Type 2 diabetes prevention in high-risk individuals :how might effective, equitable and sustainable service provison be achieved?

PhD ThesisBackground: Prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide, linked to the obesity epidemic. There is substantial research evidence for T2D prevention by lifestyle interventions in high-risk individuals. The span of this research provides a unique case study with which to critically examine general guidance for development and evaluation of interventions to improve health. My research question is how might can effective, equitable and sustainable service provision for T2D prevention in high-risk individuals be achieved? Methods: Five papers reporting my empirical T2D prevention research form the core of my thesis. This research extends from the European Diabetes Prevention Study (EDIPS) RCT to the ‘New life, New you’ (NLNY) feasibility study. NLNY is a community based lifestyle intervention to reduce T2D incidence that is delivered by fitness trainers in North East England. To inform my research question I have reviewed intervention guidance history. I have then used T2D prevention as a case study, supported by my empirical research experience, to analyse this guidance Findings: Development of the NLNY intervention built on the EDIPS RCT evidence and experience. Pilot evaluation of NLNY suggests a feasible and acceptable intervention that is likely to be effective in preventing T2D. Prevention of T2D provided a useful exemplar for analysis of intervention guidance and highlighted strengths and limitations of existing guidance models. This analysis led to a proposed new guidance framework. Conclusions: The NLNY intervention provides a potential service provision model for T2D prevention in high-risk individuals. Well planned effectiveness and cost-effectiveness evaluation of the NLNY intervention is now needed. The analysis of intervention guidance and the proposed new framework will contribute to developing a robust study design. If effectiveness of the NLNY intervention is demonstrated there is potential for this community based intervention model to be further developed and adapted

Beach Quality and Recreational Values: A Pictorialized Stated Preference Analysis of Residents and Tourists

Much of Hawaii’s economy relies on its unique marine environments, which are threatened by degradation from stormwater runoff. Using a stated preference method of choice-based conjoint (CBC) analysis, based on stylized photographs, this study examines both residents’ and visitors’ marginal value for levels of attributes associated with Hawaiian beach recreation. Each attribute (sand quality, water quality, congestion and water safety conditions) was significant for both residents and tourists, with water quality being the single most important attribute. There is little distinction between resident and tourist marginal value, except for a greater value lost for below average water quality among tourists.Nonmarket Valuation, WTP, Beach, Environmental Economics and Policy, Resource /Energy Economics and Policy,

Identifying gene locus associations with promyelocytic leukemia nuclear bodies using immuno-TRAP.

Important insights into nuclear function would arise if gene loci physically interacting with particular subnuclear domains could be readily identified. Immunofluorescence microscopy combined with fluorescence in situ hybridization (immuno-FISH), the method that would typically be used in such a study, is limited by spatial resolution and requires prior assumptions for selecting genes to probe. Our new technique, immuno-TRAP, overcomes these limitations. Using promyelocytic leukemia nuclear bodies (PML NBs) as a model, we used immuno-TRAP to determine if specific genes localize within molecular dimensions with these bodies. Although we confirmed a TP53 gene-PML NB association, immuno-TRAP allowed us to uncover novel locus-PML NB associations, including the ABCA7 and TFF1 loci and, most surprisingly, the PML locus itself. These associations were cell type specific and reflected the cell's physiological state. Combined with microarrays or deep sequencing, immuno-TRAP provides powerful opportunities for identifying gene locus associations with potentially any nuclear subcompartment

Participants' perspective on maintaining behaviour change: a qualitative study within the European Diabetes Prevention Study.

BACKGROUND: The European Diabetes Prevention Study (EDIPS) is an RCT of diet and exercise interventions in people with impaired glucose tolerance. We undertook a qualitative study, nested within the EDIPS in Newcastle-upon-Tyne, UK, aiming to understand the experience of participants who maintained behaviour change, in order to inform future interventions. METHODS: Participants were purposively sampled, according to success criteria for diet and physical activity change maintenance, and invited to attend individual semi-structured interviews. Fifteen participants completed an interview and reflected on their experience over three to five years. We used the Framework method to analyse the transcribed data. RESULTS: Main themes were identified as factors that help (props) and those that hinder (burdens) behaviour change maintenance at different organisational levels: individual (both physical and psychological), social and environmental. Pre-existing physical conditions (such as arthritis) and social demands (such as caring for an ageing relative) hindered, whereas the benefits of becoming fitter and of having social and professional support helped, participants in maintaining behaviour change. Participants' long term experiences highlighted the salience of the continuous change in their physical, social and environmental conditions over time. CONCLUSION: The construct of props and burdens facilitates a holistic view of participants' behaviour. Efforts to encourage behaviour change maintenance should take account of context and the way this changes over time, and should include strategies to address these issues. The experience of participants who maintain behaviour change highlights the challenges for the wider implementation of diabetes prevention strategies. TRIAL REGISTRATION: (ISRCTN 15670600).The European Diabetes Prevention Study in Newcastle was funded by the Wellcome Trust

