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Overweight and obesity are major health challenges worldwide, often associated with morbidity and mortality. In Northern Ireland (NI), 65% of adults are living with overweight and obesity. Rising obesity levels have been accompanied by an increase in negative attitudes towards people living with obesity, including weight stigma. Systematically mapping adult obesity-policies and weight-management services in NI could help identify gaps in coverage/provision. Understanding the motivations, preferences and experiences of adults living with obesity is also an important consideration in developing appropriate interventions. The overall aim of this thesis was to comprehensively understand obesity-related policies, weight management services, public needs and weight stigma in NI to inform future programme development. This involved: a) Systematically mapping obesity-related policy actions/services for adults in NI using the Behaviour Change Wheel b) Investigating public views about obesity and regarding experiences of weight stigma/discrimination in adults; c) Exploring public perceptions relating to obesity policies/personal experiences of maintaining a healthy weight in adults, involving a qualitative framework analysis of barriers and enablers; d) Quantitatively assessing the weight management preferences of NI adults living with obesity including priorities for future programme development and; e) Conducting Personal and Public Involvement activities with adults with lived experience of overweight/obesity in NI to aid the future development of a weight management intervention. This research highlighted that obesity services were largely prevention-focused with an over-reliance on education. Development of weight management options are recommended within a flexible obesity-care pathway. The prevalence of weight stigma/discrimination on the Island of Ireland, suggested that targeted education about the causes of obesity to reduce weight stigma in society is warranted. Distilling the PhD findings along with PPI representatives helped create a strong basis to develop a future weight management intervention for adults, informed by formative research relevant to the UK/NI obesity context.

Background: Evidence from cohort studies indicates that a healthy lifestyle can improve cancer survival. However, evidence from randomised controlled trials is lacking. This study aimed to investigate the feasibility of HEAL ABC lifestyle intervention in patients after colorectal cancer (CRC) surgery and treatment. Methods: This was a mixed-methods, feasibility randomised controlled trial (RCT) based on World Cancer Research Fund Prevention Guidelines (WCRF/AICR), the Health Action Process Approach theory and Motivational Interviewing technique. Thirty-five participants were recruited and allocated to the usual care control group or a telephone-based intervention with printed resources and a website. Data on anthropometry, diet, physical activity, quality of life, and behaviour change were collected in both groups at baseline, three months post-intervention, and six-month follow-up. Data were analysed with Stata using means, confidence intervals and multiple regression model (V14, StataCorp LLC, College Station, TX). A subgroup of participants took part in in-depth interviews and framework analysis was used to analyse data. Results: Recruitment was challenging (35 recruited, 31 ineligible, 37 eligible but declined). In total, 34 participants completed the three months intervention (97% retention rate), and 31 (89%) completed six months follow up. The adherence to the intervention calls was 100%. The intervention was reported to be acceptable to participants. Participants suggested that three to six months after surgery or treatment is needed before they are ready to make lifestyle changes. Participants reported feeling left alone post-treatment and asked for further support with diet and exercise. Intervention met their needs with the content, guidance and kept them accountable towards their lifestyle goals. The WCRF/AICR score improved in the intervention group compared to control (R2 1.1, 95%CI 0.5 to 1.6, p=0.0001) at three months, and at six months (R2 0.9, 95%CI 0.1-1.7, p=0.03). The DQI-I score improved in the intervention group compared to control (R2 8.9, 95%CI 3.3 to 14.5, p=0.003) at three months, and at six months (R2 8.2, 95%CI 1.1 to 15.3, p=0.02). Total physical activity improved compared to baseline (R2 27.0, 95%CI 5.5 to 48.4, p=0.02), but no significant difference between groups was observed. Conclusion: New strategies are needed to recruit CRC survivors to RCTs. The HEAL ABC intervention was feasible to deliver, positively rated and reported as beneficial by participants, supporting them in healthy lifestyle changes after CRC.

Food selectivity is a common cause of concern in children diagnosed with Autism Spectrum Disorders. In fact, food selectivity is twice as common in children with autism than in typically developing children. The present research started with a systematic literature to review existing studies that examine the effectiveness of behaviour analytic interventions targeting an increase in diet variety. Results showed that a variety of behavioural principles and strategies were combined in these interventions, with the two most frequently used being reinforcement and escape extinction. The absence of functional assessment and preference assessments was noted. Three studies were conducted based on the above findings by implementing a rigorous and replicable intervention protocol that included functional assessment and preference assessment and resulted in the increase of variety of diet for participants diagnosed with Autism Spectrum Disorder. The studies used a changing criterion research design to evaluate food acceptance under individualised differential reinforcement of alternative behaviour (DRA) conditions. Findings are discussed in the context of intervention effectiveness and impact of using functional assessment and preference assessment.

Colorectal, breast, and prostate cancer account for nearly a third of all diagnosed cancers, and some dietary factors may influence risk. Moreover, circulating insulin-like growth factor-I (IGF-I) concentrations have been positively associated with risks of colorectal, breast, and prostate cancer, and IGF-I might mediate some diet-cancer associations. This thesis investigates the associations of dietary factors, IGF-I concentrations, and IGF-I related cancers among participants in the UK Biobank cohort. Associations between intakes of food groups (438,453 participants) and macronutrients (11,815 participants) with IGF-I concentrations were explored. Intake of fish was positively associated with IGF-I concentrations, as was protein from dairy products; however, associations differed by dairy protein source in that milk and yogurt were positively associated with IGF-I concentrations whereas protein from cheese was not. Intakes of fibre and wholegrains were also positively associated with IGF-I concentrations. The association between protein from all dairy products, milk, and cheese and colorectal, breast, and prostate cancer was explored among ~114,000 participants. Protein from all dairy products and milk were inversely associated with colorectal cancer risk, whereas a borderline positive association was observed for prostate cancer risk for men in the highest quartile of intake compared to those in the lowest quartile. IGF-I concentrations did not appear to explain these associations. Prospective associations between carbohydrate types and sources and colorectal cancer were explored among ~114,000 participants. Non-free sugars and fibre from wholegrains were inversely associated with colorectal cancer risk. Evidence of heterogeneity by genetically predicted butyrate synthesis was observed; participants with high predicted butyrate and consuming higher wholegrains had a lower risk of colorectal cancer whereas no association was observed for those with low genetically predicted butyrate synthesis. Finally, diet groups in relation to all cancer and common cancer types were investigated in prospective analyses of ~472,000 participants. In comparison to regular meat-eaters, low meat-eaters had lower risk of all cancer and colorectal cancer, fish-eaters had a lower risk of all cancer and prostate cancer, and vegetarians had a lower risk of all cancer, postmenopausal breast cancer, which may be due to their lower body mass index, and prostate cancer. Differences in IGF-I concentrations or free testosterone did not appear to mediate these associations. In conclusion, research from this thesis supports dietary factors, such as dairy protein, being associated with IGF-I concentrations. However, whether these same dietary factors are positively associated with IGF-I related cancers remains unclear, suggesting other factors or mechanisms external to the IGF-I pathway. Potential novel findings suggest that wholegrain intake and colorectal cancer risk may vary by genetic factors for butyrate production and further research is needed to replicate and explore this further. Different diet groups may also be related to IGF-I related cancers; however, IGF-I concentrations did not mediate this association. Further research exploring mechanisms through and external to the IGF-I pathway is needed.

The present thesis investigated the development of episodic memory through middle and late childhood, and how individual differences in health and lifestyle impact this development. The first study (Chapter 2) explored the developmental patterns of episodic memory including individual content elements (what, where and when) and integrated what-where-when (WWW) representation on British children aged 6-12. Results suggest that episodic memory continues to develop during this period, with item, spatial, temporal and WWW memory all improving relatively linearly with age. These improvements are driven by both associative binding and strategic control abilities. The second study (Chapter 3) extended this work by additionally exploring how variation in encoding and strategy use influences memory development in a slightly older age range of 8-13. While associative and strategic retrieval abilities showed improvement with age, strategic encoding ability seemed to stay relatively stable across this period of late childhood. Regarding the effect of strategy use, older children produced and noticed more strategies than younger children, but only the younger children benefitted more from noticing the strategies. The third study (Chapter 4) extended the developmental pattern to a diverse population by replicating the experiment with a sample of Chinese children aged 8-10. Results from Chapters 3 and 4 also indicate that executive function is likely to play a critical role in memory development. The fourth study (Chapter 5) investigated the influences of health and lifestyle factors, with particular emphasis on diet and physical activity, on memory development. The fifth study (Chapter 6) went further in trying to understand how cross-cultural differences in lifestyle may contribute to different patterns of memory development. Results from Chapters 5 and 6 suggest that individual differences in diet and exercise are linked with detectable differences in memory development, and that these effects may not be mediated by executive function. Collectively, the findings of this thesis shed light on a general pattern of episodic memory development over diverse populations across different cultures, and highlight the importance of a healthy lifestyle in promoting children's cognitive and memory development.

Food prepared out-of-home is typically energy-dense and nutrient-poor. More frequent consumption of this food is associated with poorer overall dietary patterns and obesity. Previous research has tended to focus on access to food prepared out-of-home in the physical food environment, which is often greatest in more deprived areas. However, this food can now also be accessed through online food delivery services. Although online food delivery services are globally established, there is limited public health knowledge about the prevalence of their use and factors influencing this, the sociodemographic characteristics of customers, and the extent to which the opportunity to use them is socioeconomically patterned. The aim of my thesis was to help better understand the use of online food delivery services to access food prepared out-of-home. First, I analysed survey data collected in 2018 to identify the prevalence of online food delivery service use and the sociodemographic characteristics of adult customers across Australia, Canada, Mexico, the United Kingdom, and the United States of America. From 19,378 respondents, around one in six had used an online food delivery service in the past week. Respondents who were male, younger, more highly educated, living with children and those who identified with an ethnic minority had greater odds of online food delivery service use. These patterns were similar in each country but the strength of associations varied. Notably, respondents with a high versus low level of education had greater odds of online food delivery service use in all countries except the United Kingdom. Second, I conducted telephone interviews with 22 adults living in England who were frequent online food delivery service customers. Participants reported that they could access a higher number of food outlets and a broader range of cuisines through online food delivery services compared with the physical food environment. Additionally, these services allowed participants to access exclusive price-promotions and use streamlined purchasing processes, which were seen as unique advantages. Participants reported that they believed the food available through online food delivery services was mostly unhealthy. Nevertheless, this food met their expectations about `takeaway food`. Despite reported drawbacks of online food delivery services, which included over-convenience and, paradoxically, access to unhealthy food, participants reported no intention to discontinue use because it was normal to purchase food prepared out-of-home in this manner. Informed by existing evidence and my qualitative research, I investigated associations between access to food prepared out-of-home through online food delivery services and online food delivery service use, and body weight. In my individual-level data-linkage study of 3067 adults living in Great Britain, the number of food outlets accessible online was positively associated with online food delivery service use in the past week. However, it was not associated with body weight. Despite the perspective of frequent customers, the number of cuisine types accessible online was not associated with online food delivery service use. Finally, I examined access to food prepared out-of-home through online food delivery services in England and variation according to area-level socioeconomic position. In a cross-sectional study, I found that the number of food outlets accessible online was highest in the most deprived areas of England in November 2019. I followed this with a repeat-cross sectional study that assessed changes in the number of food outlets accessible online over time, within the context of the Coronavirus Disease 2019 (COVID-19) pandemic. I found that it was only in the most deprived areas of England that the number of food outlets accessible online in March 2022 surpassed the number from November 2019. Taken together, these findings indicate that online access to food prepared out-of-home in England is socioeconomically patterned, and that inequalities therein widened over time. The findings from my thesis help better understand multiple aspects of online food delivery service use. The number of food outlets accessible online emerged as being particularly important. A higher number was positively associated with online food delivery service use, which suggests it can influence food purchasing practices. Indeed, this was supported by the views of frequent online food delivery service customers in my qualitative research. Additionally, the number of food outlets accessible online was highest in the most deprived areas of England in November 2019, and increasingly so over time compared with less deprived areas. Thus, the opportunity for online food delivery service use is unequal across the socioeconomic spectrum in England. Future research should seek to understand how food purchased through online food delivery services contributes to overall dietary patterns and health, and the need for public health intervention.

Suboptimal diets are among the leading factors fuelling the global rise in the prevalence of type 2 diabetes and other metabolic disorders. Most epidemiological studies of the associations between diet and nutritional factors and metabolic outcomes have relied on self-report instruments. Nutritional biomarkers offer a complementary objective approach but have not been widely applied in African settings to test associations between diet and metabolic outcomes. This thesis aimed to examine the relationship between diet and nutritional factors assessed using a wide range of objectively measured nutritional biomarkers and metabolic outcomes in a population-based study in adults in rural and urban Cameroon (n= 651). I spent the first part of my PhD in the laboratory measuring circulating vitamin D, folate, holotranscobalamin, carotenoids and tocopherol using mass spectrometry techniques. Subsequently, I undertook analyses to describe the patterns and identify factors affecting these nutritional biomarkers reflecting dietary intakes and plasma zinc, which was measured in an external laboratory. Most of the biomarkers showed distinct patterns by age, sex, level of education, physical activity levels and rural/urban area of residence. I then investigated the independent cross-sectional associations of these biomarkers with metabolic risk factors exploring the possibility of both linear and non-linear associations and adjusting for a wide range of potential confounders. Circulating folate and carotenoids, which are associated with intake of fruits and vegetables, showed an inverse association with the metabolic syndrome score and fasting glucose respectively. Holotranscobalamin, a biomarker that reflects intake of animal-sourced foods, was positively associated with the metabolic syndrome score. Circulating zinc, reflecting intake of protein-rich foods, was inversely associated with several markers of glucose homeostasis (fasting and 2-h glucose and homeostatic model assessment for insulin resistance). Higher 25-hydroxy-vitamin D, a marker of vitamin D status, was associated with lower fasting glucose. Finally, I investigated the potential effect modification by rural/urban area of residence, sex and body mass index on the association between the biomarker and metabolic outcomes. Overall this PhD showed 1) Rural and urban differences in the distribution of the nutritional biomarkers in Cameroon 2) Significant associations of the studied biomarkers reflecting dietary intakes with metabolic risk factors. Findings from my PhD advance the understanding of the role of diet and nutritional factors on metabolic health in adults in Cameroon. Diet is modifiable, making it a realistic target for public health intervention to improve metabolic health in this population.

