Background: In the United Kingdom (UK) 65.4% of men are overweight or obese. In England the direct costs of treating obesity were estimated in 2002 at approximately £46 million. Obesity develops when energy intake exceeds energy expenditure over a prolonged time. Reviewing weight loss initiatives reveals that most studies are undertaken on female subjects which may not take account of issues relevant to men. This research takes a multidisciplinary approach to male obesity encompassing nutrition, exercise/activity, and the psychological aspects of behaviour change as proposed in the transtheoretical model of change (TTM) Aims: To determine whether obese and overweight males go through set stages of behavioural change when trying to lose weight. Methods: Study 1 established the effectiveness of psychometric tests as screening tools for weight management. Data on current nutritional and activity habits were collected. Forty six males were recruited. In Study 2 nineteen Trainers delivered a l2-week weight management course, evaluated by weight loss and reduction in waist measurement in 54 Clients. Results: Data from the psychometric tests used in study 1 informed the screening criteria for Study 2. Clients achieved a mean weight loss of 4.65kg (P<0.001) and mean waist circumference reduction of nearly 5cm (P<0.001). In addition, daily steps increased by 3947 (P<0.001) and energy intake decreased by 315 kcal (P<0.05). Weight loss efficacy significantly increased (P<0.01) as did decisional balance difference (P<0.01). An increase in the level of efficacy correlated with reductions in waist measurement (P<0.05). Conclusion: It is possible to train novice trainers to deliver an effective weight management course. Increases in self-efficacy and decisional balance were in line with TTM theory. This research provides a programme of weight management for men, meeting the need for "Accredited Health Trainers" highlighted in the UK government white paper "Choosing Health".

Introduction: Interest in intra-abdominal pressure (IAP) measurement has increased significantly, with evidence of its deleterious effects demonstrated on every organ. Despite the volume of publications – several assumptions relating to the measurement of IAP remain unproven and there is a paucity of data relating to patients in a specialised liver Intensive Therapy Unit (ITU). Methods: This thesis encompasses a survey of the available literature and national attitudes / practice with several clinical experiments; Generic Questions 1. IAP measurement technique – validation of current gold-standard against alternatives. 2. Identification of potential sources of error in measurement of IAP 3. Impact of body position and zero-reference point on IAP Specialty Specific Questions. 1. Incidence of raised IAP in specialised liver ITU and its link to complications/length of stay. 2. Identification of early predictors of raised IAP 3. Study of regional abdominal compartmental variation in IAP Results & Conclusions: • IAP is widely accepted by UK anaesthetists and surgeons, especially amongst those more recently graduated. Knowledge and practice is variable however and requires better education. • The Foley Catheter Manometer represents a reliable and valid tool for the measurement of IAP, with excellent agreement to measurements obtained by other devices and directly transduced intra-peritoneal pressure. • Body-position and bladder priming volumes both introduce significant clinical error in the measurement of IAP. • Patients in liver ITU are at higher risk of developing elevated IAP than those in a general ITU. Within this patient cohort, complications are associated with elevated IAP and IAP is a better predictor of length of stay than other severity scores. A normal Day 1 IAP reliably predicts that abdominal compartment syndrome will not occur during the admission. • Significant variation in upper and lower IAP occurs following liver transplantation and this regional variation can be manipulated by body positioning.

