This thesis explores the views and experiences of people with lung cancer, and family members, of discussing preferences and wishes for end of life treatment and care. It presents an interpretive analysis based on the application of a constructivist grounded theory approach. Study participants included: eighteen men and seven women with lung cancer and nineteen family members. Participants were mainly from lower socio-economic groups living in the north of England. Single, joint and group interviews were used to gather data. Interview transcripts were analysed using a constant comparative method and conceptual models were drawn to aid the development of the theoretical interpretation. The study found that preferences and wishes for future care and treatment were not the main concern of people with cancer; rather, any concerns for the future were about the social aspects of death. Participants talked about their experiences of facing death whilst striving to live in the present. Planning for one’s own dying and eventual death was not something that people with lung cancer reported having discussed, except when, out of concern for their families, practical arrangements needed to be made following death. The disclosure of a poor prognosis had a huge emotional effect on participants, who ascribed a variety of meanings to this news. Participants’ reported that clinicians usually focused on their disease; they did not recall being offered any ‘options’ or ‘choices’ for future care. They commented that their preferences and wishes for future treatment and care were influenced by their clinician, spouse, other family members and their knowledge of others affected by cancer. The theory ‘maintaining integrity in the face of death’ is proposed. This theory purports that patients with advanced lung cancer and their families focus on acting and talking as ‘normal’ to help them balance living in the present whilst facing death. This thesis makes several contributions to knowledge. First, it provides the views of people from an underrepresented group of cancer patients from lower socioeconomic classes who are rarely included in research. Secondly, it shows how people facing the end of their life place little importance on choice. They focus instead on living in the present and carrying on as normal, which challenges current UK policy that seeks to promote individual patient choice at the end of life through advance care planning. The study findings suggest that policy makers and health and social care professionals need to develop ways of helping people prepare for a ‘social’ rather than a physical or ‘medicalised’ death: a focus on developing advance care planning that provides information to support people’s practical needs at the end of life, delivered as a family intervention, thereby helping people living with lung cancer to maintain their integrity in the face of death.

Background: South Asians constitute the single largest ethnic minority group in the United Kingdom, yet little is known about their perspectives and experiences on end of life and its related care. Aim: To explore and critically examine views and perceptions about end of life issues among older South Asians living in East London. Methodology and methods: After gaining ethical approval, five focus groups and 29 in-depth, semi-structured interviews were conducted with total of 55 older adults (24 men and 31 women) aged between 52 to 78 years. Participants from six South Asian ethnic groups were recruited through 11 local community organisations. Where possible the focus groups and interviews were conducted in the participants' preferred language. Tape recorded multilingual data were translated and transcribed into English. Using a constructive grounded theory approach, data analysis resulted in the development of a theory of “continuity and reconstruction” that captured three categories of ‘home’; ‘family’ and ‘trust’ at end of life. Findings: The theory of “continuity and reconstruction” is explored in three ways. Firstly, the theory is explored through examination of beliefs, attitudes and expectations about the place of ‘home’ and ‘homeland’ in care of the dying. Secondly, the theory is explored as accounts of “family” in terms of how family are bound towards caring for their dying relatives at end of life and the importance of support from social networks in family care giving. Finally, the theory is explored in terms of how participants place “trust” in their family and medical professionals to lead any related discussion and to make decisions related to their death and dying. Conclusion: The theoretical framework of “continuity and reconstruction” explains how older South Asians make efforts to adhere to important social and cultural values relating to death and dying, while rebuilding and adapting those values during the challenges of living in an emigrant society. This study highlights the need for further exploration of family care giving needs among South Asian population and concludes by drawing attention to some practical implications for health professionals who are responsible for initiating end of life discussions and are involved in end of life decisions when caring for people from these ethnic minority groups.