Background There is a limited understanding of factors determining obesity in Sub-Saharan Africa, particularly Ghana. This thesis, therefore, aimed to contribute to knowledge on obesity determinants in Ghana to guide evidence-informed obesity policies. Methods Multiple approaches were used in this study. These approaches included a literature review, two stakeholder engagements, a survey, Geospatial Information Systems (GIS) techniques and regression analyses. First, a literature review was conducted to identify literature gaps on determinants of obesity to direct this study. Then, key stakeholders were engaged to prioritise the literature gaps whose exploration was critical for obesity policies in Ghana. After, a multi-stage sampling approach was used to generate a current obesity dataset to address the stakeholder-prioritised research questions. Geospatial Information Systems (GIS) techniques and regression analyses were then conducted to identify single and multi-level determinants of obesity in Ghana. Finally, the stakeholders were engaged again to explore interventions to tackle the identified obesity determinants. Results The literature review showed gaps in multi-level determinants of obesity, the interrelationship between obesity and other lifestyle behaviours and the relationship between religion, culture, and obesity. The analysis of these gaps showed that a unit increase in the number of fast-food joints and supermarkets within a shorter radius (2km & 5km) increases the odds of obesity in Ghana. Additionally, being a Muslim (correlation coefficient (r) = 0.45) or Ga (r = 0.39) is associated with a 11% and 9% increased risk of obesity, respectively. Diet and physical activity are also interconnected lifestyle determinants of obesity. These lifestyle factors are determined by factors like sex, income status and perceptions. For example, individuals who perceive obesity as an inherited condition are less likely to consume a healthy diet (r = -0.24 and engage in physical activity (r = -0.29). However, those earning 2,000 Ghana cedis and above are more likely to eat healthily (r = 0.46) and exercise (r = 0.49). Additionally, men are 16% more likely to engage in physical activity and 5% less likely to consume a healthy diet, indicating that the predictors of the lifestyle determinants are comparable but dissimilar in some instances. Finally, the thesis also showed that obesity is prevalent in Ghana (53%), and about 45% of the population are neither physically active nor consume healthy diets. Conclusion Obesity is determined by religion, ethnicity, physical activity & diet, and the local food environment. These determinants could be mitigated by a trade-off between awareness campaigns and economic regulations, like taxation and food subsidies. Therefore, the government of Ghana and other relevant agencies should factor in these determinants and interventions when reviewing and implementing obesity policies in Ghana.

Autoimmunity encompasses a range of chronic inflammatory conditions resultant from inappropriate immune response against self-antigens. The exact etiology of autoimmune conditions remains elusive, with many genetic and environmental factors implicated. One of proposed environmental factor is mercury (Hg). Humans are primarily exposed to Hg predominantly through the consumtion of fish which contain methylmercury (MeHg). The impact of Hg exposure through fish consumption on autoimmunity has gained public health interest, owing to the high importance of fish in the human diet. Fish are a rich source of nutrients, especially the n-3 long chain polyunsaturated fatty acids (LCPUFA) which have immunomodulatory properties and have been proposed to mitigate against adverse effects of MeHg. Although, human studies were focused on the impact of Hg exposure on autoantibody production there is increasing interest in how Hg may influence Th17 response, an immune cell lineage implicated in autoimmune pathogenesis, notably in Systemic Lupus Erythematosus (SLE). Therefore, this PhD thesis aimed to investigate associations between Hg exposure and cytokines associated with the Th17 axis in both fish consumers and autoimmune patients with SLE. A narrative literature review was undertaken to evaluate the contribution of dietary sources to Hg/MeHg exposure. This chapter provided a comprehensive review of foods that may contain Hg/MeHg, including both plant and animal products and discussed how other nutrients present within these foods may influence the adverse effects of Hg exposure. A study of a high fish-consuming young adults from the Republic of Seychelles, found no association between MeHg exposure (hair Hg concentrations 10.21 (5.98) ppm) and Th17 response, with or without adjustment for LCPUFA status. In this study, IL-17F was negatively associated with female status in models which controlled for total n-6 and n-3 LCPUFA (β = ‐0.292; 95% CI: ‐0.532, ‐0.052; p = 0.017) and n-6:n-3 LCPUFA ratio (β = ‐0.290; 95% CI: -0.529, -0.051; p = 0.018). Also, there was an association between IL-27 and maternal socioeconomic status (β = ‐0.005; 95% CI: -0.010, 0.000; p = 0.044) in the model adjusted for n-6:n-3 LCPUFA ratio and IL-27 concentrations were negatively associated with smoking status in adjusted for total n-6 and n-3 LCPUFA (β = -0.157; 95% CI: ‐0.284, ‐0.029; p = 0.016) and for n-6:n-3 LPCUFA ratio (β = -0.158; 95% CI: -0.285, -0.031; p = 0.015). A separate study investigated the relationship between Hg exposure and disease activity in a cohort of SLE patients, and demonstrated that exposure to Hg, measured as inorganic Hg (iHg) in urine (median 1.99 ng/g creatinine) and as MeHg in hair (median 0.59 ppm), did not significantly influence the relationship between Th17 cytokines and clinical measures of disease activity and disease-associated damage. Furthermore, in this study IL-17E was positively associated with SLICC/ACR+ in unadjusted (β = 0.465, 95% CI: 0.432, 0.786, p = 0.005) and adjusted (β = 0.355, 95% CI: 0.050, 0.660, p = 0.023) models. Finally, the influence of fish consumption on MeHg status and IL-17A and IL-22 was determined following an 8-week long intervention, in which women of child-bearing age consumed either one or two portions of fish high in MeHg (tuna), fish low in MeHg (sardines) or a meal without fish. Whilst the intervention with tuna resulted in a significant increase in MeHg status, no significant changes in Th17 cytokines were noted between the intervention groups, thereby indicating that MeHg exposure did not alter the Th17 response. Overall, results from this thesis suggest that exposure to MeHg, through regular fish intake, does not contribute to Th17-associated autoimmunity in young adults and has no effect on the cytokines associated with Th17 response in SLE or young women of child-bearing age. These findings contribute to the evidence supporting a public health message recommending regular fish intake, as a part of well-balanced diet among general population.

People with type 2 diabetes mellitus (T2DM) need information about what to eat in order to be able to self-manage their diabetes and to prevent long term complications. Their information activities involve accessing information from a wide range of sources. While studies have explored nutrition information activities, few have identified the instinctive, embodied and hidden nature of everyday information practice. This study aims to investigate the nutrition information practices undertaken by people with T2DM, to identify information accessed and used, and its perceived value. The study consisted of a systematic review which informed an empirical research study. The systematic review utilised a narrative approach to the analysis of the 28 included studies. The empirical research study involved 20 people, 19 with T2DM (and one partner without T2DM) who were recruited through diabetes support groups and the researcher's workplace. Practice theory underpinned a social constructionist qualitative methodological approach. The diary-interview method involved participants completing diaries to capture their nutrition information experiences followed by an in-depth interview, to further explore these experiences. Data were analysed using thematic analysis. The systematic review identified that nutrition information practices were key to the self-management of people with T2DM. The complexity of nutrition information and the tacit nature of information practice made this worthy of further research. The empirical study identified that experiences of diagnosis affected the way that T2DM was integrated into everyday lives and impacted on participants' T2DM self-management. Participants developed personal embodied 'rules of thumb' towards the way they managed their diabetes and expressed feelings of guilt if they strayed from these. Beliefs, embodied knowledge and skills affected engagement with information sources such as food labels and peer support groups. Information practices were influenced by the degree to which diabetes was embodied and were interconnected with food-related practices. The study highlighted that some information, for example designed to assist in self-management and making food provisioning decisions, is challenging for people with T2DM to use. Sharing of information with peers in a support group setting could be of value to people with T2DM. People living with T2DM need ongoing support and encouragement in developing information practices that assist with their self-management. Patient-led dietetic consultations could be enhanced through the use of nutrition information diaries to help identify and develop embodied nutrition information practices. Peer support groups could be recommended to help people who are newly diagnosed to come to terms with diabetes and to encourage diabetes self-management. The content and format of food labels is in need of review to enable interpretation by those with T2DM and to support the choice of foods with inherent nutritional value. This study challenges the current body of research relating to information activity and proposes information practice as a theoretical framework that could be used by practitioners and academics to explore information activities further.

This thesis explores sugar consumption and kin-making in a north Edinburgh neighbourhood, and shows that sugar is central to processes of social relatedness. I argue that sugar reveals the meaning of kinship in Scotland, and that experiences of kinship reveal the material and symbolic potentialities of sugar. During 13 months of fieldwork in primary schools, homes and community groups, I traced the values and meanings attributed to sugar, and its role in processes of socialisation. Sugar poses ethical problems. It is marked out as by educational and medical institutions as publicly bad - for individual health and bodies. Yet sugar is also marked out as privately good - for social bonding, for indexing intimacy, for recognition, compensation, and for marking out the meanings of particular times, spaces, types of relationship, and the kind of authority that infuses them. Perhaps above all, sugar stands in for instances of care and particular kinds of (dangerous?) pleasure. How people and institutions resolve the ethical problems sugar poses in their everyday relationships tells us about these relationships, about the contested place of pleasure, and notions of responsibility. This thesis is split into two parts. Part one examines sugar 'in public', and moves outwards from schools and medical institutions towards the home. Part two explores sugar 'at home', and examines the gendered nature of parenting, as well as other kinds of homes - those of grandparents for example. Both sections overlap in showing that public and private are not given but brought into being, with sugar used to generate and negotiate boundaries between the two. We see values of home brought into school - through home-baking - to mark out practices of care in school, and public health values that travel homewards. I theorise sugar as a substance of relatedness, which reveals kinship in Scotland as processual. Sugar reveals perceptions of children, and relationships with children, as fragile, and highlights the primacy of the bounded nuclear family home as the ideal site of good kinship and successful growing of children - even as kinship in Scotland unfolds in many places and possible configurations. I use the term 'living with sugar' to challenge conceptions of sugar consumption as an individual choice. In showing the pervasiveness of sugar in its many forms and negative messages about sugar in this environment, I argue that sugar's constant structural availability - and its status as a less-than-good moral option - can be rethought as a condition of life for those bringing up children. This framing of sugar as bad, yet safe to consume in moderation, expands the value attributed to sugar, increasing its specialness and the pleasures it enables. As diet becomes an arena in which good kinship can be evaluated, the management of sugar in children's diets can become burdensome for parents - an effort often distributed along gendered lines. The common-sense, yet ambiguous, notions of balance and moderation, presented as a relatively straightforward 'choice', sets up many parents (especially mothers) for feelings of failure.

Background: Cancer treatments are evolving, so that in many cases cancer is becoming a chronic disease. Rehabilitation is a cornerstone in the management of many chronic diseases, however, it is not yet a routine component of cancer care, in spite of this being advocated (Tiberini R, 2015, Alfano et al., 2016). There is limited evidence for the core components of a rehabilitation programme for patients with incurable cancer. The progressive decline in function and nutritional status in these patients would support an approach that targets these factors. The multi-modal therapeutic approach proposed to treat cancer cachexia, which incorporates exercise and nutrition (Fearon, 2008, Solheim, 2018), has the potential to be adapted as a rehabilitation programme for patients with any type of incurable cancer. However, the feasibility of such a programme remains to be tested. Aims: The aims of this thesis were: firstly, to examine the evidence for combined exercise and nutritional interventions in patients with incurable cancer. A phase II, randomised controlled feasibility trial of an exercise and nutritional rehabilitation programme (ENeRgy) versus standard care was designed and undertaken for patients with incurable cancer. Assessing the primary (feasibility) and secondary (exploratory) endpoints of this trial constitute the second and third aims of this thesis. Methods: A systematic review was undertaken to assess existing evidence for combined exercise and nutritional interventions for patients with incurable cancer. The internationally recognised Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria were applied to rank evidence relating to patient-important outcomes, detailed in chapter two. The ENeRgy trial was undertaken as detailed in chapter three. Eligible participants came from two Edinburgh Hospice community palliative care teams or the Edinburgh tertiary Oncology centre. Participants were ≥18 years of age; Karnofsky Performance Status (KPS) ≥ 60; had a diagnosis of incurable cancer (defined as metastatic or locally advanced cancer not amenable to curative treatment); and were not undergoing anti-cancer therapy. Participants were randomised in a 1:1 ratio to receive an eight-week exercise and nutritional rehabilitation programme (intervention arm) or standard care (control arm). The primary endpoints examined feasibility of the trial and compliance with interventions, while secondary endpoints examined recruitment, retention, participant and carer quality of life (QoL) including sleep parameters. Physical activity measures included mean daily step count measured by physical activity monitor (PAM), two minute walk test (TMWT), timed up and go test (TUG), Life Space Assessment (LSA) and KPS. Nutritional status was measured using weight, the abridged Patient Generated Subjective Global Assessment (aPG-SGA) questionnaire and a ten point verbal scale assessment of nutritional intake (AveS). Overall survival was also measured. All endpoints were assessed at trial baseline (week 0), midpoint (week 5) and endpoint (week 9). Results: Systematic Review: There are a limited number of published clinical trials examining combined exercise and nutritional rehabilitation in patients with incurable cancer. However, the existing evidence suggests there are multiple beneficial effects: the highest quality body of evidence pertained to improvements in physical function and depression: graded as moderate (B). Improvements in QoL and fatigue were graded as low (C), and the least quality of evidence (very low, D) related to improvements in overall function and nutrition/ weight. ENeRgy Trial: Forty-five people (28 males) were recruited over 15 months with an attrition rate of 36% (n=16) with a higher rate of attrition in the control arm (41% vs. 30%). Attrition was mainly due to deterioration in health and no participants withdrew due to the intervention being overly burdensome. Twenty-one participants had a GI or thoracic malignancy and the median [inter-quartile range, IQR] age was 78 years [69-84]. Trial procedures were well tolerated and at least 76% of participants in the treatment arm complied with >80% of the trial interventions. There were no significant differences in participant QoL, with the exception of emotional functioning which remained significantly higher in the intervention arm [P=0.006]. A non-significant improvement in carer QoL was seen in the intervention arm compared to the control arm. There was a non-significant increase in weight in the intervention arm compared to a loss in the control arm (P=0.184). There were no significant differences in step count (P=0.55), TUG (P=0.78), TMWT (P=0.48) and LSA (P=1.0), a-PG-SGA scores (P=0.249), AveS (P=0.398), KPS scores or survival between trial arms. Conclusions: Results of the systematic review suggest that there are multiple benefits to be gained for patients with incurable cancer from combined exercise and nutritional rehabilitation programmes, most notably in terms of physical function and mood. This ostensibly could result in improvements in QoL, but adequately powered trials are lacking. Results from the ENeRgy trial demonstrate that delivering an exercise and nutritional rehabilitation programme in a hospice outpatient setting is feasible in terms of patient recruitment and compliance with interventions, despite attrition. Furthermore there are potential benefits, including improvements in emotional functioning, carer quality of life and weight, which require a larger phase three trial to fully elucidate. Funding for the follow- on phase three trial 'ENeRgise' is currently being sought and the results of this trial could lead to fundamental changes in the way we approach rehabilitation in Palliative Medicine.