Values for Recreational Beach Quality in Oahu, Hawaii

Pristine coastal environments are the key to Hawaii’s worldwide fame and attraction to tourists, yet their economic value remains understudied. This article examines preferences for characteristics associated with beach recreation in Oahu, Hawaii, among residents and tourists. Consideration is given to sand quality, water quality, congestion levels, and swimming safety conditions in the context of a choice experiment. The choice experiment conveys attribute levels almost entirely through pictures, and results suggest that this novel portrayal is well understood by respondents. Excessive congestion and water quality are regarded as the most important beach attributes, specifically the avoidance of poor water quality in favor of a chance to experience excellent water quality. Some evidence suggests that significantly different willingness to pay (WTP) exists among residents and tourists on Oahu with poor water quality and excellent water quality being more important to tourists, while residents place greater value on avoiding excessive congestion

Perspectives of UK Pakistani women on their behaviour change to prevent type 2 diabetes: Qualitative study using the theory domain framework

Background: Type 2 diabetes (T2D) is a debilitating disease, highly prevalent in UK South Asians, and preventable by lifestyle intervention. The ‘New life, New you' (NLNY) physical activity (PA) and dietary intervention for T2D prevention was culturally adapted to better engage minority ethnic populations and tested for feasibility. Objectives: To investigate Pakistani female participants' perspectives of their behaviour change and of salient intervention features. Setting: A community-based 8-week programme of group delivered PA sessions with behavioural counselling and dietary advice, culturally adapted for ethnic minority populations, in an area of socioeconomic deprivation. Participants to NLNY were recruited through screening events in community venues across the town. Participants: Interviews were conducted with 20 Pakistani female NLNY participants, aged 26-45 (mean 33.5) years, from different parts of town. Results: Within the a priori Theoretical Domains Framework (intentions and goals, reinforcement, knowledge, nature of the activity, social role and identity, social influences, capabilities and skills, regulation and decision, emotion and environment), we identified the importance of social factors relating to participants' own PA and dietary behaviour change. We also identified cross-cutting themes as collateral benefits of the intervention including participants' ‘psychological health'; ‘responsibility' (for others' health, especially family members included in the new PA and diet regimes) and ‘inclusion' (an ethos of accommodating differences). Conclusions:  Our findings suggest that culturally adapted interventions for Pakistani women at risk of T2D, delivered via group PA sessions with counselling and dietary advice, may encourage their PA and dietary behaviour change, and have collateral health and social benefits. The NLNY intervention appeared to be acceptable. We plan to evaluate recruitment, retention and likely effect of the intervention on participant behaviour prior to definitive evaluation

Participants' perspectives on making and maintaining behavioural changes in a lifestyle intervention for type 2 diabetes prevention: A qualitative study using the theory domain framework

Objectives: In a qualitative substudy, we sought to elicit participants' perspectives of their behavioural change and maintenance of new behaviours towards intervention optimisation. Setting: The intervention was delivered in leisure and community settings in a local authority, which according to the UK government statistics ranks as 1 of the 10 most socioeconomically deprived areas in England. Participants: We recruited 218 adults aged 40-65 years at elevated risk of type 2 diabetes (Finnish Diabetes Risk Score≥11) to the intervention. Follow-up at 12 months was completed by 134 (62%). We recruited 15 participants, purposively sampled for physical activity increase, to the qualitative substudy. Intervention: Lifestyle intervention can prevent type 2 diabetes, but translation to service provision remains challenging. The ‘New life, New you' intervention aimed to promote physical activity, healthy eating and weight loss, and included supervised group physical activity sessions. Behavioural change and weight loss at 12-month follow-up were encouraging. Design: We conducted 15 individual semistructured interviews. The Framework approach, with a comparison of emerging themes, was used in analysis of the transcribed data and complemented by the Theory Domains Framework. Results: Themes emerging from the data were grouped as perceptions that promoted initiating, enacting and maintaining behavioural change. The data were then categorised in accordance with the Theory Domains Framework: intentions and goals; reinforcement; knowledge; social role and identity; social influences; skills and beliefs about capabilities; behavioural regulation, memory, emotion, attention and decision processes and environmental context and resources. Participant perceptions of intervention features that facilitated behavioural change processes were then similarly analysed. Conclusions: Social influences, reference to social role and identity (eg, peer support), and intentions and goals (eg, to lose weight) were dominant themes across the three phases of behavioural change. Reinforcement, regulation and decision processes were more evident in the maintenance phase. The socioeconomic status of participants was reflected in the environmental context and resource theme. Analysis of phases and theoretical domains of behavioural change added depth and utility to inform intervention optimisation. We will develop the intervention with improved peer support and explicit monitoring of the behavioural change techniques used, prior to a definitive trial

Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

<p>Abstract</p> <p>Background</p> <p>Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action.</p> <p>Methods</p> <p>The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches.</p> <p>Results</p> <p>We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis.</p> <p>Conclusions</p> <p>The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes with doxorubicin, an agent administered for recurrent disease. This synergy occurs by a novel mevalonate-independent mechanism that antagonizes drug resistance, likely by inhibiting P-glycoprotein. These data raise important issues that may impact how statins can best be included in chemotherapy regimens.</p