Altering maternal nutrition affects fetal development and can have long-lasting effects on the offspring, potentially predisposing them to later metabolic disease. These effects can occur without affecting birth weight, although small for date offspring appear to be at increased risk. One mechanism linking changes in the maternal environment to an increased risk of later disease is enhanced exposure to glucocorticoids (GC). Tissue sensitivity to cortisol is regulated, in part, by the GC receptor (GR) and 11-beta-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2. Several studies have shown the effects of maternal nutrient restriction on the programming of GC action in the offspring, however, dietary excess is far more characteristic of the diets consumed by contemporary pregnant women. The aim of this thesis was to provide a novel insight into the effects of moderate changes in the macronutrient ratio, within the maternal diet fed to pigs (whilst maintaining energy content), on offspring growth, development and liver metabolism until adolescence. Fat supplementation (Fat supplemented (FS): 9 %; Control (C): 2.5 %) from day 0 until 110 of gestation, reduced maternal glucose tolerance at term and decreased the survival rate of piglets after birth, possibly due to hypoglycaemia. In addition, supplementing the maternal diet with protein (Protein supplemented (PS): 16.3 %; C: 12.3 %) also increased the incidence of postnatal mortality, with surviving offspring demonstrating an up-regulation of mRNA transcripts involved in GC sensitivity i.e. GC receptor and 11βHSD-1, in the liver. Furthermore, this thesis demonstrated no negative effects of accelerated postnatal growth on low-birth weight piglets as others have suggested. In conclusion, this thesis has demonstrated a detrimental effect of fat and protein supplementation until day 110 of gestation on postnatal mortality. These findings could have profound consequences for the pig industry where reducing piglet mortality is of economic importance. In addition, an increased level of protein in the diet during gestation increases GC sensitivity in the offspring which may be indicative of excess GC exposure in utero. These types of adaptations could have significant implications in determining the programming effects of maternal diet on adult disease risk.

Evidence from human and animal studies has highlighted the sensitivity of the developing fetus to environmental insults, such as maternal undernutrition, during gestation. These nutritional perturbations to the intrauterine milieu may engender a legacy of deleterious health consequences in adulthood. This thesis presents a series of studies which test the `mis-match‘ fetal programming theory; that is, whether a nutritionally poor diet prenatally interacts with a nutritionally excessive diet postnatally to overtly increase risk factors for adult disease. The effect of a maternal global energy restriction is contrasted against a maternal specific protein restriction, each fed during either early or late gestation. Adult offspring were subsequently exposed to an obesogenic environment (elevated feed with increased lipid content whilst restricting physical activity). Offspring metabolic flexibility and competence were assessed through routine blood samples throughout postnatal life and at 7, 18 and 24 months of age by glucose (GTT) and insulin (ITT) tolerance tests and body composition by dual energy x-ray absorptiometry. In general males appeared more susceptible to developmental programming than females at a number of timepoints. Furthermore, an increased first-phase or incremental area-under-the-insulin-response curve was observed in 1) offspring following maternal protein restriction in early gestation at 7 and 24 months of age, despite maternal protein restriction in late gestation significantly reducing birthweight and 2) in offspring exposed to maternal energy restriction during late gestation at 24 months of age in response to a GTT. Since, in both groups, the response of all offspring to an ITT (from a euglycemic baseline) was similar, infers that developmental programming in sheep followed by nutritional excess is first revealed as affecting either the pancreas (~insulin hypersecretion) or the liver (hepatic insulin resistance, reduced first-pass insulin metabolism). The studies illustrate the importance of habitual consumption of an `optimal’ balanced diet through gestation on postnatal health, especially in light of the current obesity epidemic.

