From a public health perspective there is considerable interest in nutrigenetics because it offers potential for reducing penetrance of high risk genotypes/ haplotypes via focused ( individualised ) dietary change. However, the underpinning science is yet in its infancy, with need for studies at a number of levels: (1) epidemiological studies to identify putative genotype-disease associations (e.g. The Wellcome Trust Case-Control Consortium); (2) unequivocal demonstration of the efficacy of diet to reduce/ reverse adverse effects of genotype on risk biomarkers, and; (3) demonstration of the molecular basis of the genotype/ phenotype association. The specific goals of the present research are to: 1) quantify, using a controlled dietary intervention trial, with prospective recruitment according to genotype, the impact of the apoE genotype on the responsiveness of LDLC to dietary fat manipulation, 2) verify the ability of dietary fat manipulation to reduce risk of CHD in carriers o f the apoE4 variant, 3) investigate, using a range of ex vivo techniques, the molecular basis of these genotype-dietary fat-LDLC associations, 4) establish prospective genotypying/ haplotyping as the gold standard for verifying putative (common) genotype-phenotype associations where there is potential for modifying disease risk through lifestyle modification.

This thesis will investigate the impact of illness and infirmity on the lives of older people and their families in England, c.1570-1730. At this time, approximately twenty percent of the adult population was aged over sixty, and yet the health conditions of this demographic have attracted little attention. There are two key goals: the first is to ascertain how medical providers and laypeople understood and treated the diseases and disabilities of older people, and whether this constituted a concept of elderly medical care. The second aim is to uncover the personal experiences of ageing sufferers themselves, together with their carers and relatives, investigating what it was like to suffer or witness pain, sensory loss, ‘dotage’, and the prospect of death. Drawing on a range of printed and archival materials, the project will transform understandings of both old age and disease in early modern England, revealing the hitherto unnoticed importance of 'state of health' in definitions of old age. The project is of vital relevance to an array of historiographical areas, including bodies, emotions, pain, senses, religion, death, gender, and family and community relationships. It also has modern-day significance, and may spark debates about the wellbeing of an expanding ageing population. Contrary to common assumptions, twenty percent of the adult population was aged over sixty in early modern England. My PhD will open a window on the health experiences of this forgotten demographic: it asks how doctors and laypeople understood and treated the diseases and infirmities of older patients, and uncovers the impact of these conditions on the lives of older people and their families, c.1570-1730. Drawing on sources such as diaries and doctors’ casebooks, the study will: • Overturn the view that medical providers were reluctant to treat the infirmities of older patients; • Provide poignant insights into the emotional experiences of older sufferers and their loved ones and carers; • Transform understandings of old age itself, revealing the vital but overlooked role of health as a measure of age at this time. The study also has great modern-day relevance, with potential to spark debates on the wellbeing of an expanding ageing population.

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