Similarity to prototypical heavy drinkers and non-drinkers predicts AUDIT-C and risky drinking in young adults: prospective study

Objective. The aim of the present study was to explore whether constructs within the Prototype Willingness Model (PWM) predicted risky drinking as measured by AUDIT-C, drinking harms and unplanned drunkenness in a sample of UK young adults. Previous studies exploring the PWM often do not use validated measures of alcohol consumption, and the outcomes of risky drinking are underexplored. Design. An online prospective study design with four week follow up was employed and 385 young adults completed the study (M age = 21.76, SD = 3.39, 69.6% female; 85.2% students). Main outcome measures. Intentions to get drunk, AUDIT-C, drinking harms experienced in the last four weeks, and unplanned drunkenness in the last four weeks. Results. Heavy and non-drinker prototype similarity predicted AUDIT-C, drinking harms and unplanned drunkenness when controlling for past behaviour and reasoned action pathway constructs. Intentions and willingness both mediated the relationship between prototype perceptions and AUDIT-C. Conclusion. This study supports the use of the PWM in the prediction of AUDIT-C, drinking harms and unplanned drinking in a UK sample. Prototype perceptions influenced behaviour via both reasoned and reactive cognitions. Targeting similarity to heavy and non-drinker prototypes should be the focus of future interventions in this population

Somatic cell gene therapy for diabetes mellitus: engineering a surrogate B-cell

Improved methods of insulin delivery are required for the treatment of insulin-dependent diabetes mellitus (IDDM) to achieve a more physiological profile of glucose homeostasis. Somatic cell gene therapy offers the prospect that insulin could be delivered by an autologous cell implant, engineered to secrete insulin in response to glucose. This study explores the feasibility of manipulating somatic cells to behave as a surrogate insulin-secreting β-cells. Initial studies were conducted using mouse pituitary AtT20 cells as a model, since these cells possess an endogenous complement of enzymes capable of processing proinsulin to mature insulin. Glucose sensitive insulin secretion was conferred to these cells by transfection with plasmids containing the human preproinsulin gene (hppI-1) and the GLUT2 gene for the glucose transporter isoform 2. Insulin secretion was responsive to changes in the glucose concentration up to about 50μM. Further studies to up-rate this glucose sensitivity into the mM range will require manipulation of the hexokinase and glucokinase enzymes. Intraperitoneal implantation of the manipulated AtT20 cells into athymic nude mice with streptozotocin-induced diabetes resulted in decreased plasma glucose concentrations. The cells formed vascularised tumours in vivo which were shown to contain insulin-secreting cells. To achieve proinsulin processing in non-endocrine cells, co-transfection with a suitable enzyme, or mutagenesis of the proinsulin itself are necessary. The mutation of the human preproinsulin gene to the consensus sequence for cleavage by the subtilisin-like serine protease, furin, was carried out. Co-transfection of human fibroblasts with wild-type proinsulin and furin resulted in 58% conversion to mature insulin by these cells. Intraperitoneal implantation of the mature-insulin secreting human fibroblasts into the diabetic nude mouse animal model gave less encouraging results than the AtT20 cells, apparently due to poor vascularisation. Cell aggregations removed from the mice at autopsy were shown to contain insulin secreting cells only at the periphery. This thesis provides evidence that it is possible to construct, by cellular engineering, a glucose-sensitive insulin-secreting surrogate β-cell. Therefore, somatic cell gene therapy offers a feasible alternative for insulin delivery in IDDM patients

Public self-consciousness, pre-loading and drinking harms among university students

Background: Social anxiety and self-consciousness are associated with alcohol-related problems in students. The practice of pre-loading is one avenue for exploration regarding this relationship. Individuals may pre-load to reduce social anxiety and feel more confident when socialising, which could lead to the increased harms experienced. The current study aimed to explore reasons for pre-loading, and whether public and private self-consciousness and social anxiety were related to pre-loading, increased drinking and harms. Method: Prospective study with four-week follow up of 325 UK students aged 18-30 years old. Participants completed measures of private and public self-consciousness, social anxiety, alcohol consumption, alcohol-related harms and pre-loading. Results: Financial motives and mood-related reasons, such as gaining confidence were reported as reasons for pre-loading. Pre-loading predicted hazardous alcohol consumption, but social anxiety, and public and private self-consciousness did not. However, pre-loading, public self-consciousness and social anxiety predicted alcohol-related harms. Furthermore, public self-consciousness mediated the relationship between pre-loading and harms in a positive direction and this appeared to be more relevant in high risk (AUDIT 8+) than low risk drinkers. Conclusion: Students who scored higher in public self-consciousness appeared to be at greater risk of harms from pre-loading. Further research should examine this relationship further with particular attention to high risk drinkers, and explore which aspects of a night out are related to heightened self-consciousness. Interventions could incorporate measures to reduce public self-consciousness, in order to reduce the negative impacts of pre-loading

