Obesity is a significant problem in young people. Relative to other age groups, less is known about health related lifestyle behaviours of young people, particularly in the transition period from adolescence to adulthood. Food choices are made within the food environment, which encompasses any opportunity to obtain food or influence food choice. Environmental exposures such as the availability and accessibility of ‘more healthy’ and ‘less healthy’ food options interact with individual factors to drive food choice. The aim of this work was to explore whether, and to what extent, the food environment to which a young person is exposed has an influence on individual dietary intake. A range of methods including food diaries in conjunction with text messaging and photography, questionnaires, Global Positioning Systems (GPS), Geographical Information Systems (GIS), and qualitative interviews were used. The majority of young people (96%) reported using a food outlet at least once over a 4-day period. Less healthy food outlets, such as takeaways and convenience stores, were the most frequently used. Being exposed to a greater number of food outlets was significantly associated with visiting a greater number of food outlets. Similarly, being exposed to a greater proportion of ‘less healthy’ food outlets was associated with visiting a greater proportion of ‘less healthy’ food outlets. However, relationships between the number of food outlets visited and dietary intake were weak and there was little evidence to suggest an association between exposure to food outlets and dietary intake. Qualitative results indicated that time, geographic location, economic cost and social occasion influenced choice of food outlet. In addition, the particular food outlet chosen appeared to dictate the food choices made with habitual repeat ordering of meals an emerging theme. No previous research has linked individual eating behaviour to the food environment. Identifying the types of outlets young people use, the food choices made within and the factors influencing decisions and behaviours is important for the development of targeted long term obesity prevention strategies to facilitate healthier food outlet environments.

Obesity has more than doubled over the past three decades, and due to its association with physical and psychological morbidities, it is now one of the fastest growing health problems. Consequently, bariatric surgery has become more popular when all other treatment options have failed. This thesis sought to better understand the presence and relationships of psychosocial factors after bariatric surgery patients. Literature Review : Excess skin after massive weight loss is common in bariatric patients. The current review examined studies that quantitatively explored psychosocial outcomes after body contouring (reconstructive surgery). Ten studies were included and the findings were equivocal with some suggesting positive psychosocial outcomes and others implying a negative association. Research Report : The empirical paper examined the role of shame in post bariatric surgery patients. Shame has been frequently explored in eating disorders but it has not been examined in a bariatric surgery sample. This study aimed to explore the extent to which shame was present and predicted psychological morbidity, low self-esteem, impaired quality of life and body image disturbance in this population. Questionnaires were posted to 265 eligible participants, of which, 80 participants returned completed measures. The data were examined using descriptive, correlation and multiple regression analyses. The findings suggest that post bariatric surgery patients experienced higher levels of shame, anxiety and depression, lower self-esteem, impaired quality of life and problematic body image disturbance compared to the normal population. Shame also predicted the variance in psychological morbidity, self-esteem, quality of life and body image disturbance. Critical Appraisal : The critical appraisal is a reflective and personal account that discusses the research journey and some important issues relating to quantitative research.

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Biofilm and complex microbial community formation are fundamental processes in colonisation of the human oral cavity. Defining the mechanisms by which microbes interact with each other will lead to better understanding of how these communities are assembled. Many species of oral bacteria express cell-surface proteins (adhesins) that promote colonisation and infection through host receptor recognition. Streptococcus gordonii is ' a commensal primary coloniser of the oral cavity, and is also implicated as a leading cause of infective endocarditis . S. gordonii expresses a number of cell-surface proteins that enable the bacteria to colonise a variety of sites throughout the human body and to coaggregate with other microorganisms in biofilm community development. These include two Antigen I/ ll-family proteins, 'termed SspA and SspB, that have been implicated in colonisation and pathogenic mechanisms utilised by S. gordonii. The first aim of this study was to determine the molecular basis of interaction between two early colonisers of the oral cavity, S. gordonii and Actinomyces oris. This work identified a novel primary coloniser interaction involving recognition by SspB of cell surface polysaccharide expressed by A. oris. Another adhesin expressed by S. gordonii is CshA, which forms fibrils that extend away from the bacterial cell surface, interacts with fibronectin, and mediates coaggregation with other oral microorganisms in the formation of biofilm communities. However, the molecular mechanisms that underpin these interactions were unknown. The second aim of this study was to obtain detailed structural information about CshA, and to define functional regions relevant to S. gordonii colonisation and pathogenesis. This work showed that CshA had a unique structure with new protein folds, not previously reported for bacterial adhesins, and identified specific functional regions. Better understanding of molecular mechanisms involved in bacterial colonisation will assist development of new clinical interventions for diseases caused by oral microorganisms.