China is experiencing a dramatically increasing process of rural-urban migration, which is almost parallel with the phenomenal economic growth and development in China in the last decades. Given the massive scale of rural-urban migration in China, the health services access and health constraints not only matter to rural-urban migrants but also have important implications for broad public health concerns. However, this issue has not been paid enough attention in academic research. This study focuses on the multifaceted reality of health constraints and health services access among migrants by originally exploring the social strata, social networks, and the understanding of health and health services among migrants. The research questions are stated as follows: What constraints and difficulties do migrants face with respect to their health and health services access? Is there a hierarchical structure in health services access and medical treatment access among migrants? When there is a shortage of financial resources, do they resort to informal social support (such as informal social networks/ guanxi) to obtain help and why? What are their understanding and experience of health and why? Furthermore, this study investigates the health constraints and health services access of rural-urban migrants in the absence of equal social protection by the government. By conducting 36 qualitative interviews in Dengcun Village, a migrant community in Beijing, China, this paper: (1) Investigates issues concerning environmental health risks of migrants, their health seeking behaviours, and the constraints they encountered in accessing health services with respect to the social strata among migrants. It argues that the main obstacles to access health services are not only the shortage of financial resources among rural-urban migrants, but also lie in the institutional blindness regarding health security provision, rural-urban dualism and the household registration system in China. (2) Highlights the key function that social networks play in health and health services access among migrants in China, which has rarely been discussed in previous studies. Examines the range of social networks among migrants, from which they can acquire support, including financial and spiritual, when they are dealing with health problems. The study argues that social networks resemble a double-edged sword to rural-urban migrants in terms of health care access. The fact that migrants lack savings may not be the sole and essential reason for their extreme vulnerability in times of illness. Some migrants, who are in financial difficulties though, may have some assistance, including financial support and emotional support from their social networks. However, on the other hand, the assistance from social networks on their health and heath care access is limited, not only because their social networks is limited, but because the social networks should not bear the responsibility to support health services access of migrants, similar to or more than the state and migrants' employers. (3) Discusses the understanding of health among migrants, and further analyses that although many migrants have not formed proper understanding of the connotation of health and have limited knowledge of health, prime responsibility should not be put on the migrants because their poor understanding of health mainly results from their rural perspective while health and health services access depend on the social-economic environment in which they live and work.

This research analyses the role and action of the Trade Related Intellectual Property Agreements (TRIPS) and pharmaceutical patents in the public health network of Djibouti, by using an approach largely inspired by actor-network theory (ANT). In doing so, it addresses issues that run beyond the specificities of this case study and relate more broadly to the relevance of ANT to socio-legal analysis. The relation between TRIPS, pharmaceutical patents and public health in developing countries has been a widely debated issue in the past decade. However, the field remains limited by a relative uniformity in the range of approaches and case studies chosen in existing research. This project aims to address some of these limits, by looking at the role of TRIPS and pharmaceutical patents in a small country with no local pharmaceutical industry, no pre-existing official system of intellectual property, and with a largely undocumented public health system. Using ANT in this project allowed for the complexity of the mechanisms of both TRIPS and pharmaceutical patents to be highlighted. It participated in emphasising that they need to be understood as made of multiple, co-existing dimensions. By demonstrating how specific connections and associations have shaped what TRIPS and pharmaceutical patents are and do in the networks of Djibouti, this research emphasises the artificiality of the dichotomy between social and legal, and proposes an understanding of social connections as symmetrical and co-dependent. It discusses the more general relevance of this approach to socio-legal research. The example of Djibouti also allows for new questions to be raised in relation to the actual impact of TRIPS and pharmaceutical patents in “developing countries”. In particular, it emphasises the need to return to a more balanced approach to the relation between pharmaceutical patents and health in poor countries.

