This thesis explores the phenomenon of workforce modernisation through the reconfiguration of professional roles, which represents a policy priority in healthcare systems in the United Kingdom (UK) and globally. Heavily informed by conflict or power accounts of professionalism, the literature presents attempts to reconfigure professional roles as opportunities for the reallocation of professional knowledge and expertise and therefore power and status. Existing work emphasises the strategic, competitive activity of professionals to establish, extend and defend jurisdiction in the face of such change. Utilising an organisational neoinstitutional approach this thesis provides a novel theoretical interpretation of the opportunities and threats that the renegotiation of roles presents to the professional groups involved, adding complexity to the accounts that dominate the literature. The thesis draws upon work that describes the evolving nature and function of professionalism to demonstrate that in the contemporary organisational environment, focussed on accountability and risk management, attempts to reconfigure professional roles are understood not only in terms of the transfer of professional knowledge and expertise but the concurrent transfer of accountability for the management of risk. This represents a more complex commodity potentially associated with professional risk in the event of untoward incidents. Using the case of changes to the roles of consultant psychiatrists in the UK National Health Service (NHS) that propose the redistribution of clinical activity and responsibility from psychiatrists across the wider mental health workforce, the thesis demonstrates that rather than competing for jurisdiction associated with the management of significant risk, professionals carefully renegotiate their roles in a manner that ensures the protection, not just of their clients, but of the professionals involved. In this case, despite institutional work from professionals and managers to create change in established practice, concern with accountability for the management of risk drove adherence to traditional, readily accepted and organisationally sanctioned interprofessional boundaries, limiting the degree of change enacted. These findings have important practical implications for those involved in the management of change as well as theoretical implications for our understandings of professional role reconfiguration attempts and the nature of contemporary professionalism more broadly.

The aim of these studies was to improve laboratory methods for the detection of virus-specific antibody to mumps and rubella. The presence of virus-specific antibody is indicative of immunity to disease so simple and effective antibody detection allows for the planning and monitoring of immunisation programmes. In facilitating antibody surveillance, oral fluid has advantages as a sample compared with blood. It is simple, safe and cheap to collect and being non-invasive encourages subject recruitment. In this study, an ‘IgG’ antibody capture enzyme-linked immunosorbent assay (GACELISA) was developed and evaluated for the detection of mump-specific IgG in oral fluid. Compared to an indirect commercial ELISA for the detection of mumps-specific IgG in serum, the oral fluid GACELISA was 100% sensitive and specific. The GACELISA should therefore be useful for future antibody prevalence studies. The limitation of oral fluid samples compared with blood are that they contain lower antibody concentrations. Immuno-polymerase chain reaction (I-PCR) is an ultrasensitive method and in this study was adapted to detect antibodies to mumps virus. Though the method was shown to be feasible for antibody detection and quantification, its sensitivity and specificity did not exceed that of a conventional ELISA. Sensitivity was limited by non-specific binding of human IgG to the solid phase. In this study, the PinPointTM Xa-1 T-Vector system was used to produce recombinant rubella virus (RV) E1 fusion proteins in Escherichia coli. Their antigenicity was assessed by Western blotting and ELISA. One of these antigens may be a suitable reagent for immunity studies as it reacted with RV E1-specific monoclonal antibodies (MAb’s) and a high percentage (80%) of RV antibody positive sera.

Various aspects of impulsivity, including risk-taking, were investigated by comparing the responses of control groups with those of three populations that were believed to exhibit problems with impulse regulation: those with eating disorders, attention deficit hyperactivity disorder (ADHD) and recreational drug users. Impulsivity was regarded as a multi-dimensional construct, tests were selected or developed to tap into various aspects of impulsivity, including self-report questionnaires, a novel discrete trials delayed reinforcement operant choice paradigm, a novel measure of financial risk-taking, and the continuous performance test which provides measures of both inattention and impulsivity. These tests varied in their ability to discriminate between groups, and the correlations between measures, as in previous studies, were typically low and mostly non-significant. Findings supported the proposal that impulsivity is a multidimensional construct that must be assessed using a wide range of measures including self-report questionnaires and more objective behavioural measures. The profile of effects found in the three targeted groups supported the proposal that impulsivity manifests itself differently in different populations. Women with anorexia nervosa scored low on impulsiveness and venturesomeness, and demonstrated behavioural impulsivity. Recreational drug users scored high on impulsiveness, venturesomeness and risk-taking, whereas ADHD individuals were inattentive and scored high on impulsiveness and risk-taking taking, but not venturesomeness. Overall the findings highlight the complexity of the impulsivity concept and demonstrate the need to acknowledge its multi-dimensional nature by using a variety of tests to capture its variable expression. Whether impulsivity in particular groups reflects state or trait remains to be determined.

