Hepatitis C virus (HCV) infects hepatocytes of the liver causing progressive liver disease including; fibrosis, cirrhosis and hepatocellular carcinoma. However, the precise mechanism(s) underlying HCV induced liver injury are poorly understood. Hepatocytes are highly polarized with distinct apical and basolateral membranes separated by tight junctions that maintain a normal liver physiology. We studied the role of HCV infection in driving hepatic injury. Our studies show that HCV infection induces hepatocellular reprogramming via hypoxia inducible factor-1α (HIF-1α) stabilization and increased glucocorticoid receptor (GR) signaling. HIF-1α stabilization promoted epithelial to mesenchymal transition accompanied by reduced polarity and cell adhesion. Whereas GR signaling increased cholesterol synthesis and altered HCV receptor expression. Alterations in hepatocellular biology induced a cellular state conducive for virus entry and replication. Consequently, cells de-differentiate to acquire a malignant phenotype via HIF-1α target genes including vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF). In addition, GR transcription induced by glucocorticoid treatment or HCV infection enhanced virus uptake, highlighting the caveat for glucocorticoid immunosuppression post liver transplantation. Importantly, HIF-1α inhibitors and GR antagonist reversed the effects of both transcription factors on virus infection and hepatocellular biology. These findings suggest that HCV potentiate liver injury via indirect mechanisms.

Public health agencies engage in the public discourse through the creation and promulgation of various health-related campaigns. Using anti-obesity messages for context, I analyse the ethics of the communicative actions that public health engages in, finding that the ethical standards of truth-telling and respect for agents are frequently sacrificed in favour of quick, catchy, and manipulative messages. This is morally problematic. For example, in the case of anti-obesity communications, manipulative messages utilise and contribute to the on-going discrimination, marginalisation, and imperialisation of the fat body, which contributes to and reproduces oppression. This oppression is observable in the lives of fat people, with research showing negative impacts upon important aspects of social identity, and upon self-regarding attitudes. An impact of manipulative campaigns upon attitudes that contribute to the capacity for self-governance and self-authorisation may be that individuals become less able and less likely to undertake the behavioural changes that public health encourages. Further, a central aim of public health activity is the achievement of greater equity in society. I argue, in sum, that public health defeats its own behaviour-change efforts, while also undermining its central equity-focussed aim, in engaging in manipulative campaigns in the public discourse.

This thesis addressed gaps in the literature regarding the effects of Mindfulness-based interventions (MBIs) for Type 2 diabetes (T2D) and sought to investigate the acceptability and feasibility of an MBI for a group at high risk for T2D, South Asians. A mixed-methods approach was utilised to produce four studies: 1) a systematic review evaluating the psychological and physiological effects of MBIs applied to T2D; 2) a modelling phase to gauge interest in, and cultural considerations for, a modified MBI for young adult South Asians as a diabetes prevention strategy; 3) an examination of the acceptability and feasibility of a modified MBI; and 4) a comparison of the perceived and objective effects of the modified MBI. The review found evidence for psychological benefits and mixed results for physiological effects. The modelling phase indicated that Mindfulness is acceptable to young South Asians pending minor adaptations. The subsequent feasibility study found the modified MBI to be acceptable and feasible, warranting a future full-scale trial. Across these studies, Mindfulness bore psychological benefits, and to a lesser degree physiological and behavioural benefits. The final study’s triangulation approach (using quantitative and qualitative methods) suggests the intervention has a potential positive impact on stress, anxiety, energy levels, emotional wellbeing, and systolic blood pressure in this sample.