High habitual dietary glycaemic index (GI) and glycaemic load (GL) may relate to elevated insulin resistance and therefore may be more important and relevant in South Asian populations known for high prevalence of insulin resistance. The main objective of this research was to investigate the dietary GI, GL and insulin resistance of a sample of healthy South Asians in Glasgow, UK (a total of 111 healthy individuals: 60 males, 30 South Asians and 30 Europeans; 51 females, 22 South Asians and 29 Europeans). Estimation of dietary GI and GL (from weighed food intake records) considered the GI values of single foods and mixed-meals from relevant publications and from laboratory food/mixed-meal GI measurements (Chapter 3). The GI of key staple South Asian foods alone (chapatti, rice, pilau rice) and as mixed meals with curried chicken was measured using standard methods on 13 healthy subjects. The key staples had medium GI (chapatti, 68; rice, 66 and pilau rice, 60) and glycaemic responses to the mixed-meal of staples with curried chicken were found to be lower than the staples eaten alone. GI of the mixed-meals fell in the low GI category (chapatti with curried chicken, 45 and pilau rice with curried chicken, 41). Weighed food intake records (WFR) (recorded for 3-7 days) and self-administered previously validated food frequency questionnaires (FFQ) (applied to habitual food intakes in the past 6 months) was assessed for agreement through correlation analyses, cross-classification analysis, weighted Kappa statistics and Bland and Altman statistics. The two methods mostly agreed in carbohydrate (CHO) food intakes implying that the WFR reflected habitual intakes (Chapter 4). In consideration of potential confounding effect of physical activity on the relationship between dietary variables and HOMAIR, physical activity level (PAL) and Metabolic equivalent score (METS) of main daily activities of study subjects were derived from self-reported physical activity records (Chapter 5). Mean PAL were similar between South Asian and European males (median PAL of 1.61 and 1.60, respectively) but South Asian females tended to be less physically active than European females (mean PAL of 1.57 and 1.66, respectively). South Asians were less physically active in structured exercise and sports activities, particularly South Asian females and South Asians (males and females combined) with reported family history of diabetes showed inverse relationship between daily energy expenditure and HOMAIR. South Asians were found to be more insulin resistant than Europeans (HOMAIR median (IQR) of 1.06 (0.58) and 0.91 (0.47), p-value= 0.024 respectively in males; mean (SD) of 1.57 (0.80) and 1.16 (0.58), p-value= 0.037, respectively in females) despite similarities in habitual diet including dietary GI and GL. The mean habitual dietary GI of South Asians was within the medium GI category and did not differ significantly from Europeans. South Asian and European males’ dietary GI (mean, SD) was: 56.20, 2.78 and 54.77, 3.53 respectively; p-value=0.086. South Asian and European females also did not differ in their dietary GI (median, IQR) was: 54, 4.25 and 54, 5.00; p-value=0.071). Top three staples ranked from highest to lowest intakes in the South Asian diet were: unleavened breads (chapatti, Naan/Pitta, Paratha), rice, bread (white, wholemeal, brown), and potatoes. After statistically controlling for energy intake, body mass index, age, physical activity level and socio-demographic status, an inverse relationship (Spearman partial correlation analyses) between dietary GI and HOMAIR was observed (r, -0.435; p-value, 0.030) in South Asian males. This may be explained by the observation that the lower the dietary GI, the lower also, the total carbohydrates and fibre intakes and the higher the fat intake. In South Asian females, dietary GI and GL respectively, did not relate to HOMAIR but sugars intake related positively with HOMAIR (r, 0.486; p-value, 0.048). South Asian females, compared to European females, reported higher intakes of dietary fat (38.5% and 34.2% energy from fat, respectively; p-value=0.035). Saturated fatty acid (SFA) intakes did not differ between ethnic groups but SFA intakes were above the recommended level of 10% of total dietary energy for the UK in all groups, the highest being in SA females. In conclusion, Ethnicity (South Asian), having family history of diabetes, the wider diet profile rather than habitual dietary glycaemic index and glycaemic load alone (low GI, low fibre and high fat diets in males for instance; and high fat, high sugar diets in females) as well as low physical activity particularly in structured exercise and sports may contribute to insulin resistance in South Asians. These observations should be confirmed in larger future studies.

