Background: Cardiovascular disease (CVD) is one of the leading causes of death worldwide, driven by various metabolic risk factors and diabetes. Diet is a key modifiable component in the development of these risk factors. This study aimed to investigate cardio-metabolic risk factors associated with diet. Secondly, dietary interaction with genetic risk of diabetes. Methods: A cross-sectional analysis was conducted on 5,864 participants’ baseline data from the Airwave Health Monitoring Study. Participants completed a 7-day food diary and a health screening including blood sample, blood pressure and anthropometrics. Diet quality was assessed according to UK Dietary Reference Values (DRV) using the novel DRV index and the established UK nutrient profile model. The nutritional genomic association with diabetes and HbA1c% was studied using a polygenetic risk score (GRS). Results: A higher DRV score was associated with a lower waist circumference ( -0.56 p < 0.0001), total cholesterol ( -0.06, p < 0.0001) and glycated haemoglobin A1c ( -0.02, p=0.003). Individuals with a higher DRV score (top quartile vs bottom quartile) were less likely to have diabetes (OR 0.75, p=0.04), elevated blood sugar (OR 0.80, p=0.01) and abdominal obesity (OR 0.64, p < 0.0001). GRS was associated with a higher HbA1c ( 0.03, p < 0.0001) and higher risk of diabetes (OR 1.13, 95%CI 1.04-1.24). Interactions between GRS and higher diet quality modified the genetic effect on HbA1c (-0.017, pinteraction=0.02) in high-risk individuals. High alcohol intake (>16g/day) modified the genetic effect on HbA1c ( 1.22, p=0.002). Obesity (BMI >30kg/m2) increased the effect on HbA1c by =1.90 pinteraction =0.0006. Conclusion: Individuals consuming a high quality diet (high in complex carbohydrates, fibre, fruit and vegetables and wholegrain) aligned with the UK guidelines were associated with fewer metabolic risk factors for CVD and diabetes. A high quality diet also reduced the genetic effect on HbA1c and diabetes in high-risk individuals. These findings support the importance of encouraging a healthy diet, along with moderate alcohol consumption, as part of public health advice for a lower risk of CVD and diabetes, especially in high genetic risk groups.

Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) has recently been shown to be an efficacious HIV prevention strategy for key populations at high risk of acquiring HIV-1, including serodiscordant couples. This thesis addresses the following research question: what is the projected impact and cost-effectiveness of PrEP for serodiscordant couples in sub-Saharan Africa, and would it be a worthwhile intervention? By using statistical analysis and mathematical modelling, I answer this question and provide recommendations for the optimisation of antiretroviral-based HIV prevention this population. In this thesis, I begin by exploring the effect of the reduced risk of herpes simplex virus type 2 (HSV-2) acquisition by means of PrEP on the outcomes of an intervention, but conclude that the supplementary benefit is unlikely to substantially alter the costeffectiveness. I also perform statistical analysis of daily adherence patterns to PrEP, according to electronic monitoring, from the Partners PrEP Study and the Partners Demonstration Project in Kenya and Uganda and find that adherence was high in both settings. Finally, I adapt a microsimulation model of serodiscordant couples in Africa to include realistic PrEP adherence patterns, HIV-1 transmission, external partnerships, and empirical costs. Using this model, I simulate the likely impact and cost-effectiveness of a PrEP intervention according to characteristics and behaviours of couples in the context of a clinical trial and a demonstration project. Overall, I conclude that a PrEP intervention could be cost-effective or cost-saving when targeted to high-risk couples, but is unlikely to be cost-effective if expected incidence is low. In addition, the utility of PrEP for serodiscordant couples could be compromised if the resources needed to find high-risk couples are expensive or if couples are not found easily.