Cytokines are important mediators of immune functions in humans and animals, interleukin (IL)-15 is a proinflammatory cytokine, which is mainly produced by monocytes. It shares many of its functions with IL-2, which is partly due to the shared use of receptor subunits on target cells, and serves as a growth and survival factor for T lymphocytes. The type IIL-15 receptor is composed of the IL-2R β and γ subunits, which form a trimeric complex with the high affinity IL-15Rα chain. The expression of IL-15 is tightly regulated both at the transcriptional and translational level. The production of IL-15 is associated with immune responses against bacterial and parasitic pathogens but has also been associated with the pathology of human autoimmune diseases, in particular Rheumatoid Arthritis (RA). RA is characterized by chronic inflammation within the synovial membrane accompanied by infiltration of lymphocytes leading to progressive, erosive destruction of cartilage and underlying bone. The severity of RA is associated with the overexpression of proinflammatory cytokines within the synovial tissue, in particular tumor necrosis factor alpha (TNF α) which is thought to play a central role in maintaining the inflammatory processes within the arthritic joint. So far, little is known about the processes that initiate and perpetuate RA. IL-15 was found in the synovial tissue of RA patients where it stimulated the production of TNFα, placing IL-15 in a central position orchestrating the cytokine cascade that causes inflammation and pathology in RA. Antagonists to IL-15 may therefore have an important therapeutic potential for the treatment of RA in humans. A major aim of this project has been to clone and express a recombinant IL-15 antagonist to use as a therapeutic agent in a murine model of RA closely related to the human disease, collagen-induced arthritis (CIA). A soluble IL-15Rα was cloned from a murine macrophage cell line and expressed in a bacterial expression system. The resulting protein has a molecular weight of 26kD and bound to IL-15 specifically. It also had a neutralizing effect on IL-15-induced proliferation of T cell lines. Administration of soluble IL-15Rα to mice prevented the onset of CIA and had a suppressive effect on disease severity and incidence. Mice treated with the recombinant IL-15Rα also showed reduced serum cytokine production and altered humoral responses against collagen. These results consolidate the therapeutic potential of IL-15 antagonists for the treatment of inflammatory diseases. To further enhance the therapeutic properties of recombinant IL-15Rα, a second expression construct has been cloned fusing the extracellular region of native IL-15Rα to the constant region of the murine immunoglobulin heavy chain. This construct was expressed in a mammalian expression system and results in a product of 66kD, which also bound to IL-15. The generation of knockout mice by gene targeting is a powerful tool to study the function of gene products in vivo. The Cre/lox system provides a novel strategy to generate inducible and tissue specific genomic alterations that allow the detailed analysis of gene function. The second part of this project was concerned with the generation of a mouse model lacking IL-15Rα in a tissue specific way by conditional mutagenesis in embryonic stem (ES) cells. Using cDNA encoding the extracellular domain of IL-15Rα as a radiolabeled probe, a murine genomic library was screened. Two clones containing part of the gene encoding IL-15Rα were characterized. A DNA construct was cloned to target the IL-15Rα gene in murine ES cells. Homologous recombination of the construct with the target locus resulted in the flanking of the critical regions of the IL-15Rα-gene by loxP sites. Cre-mediated recombination in vitro caused the deletion of loxP site flanked sequences within the genome of the targeted clone. Using this technique, two ES cell clones have been generated that allow the generation of mice that either lack IL-15Rα in all tissues or are suitable for conditional mutagenesis mediated by Cre recombinase. The resulting model may provide a useful tool to study the effects of IL-15 in inflammatory processes in vivo.