Obesity is currently a worldwide health problem associated with conditions such as type 2 diabetes. It has been reported that connexins may be involved in adipogenesis but the underlying mechanism remains unresolved. Adipose tissue from male Zucker fatty rats (falfa), male lean rats (fa-I-) and 3T3-Ll cells were investigated for connexin (Cx) and pannexin expression profiles, Cx localization and function and lipid accumulation during the differentiation programme.

Morbid obesity is associated with increased cardiovascular risk and thrombosis is a critical component of cardiovascular risk. Although obesity is considered a modifiable risk factor for venous thromboembolism (VTE) , the mechanism and impact of fat distribution is not clearly defined. This is the first comprehensive study to assess the prothrombotic phenotype in morbidly obese patients as well as linking with abdominal fat distribution markers and obstructive sleep apnoea. A cross-sectional study on morbidly obese patients aged 18 -65 years was initiated to characterise the prothrombotic phenotype in this patient group. Eighty nine patients with a BMI >30kgm-2 and no history of VTE were recruited from the obesity clinic at King's college hospital. Seventy-seven age and sex matched ambulatory control subjects were also recruited from volunteers. The study also investigated the impact of obesity comorbidities; sleep apnoea and metabolic syndrome on the hypercoagulable state. Obesity was assessed by BMI and abdominal fat distribution was determined by analysing computerised tomography (CT) images taken at lumber 4 (L4). Fasting samples were obtained for thrombophilia screening, thrombin generation test, plasminogen activator I inhibitor (PAl), free tissue plasminogen activator inhibitor (TFPI), factor VII, factor VIII, D Dimer (DD), glucose, insulin, full lipid profile and adiponectin. Thrombin generation as measured by endogenous thrombin potential (ETP) was significantly increased in the patient group (p<0.001). The thrombin lag time was unexpectedly extended in the patient group (p< 0.001) suggesting some unexplained attenuation. Other prothrombotic markers such as fibrinogen and factor VIII were also raised. Visceral abdominal adipose tissue area (VAT) was directly associated with haemostatic markers and there was no association with subcutaneous abdominal adipose tissue area (SAT). Obstructive sleep apnoea prevalence and severity was directly associated with VAT but not with SAT. The study concludes that morbid obesity confers a prothrombotic phenotype characterised by raised prothrombotic markers and hypofibrinolysis. The study demonstrates for the first time that VAT is much more significant in defining the hypercogulability state and SAT may not be significant in defining the prothrombotic state. The study also confirms that VAT is the more pathologic fat compartment in OSA prevalence and severity.

Obesity is a major global and national problem with a variety of consequences and effects. The relationship of fetal programming with obesity has been discovered through both human and animal studies and it has been found that nutritional programming can predispose the developing offspring to obesity later in life. However, many aspects of this fetal programming have yet to be fully determined, for instance the environmental and metabolic factors involved. This thesis has investigated the programming effects of maternal low protein restriction (MLP) and maternal age (2 month, 4 month and 6-9 month old mothers) in the rat, looking at both immature (4 weeks old) and mature (9 months old) adult offspring. Postnatal high fat diets were fed for 9 weeks to exacerbate potential obesogenic effects. During the trials various measures were studied, body weight, feed intake, energy expenditure, metabolism, body composition, body fat distribution, activity and behaviour.

Helicobacter pylori is a Gram-negative bacterium that infects the human stomach and can cause peptic ulcer disease CPUD) and gastric adenocarcinoma. Around 50% of the world's population is infected with H. pylori, but only about 10-15% of infected people go on to develop clinical symptoms, with around 1 % developing gastric cancer. There is evidence that H. pylori may also provide protection against some disease including gastric reflux and more controversially extra-gastric conditions such as asthma and allergy. The anti-inflammatory regulatory T-cell (Treg) response is increased during H. pylori infection and patients with the greatest Treg responses are less likely to have PUD. The experiments presented in this thesis aimed to increase understanding of the Treg response to H. pylori infection and its role in health and disease. Blood samples and gastric biopsies were collect from patients attending the Queens Medical Centre, Nottingham. In vivo and in vitro models were utilised to investigate aspects of the Treg response to H. pylori infection. The results show that the CCR6/CCL20 axis is involved in Treg recruitment to the human gastric mucosa. In vivo models were developed that will help to further investigate the importance of this axis in Treg migration during H. pylori infection. The protective role of H. pylori-associated Tregs in EAE, a mouse model of MS was investigated. Finally, work was begun to assess the role of H. pylori virulence factors in determining the Treg response to infection.