Ischaemic heart disease (IHD) is a leading cause of hospitalisation, mortality and healthcare spending in the industrialised world. Wide temporal, spatial and social class variations show that high IHD mortality is not inevitable. The temporal decline in IHD in the UK and other industrialised countries since the 1960’s and 1970’s has been decomposed into that caused by reductions in population risk which affect event rate versus that caused by changes in case fatality which can potentially be ameliorated by the health system. The persistent Northern excess in IHD mortality in England has not been studied in the same way. This is because there is no national database of IHD events and thus no systematic way to assess sub-national variation. I focused on the acute, life-threatening component of IHD – acute coronary syndrome (ACS). I constructed a national data set of ACS events using routine hospitalisation and mortality data and estimated ACS event rates, mortality and case fatality for each of the 354 English Local Authority Districts using a Bayesian spatial model to smooth away unwarranted variability. I decomposed spatial variation in ACS mortality into its constituent components of event rates and case fatality. 60-80% of the between district variation in mortality is due to variation in event rates depending on age and sex, and an additional 15-30% is due to variation in case fatality. Further, the proportion of events resulting in an out-of-hospital ACS death has more impact on differences in case fatality than do deaths following hospitalisation. These findings have important implications for directing health policies aimed at reducing ACS burden and addressing regional inequalities in health in England.

Fusarium Head Blight (FHB), a devastating disease of cereal crops worldwide, is receiving much attention to all facets of its biology. Given that a major challenge for agriculture is the changes driven by climate change, this thesis explored the effect of environmental conditions on three aspects of the biology of the causal fungi. At the within-season level, data on contamination of crops by FHB toxins were used to create a statistical model linking weather to toxin level, which closely follows the weather stated in guidance to farmers as increasing risk and performs similarly to other weather-only models for FHB. The model was used in conjunction with downscaled climate model output driven by a high emissions scenario to assess whether changes in risk due to changing weather are projected. Those projections do not suggest a large change in risk if the relationship with weather remains constant, but caveats for the projections are explained within. At the global level, published data on the distribution of two key Fusarium fungi were examined. The data were linked with agroecological data and statistical models built to test hypotheses on the influence of the presence of rice, maize, and climate factors on the relative prevalences of the species. The models support the hypotheses that rice presence increases the prevalence of F. asiaticum, while maize increases the presence of F. graminearum. The models add to the literature on fungal species distributions utilizing generalized linear mixed models. Finally, a large collection of isolates was studied with respect to growth at different temperatures to ascertain within- and between-population variation in this phenotype. The work was incomplete and inconclusive; results suggest little definitive relationship with examined variables but the protocols and further work suggested could be carried out on other fungal populations and then incorporated with genetic data to assess the potential for survival and evolution under environmental change.

Schistosoma mansoni is a metazoan parasite that infects millions of people across the developing world. I applied coalescence models to genome-wide single nucleotide polymorphisms (SNPs) from ten global isolates of S. mansoni and an isolate of the closely related Schistosoma rodhaini to infer the dates of: i) the speciation between S. mansoni and S. rodhaini; ii) the spread of S. mansoni across sub-Saharan Africa; and iii) the migration to the New World. Further, I used this sequence data to document signatures of directional selection between S. mansoni and S. rodhaini to uncover genes involved in host adaptation and under balancing selection in S. mansoni. I conducted a field study in Uganda to collect epidemiological data from primary schools that had been subject to contrasting intensities and durations of Mass Drug Administration (MDA). Children in endemic areas were examined for S. mansoni up to three days before and after treatment with praziquantel. I fitted a mixed-effects model to the egg count data and found that individuals from schools that were treated most intensively had a lower estimated mean egg reduction rate compared with individuals from less intensively treated schools, suggesting that more rounds of MDA may be resulting in S. mansoni parasites that are better tolerating anthelmintic treatment. Finally, I collected S. mansoni miracidia from patients in Uganda and developed a novel method for generating whole-genome sequences. In total, 213 miracidia from 35 patients were sequenced. Using a dataset of 5.4 million SNPs, I documented the population structure, characterised regions of the genome under selection and associated SNPs against the clearance phenotype. I uncovered the strongest signal of selection and the highest association with host clearance phenotype in a region at the beginning of chromosome 2 that contains two calcium channels; variants in this region may therefore be underlying the observed reduction in praziquantel efficacy.

