usually managed their health appropriately and had far more knowledge than nurses recognised. The thesis offers conceptual insights to the pre-travel consultation which relate to patient safety, quality and the legal integrity of practitioners. It offers a prototype model of the pre-travel consultation that takes account of the challenges associated with current practice. The implications for practice relate to education for nurses in consultation management, patient-centredness, proactive versus reactive service provision, and patient education. PRE-TRAVEL - the new model for consultations - contributes a framework for engaging with these issues, subject to post-doctoral testing.

Climate change presents a major threat to global health and will further exacerbate the health inequalities that exist internationally. However, the provision of healthcare results in considerable greenhouse gas (GHG) emissions and is therefore contributing to climate change itself. Meanwhile, the integration of strategies to address climate change into global health efforts will realise health co-benefits. Meeting the challenging carbon reduction targets set within the NHS will require an improved understanding of the GHG emissions association with different forms of healthcare. This thesis explores the environmental impact of the provision of renal medicine services within the United Kingdom, placing a particular emphasis upon GHG emissions. The approach required, and the opportunities that exist, to reduce the environmental impact of renal medicine services are first explored through a review of the existing literature and a survey of the current practices of renal services in England, Scotland and Wales. A study, adhering to the principles of PAS2050, of the GHG emissions attributable to an individual renal service is then reported. This is the first assessment of the carbon footprint of an individual specialty service to include both direct and indirect GHG emissions. Consideration is given to how the results might inform carbon reduction strategies. Indicative carbon burdens for outpatient appointments and inpatient admissions are derived in order to facilitate future modelling of the emissions attributable to different clinical pathways of care. A second study, in which the GHG emissions attributable to different forms of an individual treatment (haemodialysis) are determined, is then presented. Finally, four case studies of good environmental practice within renal medicine, identified from the earlier literature search and survey, are presented in the context of the results of these studies.

Aim: To explore and understand parents' experiences of their child's genital ambiguity and the reconstructive surgeries for ambiguous genitalia that occurred in infancy and middle childhood. Background: The determination of sex and gender for a child born with ambiguous genitalia is an extremely complex medical and social process. Academic debate, professional practice, the law and increased political and ethical debate have all more recently challenged the evidence base for practice. Currently the 'optimal gender policy' and the 'informed consent policy' drive treatment options. Little research has been conducted to understand the significance gender ambiguity has in parents' lives and how the child's genital surgery affects parents. Methods: An exploratory design of narrative inquiry was chosen and data were collected through eighteen in-depth narrative interviews with a purposive non-random sample of fifteen parents of 11 children (aged 0-11 years). Findings: Narrative analysis resulted in three keystone stories which contained in total eight aggregate stories and twenty foundational stories. The three keystone story themes were firstly, parents' stories about their child. Secondly, stories about being a parent of a child with AG and finally stories about healthcare professionals. Interpretation and synthesis of the three keystone stories revealed three core elements fundamental to parents stories; shock protection and anxiety. Parents had to develop new skills in order to deal with the challenges of living with a child with AG. Parents endeavoured to find a sense of harmony from their experiences of shock, anxiety and the need to protect their child. Harmony is a concept that brought consistency and agreement together resulting in parents embracing their experiences holistically and giving their experiences meaning. Conclusion: Parents overcame the tensions inherent in their experience of their child's AG and found a sense of harmony which has not previously been described in the literature.

This project is an investigation of the issue of human biomedical enhancement, taking human growth hormone as a case study. Growth hormone is mainly used to increase the adult height of short children, and is also employed illicitly as an anti-ageing treatment. Both these applications are viewed by bioethicists as going beyond the scope of therapeutic medicine by enhancing normal human traits rather than treating diseases and as such are considered ethically suspect. This project adopts a comparative and retrospective stance, examining the socio-historical development of human growth hormone in the US, where much of the impetus for enhancement uses has originated, and also in the UK where the potential for enhancement uses of pharmaceuticals and other medical technologies is a growing concern. This project combines a social constructivist approach to bodies and disease categories with science and technology studies theory on the emergence and shaping of new (medical) technologies. Research focuses on the development of growth hormone as a medical technology and the construction of the diagnostic categories that define the illness it is employed to treat. A combination of archive material and contemporary interview data is used to investigate and identify factors that shape the way some applications of hGH have come to be viewed as legitimate, accepted practices while others remain unstable and controversial. Enhancement suggests an inappropriate use of biomedicine, but in the case of growth hormone at least, the determination of medical need and entitlement is shown to be more than a matter of instrumental measurements. It is a contingent and socially shaped procedure that is applied in heterogeneous ways at different sites in the networks of healthcare provision. This technique provides a different model for thinking about those biomedical practices labelled as enhancement, which does not share the limitations of that framing.