Serial peak expiratory flow measurements (PEF) are recommended as an initial investigation in the confirmation of occupational asthma. Plotting measurements in Oasys gives reproducible results and can be used by non-experts. I report a new analysis, the area between curves (ABC) score, which gives 72% sensitivity and 100% specificity using a cut off of 15 L/min/h. Two-hourly measurements of PEF require 8 work days and 3 rest days for sensitive and specific analysis. Serial PEF records with long periods off work (≥ 4 consecutive days) show improved sensitivity from 73% to 80%, implying that 7 more workers in every 100 would be diagnosed. In a comparison of forced expiratory volume in one second (FEV1) to PEF, PEF was more sensitive to diurnal changes than FEV1, although FEV1 was more reproducible. Exhaled breath nitric oxide (FENO) showed similar ABC scores between those with normal and raised FENO. FENO was significantly correlated to methacholine reactivity. In shift workers, mean ABC scores were increased on morning shifts compared to nights, but the cut off of 15 L/min/h would be applicable across all shift types. The ABC score is a new robust method of confirming occupational asthma requiring shorter records than the Oasys score.

Smokers attend preferentially to smoking-related cues in the environment, known as attentional bias. Evidence suggests that attentional bias is related to craving and relapse. Attentional retraining (AR) procedures have been used in laboratory studies to modify attentional bias and processes related to drug use, but investigations on the clinical value of AR in addiction are scarce. This thesis reports on two randomised controlled trials investigating the efficacy of AR with modified visual probe tasks in smokers. The first study explored the effects of varying the length of AR on attentional bias, craving, mood and withdrawal in current smokers. No retraining effects were observed after either a short, medium or long block of AR. The second study explored the efficacy of AR on attentional bias and smoking cessation outcomes in treatment-seeking smokers. While AR procedures were feasible to deliver within smoking cessation clinics, the intervention did not significantly reduce attentional bias, craving, withdrawal symptoms or the likelihood of relapse. These results and the literature in general show that there is no clear association between attentional bias and craving and relapse. Current AR procedures are not effective in smokers and should not be used in smoking cessation treatments, as they currently stand.

There are gaps in the UK knowledge base for understanding the implementation and evaluation of public health interventions which aim to improve the mental health and wellbeing of participants. In this thesis I examine the measurement of mental wellbeing and the implementation of health improvement interventions in a community setting and investigate the practicalities of their evaluation using a measure of mental wellbeing -- WEMWBS. Methods: Using a mixed methods approach I collected and analysed i) three cross sectional surveys of Coventry residents, ii) quasi-experimental before and after outcome evaluations of three CHIP projects, and iii) undertook semi-structured interviews with CHIP stakeholders. Data were integrated using a matrix technique. Results: A total of 8188 individuals (~40% response rate) completed valid survey questionnaires in 2010-2012, while 590 individuals (~88% response rate) completed valid before-after mental wellbeing outcome evaluations in 2011 and 2012 from three CHIP projects. Fifteen one-on-one interviews were completed. I found that health and lifestyle variables ‘sleep quality’ ‘physical activity’ and ‘fruit and vegetable consumption’ showed the strongest and most consistent patterns of association with levels of mental wellbeing measured using WEMWBS. CHIP projects demonstrated associations between the intervention and increases in mental wellbeing, some of which were both statistically significant and clinically meaningful. Some were sustained at three months. Interview findings showed that the difference between the plans and the observed implementation practices resulted in some of the projects struggling to cope with the evolving and changing needs of the programme, for example moving from outputs to outcomes, introducing mental wellbeing and changing concepts of health, and the work required to achieve partnership with the local authority). The effect on programme level outcomes and outcome measurement of these struggles was a reduction in the number and quality of valid evaluation returns from some of the projects in the programme and reduced staff capacity to deliver project objectives. The introduction of mental wellbeing as an outcome measure created a momentum of change for understanding complex health interventions and outcomes among stakeholders; it assisted those delivering the CHIP programme to understand the underlying health improvement rationale for their programme better. Through integrating quantitative datasets I provided a benchmark from which to make comparisons between population estimates of WEMWBS and observed evaluation findings. Integrating quantitative evaluation process challenges and qualitative insights from stakeholder interviews allowed for complex issues to be ‘untangled’. Interrelated mechanisms affected facilitators and barriers of programme planning, implementation, evaluation and sustainability. Integrating my quantitative and qualitative findings highlighted some clear health benefits from the projects but also highlighted a lack of congruence between the documented linear, unidirectional and unrealistic operational planning which I found in CHIP at a programme level, compared to practical implementation on the ground, which was nonlinear, complex and dynamic. Conclusion: Iterative, transitional stages of programme development could benefit implementation processes and potentially health outcomes, including mental wellbeing, in future public health practice. Further research in this area should explore the extent to which complex, collective, and adaptive operational planning can result in more successful public health improvement programmes.

