Politics, coercion and power: An analysis of economic failure in healthcare systems

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This study examines notions of government and market failure in British healthcare by tracking and analysing the changing views of opinion formers. Presenting original data that highlights the attitudes of today's opinion formers towards populist notions in health economics it provides a unique insight into the limits and boundaries of contemporary debate. Significantly, the research concludes that swathes of elite opinion no longer support the National Health Service (NHS) in its traditional nationalised guise. While opinion formers instead now believe in a much greater plurality of public and private healthcare today's elite not only question the idea of state healthcare but they also remain sceptical of a purist libertarian market. Indeed, in noting that healthcare has always attracted the interventionist attentions of those with state power, the study questions in fundamental ways the meaning of such terms as 'market' and 'private sector'. In highlighting the timeless propensity for medical and health professionals to seek legislative favour, it argues that the world has never actually seen anything resembling a real market in the bio-medical paradigm and its forbears. Healthcare has always been a deeply corporatist venture run in association with a range of mystical, military, religious, or purely political statist elites. The study begins with an historical overview of healthcare from the military hospitals of the Roman period, through the religiosity of the Middle Ages, the mutuality of the nineteenth century, the statism of the National Health Service and the recent rise of public private partnerships. Examining such concepts as monopoly, consumer ignorance, moral hazard and externality, it also analyses notions of public versus private goods in the context of today's healthcare

Letter from Helen Evans to John Muir, 1910 Jun 11.

[letterhead]Riverside, California, June 11th 1910Mr John MuirMartinezCalif.Dear Sir: By request thro Miss Mary Beal - I have received a beautiful autographed photograph of Mr Burroughs and would like very much to have one of yours to hang with it in this Library.SincerelyHelen Evans0478

Bioorthogonal Chemistry for Pretargeted PET Imaging

Positron Emission Tomography (PET) is emerging as a powerful method for imaging cancer through the design and development of new radiotracers. Antibodies have promising properties as ligands for targeting cancer, as they have the advantage of displaying high affinity for their respective receptors. However, the use of antibodies as radiotracers is limited to the use of long-lived isotopes, as these large biomolecules additionally display slow blood circulation and clearance. The use of short-lived isotopes such as 18F or 68Ga, in combination with antibodies, would provide the ideal balance between targetability and clearance. This may be achieved by use of a two-step pretargeting strategy, whereby a reactive tag is conjugated to the antibody and allowed to localise in the tissue to be imaged, before systemic administration of a chemical reporter (e.g. a labelled reactive partner) which allows the ‘pretargeted’ tissue to be imaged. The Strain-Promoted Azide/Alkyne Cycloaddition (SPAAC) reaction between cyclooctynes and azides was evaluated as an appropriate bioorthogonal reaction for application to a pretargeting strategy using short-lived isotopes. The synthesis of a library of cyclooctyne precursors was carried out, which were evaluated in terms of their reactivity with azides, and their suitability for in vivo applications. An 18F-labelled version of the SPAAC reaction was developed, demonstrating the ability of the reaction to be carried out under different conditions. This model reaction was translated to in vivo pretargeting using a cyclooctyne modified Herceptin monoclonal antibody and an 18F-labelled azide. These initial experiments indicated that the SPAAC reaction may not be fast enough to occur at the low concentrations which are found in vivo. The reaction was thoroughly examined in terms of kinetics at different concentrations, and a high concentration-dependence upon rate of reaction was confirmed. This was supported by a 68Ga-labelled SPAAC reaction, which was carried out using reportedly more reactive cyclooctynes than those used in the initial experiments. In general, the reaction showed a greater preference to be carried out in organic solvents such as acetonitrile, and under closer to physiological conditions the reactions were less likely to proceed. The Inverse-electron-Demand Diels-Alder (IeDDA) reaction between tetrazines and strained alkenes was evaluated as an alternative bioorthogonal reaction for demonstrating in vivo pretargeting. A series of 68Ga-labelled IeDDA reactions between a 68Ga-labelled tetrazine and a series of norbornene analogues demonstrated the superior reaction kinetics and biocompatibility of the IeDDA reaction. The initial translation of the IeDDA reaction to a proof-of-concept for pretargeting using cyclic RGD pentapeptides was initially unsuccessful, attributed to the surprisingly poor reactivity of norbornene-modified cyclic RGD pentapeptides towards a 68Ga-labelled tetrazine. The reaction between a 68Ga-labelled tetrazine and a Cetuximab antibody, which had been modified with the more reactive trans-cyclooctene (TCO) moeity, was successfully demonstrated. The hypothesised pretargeting strategy using this model reaction was achieved on high EGFR expressing cells, validating the IeDDA reaction in this context. These results suggested tantalising opportunities for application of the IeDDA reaction to in vivo pretargeting for PET imaging using short-lived isotopes such as 18F and 68Ga.Open Acces