Homeopathic treatment has been available on the UK’s National Health Service (NHS) since 1948. In recent years the continued provision of homeopathy through the NHS has been increasingly questioned as part of the ascendency of evidence-based medicine (EBM). Indeed, in 2009 the House of Common’s Science and Technology committee commenced an ‘Evidence Check’ inquiry into Government policy supporting the NHS provision of homeopathic treatments. The controversy over whether homeopathic treatments ‘really’ work and whether they should be available through the NHS has generated much debate: at the heart of the controversy are questions about the nature of evidence in medicine, the validity of randomised trials and the nature and utility of ‘placebo effects’. Critics of homeopathy put forward the simple argument that best available evidence shows homeopathic treatments to be equivalent to placebo, and therefore conclude that it should not be available through publically funded healthcare. This thesis presents a critical examination of the concepts of EBM and ‘placebos’ and re-evaluates their role in the controversy around homeopathy. This thesis examines what kind of foundation the EBM philosophy of evidence provides for the arguments made in the controversy, and the role that ‘placebos’ play as both an evidential and normative standard. There are two basic arguments: first, that the arguments justifying the EBM philosophy of evidence are fundamentally unclear, but also that the interpretation given to EBM, in debates about homeopathy, cannot be sustained. Second, that the concept of ‘placebos’ should be abandoned entirely: a framework is developed for talking about the effectiveness of treatments that removes much confusion about the epistemological and ethical standards that effective treatments should be held to. In addition to attempting to provide conceptual clarity to the controversy, the main conclusion is that the Science and Technology Committee have (on the basis of their own assumptions) understated their evidential arguments, by ignoring mechanistic evidence for whether homeopathic treatments are effective, and they have overstated their ethical arguments, they do not provide good reasons to remove provision of homeopathic treatment through the NHS.

A further assumption made by these methods is that of assuming knowledge of the error variance. Theoretical results are presented with respect to estimating all the model parameters from a single study dataset. An investigation into the practical elements of this theoretical work is presented, concluding that there is not enough information within the data to practically estimate all the model parameters.

Recent developments spurred on by the Human Genome Project have for the first time permitted genome wide association studies leading to identification of multiple novel variants for complex diseases. This thesis consists of a series of studies exploring recent genetic findings for coronary heart disease (CHD) within the broader context of the promises of the genomic era that new findings would ultimately lead to 1) Identification of new disease mechanisms 2) Permit genotype based risk prediction and 3) Promote development of novel and targeted therapies based on genotype. We sought to address these questions, using the Emory Genebank, a collection of angiographically phenotyped subjects with stored blood samples and long-term follow up. We first refined the phenotype for CHD to help understand underlying mechanism and demonstrated differential associations between 8 novel risk variants including 9p21, and sub-phenotypes of CHD and thereby proposed differing mechanisms of risk for these loci. With two non-CHD cohorts we then demonstrated further association between one particular risk variant at 6p24 and the intermediate phenotype of arterial elasticity and related this to a potential novel mechanism of risk. Despite significant association with first events in population cohorts, we showed that these risk variants including 9p21 have limited value in secondary risk prediction, failing to demonstrate any association with prospective events in our cohort as single markers or when combined into a cumulative genetic risk score. Finally in subjects carrying leukotriene pathway CHD risk variants, we administered an oral leukotriene synthesis inhibitor and after just 4 week of therapy observed significant improvement in their endothelial function. In summary, these studies demonstrate the value of refining the phenotype to understand potential mechanisms, the complexities of genetic risk prediction and the feasibility and benefit of targeting therapy based on risk genotype.