Background and Aims: The inflammatory bowel diseases (IBD) are chronic diseases that affect populations worldwide and impart considerable morbidity to those affected. Immunosuppression in IBD is effective but limited by side effects and non-response. We aimed to identify pharmacogenetic markers of response to commonly used immunosuppressive medication in these patients. Methods: The influence of MTHFR 677C>T, MTHFR 1298A>T, ATIC 347C>G, TSER *2/*3 tandem repeat, TYMS 3’-UTR 6 bp insertion/deletion, SLC19A1 80G>A, AOX 3404A>G polymorphisms, 14bp ins/del polymorphism in the HLA-G gene and the IL-10 -1082A>G, -819C>T and -592C>A promoter SNPs were investigated on clinical response and side effect rates in 201 patients with Inflammatory Bowel Disease (IBD) treated with methotrexate (MTX). The HLA-G 14 bp ins/del polymorphism was correlated with azathioprine (AZA) response in 97 IBD patients. The IL-10 -1082A>G, -819C>T and -592C>A promoter SNPs on chromosome 1 were examined for an influence on the effect of the 14bp ins/del polymorphism in this group. The 14bp ins/del polymorphism was examined for an influence on susceptibility to IBD in 3148 individuals compared with 1330 normal controls. Stimulated PBMC from 14 normal individuals were incubated with MTX and 6-MP and expression levels of soluble HLA-G and IL-10 were correlated with genotype. Results: A small positive correlation was seen for the MTHFR677TT genotype for clinical response and for the ATIC347GG for intolerance to MTX. The 14bp ins/del polymorphism strongly predicted clinical response to MTX (p=0.0016). The same influence was seen in 97 IBD patients treated with azathioprine (AZA) (p=0.001) and neither of these effects were affected by variant IL-10 promoter haplotypes. The described polymorphism did not influence susceptibility to IBD. Individuals with the 14bp del/del polymorphism expressed more soluble HLA-G after incubation with 6-MP (p=0.02) and MTX than carriers of the insertion allele. A dose effect was evident and carriers of the high producer IL-10 GCC promoter haplotype expressed significantly more IL-10 when incubated with 6-MP (p=0.04). This provides functional correlation of the genetic effect. Conclusion: HLA-G genotype maybe a strong and predictor of response to MTX and AZA in IBD patients. These are preliminary findings and need replication in prospective studies.

This research looks at the feasibility of colonoscopic high frequency ultrasound in the colon using mini probe technology. The objectives are across four different areas with assessment of colonic cancer, malignant colorectal polyps, rectal polyps and diverticular disease. High frequency 12 and 20 MHz ultrasound were used to locally stage colonic cancer and compare this to conventional CT in patients undergoing elective colonic resection. In addition, depth of infiltration of rectal polyps was determined by 20 MHz ultrasound and these findings compared with MRI in patients undergoing TEMS procedure. Malignant colorectal polyps were assessed after endoscopic removal to assess for the presence of residual or recurrent disease in the colonic wall and also to stage the local lymph nodes. Finally, the thickness of colonic wall in patients with diverticular disease was measured using 20 MHz ultrasound and this was compared with normal controls. The research has clearly shown that colonoscopic high frequency mini probe ultrasound is feasible in the colon with reproducible results. Overall, 12 and 20 MHz colonoscopic ultrasound are superior to CT for local staging of colonic cancer. 20 MHz ultrasound offers greater accuracy for assessment of depth of infiltration of rectal polyps compared with MRI. This probe may also be utilised to assess the colonic wall for residual disease in the polypectomy scar of malignant polyps but larger numbers are needed with longer follow up in order to draw firm conclusions. Finally, it was feasible to measure the thickness of colonic wall in patients with diverticular disease and this was greater than that seen in normal patients. In conclusion, this research has been promising in that colonoscopic high frequency mini probe ultrasound is feasible in the colon and can be used to assess colorectal polyps and cancer and diverticular disease. In order to draw firm conclusions, this pilot research needs to be taken further with larger scale studies.

Crohn’s disease (CD) is an incurable intestinal disorder in which an immune response driven by commensal gut microbiota leads to chronic inflammation. Why this occurs in specific individuals is unclear; however, a genetic predisposition is fundamental and relatives of patients with CD are at enhanced risk of developing CD. Accumulating knowledge relating to the genetic loci that predispose to CD raises the possibility of disease prediction and prevention in susceptible populations. However, the genetic basis of CD is complex, and genotyping alone is likely to be insufficient to predict disease risk accurately. Specific physiological abnormalities associated with CD, such as increased intestinal permeability and raised faecal calprotectin, are also abnormal in some relatives of patients with CD. By using the combination of genotype and biomarkers models of disease prediction become a realistic possibility, and may permit intervention to prevent disease onset. Furthermore, enhanced understanding of the genotype and phenotype of the at-risk state in relatives of patients with CD also provides insights into the earliest, pre-disease stages of the pathogenesis of CD. This thesis reports a case-control study comparing 22 patients with quiescent CD with 21 of their healthy siblings and 25 healthy, unrelated controls. In addition to genotyping each participant, the CD-risk phenotype was found to encompass alterations in the intestinal microbiota, blood T-cell phenotype, concentrations of faecal calprotectin and intestinal permeability. A combination of these factors could be used to discriminate healthy siblings from healthy controls. Prior to commencement of the case-control study, a detailed survey of the prevalence of probiotic and prebiotic use in the intended patient population was carried out. Furthermore, a subset of the participants in the case-control study subsequently undertook a 3 week open-label trial of oral prebiotic oligofructose-enriched inulin in order to assess the potential of prebiotics to influence the at-risk phenotype.