Post-licensure surveillance of vaccine safety comprises of monitoring of adverse events, identification of those events that may be vaccine associated and, where necessary, controlled epidemiological studies to help assess causality. At the Health Protection Agency (HPA) in England a system for performing epidemiological studies using linked hospital episodes and immunisation data was established in the 1990s along with a new statistical approach called the self-controlled case-series (SCCS) for use on datasets which only include individuals with the adverse event of interest. In this thesis by published works I use seven publications from HPA studies addressing a variety of safety concerns to demonstrate the importance of such epidemiological studies and to form a framework which helps address the issues that need considering when doing vaccine safety studies. The seven studies are i) intussusception and oral polio vaccine, ii) measles-mumps rubella (MMR) vaccine and autism, iii) thimerosal in vaccines and neurodevelopment, iv) meningococcal group C conjugate vaccine and purpura/convulsions, v) diphtheria-tetanus-pertussis vaccines and various common and rare events, vi) pandemic influenza vaccine and Guillain-Barré syndrome, and finally vii) MMR vaccine and thrombocytopenic purpura (TP). These studies helped allay safety concerns or, in the case of MMR and TP quantify a true risk. The framework developed covers issues around defining the question, data sources and case-finding, study design and study implementation. In particular issues relevant to the use of the SCCS method are addressed such as ensuring independence of multiple events and bias due to vaccine contraindication. In conclusion the usefulness of epidemiological studies on vaccine safety and of the SCCS method has been demonstrated within a framework that can help with performing future studies.

This study aims to analyse policy and political processes at multiple levels, and examine the consequences for Sexual and Reproductive Health (SRH) care development arising from the engagement of a participatory movement in Peru. I used Associations of Local Community of Health Administration (CLAS) as a core organisation for Peru’s major participatory model at local level. With policy makers, NGOs, health workers and (potential) service users, I explored factors that facilitated/prevented women’s participation in decision-making mechanisms and health practices. I employed a case study and multi-disciplinary approach at national, regional and local levels, focused upon women from multiple aspects in Andean Peru. I studied rural, periurban CLAS and non-CLAS models to compare across the case studies. I conducted semi-structured in-depth interviews with 116 respondents, unstructured observation, and documentary analysis in 2004. My analytical frameworks focused upon: ‘policy content’, ‘context’, ‘actors’, ‘process’, ‘patterns of participation’, and ‘outcomes and impacts’. Political, economic, legal and technical were identified which reflected the stagnant state of the development of SRH and CLAS policies. The central policy focuses on a narrow sense of SRH care, and neglects Reproductive Tract Infections (RTIs). Central government’s weak political leadership and stewardship to CLAS policies reflected that personal leadership (e.g. regional health directors) can define the destiny of regional CLAS development. Facilitating factors were led by NGOs and mixed factors were led by donors. CLAS appeared to create favourable conditions/environment for women’s participation in the community. Local respondents in the CLAS system understood the importance of participation to solve local problems compared to their non-CLAS system counterparts. Nevertheless, women in CLAS model had no influence on changes of SRH agenda, despite difficulties in the acquisition of contraceptives and effective RTIs medicines. The following actors must be incorporated into the decision-making and evaluation/feedback mechanisms in CLAS model to achieve more gender, age-gentle, and ethnically-sensitive Local Health Programmes and strengthen a rights- and trust-based approach: women’s Grassroots organisations, Defence Committees of Women’s Rights, Community Health Agents, Committees of Communal Development or Health (CODECOS)/(COSACOS), and traditional health providers. Alternative relationships (e.g. rapprochement) between CLAS and government authorities must be sought.