Patient confidentiality has received much attention in recent years because of the rise in the number of confidentiality breach incidents and the need to improve the provision of health services in general. Patient confidentiality is defined as the patients‟ right to the protection of their personal medical information within health institutions under normal conditions. While literature on the protection of patient confidentiality exists, there is little or no attempt made to use a theoretical model to represent this, and hence, with which to appraise the practice of patient confidentiality in health care systems. The main aim of this research study is to contribute to the development of a model for the protection of patient confidentiality in Libya, using experience and evidence from elsewhere, and also to suggest means to improve confidentiality through the application of lessons from the UK health service. The standpoint taken is a pragmatic one, as the focus is on the utility of the proposed model. There are two principal strands to the research: one concerns the views of experts as to factors that influence patient confidentiality. The second major one is the development of a System Dynamics Model to present the flow of patient data and the places where breaches of confidentiality are likely to occur. These two strands are then considered jointly to provide a basis for conclusions and recommendations of particular relevance in Libya (and perhaps more generally). The data used to identify the main factors that affect the practice of patient confidentiality were collected using two stages: literature review and expert surveys. The first iteration requesting views was sent to experts from Libya, Europe and elsewhere in the field of patient confidentiality, to establish a set of factors that might influence the practice of patient confidentiality. A second iteration followed with selected respondents to rank the relative importance of elements of contributing to two factors, trust and ethics, that were identified in the first expert letter survey. The results from the expert letters indicated that the main factors that influence the practice of patient confidentiality, especially in Libya, were trust, ethics, regulation and technology. The results from the interviews and the focus group showed that the findings of the current research had ecological validity. This is based on the Libyan participants‟ views, which strongly supported the research results as having the potential to improve Libyan patient confidentiality systems by learning from the UK experience. The responses were used to inform the insights obtained from the UK NHS model of patient confidentiality of 2003, which was developed into an innovative simulation using Systems Dynamics Modelling (SDM). Quantitative data to populate the model was drawn from NHS statistics. The model was „validated‟ through personal interviews and a focus group with individuals who had experience in the practice of patient confidentiality in the Libyan health service. The results of the running of the SDM model were also compared to known data to provide a check on validity. The proposed SDM model of patient confidentiality was shown to have ecological validity though the views of medical staff and medical records managers in two major general UK hospitals. The premise was that breaches of patient confidentiality could occur either from (i) human error when dealing with patient medical data within the national health services by staff such as frontline medical staff, doctors and nurses, or (ii) at locations of safe-keeping of patient notes, where medical records managers and others store patient medical data on IT systems, with varying dynamics and volume. The results obtained from the developed model of patient confidentiality are encouraging; they may assist health service managers to minimize breaches of patient confidentiality occurrences. Therefore, the current study proposes a framework and recommendations that can help to improve the protection of patient confidentiality systems in the Libyan health service and assist in delivering a good quality of health care.

Background: UK welfare reform endeavours to reduce out-of-work health-related benefit receipt and support people into employment. Such reforms assume that work is good for health and that targeting welfare-to-work interventions at individuals will result in moves from benefit receipt to employment. The research in this thesis tackles two questions associated with UK welfare reforms: (1) Is work always good for health? And, (2) Is the focus on motivating individual Incapacity Benefit (IB) and Employment and Support Allowance (ESA) recipients appropriate, or are there barriers to return to work that this approach cannot address? Methods: Three approaches were taken to address the aims: 1) Longitudinal analysis, using Generalised Estimating Equations, of the West of Scotland Twenty-07 Study (Twenty-07), to explore transitions from worklessness to employment. The analyses looked at both employment and health outcomes (self-rated and anxiety or depression) and took account of the psychosocial quality of the jobs obtained. 2) A systematic review of qualitative studies that explored the barriers and/or facilitators to employment from the perspective of people out of work because of health conditions or disabilities. A qualitative synthesis, using meta-ethnography, of the included studies was conducted. 