Non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease throughout much of the World. It affects between one in five and one in three adults in the general population. It is now believed to be the leading cause of liver cirrhosis and hepatocellular carcinoma. However, the majority of people with NAFLD do not go on to develop terminal liver disease but instead have an uncertain prognosis that can often include type 2 diabetes, cardiovascular disease, and/or non-hepatic cancers. Indeed, NAFLD is frequently accompanied impaired glucose control, and almost always suboptimal insulin sensitivity. This thesis explores the only currently recommended therapy – weight reduction by lifestyle modification. It reviews the published evidence supporting this recommendation by applying a systematic approach to review the literature, but examines the findings in the broader context of common NAFLD comorbidities and sequelae. It also examines interaction of age and physical activity with liver fat, specifically in women, using both primary and secondary research methods. Finally, it explores exercise, particularly high-intensity intermittent training as a means to reduce liver fat, improve body composition, and attenuate insulin resistance independent of weight change and dietary advice. The principle finding is that, although the literature supports the recommendation of weight reduction, exercise can be an effective therapy to reduce liver fat and improve glucose control/insulin independent of weight change in adults with NAFLD. High-intensity intermittent training is particularly ii effective for liver fat reduction, improves glucose control/insulin resistance, and results in positive changes to body composition.

Neuroendocrine tumours (NETs) are uncommon tumours which have a diverse biology. The aims of this thesis were to identify potential new biomarkers and further develop understanding of tumour biology in NETs. The following were assessed i) somatostatin receptor (SSTR) and dopamine-2 receptor (D2R) expression in NETs, ii)HER expression and their associated prognosis, iii) Angiopoietin expression in NETs and their prognostic significance, iv) proteomic analysis of serum and NET cell lines to identify novel markers and finally v) the role of 68Ga-DOTATATE PET in imaging of NETs. Immunohistochemical studies were performed to determine whether SSTR and D2R are co-expressed in NETs. D2R was co-expressed with SSTR-2 and -5 in 93% of low grade tumours, with lower co-expression in higher grade tumours. HER family of receptors are involved in oncogenesis; the expressions of these receptors were assessed. Immunohistochemical analysis of these receptors was performed in 82 cases. EGFR was expressed in 86%, HER-2 0%, HER-3 8.5% and HER-4 91.5%. The expression of EGFR was not associated with poor prognosis. Angiopoietins (Ang) are involved in tumourogenesis. Serum Ang-1 and Ang-2 were measured in patients and healthy controls. Ang-2 was significantly higher in patients compared to controls. Patients with Ang-2 levels >4756pg/ml had a shorter time to progression. Proteomic analysis using gel electrophoresis and LC/MS/MS of plasma from NET patients and established NET cell lines was performed to identify biomarkers. Proteomic cell line analysis identified 17 proteins in all cell lines including Mac-2 binding protein. We validated Mac-2 binding protein and it appears to be a potential marker for NETs. Finally, we performed a study to ascertain whether 68Ga-DOTATATE PET identifies more lesions in NET patients in whom 111In-DTPA-Octreotide showed faint/negative lesion uptake. 111In-DTPA-Octreotide scintigraphy identified 27 lesions compared to 168 lesions identified with Ga-68-DOTATATE PET. 68Ga-DOTATATE PET is a sensitive imaging modality for identifying NETs.

