The Department of Health aim to reduce smoking prevalence to 10% by 2020; however estimates suggest this shall not be achieved. One way to increase the decline may be to introduce new cessation interventions into NHS Stop Smoking Services. Literature reviews and meta-analyses were used to test the efficacy of smoking reduction and nicotine preloading in comparison to current NHS treatments (abrupt quitting and nicotine replacement therapy post-quit, respectively), in smokers who wanted to quit. Results of the two reviews suggest that both approaches produce similar quit rates to their comparators. We suggest that pre-quit reduction should be offered alongside abrupt quitting, to encourage more smokers to use cessation services. However the use of nicotine preloading would be premature, as evidence of benefit is inconclusive. The protocol for a randomised controlled non-inferiority trial using both approaches is presented. Trial participant interviews suggest that reduction methods are feasible and may have more enduring popularity than abrupt quitting, providing further support for this approach. Accounts also suggest potential mechanisms of preloading, although a literature review provided little evidence of these. Further research should establish the effect of preloading, its mechanisms of action, and the best way to advise smokers to reduce.

The widespread usage of extended spectrum cephalosporins in the 1980s led to the emergence of β-lactamases capable of destroying them. Extended spectrum β-lactamases (ESBL) are the most common β-lactamases in some parts of the world and represent a pandemic of CTX-M ESBLs. Work examining the epidemiology and distribution of specific genotypes both in the UK and across the world particularly in China and India is presented. The faecal carriage by humans and dispersal into the environment is described. The environment and release of CTX-M producing Enterobacteriaceae into the environment following sewage treatment is reported and that arising from fish and poultry production. The work describes the isolation and characterization of the second most important CTX-M genotype (CTX-M-14) and the development of novel methods for the characterisation of genotypes. The publications were important in the recognition of the significance of CTX-M and drew attention to the characteristic genotype distribution around the world. The importance of faecal carriage as a dispersion mechanism and the association of specific genotypes with ethnic groups was a novel finding. The work also was the first to genotype ESBLs in India identifying that CTXM-15 was the only CTX-M genotype carried by one of the world's largest populations.

Climbing stairs is a lifestyle physical activity with effects on a range of CVD risk factors. This thesis explored the potential of stair climbing at home as a public health intervention in three empirical studies. A pilot study tested the feasibility of progressive increases in stair climbing and descent at home. Eight participants progressed from 10 floors.day-1 in week one to 19 floors.day-1 in week four. Percent body fat, SBP and leg power were improved at the end of the brief intervention. The second study randomly allocated 24 healthy weight (BMI = 22.1) and 26 overweight (BMI = 31.7) sedentary women to gym-based and home-based stair climbing for 5 days.week-1 over 8 weeks, with a healthy weight control group recruited for comparison. Intervention participants progressed from 2 continuous 32.8m ascents.day-1 in weeks 1-2 to 5 ascents.day-1 in weeks 7-8. Stair climbing improved body composition, cardio-respiratory fitness and serum lipid profiles. Increases in leg power were found in the stair climbing group. Overall, effects were similar for gym-based and home-based interventions. Given the effects of leg power, and the importance of leg power in the elderly, the third study investigated the potential psychological determinants of increased stair climbing at home for an older population. Participants (n = 281; age = 69.2 years) reported the number of floors that they were willing to climb continuously at home, as well as potential barriers and facilitators of the behaviour. Positive beliefs about the benefits of regular stair climbing and fear of falling, both on stairs and in general, were the major predictors of willingness to climb stairs at home. Discussion focuses on the potential of home-based stair climbing as a cost-effective intervention for preservation of function and CVD risk in public health.

Two-thirds of UK mothers begin breastfeeding, but many soon stop. Although breastfeeding benefits health, infant feeding is influenced by social and attitudinal factors. Study one prospectively investigated the attitudes and experiences of 514 women. Past experience predicted which multiparae would stop by six weeks. Manual social class and considering bottle feeding did so for primiparae. Perceived insufficient milk was the commonest reason for stopping. Study two, a randomised trial of support from breastfeeding counsellors, recruited 720 women. At four months, 46.1% (143/310) intervention and 42.3% (131/310) control women breastfed (Chi\(^2\)=0.942, P=0.33); 73.9% (229/310) vs 79.4% (246/310) gave bottle feeds (Chi\(^2\)=2.60, P=0.11). Survival analysis confirmed that differences between intervention and control women's partial and full breastfeeding duration were not significant (P=0.45 and 0.15 respectively.) Significantly fewer intervention women felt they had insufficient milk. Qualitative analysis of women’s comments revealed they wanted better information, practical help with positioning, effective advice, encouragement and their feelings acknowledged. Women valued counselling, but their feeding behaviour changed little, which may reflect the strength of social influences and that not all mothers contacted the counsellors postnatally. Practical support in the early postnatal period is important. Counselling may increase women's confidence in breastfeeding and producing enough milk.