This research examines sexual health (SH) policies and experiences of youth, using the Maldives as a case study. Youth SH is a controversial and under-researched issue in The Maldives, an Islamic state where premarital sexual activity is a punishable offence. This thesis addresses the question: To what extent, and why is there a mismatch between official Maldivian SH policies, services and data and the lived experiences of youth in Maldives? It is a mixed methods study involving four research methods and sets of data: i) qualitative in-depth interviews (n=61) with youth aged 18-24 years from three sites within the Maldives; ii) key informant interviews (n=17) with policy actors and service providers; iii) a web-based quantitative survey of Maldivian youth (n=480); and iv) secondary analysis of the Maldives DHS 2009. There are four main findings from this research, three of which are substantive, and one of which is methodological. Sociocultural and religious factors heavily influenced policymaking, service provision and youth experiences. Contrary to most theocratic states, the SH policymaking process in the Maldives is shaped by policy actors and institutions whose strengths have more sociocultural basis than religious expertise. Whilst published official data and original secondary analyses of the MDHS suggest that premarital sexual activity among youth is very limited; this thesis finds extensive reporting of sexual activity. This contrast was also reflected in youth’s knowledge of STIs- where official data displayed a higher level of awareness than found through in-depth interviews and the web-based survey- and their experience of unwanted pregnancies and abortions, which appear to be under-reported in official data. Analyses of the web-based survey using the same questions as the DHS show significantly higher levels of reporting of sexual activity, showing a strong modality effect on survey response. Results from the web-based survey demonstrated that if sociocultural factors were removed from questionnaire design (e.g. censorship of certain issues) and administration (e.g., privacy and anonymity- difficult to achieve in small island communities typical of the Maldives); it is possible to improve response rates and quality of the data. Finally, this thesis highlights two key characteristics of the relationship between SH policy, services, data and youth experiences in the Maldives. Firstly, youth SH experiences appear to be disconnected from SH policies, services and data. Secondly, there is a mutually reinforcing relationship between official SH data and policies, where restrictive policies dictate the type and extent of data that may be collected, which then reinforce justifications for the current restrictive policies and limited services. Policy implications of this research include identifying and addressing the links between SH policymaking and religious and sociocultural factors, and addressing the subsequent effect on SH policy and services for youth.

This descriptive study was conducted in the State of Bahrain using: firstly, a questionnaire for students in the final year of their school education, together with a similar questionnaire for their parents, teachers and all Bahraini health promoters; secondly, focus group interviews; thirdly, hazard analyses critical control point (HACCP) model and a checklist to assess schools' canteen, and finally, an evaluation of school's textbooks and health education materials. The study was designed to answer three principal research questions: 1. Do Bahrainis have appropriate knowledge, healthy beliefs and opinions which will empower them to control food poisoning; 2. Are the canteen environments and the practices within the canteens supportive to health; 3. Do school textbooks and health education materials empower the community in food safety? This study describes for the first time the knowledge, attitudes, beliefs of students, parents, teachers, and health promoters in food safety and HACCP in schools and TLMs and linked these three areas to suggest empowering control measures. The results of this study indicate that future health promotion programmes should start at primary school level and teachers need to be further trained in environmental health issues. Canteen environment, and practices need to be further addressed by authorities. Particular attention should be focused on the critical control points which are the time of preparation, transportation, storage and temperature control during display of foods. There is a need for providing appropriate resources which influence learning and community empowerment. Recommendations also suggested the implementation of the Ottawa Charter for Health Promotion which mobilises all the community, resources and the media.