The target groups for many nutrition interventions are mothers and children under the age of two, as evidence has shown significant and substantial benefit for these age groups. Less is known about the potential for school-age children to benefit nutritionally from interventions through a complementary, life-cycle approach. The central hypothesis tested here is that nutrition-sensitive interventions can improve growth at school-age and that schools are an effective platform for children to be able to access these interventions. I address this hypothesis by examining three key research questions: 1) whether and to what extent catch-up growth can occur at school age; 2) how household characteristics (agriculture and dietary quantity and quality in particular) are related to nutrition at school age and what entry points may exist for holistic intervention; and 3) how school feeding programs are related to education participation (and thus access to nutritional inputs through programming) and how programs may be strengthened to improve links with local agriculture. Examining the first question, in a review of the potential for catch-up growth at school age, a range of intervention studies counter claims of the irreversibility of pre-school growth faltering with evidence that early deficits can, at least to some extent, be made up in childhood and adolescence. For the second question, in analysis of relationships between school-age nutritional status and household agriculture in Mali, associations were observed between household agricultural production variety and measures of dietary diversity and food variety, but no associations between these measures and school-age child nutrition outcomes were found. In making the link to programming through the third question, no significant associations were found between school feeding and the education participation outcomes measured at the school level in Kenya. I conclude that opportunities for improving the nutrition of school-age children do exist and that understanding the potential for agriculture-nutrition disconnects and the dynamic nature of school feeding programs could help improve the design of multi-sectoral, nutrition-sensitive interventions at school age, including Home Grown School Feeding (HGSF).

Background Mobile medical apps – interactive software tools for consumer mobile devices such as smartphones – offer a novel context to support self-care by individuals with prevalent long-term conditions, such as diabetes and asthma. However, little is known about the quality and safety of available mobile medical apps, their potential to support desired health outcomes, or their acceptability to patients. The contribution of this thesis is to provide a detailed characterisation of issues of quality and safety affecting mobile medical apps for self-care that combines research, clinical and patient perspectives and to use these data to critique recent proposals from the UK National Health Services to offer self-care apps ‘on prescription’. Methods A multiple methods design to assess the state of research on mobile medical apps for self-care, appraise the quality of publicly-available apps and understand how and why individuals use mobile medical apps for self-care, using asthma and diabetes as representative long-term conditions. Results A limited research literature of moderate quality suggests modest benefits of app-supported interventions (defined as those that incorporate mobile medical apps as a major delivery mechanism) for the biochemical control of diabetes and equivalence to existing methods for asthma self-care. Evidence for cost-effectiveness is lacking. Mobile medical apps available through public stores rarely conform to guideline standards for information content or functionality and some, such as insulin dose calculators, pose a safety risk to patients. A range of motivational factors influence patient use of mobile medical apps for self-care, including concrete needs for data arising from changes in health status and the emotional consequences of greater awareness of disease state. Discussion Ubiquitous gaps in the quality of apps for self-care represent a potential challenge to healthcare professionals and policy-makers wishing to incorporate them into practice. A stratified response, which extends the principle of proportionality established in medical device regulation, is presented as a potential strategy to address these gaps while recognising resource and capacity constraints. Without such triangulation, the vision of ‘mobile medical apps on prescription’ is probably unrealistic.

This thesis includes the research, assignments and clinical placements that were undertaken for the degree of Doctor of Psychology (Clinical Psychology). The Major Research Project was focused on the concepts of guilt and shame and treatment motivation and readiness in forensic patients. Treatment motivation and readiness are important considerations in forensic settings. Models and theories of these concepts suggest affective factors such as the experience of guilt and shame are likely to have some impact on motivation and readiness for treatment. These models have been validated in general forensic settings, but although applied to forensic mental health settings, the validity of the different aspects of these models has not been directly examined with forensic mental health patients. This thesis aimed to investigate whether there was any relationship between guilt and shame and motivation and readiness for treatment in a sample of forensic patients. Part one of this thesis presents a narrative review of guilt and shame in forensic mental health participants. The findings of the review suggested that guilt and shame were relevant emotional experiences for forensic patients. Links between these emotions and motivation and readiness for treatment had not been empirically tested. Part two presents an empirical paper that investigated the association between guilt and shame and treatment motivation and readiness in patients residing in forensic mental health settings. The findings suggested that offence-related guilt was associated with readiness for treatment, whereas shame did not have a relationship with motivation or readiness. Part three presents a summary of clinical experience gained within this training programme and Part four contains the assessments completed during training.