Data from this thesis has extended our understanding of the molecular epidemiology and transmission of Mycobacterium tuberculosis in the Midlands. A novel DNA fingerprinting method called Mycobacterial Interspersed Repetitive Units containing Variable Number Tandem Repeats (MIRU-VNTR) typing provided equivalent results when compared to the current gold standard for DNA fingerprinting (IS6110 RFLP). To improve our understanding of TB in the Midlands, MIRU-VNTR typing was then developed to be assayed by non-dHPLC for the first time. Using this high-throughput rapid method a prospective and universal typing study was undertaken. This work identified the predominance of the Euro-American and East African Indian global clades in the Midlands and linked them to particular human population groups using novel software based on names. DNA fingerprinting also discovered the most prevalent single strain in the Midlands. This strain is geographically restricted to the West Midlands within the UK and globally. From this geographical association, we have called this strain the "Mercian" strain. The Mercian strain was not associated with patients who originated from the Indian Sub-Continent but was significantly associated with UK-born, Black Caribbean patients in Wolverhampton. These findings show that strains have been imported into the Midlands from around the world and there has also been continued transmission of these and other strains which may have been present in the Midlands for years. Molecular tools developed in this thesis will have regional, national, and international impact on TB control.

Health Inequalities and the Right to Healthcare of Negev Bedouin in Israel with Diabetes: A case study of a Marginalized Arab Indigenous Minority Diabetes is one of the world’s most pervasive chronic diseases and there are high rates of prevalence in the Arab world and amongst indigenous peoples. It is widespread amongst older Bedouin in the Negev, who are a marginalized Arab indigenous minority in Israel. This is a multi-method case study using non participant observation in clinic settings, analysis of medical records and semi-structured interviews in a Health Centre and Hospital Outpatient Clinic and household interviews. The fieldwork took place over eight months in 2007. Statistical analysis was done using SPSS and thematic qualitative analysis was conducted using NVIVO 7 with supplementary manual analysis. The conceptual frameworks used are the right to heath and health care approach as set out in UN Special Comment 14 in relation to the availability, accessibility acceptability and quality of health care, as well as neo materialist, materialist and socio-behavioural explanations of health inequalities linked to lay and professional explanatory models of illness. The findings show that there are limitations on the right to health care in terms of availability of clinics and clinic hours, accessibility in terms of distance, language, cost, and information, acceptability in terms of linguistic and cultural differences between staff and patients and quality in terms of medical records, monitoring and appropriate context specific lifestyle advice. The issue of non-discriminatory care needs to be addressed. Explanatory models of illness used by Bedouin and health professionals differ although both reflect awareness of changing lifestyles. These models link to explanations of health inequalities. There are gender differences in how Bedouin men and women understand and live with diabetes which is related to their social status and circumstances. Some aspects of the findings are generalisable to Bedouin in the Arab world and to indigenous peoples in relation to health care provision, health inequalities and explanatory models. However, there were specific areas of health care provision that related to the marginalized minority status and situation of this population in Israel which needs to be addressed and the rights to health and health care framework provides a potential means of monitoring improvement.

Contact structure between individuals in a population has a large impact on the spread of an epidemic within this population. Many techniques and models are used to investigate this, from heterogeneous age-age mixing matrices to the use of network models in order to quantify the heterogeneity in the populations contacts. For many diseases, the probability of infection per contact, along with the exact contact structure are unknown, compounding the difficulty of identifying accurate contact structures. In this thesis, the impact that the contact structure has on the epidemic is examined in several different ways. Analytical expressions for the variance in the spread of an epidemic in its early exponential growth phase on heterogeneous networks are derived, showing that the third moment of the degree distribution is needed to fully specify this variance. This quantifies the impact that very well connected individuals can have on the early spread of an epidemic through a network. The dependency of the potential epidemic on the heterogeneity in workplace sizes and transmission rates is examined. It is shown that large workplaces can increase the expected size of the epidemic significantly, along with increasing the effectiveness of control strategies enacted during the early stages of an epidemic. In addition to this, a synthetic population is constructed for England and Wales from available datasets, in an attempt to model the spread of an epidemic through a realistic network of comparable size to the true population. The contact structure that is derived from this is compared with that taken from two surveys of contact structure in the same population, using simple models, and qualitative differences are seen to exist between the surveyed structures and the synthetic population structure.