Type 2 diabetes mellitus is associated with a significant increased morbidity and mortality resulting from microvascular and macrovascular complications, in particular diabetic nephropathy and cardiovascular disease. Treatment of these conditions has involved improving diabetic control, reducing blood pressure and addressing other cardiovascular risk factors. Dietary fibre has wide reaching health benefits, including improvement of diabetic control and blood pressure, potentially by alterations in colonic bacterial populations that result in changes in serum short chain fatty acids. An open labelled study with a washout period was undertaken to examine the potential effects of Gum arabic on blood pressure and renal function. A daily supplement of gum arabic (25g), a soluble dietary fibre, was administered for a period of 12 weeks. An initial pilot study was conducted in healthy subjects (n=10) and subjects with overt nephropathy (n=14). A follow on study investigated subjects with incipient nephropathy (n=23) in more detail. Measurements of renal function, including isotope GFR and ERPF, blood pressure and vascular stiffness (follow on only), and short chain fatty acids were measured. A significant drop in GFR was seen in the healthy individuals with no associated change in filtration fraction, which could convey some renal protective effect. No changes were seen in the diabetic subjects. Significant drops in blood pressure were seen each of the individual groups. Results of pulse wave analysis and central blood pressure measurements suggest this is not as a result of changes in vascular stiffness. Significant changes in short chain fatty acid production were seen, in particular an increase in acetate (p=0.033) in the incipient nephropaths and butyrate (p=0.03) in the healthy subjects. This study suggests that Gum arabic has beneficial effects on blood pressure but no immediate beneficial effects on renal function in either diabetic cohort.

All inflammatory events are mark by infiltration by leukocytes including neutrophils, which cross the endothelium before following migratory cues to the site of infection, and phagocytosing the infectious microorganisms. Before crossing the endothelial wall, the neutrophils spread on the endothelium. It has been proposed that the necessary additional membrane for cell spreading results from unfolding of wrinkled cell membrane held in place by molecule like membrane linker protein (such as talin or ezrin). Both talin and ezrin are potential substrates for cleavage by the Ca2+ activated proteolytic enzyme, calpain-1. It is possible that this mechanism underlies the membrane unwrinkling events but it is yet to be proved. The major aim of this thesis was to look for evidence that proteolysis and redistribution of these proteins occurred during neutrophil shape change. This thesis provide confirmatory evidence that ezrin is cleaved during extravasation of neutrophils and also provide evidence that the subcellular location of talin and ezrin protein can serve as an biological marker to identify extravasted neutrophils. The subcellular locations of talin and ezrin were identified using immunocytochemistry. Both ezrin (87%) and talin (92%) were detected at the cell membrane of neutrophils. This pattern was lost in polarized neutrophils, as well as after an elevation of cytosolic calcium level and also after transmigration through endothelial monolayers in vitro. Under these conditions, the detected ezrin and talin was mainly cytosolic. The same translocation was observed in extravasated oral neutrophils and also neutrophils which had extravasted under pathological conditions (gingivitis and osteoarthritis). GFP-tagged ezrin was expressed in RAW cells, in order to investigate the mechanism behind the relocation of ezrin. It was found to be triggered by an elevation of cytosolic calcium and was irreversible. It was also triggered locally during phagocytosis at the site where the membrane expanded. Western blotting showed that ezrin (72-69 kDa intact) was cleaved under similar conditions with fragments at 55kDa, 51kDa and 49kDa being generated by elavated calcium and extravasation. This cleavage was sensitive to calcium and calpain inhibition. It was concluded that ezrin is present in the plasma membrane wrinkles of resting neutrophils, but that changes when the cytosolic calcium level changes, as occur during extravsation and phagocytosis. Addition to this, any dynamic change in the surface area of the plasma membrane (phagocytosis), cause a relocation of ezrin away from the plasma membrane. Evidence was also provided that ezrin can be uses as a biological marker to identify extravasated neutrophils