Background: Ileostomy formation is a common surgical procedure. Complications include high output and obstruction for which dietary management is common but not clearly defined. Aim: To explore dietary advice and modifications for ileostomy management through investigation of the current evidence and experiences of people with an ileostomy, and healthcare professionals (HCPs). Methods: 1) A systematic scoping review of the evidence for dietary management in people with an ileostomy, following JBI methodology. Experimental, observational, and qualitative studies were included, as well as published expert opinion from the last decade. 2) An online survey asking adults with an ileostomy about dietary advice they received and would have preferred to receive. 3) A qualitative study involving in-depth interviews with hospital-based HCPs; analysed thematically using the framework method. Results: The review found an abundance of literature, particularly expert opinion, on dietary management for people with an ileostomy. However, this literature was highly heterogenous in terms of dietary strategies and outcomes reported. Of 291 survey respondents, 90 did not receive dietary advice; however, 82 (91%) of these would have liked advice. >1/3 of respondents experienced anxiety, confusion, and frustration relating to their diet. Stoma nurses were the most common source of dietary advice. Qualitative findings revealed differences in understanding, priorities and framing of dietary advice between professions which may contribute to conflicting information. Inter-disciplinary working increased HCP confidence in, and consistency of, dietary advice to patients with an ileostomy but varied between hospitals. Conclusion: People with an ileostomy need better dietary advice. This could reduce anxiety and physical complications, improving quality of life and reducing burden on the NHS. To achieve this, high quality research evaluating dietary management and provision of dietary advice for people with an ileostomy is a priority to inform best practice. Findings from this thesis will inform future development of relevant and realistic dietary interventions.

The Scottish diet contains an excess of energy, saturated fat, and salt, while at the same time is poor in several key micronutrients. An animal model has been used to test the hypothesis that this imbalanced diet programs offspring metabolism. Female rats have been fed a diet(SIMD) formulated to reflect the diet of the poorest pregnant women and compared with animals fed a diet (SACN) formulated to incorporate the current UK recommendations. For comparison a third groups of animals were fed the widely used AIN-93G diet. Animals fed the SACN diet had more body fat compared to the AIN-93G group prior to mating. Fetal weights were comparable in all three groups, however postnatal lean tissue growth in the SIMD and SACN offspring was reduced. This was associated with lower dietary protein content and quality. There were extensive changes in the fatty acid profiles of maternal tissues and animals fed the SIMD diet accumulated triglyceride in the liver. LCPUFA, notably arachidonic acid was lower in the fetal brain, however by weaning, the profiles were similar, suggesting fetal brain development is susceptible to an imbalanced maternal diet. To test the long-term consequences, offspring were maintained on stock diet up to 37 weeks of age. At 4-weeks of age, pups from dams fed SACN diet had a greater proportion of body fat however this was transient and by 10 weeks of age the proportion of body fat was similar in all three groups. The maternal diet did not create persistent changes in food intake or differences in glucosehomeostasis (assessed by HOMA or insulin tolerance test) in the adult offspring. In conclusion, maternal metabolism and the mobilisation of maternal reserves serves to protect the developing offspring.

Mandibular cortical bone morphology varies considerably across mammals and has been attributed to changes in feeding behaviour related to diet, subsistence and food mechanical properties (FMPs), including the shift from hunter-gathering to agriculture within humans during the Neolithic. Trabecular bone is the internal structure that resides within most bones in the mammalian skeleton, and it also varies in response to differing levels of strain according to the Bone Functional Adaptation theory. Trabecular bone has been analysed in a variety of contexts in the post-cranial skeleton and the primate mandible in relation to both locomotor functions and FMPs. However, there is little research into trabecular bone diversity in relation to intraspecific variation of masticatory function. Understanding how trabecular bone differs in response to dietary variation in human and non-human primate groups can be used to improve interpretations of evolutionary and temporal variation of diet in the past. Furthermore, comparisons of trabecular morphology of mice in a controlled experimental model allows for validation of any observations evidenced in the humans and non-human primates and effects of extrasomatic processing of food in humans. This thesis investigates, a) whether variation in diet corresponds with trabecular bone morphology in the mandible among closely related groups of the same species; and b) how this variation differs between each of these species. This research uses three-dimensional volumetric analyses to quantify the trabecular bone across a sample of 9 human, 5 macaque, 3 baboon and 2 mouse groups with documented dietary differences, which represent a number of diverse ecologies and locomotor behaviours. Data was collected via μCT scanning at the Cambridge Biotomography centre and the London Natural History Museum. Trabecular bone was analysed via BoneJ and consisted of three volumes of interest (VOI) from the condyle in humans and cercopithecoids, and one from the corpus in mice. Statistical analysis consisted of a combination of tests, including ANOVA, Kruskal-Wallis, Mantel, Principal Component Analyses, Multiple Multivariate Regression, and General Linear Models to determine any intra- and inter-species variation. Results illustrated significant variation amongst trabecular parameters that corresponded with differences in diet among humans and mice, however, limited differences were seen between the baboons and macaques. Significant differences were found between both human and macaque groups that could not be explained by dietary variation, suggesting strong influences from phylogenetics, as well as effects from ontogeny and sex in mice. Similarities between mice and humans suggest there are significant impacts on trabecular bone variation due to extrasomatic processing of food. These data illustrate that multiple factors may influence trabecular morphology in the mandible, which may or may not be consistent with known genetic relationships among taxa. In addition, distinctions were found between the different VOIs of the mandibular condyle that differed between human groups from the same subsistence strategy, suggesting that paramasticatory behaviour, or influences from health and nutrition, likely impact trabecular morphology. This research demonstrates that trabecular morphology in the mandibular condyle and corpus may be used to interpret behaviour relating to mastication and diet across humans, non-human primates and mice.

This thesis studies how economic circumstances and psychological factors in the decision environment affect individuals' behaviours and choices, particularly in the context of dietary and economic decisions. Using both theoretical models, observational data and behavioural experiments, the role played by economic uncertainty, stress and failure is studied. Understanding what drives individuals' dietary choices and economic decisions is an important basis for developing policies aimed at tackling obesity and poverty. The first chapter examines the relevance of economic uncertainty as a pathway in the causal link from education to dietary choices and body weight, both theoretically and empirically. Previous research argues that instincts to hedge starvation risks in historic times of food insecurity might cause individuals today to non-optimally gain body weight in the face of uncertainty. In my theoretical analysis, I show that rational economic decisions can also lead to adjustments in diet when facing uncertainty. If eating healthy is an investment in future health, rational utility-maximizing individuals will reduce their consumption of healthy foods when facing economic uncertainty. In my empirical analysis, data from the British Cohort Study 1970 (BCS70) and the Quarterly Labour Force Survey (QLFS) is used to examine the relevance of financial, wage and job security as mediating factors in the link between education and body weight. My results suggest job and wage security among men and financial security among both genders to be significant mediating factors. The second chapter examines whether stress leads to unhealthy dietary choices using a lab experiment, conducted jointly with Michèle Belot, Jonathan James and Martina Vecchi. We propose a novel stress protocol that aims to mimic everyday stressors experienced by low socioeconomic status individuals, specifically mothers of young children. The protocol consists of computerized tasks under time and financial pressure. We evaluate the impact of (mild) stress on immediate and planned food choices, comparing a group exposed to our stress protocol relative to a control group. Immediate consumption is measured with in-laboratory consumption of low calorie and high calorie snacks; planned consumption is measured with an incentivized food shopping task. The stressfulness of the stress protocol is evaluated using subjective assessments, as well as physiological measurements (heart rate and salivary cortisol levels). We find no statistically significant effect of stress on the nutritional content of immediate or planned food consumption, thus no support for the hypothesis that everyday stressors are a likely explanation for unhealthy food choices. The third chapter examines the individual and combined influences of short-term stress, failure and success on economic decision making using an online experiment with a novel experimental protocol, conducted jointly with Martina Vecchi. Participants completed two online sessions, during each of which they carried out a variety of economic decision making tasks: decisions on altruistic behaviours, choices under risk, intertemporal substitution choices, and effort choices. To introduce experimental variation in participants' stress levels, they were assigned to complete an incentivized cognitive task aimed at inducing mild stress, either at the beginning of the first or the second session. The incentive structure for the stress task involved a deduction from participants' pay-off if they performed below an unknown threshold. With the second experimental treatment we introduced variation in participants' perceived failure or success by randomizing feedback about their performance relative to the threshold and by varying the threshold. Independent of the timing of the stress task, participants were assigned to receive either no feedback, feedback with a low threshold level (success condition) or feedback with a high threshold level (failure condition) prior to the economic decision making tasks in the second session. The stress protocol was perceived as significantly more stressful than a control task, and it induced a sizeable and significant rise in state anxiety. The provision of negative feedback ("failure") significantly lowered participants' assessment of their performance, induced feelings of failure and raised state anxiety. Despite successfully inducing psychological short-term stress and failure, we find no statistically significant evidence of an impact of stress, failure or success on economic decision making.

Background: The incidence of dementia is predicted to double every 20 years, with prevalence in the UK to reach 2.1 million by 2050. Modifiable risk factors such as diet in midlife have been shown to be associated with a reduced risk of dementia in later life. The aim of the research was to use the Behaviour Change Wheel and COM-B model to explore barriers and facilitators to the uptake of the MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) which was designed to promote brain health, and examine the effects of a dietary intervention on the cognitive function, mood and quality of life of Northern Ireland adults in midlife. Design: The Behaviour Change Wheel (BCW) was used to guide and inform intervention development which involved the use of several methodological approaches. A systematic review was conducted to assess the effectiveness and use of psychological theory in dietary interventions that promote a whole diet. Content of the interventions were coded according to the Theory Coding Scheme. Focus groups and interviews based on the COM-B model and Theoretical Domains Framework (TDF) explored barriers and facilitators to the uptake of the MIND diet (n=25). The BCW guided the systematic selection of intervention function, behaviour change techniques and mode of delivery in designing a 12-week randomised controlled feasibility dietary intervention (n=41). Outcome measures for COM-B, cognitive function, mood, and quality of life was recorded for both the intervention and control groups. Participants were healthy males and females aged between 40-55 years old, living in Northern Ireland. Results: Nine intervention studies were included in the systematic review. Results found that dietary scores improved for at least one food group. Overall, studies reported a moderate application of the theory coding scheme, with poor reporting on fidelity. Content analysis revealed that the main perceived barriers and facilitators to the uptake of the MIND diet were; time, work environment, taste preference and convenience, improved health, planning and organisation, and access to good quality food. A repeated measures ANOVA showed that in comparison to the control group, the 12-week dietary intervention improved mood, quality of life, MIND diet score and capability, opportunity, and motivation towards MIND diet consumption. Conclusion: Findings from this research provide insight into the personal, social, and environmental factors that participants report as barriers and facilitators to the uptake of the MIND diet. To our knowledge, this is the first study to use a theoretical framework to explore people's attitudes towards consuming the MIND diet, and the first RCT examining the effectiveness of the MIND diet on health outcomes. The results add to the dietary and cognitive function literature and to the behaviour change literature by describing and specifying the design, content, proposed mechanism of action and implementation for a theoretically informed dietary intervention. Recommendations for enhancing the role of health professionals in promoting cognitive function at midlife in an attempt to promote functional independence and better cognitive function in later life.

This thesis is concerned with the impact of socio-economic, political and environmental shifts on Early Medieval communities, specifically England and its links with continental Europe. I have utilised multi-tissue (bone, dentine and enamel), multi-isotope (δ13C, δ15N, δ18O and 87/86Sr) and multi-proxy data to analyse the lifeways of people in Early Medieval England within a European context in a multi-scalar way (sub-continental, regional, kingdom and community scales). This meta-analytical approach has allowed me to investigate Early Medieval transitions across the first millennium AD and better characterise and disentangle human-environment interactions in the period. Throughout this thesis high levels of isotopic variability and cultural dynamism within Early Medieval communities are clear. The core themes of this work are – climate and environment, changing foodways and migration. This approach has allowed me to better provenance people based on isotopic diversity and see cross-cultural contact. It also highlights the impact of climate change (the Late Antique Little Ice Age and Medieval Warm Period) on human δ18O values, showing the widespread and relatively rapid impact these events had on climate and on drinking water sources. The significant diachronic changes in both diet and in mobility patterns found here reflect the highly dynamic and far from insular position of England within Europe in the first millennium AD. My analyses support a model of continual and relatively large-scale migration from the continent Europe across the period, and changes to foodways which reflect not just shifts in economics and agricultural practice but changing worldviews (e.g. the impacts of Christianisation). Isotopic data when combined with archaeo-historical evidence show that identity construction in Early Medieval communities was highly complex, and there is no clear link between isotopic patterns, genetics and grave goods usually seen as “ethnic” signifiers. I show that these were multi-origin communities in continual contact through long-distance networks which influenced the changes we see throughout the first millennium AD.