Acute infective conjunctivitis (AlC) is a common self-limiting condition presenting to general practice. However, evidence is limited on GPs current management of AlC, patients' understanding of conjunctivitis or the most appropriate management strategy for AlC in general practice. The aims of this thesis where to: 1) To determine GPs' current management strategies for AlC 2) To gain an understanding of patients concerns and beliefs about AlC and develop a patient information leaflet (PIL). 3) To assess the effect of common management strategies for AlC on symptom resolution and patients belief in antibiotics. Three complementary studies were used: 1) A postal survey of 300 GPs regarding their diagnosis and management of AlC. 2) A qualitative study involving interviews with 25 patients to explore conjunctivitis from the patients' perspective. 3) An open randomised controlled tria~ with 307 recruits, to assess the effect of different management strategies (immediate, delayed or no offer of antibiotics; a patient information leaflet and an eye swab) for AlC in general practice. The results were: 1) Survey: 95% of responding GPs usually prescribe topical antibiotics for AlC despite 58% stating that they thought at least half of the cases they see are viral in origin. Only 36% of GPs believed they could discriminate between viral and bacterial infection 2) Qualitative study: patients regarded conjunctivitis as a minor illness although some considered it might become more serious if not treated. They stated a preference not to take medication but believed that conjunctivitis would not clear without treatment. However, they were open to alternative management approaches (e.g. delayed prescription approach) because they trusted their GPs judgement. Once aware of the selflimiting nature of conjunctivitis, patients felt they would prefer to wait a few days to see if it improved before seeking medical advice even if this resulted in a few more days of symptoms. 3) Randomised trial: different prescribing strategies did not affect symptom severity in the ftrst 3 days, but duration of moderately bad symptoms was less with antibiotics (control 4.83 days, immediate 3.26 days (p=O.OOl), delayed 3.86 days (p=O.002)). Compared with no initial offer of antibiotics, antibiotic use was higher in the immediate group (control 30%, immediate 99% (p=0.001), delayed 53% (p=O.004)) as was belief in the effectiveness of antibiotics (control 47%, immediate 67% (p=0.03); delayed 55% (p=0.35)) and intention to re-consult (control 40%, immediate 68% (p=0.001), delayed 41 % (p=0.98)). A patient information leaflet or an eye swab had no affect on the main outcomes, but an eye swab seemed to increase patient worry about AlC and a PIL seemed to increase satisfaction with the consultation and the amount of information received. Re-attendance in the next two weeks was less in the delayed group (delayed OR 0.33 (0.11;0.98); immediate OR 0.65 (0.26; 1.63)). In conclusion: Most general practitioners prescribe topical antibiotics for most cases of acute infective conjunctivitis -a self-limiting condition. Most patients are unaware of the self-limiting nature of AlC. A delayed prescribing approach is probably the most appropriate strategy to use for the management of acute conjunctivitis in primary care - it reduces antibiotic use by nearly 50%, shows no evidence of 'medicalisation', provides similar symptom duration and severity to immediate prescribing and reduces re-attendance in the short term compared with no offer of antibiotics.

Chapter 1 of the thesis is divided into 5 sections. Section A begins by defining a Discrete Choice Experiment (DCE), and outlines the key stages involved in conducting a DCE. Sections B and C outline theories underpinning DCE analysis. Section B outlines the characteristics theory of demand, whilst section C, explains random utility theory (RUT), compensating variation (CV), marginal willingness to pay (MWTP), and willingness to pay (WTP) analysis. Section D of the thesis provides a review of the DCE literature. Section E outlines the research questions addressed in the thesis including calculating WTP and hypothetical bias; the description of the cost attribute; preference heterogeneity; and altruism. Chapter 2 shows how DCEs can be used to calculate WTP, using a DCE relating to Deep Vein Thrombosis (DVT). Chapter 3 uses data from a DCE applied to Menstrual disorder and Gynaecology patients. It evaluates an experimental method I developed to establish whether respondents might fail to factor in the monetary attribute into their DCE decision making, leading to hypothetical bias. Chapter 4 applies essentially the same DCE design but only analyses data from Gynaecology patients. Chapters 4-8 all use data obtained from a DCE relating to preferences for different allocation criteria for allocating kidneys for transplantation. Chapters 5 and 6 look at preference heterogeneity which is observable using interaction dummy variables (the issue of unobserved preference heterogeneity is considered in chapter 7). Chapter 5 establishes how marginal rates of substitution (MRS) differ between different respondent groups including renal patients, healthcare professionals, live donors / relatives of deceased donors, carers, and ethnic minority versus non-ethnic minority patients. Chapter 6 establishes how MRS differs between non-white ethnic minority patients versus other patients; South Asian patients versus other patients; and according to respondent gender. Chapter 7 of the thesis compares results from models which do not cater for unobserved preference heterogeneity, with results from models which do. Initially 2 basic models which do not cater for preference heterogeneity at all (because they do not include dummy variables) are applied including random effects logit and conditional logit. Then models catering for unobserved preference heterogeneity including Mixed Logit and a Latent Class Model (LCM) are used. Finally there is an analysis involving the application of conditional logit with interaction dummy variables. Chapter 8 of the thesis explores how preferences might differ according to how altruistic respondents are. It establishes how respondent preferences differ according to respondent self-disclosed perspective when answering DCEs. In other words whether they claimed to answer the DCE in terms of what would be best for me; what would be best for me and others; or what is best for others. Finally chapter 9 involves a discussion of the findings emerging from the thesis, and draws conclusions about the merits of material contained in it.