Cardiac amyloidosis is a condition characterised by infiltration of the myocardium with fibrillar proteins. Transthyretin (TTR) is a plasma protein that may form amyloid fibrils and the V122I mutant form of TTR is associated with isolated cardiac amyloidosis. Previous studies have estimated a 4% V122I allele frequency in African Americans. The prevalence of cardiac transthyretin amyloidosis (ATTR) V122I in the British population is not known. I was awarded a British Heart Foundation Clinical Research Fellowship to investigate the diagnosis and prevalence of ATTR V122I in the UK population. More than one million people of Afro-Caribbean ethnicity live in the Greater London area, and in the local ward of Wandsworth make up more than 10% of the population (2011 census data). The prevalence of ATTR V122I at St George's Hospital was high, affecting 12% of all Afro-Caribbean heart failure patients aged ~60 years. The estimated incidence of ATTR V122I in Afro-Caribbean subjects in the St George's Hospital catchment area was over twice the reported incidence of amyloidosis of all types in the general, predominantly Caucasian, UK population. The clinical phenotype is characterised by resistant heart failure, increased wall thickness and diastolic dysfunction on echocardiography and poor outcomes (median survival 29 months). The ECG had poor sensitivity to detect ATTR V122I because 25% of patients present with left ventricular hypertrophy criteria, contrary to the reported low voltage complexes widely reported in AL amyloidosis. Cardiovascular magnetic resonance (CMR) imaging demonstrated extensive late gadolinium enhancement (LGE) and I developed a novel LGE scoring system to differentiate ATTR from AL amyloidosis with high accuracy. A simple diagnostic algorithm to detect new cases of ATTR amyloidosis was retrospectively employed at a separate tertiary heart failure clinic and demonstrated that 5.2% of elderly black patients had ATTR amyloidosis, having previously been given a diagnosis of hypertensive heart failure. Improved detection of ATTR amyloidosis is increasingly important as novel treatments are now undergoing phase 3 clinical trial assessment and newly diagnosed patients now have the potential for disease modifying therapies. This will have implications for counselling and family screening of this inherited autosomal dominant condition in the future.

Background: Recent advances in the assessment of oesophageal function include high resolution manometry and ambulatory impedance-pH monitoring. These have improved our understanding of the pathophysiology of gastro-oesophageal reflux disease including the importance of components other than acid in the gastrooesophageal reflux ate. Aims: 1: Provide evidence of gastro-oesophago-pharyngeal reflux in patients diagnosed with extra-oesophageal reflux disease.2: Investigate the presence of pepsin in saliva in health and disease.3: Investigate the changes in gastrooesophageal motility and reflux in patients undergoing sleeve gastrectomy. Methods: High resolution oesophageal manometry was used to assess oesophageal peristalsis, upper and lower oesophageal sphincters. Ambulatory impedance-pH monitoring was used to determine the physical and chemical properties of gastrooesophageal and gastro-oesophago-pharyngeal refluxate. The presence of pepsin in saliva was detected by indirect sandwich ELISA. Gastric emptying was measured ) with a 13C labelled octanoic acid breath test. Results: 1. Approximately half of all patients diagnosed with gastro-oesophagopharyngeal reflux had evidence of pharyngeal acid or non-acid reflux. These patients were more likely to have detectable levels of pepsin in their saliva. 2. Pepsin can be detected in saliva, preceded by reflux events in health and disease. 3. After sleeve gastrectomy there is increased acid and non-acid gastro-oesophageal reflux with changes in lower oesophageal sphincter pressure and gastro-oesophageal pressure gradient. Conclusion: 1. Targeting patients with objective evidence of gastro-oesophagopharyngeal reflux for anti-reflux therapy may help to improve treatment outcomes. 2. Detection and quantification of pepsin in saliva may be a useful screening tool for patients with suspected gastro-oesophageal reflux. 3. Reduction in the lower oesophageal sphincter pressure and an increase in gastro-oesophageal pressure gradient following sleeve gastrectomy are associated with significant gastrooesophageal reflux.