Cambridge was a well-established town and an important trade centre in the High and Late Medieval period (11th-16th century). Historical accounts and archaeological evidence indicate that the Late Medieval period was a tumultuous chapter in English history, with episodes of war, climate change, famine and plague. It is argued that the social and economic changes, particularly those associated with the Black Death of 1348-50, would have significantly affected food production and procurement in England and that dramatic population reduction may have resulted in changes in population replacement and diversity. However, it is not fully understood to what extent events in the Late Medieval period affected towns like Cambridge, and whether they were experienced universally across the local population. This thesis utilises contextualised isotope analysis of human and faunal skeletal remains from cemetery sites excavated from Cambridge and its hinterlands to investigate what life was like for the population living in the High and Late Medieval period. Isotope sampling focussed on High and Late Medieval skeletal remains, but to evaluate the scale of change across the longue durée, skeletal remains dating from the Neolithic to the Post-Medieval period were also sampled. A multi-tissue (bone, dentine, enamel) multi-isotope (δ13C, δ15N, δ18O, 87Sr/86Sr) approach was used to understand how diet and mobility varied at an intra- and inter-individual and population scale. Collagen from 246 faunal bones, 227 human tooth roots and 314 human ribs was analysed for δ13C and δ15N, carbonate from 295 tooth crowns was analysed for δ18O and δ13C, and 170 tooth enamel samples were analysed for 87Sr/86Sr. Successful results were combined with previously generated data from the area, totalling 252 faunal isotope results and 1174 human isotope results. The results of the isotope analysis have allowed for the characterisation of diet across multiple sites, indicating variation based on social status, religious beliefs and locality. Isotope analysis has identified a small number of individuals who were unlikely to have spent their childhood in Cambridge and may have migrated into the town. Potential localised, short-distance migration in women has also been identified. Most importantly, this thesis concludes that the data does not show conclusive temporal changes in the High and Later Medieval periods which could be linked to events in the 14th century. Some general temporal change in diet may be present, but this is likely to be linked to the increasing popularity of marine fish consumption following the 'fish event horizon'.

The burden of neurocognitive diseases, such as Alzheimer's, is of global concern and points to an urgent need for accurate detection and prevention strategies. This thesis investigated dietary components, in particular those that affect vitamin B levels, such as white fish consumption and veganism, which have the potential to alter cognitive outcomes in the population. Also investigated were external factors, significantly caffeine consumption, time of day, and quantity of sleep, not associated with age-related impairment, that can alter neuropsychological test performance. The literature reveals that short, multi-domain cognitive tests are commonly used for dementia screening; this study has focused exclusively on cognitive domains associated with the early stages of Alzheimer's disease. Cognitively healthy adults were assessed using a cognitive test battery that focused on memory and processing speed. Memory test scores improved by 0.03 points for every gram of white fish consumed, whilst participants following a vegan diet scored significantly worse on tests of composite memory than their omnivorous counterparts. Interaction tests showed that prior caffeine consumption improved short-term memory test scores up to age 70. Participants of all ages performed best at their age-optimal times and further improved for immediate word recall tests with prior caffeine consumption. Processing speed scores increased linearly with hours of sleep. The results of this thesis suggest that nutrition and external factors have a significant impact on cognitive test performance. These novel findings have implications for research, diagnosis and prevention of chronic neurological disease, and public health guidance relating to cognitive function, for all ages.

The role of diet in the development and control of inflammatory bowel disease (IBD) remains incompletely understood. Epidemiological studies have implicated the western diet in IBD aetiopathogenesis but data from clinical studies are yet, in the main, to fully support this. People living with IBD can be left frustrated by the lack of consistent dietary advice they receive resulting in self-imposed dietary restriction and alterations in eating behaviour. For the first element of this project, we collected data from healthcare professionals regarding the dietary advice they provide to people with IBD. The results demonstrated frequent inconsistencies in the dietary recommendations provided. Beliefs regarding the role of diet in the control of inflammation and functional gastrointestinal symptoms were variable. Following this, we report the results of three studies addressing the dietary practices and beliefs of people with inactive ulcerative colitis (UC), South Asian people living with IBD and those with older-onset IBD. The study of inactive UC highlighted that, even when in remission, people demonstrated fairly consistent dietary beliefs and patterns of food avoidance. Furthermore, the study of British South Asian people with IBD showed more extreme alterations in dietary behaviour than similar studies in the Caucasian population. Finally, the cohort with older-onset IBD continued to report frequent food avoidance and use of whole food exclusion diets which may be of concern in this at risk population. The final element of this project involved conducting a novel feasibility study investigating neurocognitive aspects of appetite and dietary behaviour. Whilst recruitment was terminated early due to the COVID-19 pandemic, the results showed promise for the use of the experimental paradigm in future studies. Overall, this work has helped highlight how the current dearth of credible evidence for the role of diet in IBD may impact on both those living with this disease and the healthcare professionals who help manage them. Alterations in food related beliefs and behaviours can impact upon physical and psychosocial well-being. In the future, well-constructed, interventional dietary studies should aim to gain a better understanding of the complex relationship between diet, functional symptoms and generation of intestinal inflammation, thus allowing optimisation of IBD care.

Cerebral ischaemia occurs when cerebral blood flow (CBF) is compromised and brain tissue becomes starved of oxygen and nutrients, leading to cell death and neurological deficits. Ischaemic events in the brain can be either focal or global, and are major pathological features of age-related diseases, such as stroke and dementia. Several modifiable risk factors, such as diet, can exacerbate ischaemic damage. The aim of this thesis was to investigate how different dietary states, obesity and high sugar, affect inflammation and ischaemic outcomes in murine models of global and focal ischaemia. In order to investigate global ischaemic pathology, we sought to characterise a mouse model of chronic cerebral hypoperfusion, bilateral common carotid artery occlusion (BCAS). We demonstrated a sustained reduction in CBF at 3 months in BCAS animals; however, consequent neuropathology and cognitive deficits were absent. Additionally, we measured clinically validated markers of hypoperfusion (vascular endothelial growth factor, myelin associated protein, and proteolipid protein 1), that had not previously been investigated in the context of the BCAS, but found that there was no change in tissue oxygenation. We hypothesise that the reduction in CBF was not severe enough to induce global ischaemia and subsequent neuropathology. Turning our focus to focal ischaemic pathology, we used middle cerebral artery occlusion (MCAo) to investigate how diet affects ischaemic injury. We found that stroke induced long-term changes in depressive/anxiety-like behaviours, and also altered the levels of plasma lipids and adipokines, which may have negative impacts on vascular health. Obese mice also had long-term alterations in depressive and anxiety-like behaviours after stroke, but these changes did not differ significantly from lean mice that had equivalent lesion volumes. Next, we investigated how hyperglycaemia affects stroke outcomes. We found that hyperglycaemia exacerbates ischaemic brain damage by augmenting interleukin (IL)-1β dependent post-stroke inflammation. We showed that macrophage production of IL-1β post-stroke is glycolysis dependent, and in the context of hyperglycaemic conditions, is potentiated by increased substrate availability. Furthermore, we identify pyruvate as an essential metabolite downstream of glycolysis that regulates IL-1β production, and we hypothesise that this is mediated via succinate accumulation. This thesis produces mechanistic insight into the inflammatory pathology of focal and global ischaemia. Specifically, we have shown that obese and hyperglycaemic states have distinct impacts on post-stroke outcomes, primarily by regulating inflammatory and metabolic processes in immune cells. Ultimately, gaining a better mechanistic insight into how diet-related diseases and dietary factors modulate ischaemic pathology may help identify new therapeutic targets, increase health and lifestyle education, and improve public awareness.

The North Sea trading emporia of the early medieval period were instrumental in the redevelopment of overseas exchange networks in post-Roman Britain, southern Scandinavia, and Western Europe. These trade centres catalysed the process of urbanisation that intensified throughout the subsequent centuries, giving rise to the social and economic landscape of pre-modern England and Europe. Studying the emporia and their evolution into towns can provide insights into the factors that fuelled urbanisation, and can demonstrate the effect of this phenomenon on human diet, health, and mobility in the medieval period. This thesis approaches issues of medieval urbanisation and its effects through chemical and osteological analyses of skeletal remains from 363 humans and 99 animals from the recently excavated site of Stoke Quay, Ipswich (late 6th-late 15th centuries AD). Through stable carbon, nitrogen, oxygen, and radiogenic strontium isotope analysis, paired with osteological and palaeopathological observations, this research characterises the degree and timing of urbanisation at Ipswich, and its impact on the population buried at Stoke Quay. Specific research questions address the timing and extent of the 'fish event horizon' in England, the effects of urbanisation on health, and the extent of mobility and treatment of foreigners in medieval English towns. The paired isotopic and osteological findings challenge the current view that men were the only early consumers of marine fish, but support the hypothesis that intense marine fish consumption was linked to maritime trades. The results indicate that foreigners were subject to higher rates of violence than locals, and that this violence increased over time along with nonspecific stressors and infectious disease. This thesis demonstrates that Ipswich was an exceptional location from the outset, with significantly higher and more widespread consumption of marine resources than contemporary sites across England and around the North Sea, and with a more diverse and dynamic population than was previously imagined.

Introduction: The Mediterranean diet (Mdiet) is defined as the dietary patterns of people living around the Mediterranean regions during the 1950s and 1960s. This thesis aimed to investigate the adherence to the Mdiet by Cypriot and Greek populations, and its association with glycaemic control in people with Type 1 diabetes (T1DM) in Cyprus. Methods: Longitudinal adherence to the Mdiet in Cyprus and Greece was explored in a systematic review. The cumulative adherence, stratified by Mdiet scoring systems, was explored alongside the potential age and gender differences. Adherence to Mdiet, glycaemic control and their association (using linear regression models) were investigated in a cross-sectional study among people with T1DM in Limassol, Cyprus. The methodology of this study was tested in a pilot study. Results: The systematic review included 15 independent studies (18 papers). The adherence to the Mdiet was graded as moderate. The KIDMED and the MedDietScore were the most used scores and indicated cumulative mean adherence of 51.6% (4.3 points) and 52.5% (28.9 points), respectively. There was a suggestion of lower adherence in younger ages and a reducing trend over time; no gender difference was observed. For the cross-sectional study, 103 participants were recruited through random sample selection. The mean adherence was 57.6% (31.7 points); 80% and 19% of the participants had a moderate and high adherence, respectively. The median HbA1c and fasting glucose was 65 mmol/mol and 10.3 mmol/l, respectively. Most participants had suboptimal glycaemic control. Mdiet adherence and glycaemic control were poorer in younger ages; no gender difference was observed. The Mdiet was statistically significantly associated with HbA1c but not with fasting glucose, after adjusting for potential confounders. The fully adjusted model predicted a reduction in HbA1c (mmol/mol) by 1.5% for every additional point in the MedDietScore. Conclusion: Mdiet is associated with a clinically and statistically significant reduction of HbA1c in T1DM.

Women of low socioeconomic status (SES) can expect to live shorter and less healthy lives than women of high SES. Health inequalities arise from individual factors and the structural characteristics of the environment. Lifestyle behaviours including the adoption of a healthy diet and participating in physical activity can prevent or delay the onset of non-communicable diseases (NCDs). Healthy lifestyle behaviours are not, however, solely a matter of individual agency, they are tied to the parameters from which health inequalities develop. The first part of this research investigated two lifestyle behaviours, diet and exercise, in a group of mothers with young children, living in a London (UK) Borough, and identified the barriers and facilitators for the adoption of healthy behaviours. In the second part, the mothers contributed ideas for potential public health interventions that would help them participate in physical activity and eat a healthy diet. A focus group with a second group of mothers (Slough, UK), provided context for the development of the ideas for interventions. An Interpretive methodology, influenced by Critical Theory was adopted for the qualitative research. A series of three in depth interviews with twenty participants, provided the data. Access to the groups of mothers was gained through volunteering with a national charity and regular visits to Children's Centres. A thematic analysis identified four key themes that influenced lifestyle behaviours: the conflicted mother; concerns about the body; experience of health; and external contextual factors. Four ideas for potential public interventions were discussed with the study group: self-help group; support for all the family; volunteers in the home; and changes to the environment. The research provides important pointers for the development of public health interventions to support low SES mothers, particularly the need for practical support which takes into account the strong Ethic of Care in this group.

Amongst patients with incurable cancer, many will experience unintentional weight loss, loss of appetite and a range of symptoms that adversely affect the ability to eat and drink. This thesis explores the role of diet and nutrition in the palliative phase of cancer care as perceived by patients and their carers and the healthcare professionals involved in providing support. The work sought to explore the views on the role of diet before cancer and once diagnosed, the experience and identification of diet-related issues, what mattered and why and the suitability and adoption of management strategies. To explore the issues and complexities, a qualitative approach using case study methodology was considered the most appropriate. Semi-structured interviews were the primary source of data with secondary sources including medical records, policies, training and resources. Interviews and data collected was thematically analysed. Patients with incurable cancer, deemed palliative, were purposively sampled to include a variety of cancer types likely to experience diet-related issues. Each patient was asked to nominate a family member or friend, and two healthcare professionals who had been, or were involved in their care, to participate in the study. Four patients, three carers and seven healthcare professionals participated. Patients had the following cancers: melanoma with brain secondaries; head and neck with lung secondaries; pancreatic cancer; lung cancer with liver metastases. Several overarching themes were identified which included: the complexity of diet, cancer and symptoms; disruption and distortion: the altered meaning of food and preservation of self; identification of what mattered through nutrition conversations and observations; strategies to deal with diet-related issues including adaptations, adjustment, acceptance of a new norm; facilitators of nutritional care including knowledge acquisition, culture and environment. The findings have offered new insights into the identification and management of diet-related issues, weight loss and cachexia in advanced cancer and been used to develop a framework for training and clinical practice. It is hoped dissemination of the findings will assist in shaping strategies to improve nutritional care and provide advice for the growing numbers of patients receiving palliative care.