La teoria clàssica de l'accident considera el seu origen com a producte de tres factors incidents: el factor humà, el factor tècnic i el factor (micro)mediambiental, tots tres configurant el marc de producció.La tesi se centra en l'anàlisi dels factors macroambientals de tipus tècnic, econòmic, social i laboral, difícilment observables des de la perspectiva interna d'una empresa, i la seva incidència sobre l'accidentabilitat laboral, tot analitzant-ne les variacions produïdes al llarg del temps sobre el fenòmen de l'accidentabilitat.La hipótesis que s'intenta demostrar en la tesi és que existeix una relació causa-efecte entre el "macroambient" del sistema productiu determinat per unes variables socieconòmiques determinables i l'accidentabilitat en els diferents sectors productius. Es fa l'anàlisi al llarg del període de 10 anys, període complex en quant als canvis tecnològics, econòmics i socials.Es fa també un anàlisi de l'accidentabilitat en el període i un anàlisi de les dades econòmiques principals i al seva evolució en l'esmentat període. S'apliquen mètodes de regressió lineal (variable dependent : el nombre d'accidents).Es conclou que l'evolució económica arrastra una sèrie de conseqüències tècniques, laborals i socials que son les que realment tenen influència certa en el fenòmen de l'accidentabilitat. Més que determinar un model matemàtic predictiu s'ha aconseguit un model explicatiu de la interrelació que se suposava en la hipótesis.