One of the greatest paradoxes of our time is that people are getting heavier, even though everyone seems to be dieting to lose weight. Research has shown that dieters experience a preoccupation with food and overeating behaviour; however, little is known about what factors underpin the preoccupation with food and overeating behaviour so commonly reported in dietary restraint. The aim of this thesis is to understand why dieting produces cognitive and behavioural effects which are precisely the opposite of what one intended when they engaged in dietary restraint. Ironic Processes Theory (IPT; Wegner, 1994) was originally developed to explain why people who are instructed to suppress thoughts about a white bear reported an increase in white bear thoughts during suppression and a rebound of white bears thoughts when then the instruction to suppress was terminated. The mechanism proposed by Wegner (1994) to explain why people struggle with thought suppression can also be applied to understand why dieters struggle to control their food intake. The attempt to avoid food, both cognitively and behaviourally, initiates a monitoring process which is tuned to search for food and sends a signal to the operating process to direct attention away from food. Dieters are able to avoid food as long as they have sufficient cognitive resources. However, any threat to these resources through additional physical (time constraints) or psychological demands (stress) will disable the operating process and the dieter will find food difficult to avoid. According to IPT, avoiding food is the key factor which underpins a preoccupation with food and overeating behaviour. The relevance of IPT in dietary restraint was investigated through a series of dot probe and recognition experiments, which measure an attentional and memory bias for food. An attentional bias which directs attention away from forbidden foods and towards non-forbidden foods would support the operating and monitoring processes in dietary restraint. However, a memory bias which is more accurate for forbidden foods would support the hypothesis that avoiding food underpins a preoccupation with food. It was also decided toinvestigate whether the operating and monitoring processes could be dissociated with a threat to cognitive resources. This was achieved by measuring an attentional and memory bias for food following a violation to dietary restraint. Finally, a qualitative analysis of avoiding food, preoccupations with food and overeating behaviour was conducted to investigate the ecological relevance of these phenomena in the dieter’s natural environment. The results obtained in this thesis offered some support for the hypothesis that avoiding food underpins a preoccupation with food and overeating behaviour; however, the support available for IPT was confined to the collection of qualitative data. All participants, irrespective of level of dietary restraint, preload condition, and gender status, consistently displayed an attentional and memory bias which drew their attention towards forbidden foods and away from non-forbidden foods. This effect was observed when both pictorial and linguistic stimuli were used in the dot probe task and suggests that an attentional bias for food is not confined to restrained eaters. The non-significant effect of dietary restraint in the experimental chapters prompted an investigation of the reliability of the dot probe task. The item analysis found that participants failed to respond to food stimuli in a predictable and reliable fashion, which was required to support the division of foods into forbidden and non-forbidden categories. The results obtained in the qualitative investigation offered some support for IPT in that dieters were found to avoid food, experience a preoccupation with food and overeating behaviour. There was also considerable evidence to suggest that avoiding food underpins a preoccupation with food and overeating behaviour. However, the results revealed that avoiding food is not the only factor which underpins the negative cognitive and behavioural effects associated with dietary restraint. Dieters described a range of cognitive and behavioural phenomenon which could not be adequately explained by IPT (e.g. food addiction, compensatory behaviours and time effects). It was concluded that there is some support for IPT in dietary restraint, however the experience of dietary restraint was far more complex than IPT predicts. The results obtained in this thesis were examinedinvestigate whether the operating and monitoring processes could be dissociated with a threat to cognitive resources. This was achieved by measuring an attentional and memory bias for food following a violation to dietary restraint. Finally, a qualitative analysis of avoiding food, preoccupations with food and overeating behaviour was conducted to investigate the ecological relevance of these phenomena in the dieter’s natural environment. The results obtained in this thesis offered some support for the hypothesis that avoiding food underpins a preoccupation with food and overeating behaviour; however, the support available for IPT was confined to the collection of qualitative data. All participants, irrespective of level of dietary restraint, preload condition, and gender status, consistently displayed an attentional and memory bias which drew their attention towards forbidden foods and away from non-forbidden foods. This effect was observed when both pictorial and linguistic stimuli were used in the dot probe task and suggests that an attentional bias for food is not confined to restrained eaters. The non-significant effect of dietary restraint in the experimental chapters prompted an investigation of the reliability of the dot probe task. The item analysis found that participants failed to respond to food stimuli in a predictable and reliable fashion, which was required to support the division of foods into forbidden and non-forbidden categories. The results obtained in the qualitative investigation offered some support for IPT in that dieters were found to avoid food, experience a preoccupation with food and overeating behaviour. There was also considerable evidence to suggest that avoiding food underpins a preoccupation with food and overeating behaviour. However, the results revealed that avoiding food is not the only factor which underpins the negative cognitive and behavioural effects associated with dietary restraint. Dieters described a range of cognitive and behavioural phenomenon which could not be adequately explained by IPT (e.g. food addiction, compensatory behaviours and time effects). It was concluded that there is some support for IPT in dietary restraint, however the experience of dietary restraint was far more complex than IPT predicts. The results obtained in this thesis were examinedinvestigate whether the operating and monitoring processes could be dissociated with a threat to cognitive resources. This was achieved by measuring an attentional and memory bias for food following a violation to dietary restraint. Finally, a qualitative analysis of avoiding food, preoccupations with food and overeating behaviour was conducted to investigate the ecological relevance of these phenomena in the dieter’s natural environment. The results obtained in this thesis offered some support for the hypothesis that avoiding food underpins a preoccupation with food and overeating behaviour; however, the support available for IPT was confined to the collection of qualitative data. All participants, irrespective of level of dietary restraint, preload condition, and gender status, consistently displayed an attentional and memory bias which drew their attention towards forbidden foods and away from non-forbidden foods. This effect was observed when both pictorial and linguistic stimuli were used in the dot probe task and suggests that an attentional bias for food is not confined to restrained eaters. The non-significant effect of dietary restraint in the experimental chapters prompted an investigation of the reliability of the dot probe task. The item analysis found that participants failed to respond to food stimuli in a predictable and reliable fashion, which was required to support the division of foods into forbidden and non-forbidden categories. The results obtained in the qualitative investigation offered some support for IPT in that dieters were found to avoid food, experience a preoccupation with food and overeating behaviour. There was also considerable evidence to suggest that avoiding food underpins a preoccupation with food and overeating behaviour. However, the results revealed that avoiding food is not the only factor which underpins the negative cognitive and behavioural effects associated with dietary restraint. Dieters described a range of cognitive and behavioural phenomenon which could not be adequately explained by IPT (e.g. food addiction, compensatory behaviours and time effects). It was concluded that there is some support for IPT in dietary restraint, however the experience of dietary restraint was far more complex than IPT predicts. The results obtained in this thesis were examined