Non-alcoholic fatty liver disease (NAFLD) is associated with several metabolic comorbidities, and the excessive accumulation of hepatic lipids is strongly related to both hepatic and peripheral insulin resistance. The mechanisms underpinning the link between metabolic dysfunction and NAFLD, however, are not fully understood. Hepatokines such as fibroblast growth factor 21 (FGF21), follistatin, leukocyte cell-derived chemotaxin 2 (LECT2), fetuin-A, fetuin-B and selenoprotein P (SeP) have been identified as liver-secreted factors which may influence metabolic homeostasis in distal tissues. Energy balance plays a key role in the regulation of these hepatokines and further research is required in humans to determine the responsiveness of these proteins to acute exercise and dietary interventions. Hepatic lipid composition, which can now be assessed using proton magnetic resonance spectroscopy (1H- MRS), has also been highlighted as a potential factor impacting metabolic health in NAFLD. A hepatic lipid profile consisting of more saturated and less polyunsaturated lipids is thought to be more metabolically harmful, and the relationship between hepatic lipid composition and metabolic dysfunction in NAFLD requires further characterisation. Chapter 3 of this thesis demonstrates that a single bout of continuous, aerobic exercise transiently increases circulating FGF21 and follistatin concentrations in healthy men; with the FGF21 response being intensity-dependent. Chapters 4 and 5 show that circulating concentrations of FGF21, LECT2 and fetuin-A are elevated following short-term (1-7 days), high-fat overfeeding in healthy men; however, the time-course varies considerably between hepatokines. Specifically, the FGF21 response is rapid and transient; whilst the LECT2 response is more gradual and sustained over seven days. Initial increases in circulating fetuin- A may also begin to occur after seven days. Chapter 6 demonstrates that 1H-MRS at 3.0 tesla is a valid tool to non-invasively assess hepatic lipid composition in NAFLD; however, the technique may not be suitable for fat fractions below 5.56%. Using this methodology, Chapter 7 found that in men with NAFLD, the hepatic lipid composition of individuals with impaired glucose regulation consists of a greater proportion of saturated and a lower proportion of unsaturated/polyunsaturated lipids compared to individuals with normal glucose regulation. Furthermore, this hepatic lipid profile is associated with a lower cardiorespiratory fitness and lower levels of daily physical activity. Collectively, the studies in this thesis demonstrate that hepatokines such as FGF21, follistatin, LECT2 and fetuin-A are sensitive to acute perturbations in energy balance induced through exercise and/or overnutrition. Furthermore, H-MRS is a valid tool to assess hepatic lipid composition in NAFLD, which appears to be more saturated and less polyunsaturated in those with impaired glucose regulation compared to those with normal glucose regulation. These findings may support a potential a role of these two factors (i.e. hepatokines and hepatic lipid composition) in the link between NAFLD and impaired metabolic health; however, further experimental evidence in humans is required. Future research should investigate the impact of more chronic lifestyle interventions on these factors to explore their potential as therapeutic targets for improving metabolic health in NAFLD.

Consuming sugar-sweetened beverages (SSBs) has been associated with increased rates of obesity and type 2 diabetes, making SSBs an increasingly popular target for policy interventions such as taxation. SSB taxes are intended to reduce SSB consumption, and several national evaluations have suggested that they may be effective. However, SSB taxes have been implemented in diverse settings (e.g. in terms of baseline SSB consumption) and designed in a variety of ways (e.g. in terms of tax structure), with important implications for effectiveness. The Government of Barbados introduced a 10% excise tax on SSBs in 2015. In this thesis, I evaluated the Barbados SSB tax with the aims of 1) evaluating the impact of Barbados SSB tax on price and sales change and 2) contributing to the development of broader SSB taxation theory. My research objectives were to assess 1) price change, 2) sales change, 3) how the tax design compared with pre-tax SSB consumption patterns, and 4) whether the introduction of the tax conveyed information about the health risks of SSBs (i.e. through a risk signalling effect). I used a mixed methods approach and analysed data from a major grocery store chain, a nationally representative cross-sectional survey, interviews with members of the public and archived media data. My findings suggest that the tax was associated with an increase in the price of SSBs and a decrease in SSB sales, after controlling for pre-existing time trends, seasonality and other time-varying confounders. Prices of non-SSBs did not change and sales of non-SSBs were estimated to have increased. However, the Barbados SSB tax only addressed around 60% of SSB-related free sugars and did not clearly differentiate between high- and low-sugar SSBs. Finally, the Barbados SSB tax may have conveyed additional information about the health risks of sodas but not sugar-sweetened juice drinks. In terms of theoretical contributions, I proposed three criteria to improve the design of SSB taxes using pre-existing nutritional survey data and operationalised legal theory around an SSB taxation risk signaling effect. In addition, I found suggestive evidence that the introduction of an SSB tax may encourage industry to 1) increase SSB advertising (diminishing any potential risk signal) and/or 2) introduce low-cost SSBs (diminishing any potential price effect). Overall, I suggest that the Barbados SSB tax may have reduced consumption of taxed SSBs but had several unexpected effects, with important implications from a health perspective. After considering these findings in the context of the broader SSB taxation evidence base, I identify a number of implications for policymakers, civil society organisations and future SSB tax evaluation teams. Finally, I suggest that evaluations of SSB taxes and other population-level health interventions may benefit from the integration of multiple types of evidence, a focus on eliminating alternative explanations and an emphasis on contributing to theory development.

Diet is determined by socioeconomic factors (e.g. education, occupation, and income) and personal characteristics (e.g. ethnicity, gender, and age). Diet inequalities, whereby diet quality differs systematically across population subgroups, are well-documented. Reducing inequalities has long been prioritised by governmental bodies, yet inequalities persist and effective solutions remain elusive. My thesis aims to further understanding of diet inequalities, particularly focusing on two under-studied groups: food insecure adults and ethnic minority adults. An analysis of UK national nutrition surveys showed substantial social inequalities in diet that largely persisted from 1986 to 2012, though adherence to dietary recommendations improved over time for most population subgroups. Alongside persisting inequalities, food bank usage has risen in the UK. In an online survey, 24% of UK adults reported food insecurity (inability, or perceived inability, to afford a sufficient and nutritious diet). Food insecurity was more prevalent among certain population subgroups, and was associated with poorer diet and health. A thematic analysis of national newspapers revealed public support for the government to address the perceived root causes of food insecurity, through improving welfare support and employment policies. However, existing interventions rely heavily on charitable provision of food for individuals. Analysis of a multi-ethnic sample of Amsterdam residents illustrated that diet quality was not always associated with socioeconomic position in all ethnic groups. Together, these studies show that socioeconomic inequalities in diet persist, but are not inevitable, and demonstrate an intersection between personal characteristics and socioeconomic circumstances in their influence on diet. Socioeconomic disadvantage does not explain all diet inequalities. Community support may be protective against poor diet. Changes to the food and economic systems are likely to be necessary to improve population diet and reduce diet inequalities. Governmental action to make these structural changes is supported by the general public in the case of food insecurity.

Background: Coronary Heart Disease (CHD), with myocardial infarction (MI) as its main manifestation, is increasing at an alarming rate in South Asian countries, however evidence on its determinants is sparse. Dietary risk explains about one-third of global mortality and is a most important modifiable risk factor for CHD. Although there is extensive evidence on diet and risk of CHD from western populations, this cannot be generalised to South Asian populations where the dietary habits are very diverse. Objectives: The main aims of this thesis are to (1) summarise existing epidemiological evidence on diet and risk of CHD in South Asians; (2) characterise in detail the lifestyle socio-demographic and other correlates of dietary factors in a South Asian population; (3) investigate the association of dietary food groups, patterns and nutrients with the risk of MI and (4) discuss public health implications of the findings. Methods: BRAVE is a hospital-based case-control study from Dhaka, Bangladesh which has about 8000 cases and 8000 controls frequency matched by age and sex. This study has overlapping data looking at lifestyle (including dietary determinants), biochemical, genetic and environmental risk factors for acute MI (AMI). Using data from this study dietary determinants of AMI were investigated through (1) cross-sectional analyses of the association of diet with various correlates and (2) case-control analyses with risk of MI. Results: The systematic review demonstrated that there was scarce evidence on diet and risk of CHD from South Asia. Cross-sectional analyses from BRAVE study demonstrated that dietary food groups, patterns and nutrients had different associations with the various characteristics showing the role of modest confounding. There were few strong correlations between food groups, nutrients and dietary patterns. Findings from food group analyses showed an inverse association between fruits, vegetables, yoghurt, certain spices and risk of AMI. In contrast, higher consumption of biryani and fish was associated with higher risk of AMI. Three distinct dietary patterns were identified using principal component analysis; the "energy dense pattern", the "vegetable pattern" and the "fruits and dairy pattern". The vegetable pattern and fruit and dairy pattern had an inverse association with the risk of AMI. In contrast, "energy dense pattern" had no significant association with the risk of AMI. As for the analyses on dietary nutrients, higher intake of refined carbohydrates was not associated with the risk of AMI, while non-refined carbohydrates were associated with lower risk of AMI. Animal protein showed a higher risk of AMI, whereas plant protein showed a weak inverse association. As for specific fatty acids, modest intakes of saturated fatty acid from dairy sources and polyunsaturated fatty acids were associated with a slightly lower risk of AMI. In contrast monounsaturated fatty acids showed an increased association only in highest quintile. Conclusions: The present analyses are the largest detailed study on diet and CHD solely based on a South Asian population. It confirms previous observed association of some food groups with CHD in western populations and has also yielded some novel insights on the association of diet with CHD specific to Bangladesh. However, owing to an observational nature of the study a causal assessment could not be done, findings of this study stimulates further detailed work including prospective cohort studies which may have important potentials for the local dietary guidelines in Bangladesh and in similar settings to help reduce the rising burden of CHD.

The median eminence (ME) of the hypothalamus is a dynamic structure able to rapidly respond to nutrient availability. Both immature oligodendrocyte precursor cells (OPCs) and mature myelinating oligodendrocytes (MOLs) are found in this region in adults. While proliferation of ME OPCs has been shown to be involved in bodyweight maintenance, not much is known about the functions of other subtypes of oligodendrocytes (OLs) in the region and how they might be involved in the ME response to food intake. I first outline the use of single-cell RNA sequencing, single-molecule fluorescence in situ hybridization (FISH), and tissue clearing to characterize 3 subtypes of the OL lineage found in the ME: OPCs, MOLs, and an intermediate population designated ‘newly formed oligodendrocytes’ (NFOLs). I describe the molecular signatures of these cells and their unique organization within the ME. I then detail the transcriptomic changes in these cells between the fasted and refed state: genes and pathways related to OL differentiation and myelination are upregulated with refeeding. These transcriptional changes translate to a rapid increase in OPC differentiation into NFOLs with refeeding, as shown by FISH, BrdU labelling, and OL-specific antibody labelling. I explore the possible role of the mammalian target of rapamycin (mTOR) signalling pathway in translating increased energy availability to increased differentiation. I show mTOR signalling is transcriptionally regulated by refeeding, that mTOR is highly active specifically in OLs of the ME, and that certain nutritional stimuli can alter activation of the mTOR protein in OLs. Finally, I discuss the development of mouse models to ultimately study the effects of OPC differentiation in the control of food intake and body weight. These tools will allow specific targeting of ME OLs. These findings characterize a lesser-known population of OLs and provide evidence that these cells are nutritionally responsive.

Unhealthy diets and physical inactivity are important modifiable risk factors for premature mortality and major chronic diseases, such as cardiovascular disease (CVD) and type 2 diabetes (diabetes). However, few large-scale studies have examined the combined influence of overall diet quality and physical activity on longevity and the risk of clinically-diagnosed CVD and diabetes in adults recruited from the general population. Of popular opinion, is the notion that the health risks from poor diets can be compensated by physical activity; i.e. that one can “outrun a bad diet”. The food industry has often sought to sway public opinion towards the belief that dietary indulgences can be enjoyed as long as one engages in sufficient physical activity. However, it is unclear if the risk of premature mortality and cardiometabolic disease from unhealthy diets can be offset by physical activity, and vice versa. Therefore, the overall theme of this dissertation is to examine the epidemiological associations of diet quality and physical activity on the risk of mortality, CVD and diabetes. Specific objectives are to: 1) Study the independent associations of overall diet quality and physical activity on the primary outcomes of all-cause mortality, cardiovascular disease, and diabetes. 2) Examine the dose-response associations between physical activity and the risk of mortality and cardiovascular disease, including more of the evidence base by employing comprehensive exposure dose-harmonisation methods. 3) Examine the interactions between diet and physical activity on the health outcomes: a. If the risk of mortality and cardiometabolic disease from unhealthy diets can be offset by physical activity, and vice versa. (i.e. compensation) b. If diet and physical activity can work synergistically to further lower the risk of mortality and cardiometabolic disease, beyond the independent effect from each exposure alone (i.e. synergism) 4) Quantify the population health impacts of diet and physical activity, in terms of preventable events (deaths and disease cases) associated with both exposures, as well as the population attributable fractions (PAFs) of poor diet and inactivity contextualised with other major lifestyle risk factors. 5) Examine the long-term trajectories of physical activity (increases, decreases, and maintenance) on the risk of mortality. These investigations can bring further clarity to the public health messaging around diet and physical activity for improving longevity and the prevention of cardiovascular disease and diabetes.