3) A primary study utilising in-depth interviews with IB and ESA recipients, General Practitioners (GPs), and Employment Advisors (EAs) in Glasgow, to gain more understanding about barriers and facilitators to work and to fill the gaps identified in the qualitative synthesis. The interviews were analysed using Framework Analysis methods. Findings: Findings from Twenty-07 data showed that only 6.6% of those out of work because of ill health returned to work within the follow-up period. After a transition from worklessness to employment those in low-quality jobs had higher odds of poor health than those who moved to high-quality jobs, even after taking account of prior health. Those who remained workless had higher or similar odds of poor health as those who had moved to low-quality jobs. Nine studies were synthesised in the systematic review. Participants in the studies identified similar barriers and/or facilitators to return to work. Barriers and facilitators were related to health, workplace factors, the need to change job, financial issues, life stage and social circumstance, support, and self-construct. Synthesis and interpretation of the studies led to themes that were then further explored. These themes were: the complex pathway of return to work; competing participant and author narratives, and a difficulty of interpretation; the distinction between expected and experienced barriers to work; differences in barriers and facilitators by participant characteristics; job quality; and work-role centrality, adaptation, and financial risk. Seventeen IB or ESA recipients, six GPs, and six EAs participated in the qualitative study. Their barriers and facilitators to work confirmed the findings of the systematic review. All IB/ESA recipients had multiple and interacting barriers that were not limited to their motivation but also related to wider labour-market and social-context issues. Those with complex social situations and mental health conditions had lower expectation that they would successfully return to work. All participant groups were concerned that the policies of the welfare system did not match up with the labour-market or the social context. Conclusions: A very low proportion of those out of work because of ill health transitioned into employment. This is concerning because current policy is to reduce the number of people receiving IB and ESA. The research showed that there is a significant challenge to support this group into employment and that policies focusing on motivating individuals may miss important barriers to return to work. There appear to be health benefits from return to work; however, job quality is important, and the potential for health improvement is limited if the job is of poor quality. Supporting people into work has the potential to improve health, but more effort is required to determine how to improve support and target where it is most needed. Further research is necessary to explore the results of the current welfare reform i.e. whether IB/ESA recipients move into work, what helps them do so, and whether they experience a change in health.

This thesis concerns the role of middle managers in strategic change in the NHS. It addresses a research gap identified by Dopson and Stewart (1990) who called for more empirical studies of the role of middle managers in specific contexts and highlighted the public sector as being of particular interest. It reports qualitative research carried out across 5 successive case studies in the NHS. The contextual backdrop to the study is one of competing tensions around the role of the middle manager, both generally in organisations and specifically in NHS trusts. On the one hand, it is argued that the role of the middle manager is one of diminishing importance. On the other, it is argued that the role of middle managers is one that should be enhanced. Both sets of commentaries tend towards the speculative and lack an empirical foundation. In the NHS such tensions are reflected in government policy. An enhanced middle manager role is encouraged through the development of a general management ethos. Simultaneously there have been attacks upon middle managers from the Minister for Health in the past Conservative Government and the present Labour Government. Theoretically, a typology of involvement of middle managers upon strategic change developed by Floyd and Wooldridge (1992, 1994, 1997) is brought to bear as a conceptual lens with which to view the role of middle managers in strategic change in the NHS. Using this typology the role of middle managers is found mainly to be with the implementation of strategic change, rather than other roles, such as 'synthesising information', 'facilitating adaptability' or 'championing alternatives', although there are some illustrations of a role for middle managers beyond implementation of strategy. Despite their main role remaining within the implementation of deliberate strategy, the case studies illustrate that there is a possibility for an enhanced middle manager role in strategic change within this. However, Floyd and Wooldridge's typology does not sufficiently distinguish between the differing influence that middle managers may enjoy within the implementation of deliberate strategy. Therefore, one suggestion is that further constructs for the influence of middle managers upon strategic change be developed. It is also noted that middle managers operate under significant constraints that impact upon the possibility of taking up an enhanced role, within the implementation of deliberate strategy and in roles outside this. Principal amongst these constraints is the presence of significant medical group power and the influence of central government intervention. Therefore, middle managers' influence may be limited, on the one hand, to that which converges with the strategy set out by executive management that in turn has been driven by government prescription. On the other, it is likely to be limited mainly to that of the administrative domain rather than the medical domain or where influence is exerted upon the medical domain to changes with which the medical group is agreeable. The empirical findings also illustrate that any enhanced role for middle managers, within the constraints of government policy and medical group power, may require the presence of certain conditions. Firstly, where strategic change allows for emergence as well as deliberateness, then middle manager may exert more influence upon strategic change. Secondly, they may exert more influence upon strategic change, where it is not solely conceived in top-down rational planning terms, but where is combined with a political element of strategic change. As a result the formulation and implementation of strategic change are likely to be intertwined rather than separate and sequential. This may allow for more involvement of middle managers in the strategic change process. Finally, in order that middle managers can take up the potential for an enhanced role under these conditions, there may need to be some investment in organisation and management development and organisational structures that facilitate boundary-spanning opportunities for middle managers. NB. This ethesis has been created by scanning the typescript original and may contain inaccuracies. In case of difficulty, please refer to the original text.