Background: Diabetes is a growing public health problem affecting people worldwide both in the developed and developing countries, and poses a major socio-economic, psychological and Behavioral challenge. Consequently, diabetes takes a staggering toll on the people in Nigeria and the economic burden is very high. It is a well known fact that numerous factors influence diabetes self-care: such as patient’s physical, psychological, social, cognitive and health care system factors. In this study, the researcher set out to elicit an understanding of the association between socio-demographic, socio-cognitive, and psychological health and to specifically provide explanations for how these three factors are related and differ across ethnicity, gender and type of diabetes. Conversely, studies investigating the psychological health in people with diabetes have observed disparities in terms of gender, ethnicity and the type of diabetes. More so, the impact of socio-cognitive health indicators on psychological status in the Nigerian context remains invisible and unknown. Additional investigations were carried out to assess the pattern of the psychological health of diabetic patients using socio-demographic and socio-cognitive factors, to identify if differences occur in the psychological and socio-cognitive factors by gender, ethnicity and type of diabetes. Finally, an exploration of the contextual and explanatory factors perceived to have underlain the gender ethnicity and type of diabetes differences observed in the psychological status and socio- cognitive health was carried out. Methods: A sequential explanatory mixed methods design comprising a quantitative phase followed by a qualitative phase was employed. In the quantitative phase general survey, data from the N= 486 participants were analysed to test for significant differences of ethnic groups, gender, type of diabetes and the relationship they all have on psychological status and socio-cognitive health. The qualitative phase on the other hand, was based on a follow up of the significant results by using semi-structured focus group interviews with 18 recruited respondents across gender, ethnic groups and type of diabetes. Findings: A 2x4x2 MANOVA hypotheses: 2 and 3 from the quantitative study showed a significant interaction between gender, ethnicity and type of diabetes; ethnicity and type of diabetes; gender and type of diabetes; gender and ethnicity. From the partial eta squared 2 , type of diabetes explains more of the variance remaining (after excluding the variance attributable to other variables) (21.4% vs 20.1%); than gender (21.1% vs 13.3%); which, in turn, explains more of the variance than ethnicity (5.6% vs 6.5%) on the combined DVs Psychological and Socio-cognitive health respectively. The qualitative results revealed extreme and overwhelmingchallenges diabetes imposed on the sufferers. It provided specific insight and on patients contextual experiences such as non-adherence; concerns about the present and the future’ health care systems and the way medical practitioners interact with patients which negatively impact on psychological status. These factors broadened the quantitative result in terms of the consistence in the patients’ descriptions of living with and self-managing their diabetes. Conclusions: The outcome of the t study has extended knowledge on the complex and dynamic nature of individuals’ responses to the challenges of diabetes in day-to-day self-care management and how best diabetic patients should be supported in order to promote adherence, positive treatment processes, provide assistance to the physical discomfort associated with diabetes, and support pro-diabetes coping behaviors (diet), through psychotherapy so as to enhance optimal psycho-behavioral health.

This thesis develops probabilistic models for the spread of infectious diseases in which individuals experience a period of transient immunity after recovering from infection. Quasi-stationary distributions (QSDs) and limiting conditional distributions (LCDs) are used to describe the temporary equilibrium that is reached between an initial exponential growth phase and the epidemic dying out. This thesis includes results characterising QSDs corresponding to existing birth-death processes and epidemic models and to new processes such as the Evolving Strain SIRS model which we define to describe the progression of a disease undergoing antigenic drift, such as seasonal influenza. Existence and uniqueness results are proven for specific LCDs. Results regarding marginals of special cases of these processes are proven, including the preservation of x-invariance for Q as discussed in Pollett [1988]. Many of the models considered in this thesis are multidimensional, which makes explicit calculation of QSDs extremely challenging. To combat this, specialised techniques for simulating QSDs are developed to illustrate and explore these distributions. These novel methods, involving variants on SMC samplers, are shown to facilitate the simulation of QSDs for discrete-valued stochastic processes, particularly reducible processes. A formal proof of convergence of the SMC sampler is provided for some simple examples. The simulation methods are then used to characterise the properties of QSDs and LCDs related to endemic epidemic models with evolving strains under an equivalence relation. These QSDs are used to define a reproduction number similar to Ro when the process starts from quasi-stationarity. The epidemic models with evolving strains are shown to have the standard SIR and SIRS epidemic models arising as limiting processes as evolution at each infection becomes certain.