Background: There are a number of factors that can negatively influence dietary intake and nutritional status amongst the older adult population, both nationally and globally. These can have clear consequences, not only for the individual, but also on a wider scale. It is well recognised that oral health can affect nutritional status and dietary intake, however the exact nature of this relationship and whether or not oral health would have a similar effect on dietary change, is unclear. A number of methods exist to improve nutritional status and modify energy intake. These include methods that can be targeted to specific population groups, such as prosthodontic rehabilitation, which can improve masticatory performance and overall oral health. There is also the need for methods which can be targeted to and implemented by the general population, such as modification of eating rate to slow down eating speed. However, whether these methods can influence a number of nutritional parameters including energy and nutrient intake, nutritional status and appetite measures, is not known. Aims: This thesis set out to examine the factors affecting dietary intake, dietary change, nutritional status and appetite in older adults, and in particular how oral health status can influence nutritional status, dietary change and appetite measures. This main aim was broken down into five aims; to examine factors affecting diet in older people; to examine the effect of oral health on dietary change; to examine methods of improving and evaluating masticatory performance; to examine the relationship between masticatory performance and nutritional status; and to examine the effect of manipulating oral processing behaviours on appetite and energy intake. Methods: This PhD involved: 1. Exploration of factors influencing dietary intake and adherence to dietary patterns amongst older adults in Northern Ireland participating in wave one of the NICOLA study; 2. Investigation, amongst adults at a high risk of cardiovascular disease in Northern Ireland, of how self-reported oral health status can influence dietary change and consumption of Mediterranean Diet-associated nutrients as part of a 12-month dietary intervention study (the TEAM-MED Extend study) to promote adherence to a Mediterranean Diet; 3. Comparison of two tooth replacement strategies for partially dentate older patients, Conventional removable partial dental prosthesis treatment and functionally orientated shortened dental arch treatment, in terms of improving masticatory performance; 4. Examination of correlations between objective, obtained using a two-colour chewing gum test, and subjective, using a self-report questionnaire, methods of evaluating masticatory performance; 5. Investigation of how improvements in masticatory performance, as a result of removable partial dental prosthesis treatment or shortened dental arch methods of prosthodontic rehabilitation, can affect aspects of nutritional status as part of a randomised controlled trial in partially dentate older adults; 6. Exploration of the relationship between masticatory performance, measured objectively and subjectively, and self-reported appetite measures; 7. Investigation of whether there is a combined effect of manipulating oral processing behaviours, through consumption of foods differing in texture classified as “fast” or “slow” foods, and verbal instructions to chew slowly, on self-reported appetite measures and energy intake later in the day as part of a randomised crossover breakfast study. Results: A number of factors were found to be associated with lower fruit and vegetable intakes, lower adherence to healthy dietary patterns and higher adherence to unhealthy dietary patterns in a cross-sectional analysis of wave one data from the NICOLA study. These included being male, aged under 65, having a lower level of education, having a higher BMI, smoking, not being married, living alone, being widowed, having poor self-reported health or a long-term condition. However, the relationship between these factors and their influence on dietary intake and adherence to dietary patterns was not consistent (Chapter 2). Methods of improving and evaluating masticatory performance were compared; functionally oriented prosthodontic rehabilitation based on the shortened dental arch method was shown to improve masticatory performance to an equivalent standard as the more commonly used conventional removable partial dental prosthesis treatment (Chapter 4), however no correlation was observed between objective (two-colour chewing gum) and subjective (self-report questionnaire) methods of evaluating masticatory performance (Chapter 5). Self-reported oral health status was shown to have an influence on daily intakes of Mediterranean Diet-associated nutrients in response to an intervention to promote adherence to a Mediterranean Diet, including fat and monounsaturated fatty acids, but not Mediterranean Diet Score (Chapter 3). Associations were observed between methods of evaluating masticatory performance, and certain appetite measures (Chapter 5). Improved masticatory performance, through prosthodontic rehabilitation, was not a predictor of improved nutritional status, however certain nutritional parameters did improve 12 months post-prosthodontic rehabilitation (Chapter 4). Combining methods to manipulate oral processing behaviours, such as bite size and number of chews per bite, was not found to have an effect on appetite measures or daily intakes of energy or nutrients, however associations were observed between these and specific oral processing behaviours (Chapter 5). Conclusion: There are a number of factors that can influence dietary intake and adherence to dietary patterns amongst older adults in Northern Ireland. However, these factors may not have a consistent effect across both dietary intake and adherence to dietary patterns, and different measurements of the same age-related factor can result in varying degrees of influence on diet. Prosthodontic rehabilitation according to the shortened dental arch, which has been shown to improve oral health related quality of life and is acceptable to both clinicians and patients, was shown to improve masticatory performance to an equal standard as removable partial dental prostheses, and as these have a number of limitations, the adoption of shortened dental arch-based treatment in future clinical practice should be encouraged. As no correlations were observed between objective and subjective methods of evaluating masticatory performance, it would call into question the effectiveness of subjective methods in future work. Inconsistent relationships between oral health status and dietary change were observed, with self-reported oral health status influencing intakes of certain Mediterranean Diet-associated nutrients but not Mediterranean Diet Score. Prosthodontic rehabilitation was shown to improve masticatory performance; however, this was not a predictor of improved nutritional status, highlighting the potential need for a combined approach of dental treatment and dietary counselling. Although there was no observed combined effect of manipulating oral processing behaviours, through verbal instruction to chew slowly and modifying food texture, on energy intake and appetite measures, associations were observed between specific oral processing behaviours and certain appetite measures and nutrient intakes, therefore these should be the focus of future work in this area. The exact nature of the relationship between masticatory performance, oral health status, nutritional status and dietary change still remains unclear, and highlights the need for future intervention studies, carried out amongst older adults, incorporating multiple tools to assess oral health and diet.

Studying at university is a challenging period with many students demonstrating unfavourable changes in their eating habits, physical activity behaviour and body composition. Universities should encourage health-promoting behaviours in students. The primary aim of this research was to identify dietary and physical activity interventions among university students, estimate their effectiveness, explore the nutrition knowledge of students and the impact of an intervention (e-programme) on students' nutrition knowledge, diet quality and physical activity. First, a systematic review of systematic reviews was undertaken to identify and synthesise reviews targeting weight-related outcomes in university students globally. Eight reviews were identified, including 122 studies. The synthesis of findings demonstrated three main types of interventions: environmental, face-to-face and e interventions. A moderate overall effect was found for environmental, face-to-face and e-interventions on dietary intake and a low effect for face-to-face and e-interventions on physical activity behaviour. Second, a cross-sectional study was undertaken among UK-based university students (n=249) to explore nutrition knowledge, factors predicting a good level of knowledge and the relationship between knowledge and diet quality (n=86). The study demonstrated that students had an inadequate knowledge on fats, salt and weight management methods. Studying a health-related course, being of White ethnic origin or perceiving health as very good to excellent, predicted a good level of knowledge. An increase in knowledge of healthy food choices and diet-disease relationships was positively associated with diet quality. And third, a randomised controlled trial (RCT) was undertaken to investigate the impact of an online programme using quiz-games (e-programme) on nutrition knowledge, diet quality and physical activity in UK-based university students (n=88). No significant differences on outcomes were found between the intervention and the control group at the end of the trial (10 weeks). The null findings remained when adherence to the e-programme was considered. Quizzes had a short-term effect on students' knowledge. Finally, 11 students participated in a following evaluation study and reported that the e-programme was easy to follow and interesting but that it had minor impact on their knowledge. This research provides new knowledge that could be used in designing more successful interventions within universities to address nutritional misconceptions and promote healthy changes in dietary and physical activity behaviour in students.

Background and Aims: Cardiometabolic diseases are the principal causes of death and disability globally. This is believed to be as a consequence of globalization which has influenced lifestyles leading to consumption of more energy dense-nutrient poor foods and people being less physically active. Health inequalities between males and females have become common in the midst of this situation and women tend to be the most affected, especially in low- and middle- income countries. There is a need to broaden our understanding on risk factors for cardiometabolic diseases and how they vary by sex in Ghana. This thesis aims to fill this research gap by (1) systematically reviewing studies looking at sex differences associated with cardiometabolic disease risk in Ghana; (2) assessing the magnitude of sex differences regarding overweight/obesity prevalence and associated contributing health factors (for this the Ghana Demographic Health Survey 2014 was used); and (3) investigating sex differences in risk factors for cardiometabolic disease in Ghana with specific reference to a case study focused on young adults, from the Greater Accra region. Methods: A systematic review was conducted to look at sex differences associated with cardiometabolic disease risk in Ghana. The Ghana Demographic Health Survey (2014) was used (3913 = females and 3871= males) to establish the magnitude of sex differences in overweight and obesity. Logistic regression modelling was used to establish how these sex differences are associated with other socio-demographic factors including sex of household member, type of place of residence, age of household members, wealth index and level of education. Biological, lifestyle, anthropometric, demographic and socioeconomic data were used from 117 participants male (55) and female (62) participants aged 18-35-years old from urban areas of Accra to establish relationships between sex, lifestyle variables and risk for cardiometabolic diseases including hypertension, blood glucose, and obesity, using logistic and linear regression modelling. Results: Fifty (50) relevant studies were selected for review that included risk factors for obesity, T2DM, hypertension, and both diseases combined, as well as related cardiometabolic conditions. Thirty three of the fifty studies made comparisons between males and females and showed that females were more prone to the various risk factors (BMI, central obesity, physical inactivity Low HDL, High LDL High triglyceride and total cholesterol), with the exception of hypertension. These put them at a higher risk for cardiometabolic diseases and their consequences. The DHS 2014 data revealed that sex differences in Body-Mass-Index (BMI) for rural (X2 = 282.9, p < 0.001) and urban residents (X2 = 331.8, p < 0.001) respectively were significant with females more likely to be overweight or obese. Across all wealth quintiles, there were more overweight and obese women and more underweight men, with the exception of the rural rich where there were more underweight females than males. For the case study, males recorded a higher mean systolic blood pressure of 117.8 mmHg ± 13.58 compared to females 109.3 mmHg ± 9.9 (P < 0.01) and were more likely to be pre-hypertensive or hypertensive. More females 21 (33.9%) than males 4 (7.3%) had central obesity. More females 45.2% than males 29.1% fell into the overweight/obese category. For dietary intake, more women 25 (40.3 %) than men 14 (25.5) were in the high intake group of globalised food. There was a significant sex difference in moderate to vigorous physical activity (MVPA) (t = 7.352 p = < 0.001) and total time in physical activity (t = 2.726 p = 0.008). Conclusions: This thesis has highlighted the sex inequalities in risk factors for cardiometabolic disease in Ghana, which largely identify females as being at greater risk than males. Some epidemiological studies include sex in their research as a descriptive variable, but few analyse sex differences as their primary focus of the research. The findings presented here suggest that sex needs to be given more attention in studies of cardiometabolic disease in Africa if the sustainable development goals related to health and well-being are to be achieved with equality in the region.

There is a growing appreciation of the diversity and uniqueness of tropical organisms, but evidence about the selection pressures that shape this diversity remains sketchy. In this thesis, I investigated how variation in life history traits arises from tropical environmental seasonality, starting with the exploration of the annual cycle of the Common Bulbul Pycnonotus barbatus in Nigeria. This revealed that breeding was not seasonal, but moult was timed almost entirely to the wet season with only few individuals extending moult into the dry season This confirmed that breeding and to a lesser extent moult, are decoupled from season, thus, allowing me to test how breeding and moult affect immune function independent of seasonal environmental conditions. On testing this, I found that season explained variation in immune function better than breeding or moult, but unexpectedly, immune indices were higher in the dry season and during breeding, contrary to what I would expect if infection risk is higher in the wet season, and if breeding constrains resources for immune function. Furthermore, I compared immune indices along the cool-wet to hot-dry environmental gradient in Nigeria and found that immune indices were rather similar. I then tested the effect of diet alteration on immune function, body mass and moult of Common Bulbuls in captivity and found that bulbuls fed on fruits had a more immune function, body mass and onset of moult than those fed on invertebrates. These findings together suggest that environmental conditions affect immune function more directly than via resource allocation trade-offs, but that variation in immune function does not follow simple environmental productivity pattern as previously expected.

This thesis explores the history of healthy eating in the mid-to-late twentieth century, providing insight into the roots of contemporary anxieties about healthy lifestyles, dieting, and the prevention of chronic disease in the UK and the US. This thesis argues that during the post-war decades, British and American societies experienced a fundamental shift that enabled new forms of cultural preoccupations about health and diet to flourish. This shift created an obsession within the media, science and society about safeguarding good health, youth and vitality, especially through dieting, specific foods, and the ingestion of supplements. This shift was enabled by the simultaneous promotion and representation of healthy eating as a solution to chronic diseases, by neoromantic notions of health, by anxieties about modern living, but also by the growth of ideas around individual agency and responsibility for health. Drawing on a rich source base of self-help books, newspapers and magazines, advertisements, medical journals and comic books, chapters of this thesis explore the ways in which contemporary obsessions about diet and health were promoted, reported on and experienced in everyday life. Examining health obsessions in relation to gendered approaches to food and broader post-war concerns about the impact of modernity on health and lifestyle, on the valorisation of slim bodies and youth, and on chronic disease prevention and productivity, this thesis offers new perspectives on the multifaceted interactions between self-help advice literature, newspapers and magazines, mainstream medical thought, and comic books during the postwar decades.

A major challenge affecting complementary feeding (CF) of children 6-23 months in Ghana is poor dietary diversity of the complementary foods; because few mothers include milk and dairy products as complementary foods. Traditional fermented milk known as 'nunu' is available throughout Northern Ghana; however, it is not promoted by health care workers for CF or commonly used by mothers as a complementary food. No research to date, has been done to determine the reasons for not promoting/using nunu as complementary food. Multiple research methods were used to answer this research question. Culture, biochemical and molecular biological methods were used to assess the bacteriological safety of nunu. Also, focus group discussions and in-depth interviews were held with mothers and health care workers to assess their knowledge, attitudes, and perceptions on the promotion and use of nunu for CF. The sequence analysis and denaturing gel gradient electrophoresis (DGGE) of nunu samples indicate the most prevalent bacteria in nunu were streptococci, there was also a relatively high abundance (often exceeding 10% of total bacterial content) of other potential pathogens (E. coli or Shigella species and Enterobacter). A key finding from the discussion groups and interviews was the concern about the safety of nunu as a complementary food by mothers and health care workers. Further literature search in MEDLINE and SCOPUS databases; and grey literature search in google scholar and FAO/WHO websites identified the adoption and implementation of the Village Milk System-an initiative by FAO; Hazard Analysis Critical Control Point (HACCP) system; and the use of starter cultures as community level interventions/strategies that can improve the safety of nunu. This study findings could be used to design interventions to promote the use of nunu as a complementary food with the potential to significantly improve child growth in Northern Ghana.