Tuberculosis (TB) remains one of the most devastating diseases in humans. Nowadays, tuberculosis therapy is not sufficient to control the TB epidemic and only lasts for 6 months to cure patients and prevent relapse; therefore, the treatment of Mycobacterium tuberculosis (Mtb) is particularly challenging (1). New antibiotics, mainly those that are derived from new chemical classes, are more likely to be more effective against resistant strains. Moreover, expanding the knowledge of the mode of action of drugs has important implications in tackling TB. Only empirical approaches can be adopted in the journey of discovering new anti-tubercular drugs until a clear picture of latency and persister cells’ physiology is achieved. Mtb has the extraordinary ability to survive under hypoxia, suggesting a high degree of metabolic plasticity. The flexibility conferred by a modular respiratory system is critical to the survival of Mtb, thereby also making it a promising area of research for new drug targets. This thesis aimed towards the characterisation of cytochrome bd-I quinol oxidase (bd-I), a respiratory component that is believed to operate during both the replicative and “dormant” Mtb phenotypes. The essential nature of Mtb bd-I, which has no human homologue, has been confirmed in a recent deep sequencing study of genes required for Mtb growth by Griffin et al. (2), further confirming its potential as a novel target. Recombinant Mtb bd-I was successfully expressed under the control of the pUC19 lac promoter in the Escherichia coli ML16 bo3/bd-I and MB44 bo3/bd-I/bd-II knockout strains, allowing “noise-free” measurement of the enzyme. Initial steady-state kinetics of the enzyme was presented using a range of quinol substrates, revealing a substrate preference for dQH2 over Q1H2 and Q2H2. A number of bd-I inhibitors were identified and their pharmacodynamic profiles against Mtb H37Rv were determined. In addition, a pharmaco-metabolomics platform was initiated to explore the cellular response of Mtb to current first-line TB drugs as well as in house bd-I and type II NADH inhibitors. The initial findings are discussed in the context of the known mode of action of the drugs and future research needs in drug discovery of this devastating disease.

My original contribution to the body of knowledge is a portfolio of evidence which includes: • An evaluation of Reache (Refugee and Asylum seekers Centre for Healthcare professionals Education) North West using a PEST (Political, Economic, Social and Technological) analysis and Thematic Content Analysis of semi-structured interviews which led to the development of the Reache North West model of education and training for refugee healthcare professionals. • The development of a course entitled Safe and Effective Clinical Communication Skills and the dissemination of this course via conference posters, oral presentations and a published journal article. In the case of the conference posters, the course was identified as good practice on two occasions. • A business case which led to the development of the Salford Communication and Language Assessment Resource (SCoLAR). This thesis analyses and critically appraises the action research, ideas, reports and publications, from 10 years of organizational experience. This also includes over ten years of personal experience teaching and managing education programmes for international students, and over four years of working with refugee healthcare professionals, assisting them in returning to their professional role in the UK. The evaluation of Reache North West sought to answer the research question ‘Are we effectively preparing refugee doctors for work in the NHS?’ Although there were only 5 respondents the evaluation answered this question positively. Also discussed is the process for the development of the safe and effective clinical communication course and the difficulty in this course to other groups of internationally trained doctors. My observations and experience of working with International Medical Graduates who have encountered language and communication difficulties are also discussed with the acknowledgement that more robust research processes are needed for future research.