This interdisciplinary cultural studies research uses critical discourse analysis to review the four political declarations on HIV & AIDS adopted by the United Nations in 2001, 2006, 2011 and 2016. Religion is implicated in the tensions and conflicts around issues of HIV and sexual and reproductive health and rights in the negotiations that hinders consensus, resulting in compromises and omissions in the texts. The research identifies four dominant discourses in the declarations and an additional two in the wider HIV response of relevance to these tensions; a public health, biomedical discourse; a human rights, gender equality and community engagement discourse; political discourses of leadership and national sovereignty; and a traditional religio-cultural discourse. In the wider HIV response a broader religious discourse and secularist discourse are evident but missing from the text of the declarations. This critical discourse analysis of the declarations investigates how the discourses interact in the text; how the traditional religio-cultural discourse influences the text; what is missing from the final text; and reasons for the gaps. Close textual analysis of the declarations identifies tension between the public health, human rights/gender equality discourses and the traditional religio-cultural and national sovereignty discourses. The traditional religio-cultural discourse operates to limit public health and rights-based approaches to HIV prevention and frames women and girls as passive victims, without agency to exercise their rights. When compared against UNAIDS strategies as a standard, the declarations are missing commitments to address the risks of key populations to HIV. Missing also is reference to any contributions the faith community brings to the epidemic. The broad religious discourse includes supportive approaches to public health, human rights and gender equality, with the potential to bridge gaps in the negotiations. The traditional religious discourse is implicated in gaps in the text on key populations and rights. The dominance of secularism at the UN is implicated in exclusion of the broad religious discourse. While obstacles around rights-based approaches to HIV prevention and key populations persist, common ground and synergies between the discourses exist. Recommendations include: to ask new questions at the UN about the role secularism plays that may increase space for conservative voices to operate; seeking new ways of working to bridge some of the gaps; and including different perspectives that have the potential to bridge the gaps and open up new ways to achieve consensus.

Psoriasis is a chronic skin disease that affects up to 2% of the UK population. The clinical presentation ranges from mild disease to extensive, severe disease that causes considerable discomfort and distress. Severe disease usually requires photochemotherapy or systemic treatment. Information about the effectiveness, safety and costs of the different treatments is required to enable dermatologists to formulate evidence-based treatment guidelines. Systematic reviews of the four main treatment modalities for moderate-severe psoriasis (cyclosporin, methotrexate, systemic retinoids and photochemotherapy) were performed. Randomised controlled trials were located systematically by electronic searching, hand searching and personal communications. Data on trial characteristics and outcomes were extracted and tabulated. Where possible data were pooled to give summary effect sizes as odds ratios, rate differences or numbers needed to treat (NNTs). Firm RCf evidence of efficacy was found for cyclosporin, oral ret.inoids, particularly in combination with PUV A, phototherapy, photochemotherapy and for combinations of topical calcipotriol or steroids with phototherapy. The corresponding NNTs were low, indicating high levels of efficacy. RCI' evidence of efficacy is lacking for methotrexate. Two observational studies of patients attending the Psoriasis Specialty Clinic were performed. The first was a crosssectional study that used data in existing disease assessment docwnentation to identify the characteristics of a group of 256 patients. The second was a longitudinal study that followed the treatment pathways of 166 patients in the first group. These studies confirmed that this group of patients and their treatments were comparable with those described in the literature. An economic analysis was performed, using a previously published decisionanalytic model, to compare four treatment strategies for severe psoriasis from the health service perspective. The results (cost-effectiveness ratios) showed that methotrexate was the most cost-effective primary treatment followed by cyc1osporin, acitretin and PUV A. The rank order was not sensitive to changes in response rates. Modifications to the decision analytic model are proposed including a wider array of pathways and an allowance for adverse effects of treatment. Future analyses should include narrowband UVB alone as a primary treatment.