DNA methylation is an important epigenetic mark spanning all of life's kingdoms. In humans, DNA methylation has been associated with a wide range of age-related pathologies, including type II diabetes and cancer. More recently, in humans, changes in DNA methylation at specific positions in the genome have been found to be predictive of chronological age. Interestingly, DNA methylation age is also predictive of health status and time-to-death. A better understanding of what these DNA methylation changes represent and whether they might be causative in the ageing process will be important to ascertain. However, at present there is no animal model system with which this process can be studied at a mechanistic level. Furthermore, it is becoming increasingly apparent that many disease states that increase in prevalence with age are not caused by all cells within the individual, but are often the result of changes to a subset of cells. This underscores the importance of studying these processes at the single cell level. The recent advances in single cell sequencing approaches now mean that we can study multiple layers of biology within the same single cell, such as the epigenome and the transcriptome (scM&T-Seq). Unfortunately, we are still only able to probe these important aspects of single cell biology in a static sense. This is a major limitation in the study of ageing because ageing and age-related disease processes are inherently dynamic. As such, it is incumbent upon us to develop approaches to assay single cell biology in a dynamic manner. 
In this thesis, I describe an epigenetic age predictor in the mouse. This predictor is tissue-independent and can accurately predict age (with an error of 3.33 weeks) and can record deviations in biological age upon interventions including ovariectomy and high fat diet both of which are known to reduce lifespan. Next, I describe the analysis of a homogeneous population of muscle satellite cells (MuSCs) that I have interrogated at the single cell level, using single cell combined transcriptome and methylome sequencing (scM&T-seq). I found that with age there was increased global transcriptional variability and increased feature-specific methylome variability. These findings explain the loss of functionality of these cells with age. Lastly, I describe two imaging approaches to study DNA methylation dynamically in single cells. Using these methods, I demonstrate that it is possible to accurately determine methylation status across a wide spectrum of global methylation levels and that by using such approaches novel information about dynamic methylation processes can be obtained. These methods represent the first to study DNA methylation dynamically.

A maternal diet high in fruits and vegetables is associated with increased placental size and birthweight and decreased incidence of preeclampsia. This relationship is not explained by maternal socioeconomic status or levels of micro- and macronutrients in the diet, suggesting that an, as yet, unaccounted for nutrient could be contributing to fetal growth. Extracellular vesicles (EVs) are a recently identified component of fruits and vegetables. EVs are nanosized lipid-encased parcels of protein, RNA and other molecules that can alter the function of recipient cells. Fruit and vegetable EVs are internalised into mouse intestinal cells. It was, therefore, hypothesised that EVs from plants consumed as part of the diet would be internalised into human intestinal cells, resulting in the transmission of plant and/or intestinal-derived signals to the placenta, altering placental growth, development or function and thereby linking maternal fruit and vegetable intake to fetal growth. EVs derived from watermelon (WMEVs) were isolated using ultracentrifugation and found to be of a size and morphology consistent with the EV subtype known as exosomes. Mass spectrometry and qPCR arrays were used to identify that WMEVs exhibit protein, lipid and miRNA profiles that differ from watermelon cells, suggesting that their contents are likely actively loaded. Further analysis of the WMEV proteome predicted a possible dual origin from the endosome and plastid for these WMEVs and suggested they may have a role in watermelon fruit ripening. WMEVs were labelled with a lipid (PKH26) or RNA (SYTO RNAselect) dye and incubated apically with Caco-2 cells differentiated on transwell membranes into small intestinelike epithelial cells. Flow cytometry determined that PKH26-labelled WMEVs were internalised into Caco-2 cells in a time (49.45% of cells at 180 minutes; p < 0.0001) and dose-dependent (R2 = 0.99; p < 0.0001) manner, resulting in increased Caco-2 proliferation (7.12-fold increase; p < 0.05). WMEV RNAs, including microRNAs (analysed by qPCR array), were transferred by WMEVs into Caco-2 cells (96.16% of cells at 240 minutes; p < 0.0001) and through the Caco-2 tight barrier to the basal media compartment (16.36% apical-basal crossover; p < 0.05). Proteomic analysis of this conditioned basal media (WMEV-CBM) revealed alterations to the Caco-2 secretome (5 proteins > 1.5-fold upregulated; 13 proteins > 1.5-fold downregulated) in response to WMEVs. Caco-2 secretion of fetuin-A, an inhibitor of extravillous trophoblast (EVT) migration and trophoblast viability, was decreased (4.3-fold lower; p < 0.01) by exposure to WMEVs. Proteomic analysis of placental trophoblast BeWo cells exposed to WMEV-CBM predicted beneficial alterations to several trophoblast parameters, which were investigated experimentally. WMEV-CBM induced expression of 6 syncytialisation genes and increased cell-cell fusion in BeWo cells (1.44-fold increase; p < 0.01) and primary cytotrophoblasts (1.75-fold increase; p < 0.001). WMEV-CBM was also found to decrease apoptosis (1.98-fold; p < 0.01 in BeWo cells) and increase EVT migration (2.17- fold; p < 0.001) from first trimester placental explants. These data suggest that plant EVs, such as WMEVs have the potential to impact upon placental development, growth and function, potentially linking maternal fruit and vegetable intake to improved fetal growth. With further research, this could inform dietary advice in pregnancy and the development of plant EV-based therapies for pregnancies at risk of fetal growth restriction or preeclampsia.

This research addresses life cycle environmental and economic sustainability in the baby food sector. In the UK, this sector has been growing rapidly, expanding by around 30% between 2009 and 2014, by which time it was worth an estimated £181 million per year. This growth sits within a context of high emissions from the food sector: in 2015, UK net GHG emissions were estimated to be 496 million tonnes (Mt) and the domestic food chain was responsible for 115 Mt CO2 eq. emissions. However, within this overall food chain, very little is known about the sustainability of the baby food sector, with almost no prior literature in the area. The research presented here begins with market research to identify the characteristics of products available in the ready-made food market, in which wet and dry products in jars and pouches dominate sales. Subsequently, 12 representative products are selected from those available on the market and each is assessed in detail to establish its environmental and economic impacts using life cycle assessment (LCA), life cycle costing (LCC) and value added (VA) assessment. The findings of these product-level assessments are then compared to home-made equivalents and finally scaled up according to sales volumes to provide an overall view of the baby food sector as a whole. Wet and dry variants of ready-made porridge products are assessed first as the most commonly consumed breakfast option. The dry product is shown to have 5%-70% the impacts of the wet, on average, and the importance of product formulation is clear: for dry porridge, reformulation could reduce impacts by up to 67%. For the wet porridge, switching from glass jars to plastic pouches is also shown to decrease impacts by up to 89%. Assessment of 11 wet ready-made products demonstrates that the highest impacts are found in spaghetti Bolognese and salmon risotto, and that raw materials are the major hotspot of the life cycle, contributing 12-69%, followed by manufacturing at 2-49%. When combined into a range of weekly diets limited differences are observed between diets, except in cases where dairy-free diets result in compensatory increases in meat consumption. When the aforementioned selection of ready-made products is compared to its home-made equivalent, the home-made options are shown to have lower impacts by 50% to 17 times. This is due to the avoidance of manufacturing and extra packaging stages, as well as shorter supply chains resulting in less waste overall. At the product level, the LCC of ready-made meals ranges from £0.08 to £0.26 per 125 g product, compared to £0.02-£0.20 for the home-made equivalents. Value added is, on average, approximately four times higher for ready-made meals than homemade, illustrating the potential profit of the sector. Annually, the ready-made baby food sector has an LCC of £40m and carbon footprint of 109 kt CO2 eq. This carbon footprint represents only 0.1% of the UK food and drinks sector. The results of this research show that considerable improvements can be made to the environmental and economic sustainability of baby foods, both ready- and homemade, while home-made options tend to have lower costs and environmental impacts. The outputs provide benchmarking and improvement opportunities for industry and government, as well as insight for consumers.

Evidence synthesis is considered a corner stone of modern health care and clinical practice. Systematic reviews of randomised trials, when undertaken with meta-analysis provide summary estimates on the effectiveness of interventions. However, the findings of meta-analysis are often limited by the selective reporting of primary studies, and the variations in population, intervention and outcomes. Furthermore, difficulties in disentangling the study and individual level associations in meta-analysis make them susceptible to ecological fallacy, and may lead to incorrect conclusions. Meta-analysis using Individual Participant Data (IPD) has the potential to overcome many of the above limitations, by using raw trial data. Access to IPD minimises problems from incomplete or incorrect reporting of trial outcomes, by verifying reported results, and by standardising the definition of outcomes where possible. Importantly, this allows detecting any variation in the effects of interventions according to characteristics of the participants. Amalgamated individual datasets assembled to address the effectiveness question, can be further used to explore secondary objectives such as the relationship between surrogate and clinical outcomes. This maximises the use of available clinical data, and addresses the problem of research waste. In this thesis, I evaluated the effects of diet and physical activity based interventions in pregnancy on maternal and offspring outcomes using both study-level and IPD meta-analyses, and assessed the differential effects of interventions on outcomes according to mother's BMI pre or in early pregnancy. I reviewed the variation in outcomes reported in this field, and developed composite outcomes for IPD meta-analysis. I also evaluated the relationship between weight gain in pregnancy and clinical outcomes in pregnancy using the IPD meta-analysis methodology. Aims The aim of this thesis was to evaluate the effects of diet and physical activity based interventions in pregnancy on clinical outcomes using standard and advance methods of evidence synthesis; assess the variation in outcomes and their clinical importance in a trial with those interventions and examine the relationship between gestational weight gain and important clinical outcomes. Methods Delphi methodology, systematic reviews of literature, and meta-analyses using study-level and individual participant data of randomised controlled trials (RCTs). Results Composite outcomes Developed composite outcomes comprise of four maternal (gestational diabetes, hypertensive disorders in pregnancy, preterm birth, caesarean section) and four offspring outcomes (stillbirth, small for gestational age, large for gestational age, and admission to neonatal intensive care unit). The components to assess maternal composite outcome were available in two-thirds (66.7%, 24/36) and for offspring composite in half (50%, 18/36) of the studies in the IPD meta-analysis. The effect of interventions was not statistically significant neither on the maternal nor on the offspring composite - Odds Ratio (OR) 0.90 (95% CI 0.79, 1.03) and OR 0.94 (95% CI 0.83, 1.08), respectively. The direction of the pooled effect was consistent between the composite and its components for the maternal composite and variable for the offspring outcomes. 6 Effects of diet and physical activity based interventions The IPD meta-analysis of 36 RCTs (>12 500 women) showed a significant effect of diet and physical activity based interventions in pregnancy in reducing gestational weight gain (Mean Difference -0.70 kg, 95% CI -0.92, -0.48) and chance of caesarean section delivery (OR 0.91, 95% CI 0.83, 0.99) in comparison to routine antenatal care. There was no effect of the interventions on any of the offspring complications. Incorporation of outcome data unavailable on study-level returned more modest magnitude of the summary estimates in comparison to effects obtained using study-level data of trials that shared IPD. The addition of study-level data from non-IPD trials changed the magnitude and the statistical significance of the summary effects on GDM - from OR 0.89 with only IPD (95% CI 0.72, 1.10; 27 studies, 9 427 women) to OR 0.76 (95% CI 0.65, 0.89; 59 studies, 16 885 women). It has also changed the funnel plot structure in the meta-analysis for gestational weight gain (Egger's test p = 0.04 with only IPD to p= 0.61). The IPD meta-analysis shows that the effects of diet and physical activity based interventions on the maternal and the offspring outcomes did not differ by women's BMI status. While the study-level meta-regression indicated that the interventions might reduce gestational weight gain stronger for the obese women - coefficient -0.22 (95% CI -0.33, -0.11) for each 10% change in the proportion of women in the obese class. Outcomes in trials with diet and physical activity based interventions 66 primary publications from trials with diet and physical activity based interventions in pregnancy reported 142 outcomes. Half of those outcomes appeared in the publications once (72/142). 'Critically important' outcomes are reported less often in comparison to 'non-critical' ones (15.5%, 22/142 vs 68.3%, 97/142). The overall quality of outcome reporting varied between trials with the least frequently provided information on the methods to improve the quality of outcome measures (33.3%, 22/66 publications). 7 Gestational weight gain and pregnancy outcomes IPD from 4 429 pregnant women randomised to the control arms of RCTs with diet and physical activity based interventions were available for the analysis. Women who most often exceeded the IOM recommendation belonged to the overweight (51.5%, 641/ 1 245 women) and the obese groups (44.5%, 695/ 1 562 women) while women with normal BMI most often gained below the recommended amounts (40%, 649/1 622 women). Each kilogram of gestational weight gain within the IOM ranges was not link with a change in the chances of preterm birth, caesarean section, or birth of LGA and SGA infant. Not achieving of the recommended weight was associated with the decreasing chance of giving birth to LGA infant with each kilogram below the lower limit among the obese women (OR 0.80, 95% CI 0.65, 0.99). Each kilogram of weight gain above the upper limit was associated with an increase in the chance of caesarean section (adjusted 1.04, 95% CI 1.01, 1.08) and delivering LGA infant (adjusted 1.08, 95% CI 1.05, 1.12) regardless on women's BMI status. Conclusions Diet and physical activity based interventions in pregnancy moderately reduced gestational weight gain and decrease the odds of caesarean delivery. Overall, IPD meta-analysis improved the robustness of the evidence synthesis of RCTs with diet and physical activity based interventions. However, more attention is needed for the data-related issues in IPD meta-analysis as the purported benefits of the method are not always practically realised. The use of the composite outcomes was hampered by the variable availability of important clinical outcomes. The introduction of minimal core outcome set would facilitate the comparison of the wide range of the evaluated interventions and improve implementation of the composite outcomes. Gestational weight gain was found to be associated with the odds of delivering LGA infant and caesarean section. Future research should aim to collect and report a minimal set of outcomes, and ensure better reporting of study conduct and its findings.