US foreign policy and national development in the Caribbean, 1960-1976

The Caribbean has long been an area of intense US interest and activity. Yet at the same time, the United States has failed to articulate a distinctive Caribbean policy, separate from its policy towards Latin America. In part, this failure has resulted from the practical difficulty of determining a definition of "the Caribbean" - US policies towards the different countries within the Caribbean region have varied according to time and perspective.This thesis attempts to determine the exact nature of United States foreign policy towards the Caribbean during the period 1960 to 1976. It starts from the assumption that the Caribbean has been included within US-Latin American policy in the articulation of policy statements and objectives, but that US policy has differed in terms of both its implementation and impact on Caribbean countries. US foreign policy is, therefore, examined from a liberal-democratic perspective in terms of the distinction between national interest and development objectives and policy actions, looking at their impact on the Caribbean national development process - in particular, on economic and political development. In attempting to assess the coherence of US policy, the differences within US policy are examined with respect to two sub-groups in the Caribbean - the English speaking and the Spanish speaking countries.Three specific areas of US policy are examined: first, security policy - looking at both hemispheric defence and internal security policy, military and police assistance programmes; second, economic policy - looking at development assistance, regional integration, private investment, trade and migration; and third, diplomatic policy - looking at US policy towards dependent countries, trades unions, political parties, human rights and different forms of government. The continuity of US policy is assessed by comparing the Democratic presidencies of Kennedy and Johnson with the Republican administrations of Nixon and Ford, and the key feature of US-Caribbean policy - the primacy of security interests - is finally distinguished

Biopsychosocial factors in body dissatisfaction and disordered eating attitudes amongst preadolescent girls: cross-sectional and longitudinal perspectives

Research into the antecedents of disordered eating attitudes and body dissatisfaction in preadolescent girls is lacking, despite the physical and psychological developmental risks these phenomena pose. In response, two separate studies of school-based samples of young girls were undertaken, investigating a range of biopsychosocial risk factors using longitudinal and cross-sectional methodologies. Study 1 examined prospective predictors of disordered eating attitudes and body dissatisfaction. 138 girls completed measures of adiposity, perfectionism, anxiety, body dissatisfaction and disordered eating attitudes at 7 to 9 years old and two years later at 9 to 11 years old. Across-time predictors of body dissatisfaction and disordered eating attitudes, adjusted for other across- and within-time relationships, were assessed using regression analyses. Initial adiposity predicted subsequent body dissatisfaction with only borderline significance when adjusted for subsequent adiposity. Initial disordered eating attitudes and perfectionism predicted subsequent disordered eating attitudes. These data suggest novel prospective factors in the pathogenesis of disordered eating and body image for young girls. Study 2 cross-sectionally examined the utility of an adult sociocultural model of body dissatisfaction and disordered eating attitudes in young girls for the first time. According to the model, internalising an unrealistically thin ideal body increases the risk of disordered eating via body dissatisfaction, dietary restraint, and depression. 127 girls aged 7-11 years old completed measures of adiposity, thin-ideal internalisation, body dissatisfaction, dieting, depression, and disordered eating attitudes. Thin-ideal internalisation predicted disordered eating attitudes indirectly via body dissatisfaction, dietary restraint, and depression; it also predicted disordered eating attitudes directly (a novel parameter). Exploratory path analyses showed that this revised sociocultural model fit well with the data. These data indicate a sociocultural framework of disordered eating and body dissatisfaction in adults is useful, with minor modifications, in understanding related attitudes in young girls. Together, these studies provide a detailed picture of factors involved in the development and maintenance of body dissatisfaction and disordered eating attitudes during middle childhood. They suggest the importance of early, targeted interventions for this age group as a means to reduce girls’ current and subsequent concerns about eating, shape and weight

Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease

Neurosteroids are steroid hormones synthesised de novo in the brain and peripheral nervous tissues. In contrast to adrenal steroid hormones that act on intracellular nuclear receptors, neurosteroids directly modulate plasma membrane ion channels and regulate intracellular signalling. This review provides an overview of the work that led to the discovery of neurosteroids, our current understanding of their intracellular biosynthetic machinery, and their roles in regulating the development and function of nervous tissue. Neurosteroids mediate signalling in the brain via multiple mechanisms. Here, we describe in detail their effects on GABA (inhibitory) and NMDA (excitatory) receptors, two signalling pathways of opposing function. Furthermore, emerging evidence points to altered neurosteroid function and signalling in neurological disease. This review focuses on neurodegenerative diseases associated with altered neurosteroid metabolism, mainly Niemann-Pick type C, multiple sclerosis and Alzheimer disease. Finally, we summarise the use of natural and synthetic neurosteroids as current and emerging therapeutics alongside their potential use as disease biomarkers