The objective of this thesis was to assess the impact of altering macronutrient intakes on hepatic lipid metabolism. Two separate studies were performed, with liver triglyceride content being the principal outcome of both. In the first study 32 healthy and centrally overweight males were randomised to 2 periods, each of 2 weeks, of either a high fructose or glucose intake in a non-crossover fashion. Isoenergetic status was maintained by providing foodstuffs during the first period, followed by a 6 week washout and then a second period of ad libitum overfeeding. In the second study 55 patients with biopsy proven non-alcoholic fatty liver disease were randomised to 3 months 5g a day of capsules containing either n-3 polyunsaturated fatty acid or oleic enriched sunflower oil. The main findings are summarised. High intakes of fructose and glucose in the isoenergetic period resulted in a stable weight, and no change in hepatic, serum and ectopic triglyceride content. There was a raised serum uric acid with fructose. During the hyperenergetic period there was a tendency for greater uric acid with fructose, whilst both groups had a matched weight gain, elevation of liver biochemistry and an increase in hepatic, serum and muscle triglycerides. Changes in liver biochemistry and triglycerides were associated with changes in weight. During both periods there was calorimetric evidence for a shift in whole body metabolism towards that reflective of a high carbohydrate intake. There was no alteration in renal function or cardiovascular haemodynamic parameters or consistent change in insulin resistance. The n-3 polyunsaturated versus oleic acid study resulted in significant alterations of serum fatty acid profiles between the groups, which were in line with the capsules’ contents. These changes however failed to translate, in the whole group, to any detected metabolic or hepatic changes beyond a reduction in serum triglyceride with n-3 polyunsaturated fatty acids. Only 43 of the 55 patients had elevated liver triglycerides on baseline MRI. Amongst this 43 there was a reduction in liver triglyceride with n-3 polyunsaturated fatty acids, but no other associated metabolic changes. The uric acid findings support the notion of fructose and glucose differing in their pre triose metabolism. There was however no differing outcomes in terms of lipid synthesis or storage. There was a suggestion of reduced liver triglycerides with n-3 polyunsaturated fatty acids though this was an isolated result only found amongst those with a steatotic liver at baseline. Ultimately the exquisite sensitivity of the liver to nutrient intakes was highlighted by the 0.8% gain in weight in the fructose / glucose study resulting in a 24% increase in liver lipid. This affirms the notion that dietary energy intakes have a profound influence on hepatic metabolism, but there is no evidence from this thesis that this influence is macronutrient specific. In the future macronutrient comparisons need to be made.

Tea, from the plant Camellia Sinensis, is after water, the most consumed drink in the world. Green tea, produced by steaming freshly harvested leaves to prevent fermentation, is high in polyphenols known as catechins or flavanols. The major flavanols found in green tea include (-) epigallocatechin-3-gallate (EGCG) and (-) epicatechin. Literature reports suggest that green tea flavanols have the potential to exert anti-obesity effects by modulating weight gain and other factors such as lipogenesis, β-oxidation and adipokine release. Key features of obesity and associated insulin resistance are adipokine dysregulation, decreased sensitivity of adipocytes to insulin and subsequently, changes in glucose uptake by cells. The aims of this thesis were firstly to establish an efficient system of differentiated adipocytes and secondly to use this to investigate the effects of the flavanols EGCG and epicatechin on physiological outcomes such as adipokine release and glucose uptake. Thirdly, the question of whether these processes might be regulated by the ERK1/2 pathway and what may be happening upstream of this was explored. Finally, the effect of flavanol treatment on adipocyte gene expression of genes known to be modulated in obesity was investigated. Using the well established cell culture model of 3T3-L1 adipocytes, the studies from this thesis show that EGCG and epicatechin are able to modulate the release of the adipokines adiponectin and resistin, dependent on the media glucose concentration. This modulation may be mediated by the ERK1/2 pathway, since flavanol treatment increased ERK1/2 phosphorylation. Uptake of glucose was not altered by any time or concentration of EGCG or epicatechin, and there were no significant changes in adipocyte gene expression following EGCG or epicatechin treatment. A thorough investigation of adipokine release, ERK signalling, glucose uptake and gene expression, under the influence of flavanol treatment, showed that although molecular changes occurred in the 3T3-L1 system, these did not translate into functional readouts. Therefore, it appears unlikely that these have major direct effects on adipocyte function.