Primarily synthesised via cutaneous exposure to solar ultraviolet B (UVB) radiation, serum vitamin D concentrations, measured as 25-hydroxyvitamin D (25(OH)D), fluctuate according to solar availability. Seasonal variations in vitamin D are common in areas of high or low latitude determined by the distance from the sun. Seasonal variations in blood pressure, immune markers and some diseases including influenza, have also been reported. However, the contributions of UVB light or vitamin D on the immune markers have not been fully determined. Against this background, the purpose of this research was to investigate the effects of UVB light therapy and dietary vitamin D supplementation on markers of immune function. The D SIRe1 study aimed to assess whether dietary-derived 25(OH)D could have similar effects on immune function as light-derived 25(OH)D. The study was an 8-week comparative intervention trial in healthy adults randomised to receive either 3 times weekly UVB radiation (equivalent to doses received during a Grampian-summer) for 4 weeks; or oral vitamin D3 (1000 IU a day for 8 weeks). Total 25(OH)D was measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation, whilst regulatory T cells (Tregs), known for maintaining immune system homeostasis, by flow cytometry. The study showed similar short-term effects between oral vitamin D and UVB exposure on measured outcomes. However, study interpretation was limited by the lack of a placebo group, yet, to our knowledge, this was the first study to directly compare dose-matched UVB therapy and vitamin D supplementation in healthy participants. Using similar laboratory techniques, the D-SIRe2 study, a placebo-controlled trial, assessed short-term (12 weeks) and long-term (43 weeks) effects of vitamin D supplementation on immune markers. Commencing in spring (March) and finishing in winter (January) 2015/2016, the study showed seasonal fluctuations in most immune markers. The fluctuations did not change according to variations in 25(OH)D concentrations nor were they correlated with solar UVB doses, with the exception of T cell proliferative responses, which were positively correlated with daily solar UVB doses. An interesting finding from this study was the prevention of increases in pro-inflammatory IFN-γ cytokine concentrations in the spring and summer time in the vitamin D3 supplemental group versus placebo. IFN-γ concentrations were raised from 7940 pg/mL at baseline in March, to roughly 12400 pg/mL at week 4 and to 13909 pg/mL at week 12 in the placebo group. The concentrations were roughly 1.3 times the mean concentrations measured in the vitamin D group at the timepoints following baseline concentrations of 10678 pg/mL, and 10013 pg/mL and 10233 pg/mL at weeks 4 and 12, respectively. The interactions between solar light or seasonal effects and oral vitamin D supplementation, as well as their individual and combined effects on immune function, are yet to be fully determined. Moreover, the metabolic and physiological implications of seasonal variation in serum 25(OH)D concentration and markers of immune function are currently unknown, requiring further investigation.

This study aimed to describe nutrition transition in Nepal over the past 40 years and to explore its relationship with economic, demographic and epidemiological shifts; and further discussed how different socioeconomic groups were experiencing the nutrition transition. The current study used a multimethod study framework including quantitative and qualitative studies. In the past 40 years, nutrition transition had occurred in Nepal. In 1990s, economic shifts occurred raising the GDP per-capita income above poverty threshold level. Following this, increase in total energy supply and total fats intake in diet exceeded the average dietary energy requirement level (2250Kcal/person/day) set out for the country (end of pattern 3). During 2000s, a number of demographic shifts including increase in average life expectancy beyond 60 years occurred leading to population ageing. Imports of processed foods increased significantly due to globalisation, while domestic agricultural production decreased drastically due to the Civil War resulting in higher proportion of processed foods, fats and sugar in diet. The globalisation and the Civil War may have facilitated to shift the food supply system from primary agriculture products to convenience/processed foods. It was likely that the economic, demographic and dietary behavioural shifts had collectively influenced the epidemiological shifts leading to overweight, obesity and chronic NCDs in Nepal (pattern 4). Distinct socio-economic groups in Nepal were experiencing these transitions differently. The lower socio-economic group and rural residents continued to consume low variety and low-fat foods and had lower prevalence of overweight and obesity (pattern 3). While, the higher socioeconomic groups and urban residents retained some food from Nepalese traditional cereal but were also increasing their consumption of extra meals, which were higher in fats and had higher prevalence of overweight and obesity (pattern 4). A number of underlying drivers for these dietary shifts were identified, but further work is still needed to better understand how these drivers interact with a range of sociodemographic factors to elicit behaviour change.

This thesis investigates the acceptability and efficacy of Functional Imagery Training (FIT), a motivational intervention for weight-management. FIT is based on Elaborated Intrusion Theory, delivered in the style of Motivational interviewing (MI), and designed to promote sustained behaviour change and address cravings. It trains the habitual use of affective, goal-directed mental imagery of personal incentives, using imagery to plan behaviours, anticipate obstacles, and mentally try out solutions from previous successes. Participants are taught to update their imagery from their experience, and to generalise their imagery skills to new goals. In study 1, focus groups explored problems and wishes in regards to weight-management, including reactions to Functional Imagery Training (FIT) as a possible intervention. The issue of waning motivation and the desire for motivational app support was expressed in all groups. Participants were positive about FIT. Study 2 was an uncontrolled pilot trial of FIT. Eleven out of 17 participants (65%) lost 5% body weight or more by three months. Participants continued to lose weight during an unsupported 12-month period and experienced mean weight loss of 6kg (SD= 5.7; d=1.06) and mean waistline reduction of 11.5 cm (SD= 7.4; d=1.56) at 15 months. Study 3 compared the impact of FIT with MI on motivation and self-efficacy, over the first month of a randomised controlled trial (RCT) for weight-loss. Structured elicitation and training in goal-related imagery, i.e., FIT, increased motivation and self-efficacy for weight-loss relative to MI. Study 4 was the RCT for weight-loss, comparing FIT and MI over an intervention-supported six-month period, followed by six months unsupported. The FIT group achieved clinically meaningful weight-loss at 6 months (M kg-loss=4.11) and continued weight-loss at 12 months (M kg-loss=6.44); the MI group stabilised by 12 months (M kg-loss=.67), after minimal weight loss at 6 months (M kg-loss=.74). Study 5 qualitatively explored experiences of MI and FIT RCT participants, upon completing the 6-month intervention phase. MI participants wished for continued therapist- support and feared relapse. FIT participants described a mind-set-change and were confident they could maintain changes and overcome challenges using imagery techniques. Given the demonstrated benefit of motivational imagery in weight-control, FIT should be considered and further tested as an intervention for health behaviour change.

Background: Numerous maternal factors, such as body mass index (BMI), gestational weight gain (GWG), diet and physical activity (PA) have been shown to impact infant birth weight. In the UK, antenatal care tends to be based on pre-pregnancy BMI and women are not weighed routinely during pregnancy nor are there guidelines for GWG. However, it is widely acknowledged that maternal obesity and GWG in excess of the American Institute of Medicine guidelines are associated with increased risk of foetal macrosomia and recent studies have suggested a role of the timing and composition of GWG beyond that of BMI. The purpose of this study is to examine the effects of timing and composition of GWG on neonatal anthropometric outcomes in a prospective cohort study amongst women with a BMI≥30 kg/m2 in Plymouth, UK. Methods: Women (n=75) were recruited at 12 weeks gestation. Maternal height, weight and body composition assessed using skinfolds at biceps, triceps and subscapular were collected at baseline and repeated at 28 and 36 weeks gestation. Four-day food diaries and four days of accelerometry were collected in the days following each of the three study visits. Following delivery, infant weight and gestational age were obtained, and neonatal anthropometric measurements were recorded within 72 hours of delivery. Results: Maternal energy intake was positively associated with GWG and rate of fat mass (FM) accrual, in the second (r = 0.435 and r = 0.395, respectively, p < 0.05) and third trimesters (r = 0.333 and r = 0.317, respectively, p < 0.05), with no associations observed between maternal energy intake and rate of fat free mass (FFM) accrual in either trimester. Maternal rate of FFM accrual (in both trimester 2 and over total pregnancy), not FM nor rate of GWG, was positively associated with infant birth weight z scores (r = 0.360 and r = 468, respectively, p < 0.05) and upper arm area muscle estimate (UME) (r = 0.291 and r = 0.357, respectively, p < 0.05). Second trimester intake of sugar was positively associated with infant UME (r = 0.419, p < 0.05), while third trimester intake of sugar was positively associated with both infant UME and infant birth weight z score (r = 0.376 and r = 0.308, respectively, p < 0.05). Conclusion: The present study suggests that maternal accrual of FFM and intake of sugar during pregnancy may be associated with increased infant birth weight and lean mass. Further research is required to determine whether interventions should focus on changes in maternal body composition alongside diet and lifestyle during pregnancy, or if they should continue to focus on limiting total GWG.

Two clinical trials investigating the effect of modulating two dietary components, tea containing polyphenols and vitamin D aimed at improving non-haem iron absorption and iron status recovery, were carried out in a cohort of healthy and iron deficient UK women, respectively. Tea has been shown to be a potent inhibitor of non-haem iron absorption but it remains unclear whether the timing of tea consumption relative to a meal influences iron bioavailability, with limited published evidence, especially in human trials. The aim of the first study was to investigate the effect of tea consumption on non-haem iron absorption and to assess the effect of time interval of tea consumption on non-haem iron absorption relative to an iron-containing meal, in a cohort of healthy female participants using a stable iron isotope (57Fe).

The East Alpine region formed an important crossroads in later prehistoric Europe, through which ideas, people and objects flowed. This was particularly the case during the Late Bronze Age/ Early Iron Age, when an increasingly competitive society was evolving, with the formation of more complex social structures and the rise of 'elites'. This has been evidenced in a shift in burial customs, from Urnfield-type cremation burial to the construction of tumuli and the adoption of elaborate inhumation burial. This multidisciplinary, multi-scalar approach to the analysis of human remains aims to explore the evolving structure, homogeneity and heterogeneity of communities inhabiting central and eastern Slovenia, and north-eastern Croatia, during the Late Bronze Age and Early Iron Age. The application of multiple methods, including the osteological analysis of cremated and non-cremated human remains, radiocarbon dating, stable isotope analysis (carbon, nitrogen, oxygen and strontium) and aDNA analysis has facilitated the exploration and interpretation of later prehistoric social structure and lifestyle. The use of carbon (from enamel carbonate and collagen) and nitrogen stable isotope analysis has highlighted important dietary distinctions between communities inhabiting this region and previous studies from elsewhere in contemporary Europe - specifically a high dependence on millet as a staple crop. This has been evidenced by δ13C values of between -17‰ and -15.3‰ from bone collagen. δ15N values of between 7.6‰ and 9.1‰ support this interpretation as they do not indicate the consumption of marine protein. Increased δ15N values of up to 13.5‰ from deciduous dentine have been interpreted as the influence of dietary and metabolic conditions, particularly in the presentation of an Infant exhibited palaeopathological evidence of severe metabolic disease. Complementary isotopic methods, including oxygen isotope ratios and enamel carbonate carbon, have also highlighted heterogeneity in childhood diet, reflecting the transition from a high lipid diet of breastmilk, to a diet of carbohydrates, indicative of weaning. In addition to these findings, the application of radiocarbon dating on cremated and nio-cremated human bone has expanded the current understanding of mortuary practices in this study area. Inhumation burial, previously thought synomemous with the Iron Age, has been now been identified throughout the Bronze Age at the cemetery of Obrežje. The application of this multi-scalar approach to combining and interpreting these data sets has allowed for the investigation of individual biographies, as well as regional trends. This research illustrates the advantages of bringing together multiple lines of evidence for the creation of informed interpretations regarding the life, death and diet of prehistoric peoples of the East Alpine region, and beyond.

Health and public health services in England are under increasing financial pressure. At the same time, nearly 40% of the total disease burden is potentially amenable to known causes with two of the leading behavioural risk factors being unhealthy diets and physical inactivity. To better inform decision makers and improve health in England, this thesis aims to develop a cost-effectiveness model that can directly compare diet and physical activity interventions. Published public health economic models were reviewed and the strengths and weaknesses of the modelling structures were explored. A pre-existing multistate life table model, PRIMEtime, was developed into PRIMEtime Cost Effectiveness (PRIMEtime CE). Disease specific NHS England costs were derived from NHS England Programme Budgeting Data and unrelated disease costs from NHS cost curves. Social care costs were quantified using a Department of Health tool for estimating wider societal costs. Disease specific utility decrements were adopted from a catalogue of EuroQoL five dimensions questionnaire scores. The cost effectiveness of reformulating food to have less salt and of expanding access to leisure centres in England were modelled from an NHS and social care perspective over a 10 year time horizon, including government and industry costs. Salt reformulation was dominant with an estimated cost per quality adjusted life year (QALY) of -£17,000 (95% uncertainty interval, -£40,000 to £39,000), compared with £727,000 (£514,000 to £1,064,000) for increasing access to leisure centres. Sensitivity analyses and cross validation testing of outcomes demonstrated how cost per QALY estimates were sensitive to the choice of model scope, parameters, and structure. PRIMEtime CE is a tool for decision makers to compare interventions affecting diet and physical activity, enabling them to make better informed choices about how to spend finite resources. Future work will focus on making the model freely available and expanding its risk factors to enable comparisons of other public health interventions.

This thesis focuses on Nepalis living in Oslo and Ås, Norway, and ethnographically explores their food perceptions, habits and practices in relation to health and maternal health. With pre-existing experience of both biomedical and other understandings of health and wellbeing, the majority of my respondents could and did move between paradigms, on an individual basis deciding which to apply and when. Consequently, several demonstrated certain reasoned divergences from Norwegian state-endorsed dietary norms and expectations; differences that were, however, not simply reducible to ‘culture’. ‘Culture’ is shown here to be a favoured strategy of explanation within Norwegian public health research, which has dominated state health perceptions of all South Asians. Overall, four key arguments are advanced. Firstly, the need to disaggregate the category of ‘South Asian’, currently readily employed within public health research and policies worldwide to describe and problematise the foodways of highly diverse diaspora populations. The middle-class status of my Nepali respondents is delineated as a central example exposing the inaccuracy of such a homogenising generalisation. Secondly, that despite the hegemony of biomedical models of nutrition within health and ante-/postnatal wellbeing in Norway, my interlocutors moved between these and other ideas and practices of health and wellbeing. Describing their dietary habits and practices makes plain the narrowness of applying purely biomedically-predicated thinking to understanding these Nepalis’ foodways. Thirdly, that in ante-/postnatal care the biomedical model overprivileges the individual mother’s responsibility for her own health in order to benefit her child, ignoring the potential for alternative distributions of responsibility for, as well as emphasis on, both offspring and mother: the Nepalis I encountered showed a notable commitment to the mother’s wellbeing and also sense of pregnancy and postnatal care as a collective enterprise, relationally shaped. Fourthly, my Nepali respondents’ accounts provide a useful example demonstrating limitations to the perceived authority of Norwegian state advice on health in general. Well-informed and often highly educated, these Nepalis engaged only selectively with the state-endorsed guidance and services, instead drawing on other (re)sources – Nepali family and friends especially – to maintain health and wellbeing.