The search to unravel the complex phenomenon of obesity has been pursued for centuries. Theoretical postulations regarding the etiology of obesity and subsequent management strategies are numerous and complex. Despite decades of clinical application, the rising prevalence of obesity remains essentially unchanged. Clearly it is time to consider a new perspective. In view of the continued failure of programs to effectively achieve successful long-term weight management, a re-evaluation of the phenomenon of eating is warranted. A grounded theory design provided the opportunity to explore this phenomenon in a new light. This study attempts to understand the phenomenon of eating in adult, American, Caucasian women from the perspective of the reality of the women who experience it. The resulting theory of seeking solace through eating emerged from the context of the social process in which it was embedded. Embracing this new understanding of eating and obesity, realistic strategies may be designed to promote health and reduce the associated morbidity and mortality. Nursing interfaces with people at all phases of the life cycle and, therefore, is in a unique position to influence this continued health problem.

This dissertation explored object relations characteristics in an obese population by comparing those who relapse following treatment with those who maintain their weight losses following treatment. The impetus for this study came from the proliferation, in recent years, of weight loss programs whose long-term results have been dismal. This all-too-common trend of relapse only serves to perpetuate the negative physical and psychological concominants of obesity. This dissertation presented a psychodynamic approach to conceptualizing relapse in weight loss and conducted a preliminary exploration in an effort to glean same information to confirm or disconfirm the usefulness of this approach. Theoretically, disruptions in early attachment, through empathic failures on the part of the selfobject, interfere with internalization of self-soothing structures. consequently, when the self experiences intolerable affect, the self initiates some action to ameliorate it. In the case of obesity, the self eats compulsively. This dynamic plays a role in relapse. Assessing the theoretical concepts presented through the Bell Object Relations Inventory with particular attention to the Insecure Attachment subscale, this study proposed that those who relapsed would show greater object relations deficits than those who maintained their weight losses and that those who reported emotional eating would show greater deficits on the Insecure Attachment subscale than those who did not. The subjects included in this study were thirty-nine caucasian females who had participated in a modified fasting diet. The study contacted the subjects through mailed surveys. It analyzed the data collected through the use of a t-test. Results did not show a significant difference between the relapse and maintenance groups. However, a significant difference appeared on the Insecure Attachment subscale when it compared emotional eaters to non-emotional eaters. This finding was consistent with the theoretical link between affect motivated eating behavior and the quality of object relations.