Background: Integrated care is a policy imperative in health and social care services globally, and yet there are reported difficulties in defining, developing and sustaining this way of working. Research Question: This research explores staff views and experiences of the presence, nature and development of integrated care in two programmes of community services. Method: A case study approach was adopted using secondary analysis of qualitative data from staff questionnaires using themed content analysis and pattern matching, with findings triangulated with documentary sources. The study considers the presence and nature of integrated care using the conceptual framework “to what extent integrated care is for everyone (inclusive) and not just for some (exclusive)” as interpreted from the literature. The development of integrated care was explored using systems theory for the management of change in a complex environment. Findings: A meta-analysis of the two case studies demonstrated that integration was present in all 66 services within the two programmes. The nature of integrated care varied and was demonstrated as multiple types (in community hospitals) and processes (in community services). The most frequently reported type was multidisciplinary working. The processes most teams chose to develop were information sharing systems. The development of integration within the case studies was affected by a number of factors, such as commitment and staffing. Conclusion: This study provides new evidence of the presence, nature and development of integration within a wide range of established services spanning all ages. From this and other measures, the extent to which integrated care is presented as “exclusive” can be questioned. These findings have informed the development of a framework of five principles, reflecting whether integrated care is: for everyone, extensive, enduring, can be enabled and essential. The implications and application of this research for policy, service development and training are discussed, and proposals for further research include testing the applicability of this framework and widening this study.

Aim: I describe the original contribution my work has made to understanding individual, social and environmental influences on physical activity among young people in Scotland. The work I present is based on six publications from five studies. Design/Methodology/Approach: Two studies used quantitative methods and include a 5-year longitudinal study and a cross-sectional pupil and school-level study. Data were collected through self-administered questionnaires. Three studies used qualitative methods including focus group discussions, photography and descriptive writing. All studies involved adolescents (10-15 years) attending schools in Scotland. Key Findings: My longitudinal evidence showed significant gender and developmental effects through early-mid adolescence, particularly at the primary-secondary school transition. While boys reported higher levels of physical activity than girls at all ages, baseline physical activity was a significant predictor of later activity levels for both genders. The importance of social influences was evident across my research. Survey data showed boys to report higher peer support, parental support and independent play than girls. Among both genders, peer, paternal and maternal support decreased with age, whereas independent play increased. Time spent with friends was particularly important and was further highlighted in qualitative findings. Being with friends was a benefit of active travel to school, walking, and general physical activity. Other factors influencing physical activity included proximity and access to local facilities, and the school environment. Most notable was the importance of cost and value for money. In general, pupils were satisfied with school facilities, but felt time for physical education (PE) could be increased. Among adolescent girls, survey data showed the best predictor of physical activity to be hours allocated to PE in fourth year of secondary school. Provision of PE and extra-curricular clubs are likely to be of greater importance to girls’ participation than schools facilities. Longitudinal data showed girls reporting lower levels of perceived competence, self-esteem and physical self-worth than boys at each age. Furthermore, girls’ physical perceptions decreased markedly over time, whereas among boys, only perceived competence decreased, while global esteem increased. Influences on physical activity participation were shown to be context specific, e.g. pupils reported not having bicycle storage as a barrier to cycling to school. Walking was a popular activity among girls, although areas in which walking took place, and reasons for walking could differ between geographical locations. Conclusions: In line with the socio-ecological model, my findings demonstrate the complex interaction of individual, social and environmental factors on physical activity participation among young people. They highlight the need for all sectors to work together in developing the most suitable interventions, considering the activity, its context and the population being targeted.

BACKGROUND Oral epithelial dysplasia has a malignant potential. Three inter-related challenges currently exist for this condition. Prediction of which lesions will progress to cancer is not possible, requiring most patients to undergo unnecessary treatment. Attempts to identify prognostic biomarkers are hampered by limited tissue availability. Surgery remains the mainstay of treatment, with significant functional consequences and poor efficacy in preventing malignant transformation. All three are addressed here, through improved identification of dysplastic lesions likely to become cancerous, validating high-throughput laboratory techniques in oral dysplasia, and assessing the feasibility of a novel chemoprevention trial in the UK. IMPROVING PATIENT SELECTION Improvements to the current best predictive method of histological grading were explored. The performance of the binary grading system was validated before improvements in its predictive ability made by altering its diagnostic threshold. Current prognostic biomarkers were then identified by systematic literature review. The hypothesis generated was that the Epidermal Growth Factor Receptor and related pathway biomarkers are prognostically significant. By examining the largest published oral dysplasia cohort, it was demonstrated that EGFR, COX-2 and tetraspanins CD9 and 151 possess a significant prognostic ability in oral dysplasia. VALIDATION OF TISSUE MICROARRAYS IN ORAL DYSPLASIA Tissue microarrays can maximise the utilisation of finite pathological archives. Their use in dysplasia was validated for the first time through the development of a novel tissue-sparing virtual-array technique. ALTERNATIVES TO SURGICAL TREATMENT A feasibility chemoprevention trial was designed and initiated. The main finding was that national multicentre participation would be required for adequate recruitment. The significant resources required mean it is not currently feasible to execute such a trial in a population with a low incidence of oral dysplasia like the United Kingdom. DISCUSSION In summarising the current literature, this thesis highlights the key challenges in managing oral dysplasia. Improvements in identifying cases at highest risk of transformation have been made and will direct future work in a prospective cohort. Difficulties highlighted during the feasibility trial are already guiding the design of future trials.