Public health policies are often influenced by social-ecological interactions that affect the achievement of policy goals and may produce early interruptions of actions. Paradigms, frameworks and models most commonly used in policy analysis do not account for the complexity of this phenomenon. Because of its transdisciplinary character, Sustainability Science may provide an appropriate perspective for crafting new models that allow scientists to understand these complex and dynamic interactions, specifically, by integrating different types of knowledge that reveal the network of social-ecological relationships affecting the behavior of actors involved in policies. AIM. This research aims to define the elements making up a model for analyzing public health policies from a sustainability science perspective. METHODOLOGY. This is a research of three stages. Firstly, foundations on sustainability science, transferable to health policy analysis, were theoretically developed by a documentary review. Secondly, a theoretical model was designed by reviewing some conceptual bases of modeling. Finally, the model was applied in a real context in order to estimate its scope and practical implications. This stage was carried out by a case study research attempting to analyze the sustainability of a malaria control policy in El Bagre (Colombia). RESULTS. Stage 1. Foundations on sustainability science were structured in three axes: ontology, epistemology and methodology. In the ontological axis, a study object for sustainability science was defined. This is the `social-ecological resilience of systems¿ and is supported on an historical ontology. In the epistemological axis, this research found that epistemological frameworks based on complex systems theory (transdisciplinary epistemology, transactional e. and reflexive e.) are the most appropriate ones for understanding unsustainability problems. In the methodological axis, this research found that one of the most important features of sustainability science is the problem-solving perspective, or use-inspired science. This perspective means that researches contribute to the solution of real problems. Some characteristics favoring this perspective are transdisciplinarity, participation, social learning, co-production of knowledge, accounting for multiple scales, and uncertainty management. Stage 2. The type of model structured here was a theoretical one. The crafting of this model led to theoretically develop the concept of social-ecological resilience and to design a model made up of three components of analysis which are: the social-ecological dynamics related to the target problem of health policies, the public policy tending to solve it, and the adjustment between the health policy and the social-ecological dynamics. Stage 3. The use of the model in the analysis of the malaria control policy in El Bagre (Colombia) enabled the research team to describe each model component. In the social-ecological dynamics component, for instance, this research found that gold mining and armed conflict are strongly related to malaria. The health policy component reveals the system of actors, their positions, interests and rules of action that give shape to the malaria control policy. In the adjustment policy-dynamics component, the research permitted to understand the sufficiency of the policy to adaptively respond to social-ecological dynamics of malaria. This study revealed that this policy is barely sustainable. CONCLUSION. This model is appropriate in account for social-ecological interactions affecting health policies. Nevertheless, theoretical and methodological principles still require additional progress. / . En el análisis de políticas públicas en salud se han venido utilizando modelos, enfoques y paradigmas de análisis que no dan cuenta de la complejidad del funcionamiento de este tipo de políticas. Las políticas públicas en salud suelen estar influenciadas por un entorno de relaciones socioecológicas que afectan el cumplimiento de los propósitos de la política pública y, en ocasiones, producen su interrupción temprana. Se requieren modelos que den cuenta de tal complejidad y la ciencia de la sostenibilidad puede brindar una perspectiva apropiada. Su carácter transdisciplinar permite integrar diferentes formas de conocimiento para revelar la red de relaciones socioecológicas que pueden afectar la conducto de los actores responsables de materializar las políticas. OBJETIVO. Esta tesis tiene por objetivo establecer los elementos estructuradores de un modelo para el análisis de políticas públicas en salud a partir de algunos fundamentos de la ciencia de la sostenibilidad. METODOLOGÍA. La investigación se desarrolló en tres etapas. En la primera, mediante una revisión documental, se desarrollaron teóricamente unos fundamentos de la ciencia de la sostenibilidad que sean aplicables al análisis de políticas públicas en salud. En la segunda se revisaron algunas orientaciones conceptuales sobre modelización y se diseñó un modelo teórico; y finalmente, se llevó a cabo un estudio de caso de una política de control de malaria en la localidad de El bagre (Colombia) para aplicar el modelo y analizar su alcance en un contexto real de aplicación. RESULTADOS. Los fundamentos para la ciencia de la sostenibilidad se estructuraron en tres ejes: ontológico, epistemológico y el metodológico. En el eje ontológico se definió que el objeto de estudio de la ciencia de la sostenibilidad es la resiliencia socioecológica de los sistemas y éste a su vez se fundamenta en una ontología histórica. En el eje epistemológico se encontró que las corrientes epistemológicas basadas en la teoría de los sistemas complejos (Epistemología transdisicplinar, E. Transaccional, E. Reflexiva) son las mas apropiadas para entender los problemas de insostenibilidad. En el eje metodológico se encontró que la perspectiva de solución de problemas es un rasgo característico de la ciencia de la sostenibilidad y que algunos principios como la transdisciplianriedad, participación, aprendizaje social, co-producción de conocimiento, la consideración de múltiples escalas y el manejo de la incertidumbre favorecen las posibilidades de que las investigaciones contribuyan a mejorar procesos de toma de decisiones. Con respecto al dseño del modelo, éste implicó desarrollar teóricamente el concepto de resiliencia socioecológica de los sistemas y ello derivó en un modelo constituido por tres componentes de análisis que son: las dinámicas socioecológicas relacionadas con el problema de salud que la política pública pretender resolver, la política pública misma, y el ajuste entre la política pública y las dinámicas socioecológicas. Para estimar el alcance del modelo en contextos reales, éste fue aplicado en el análisis de la política de control de malaria del municipio de El Bagre (Colombia). Este estudio de caso permitió observar, por ejemplo, que en el componente de dinámicas socioecológicas, la minería y el conflicto armado están muy relacionadas con la malaria; en el componente de la política pública, se describieron los actores, sus posiciones, reglas de operación, e intereses que dan lugar a la política de control, y en el ajuste se analizó la suficiencia de la política pública para responder a tales dinámicas. El estudio de caso reveló que esta política pública en El bagre es escasamente sostenible. CONCLUSIÓN. El modelo es apropiado para dar cuenta de la interacciones socioecológicas que influyen en las políticas públicas. Sin embargo, los principios teóricos y metodológicos aun requieren mayores desarrollos.