Exploring the application of the Prototype Willingness Model to weight loss dieting behaviour among UK adults

Frequent weight loss dieting leads to increased BMI and is associated with eating pathologies. Theoretical models can aid the development of interventions to reduce risk behaviours such as frequent dieting if they are able to adequately account for the target behaviour. The Prototype Willingness Model (PWM) may be able to account for weight loss dieting as this behaviour is often associated with social images. This study explored whether the PWM could predict weight loss dieting status over and above the Theory of Planned Behaviour (TPB). One hundred and ninety two participants (69% female; mode age 35-44) completed PWM and TPB measures and recorded their height and weight. Males were more likely to be non-dieters than females. Frequent dieters had a higher BMI than non-dieters and rated themselves as more similar to the overweight prototype. Prototype perceptions predicted willingness to eat unhealthy foods alone. Similarity to the overweight prototype predicted weight loss dieting status over and above TPB measures and sex. Further research should explore prototype perceptions in an obese/overweight frequent dieting population as this may be a fruitful direction for developing interventions to reduce weight loss dieting

My own personal hell: Approaching and exceeding thresholds of too much alcohol

Objectives: Government guidelines aim to promote sensible alcohol consumption but such advice is disconnected from people’s lived experiences. This research investigated how people construct personal thresholds of ‘too much’ alcohol. Design and measures: 150 drinkers completed an online survey (Mage=23.29(5.51); 64.7þmale). Participants were asked whether they had an intuitive sense of what constitutes too much alcohol. They wrote open-ended descriptions of how that threshold had been established and how it felt to approach/exceed it. These qualitative accounts were coded using thematic analysis and interpreted with an experiential theoretical framework. Results: Personal thresholds were based on previously experienced embodied states rather than guidelines, or health concerns. Describing the approach to their threshold, 75% of participants fell into two distinct groups. Group 1’s approach was an entirely negative (nausea/anxiety) and Group 2’s approach was an entirely positive, embodied experience (relaxed/pleasurable). These groups differed significantly in awareness of alcohol’s effects, agency and self-perceptions, but not on alcohol consumption. Exceeding their threshold was an entirely negative embodied experience for all. Conclusion: These findings illustrate that people are guided by experientially grounded conceptions of consumption. Interventions could target different groups of drinker according to their embodied experience during the approach to ‘too much’ alcohol

Targeting risk images to reduce alcohol misuse in young people: Development of an intervention based on the social reaction pathway in the Prototype Willingness Model

Background: Alcohol misuse is associated with a number of health risks and harms that may be particularly detrimental to adolescents. Existing interventions for which there is evidence of effectiveness are time and cost intensive. Brief interventions or classroom delivered programmes are often ineffective, possibly due to their basis in rational models of behaviour. Young people’s risk taking behaviour may be better understood from a dual process perspective, which assumes two routes to behaviour; one rational and planned, the other a faster, reactive and spontaneous route. The Prototype Willingness Model (PWM) assumes that for adolescents, reactive behaviour is a result of the contemplation of ‘prototypes’ or widely held social images about the type of person who engages in a risk behaviour. Evaluation of these prototypes influences ‘willingness’ or an openness to the opportunity to engage a specific behaviour through a process of social comparison. Aim: The PWM has been applied to numerous risk behaviours and populations but there is less research in relation to its application to teenage drinking in a UK context. Thus, the overall aim of the thesis was to develop an intervention targeting constructs in the social reaction pathway in the PWM in order to explore its application to understanding and preventing alcohol misuse in young people. Method: This project used mixed methods and had a multiphase design with separate stages. A framework to guide development of a theory based intervention was proposed. This seven step framework built on existing guidance from Intervention Mapping and the Medical Research Council. The findings from each step are set out below. Findings: Step One: Evidence from a literature review suggested that the social reaction pathway in the PWM may be an appropriate theoretical basis for an intervention to reduce alcohol misuse in young people. Much of the evidence base comes from the USA or from studies that use college students. Step Two: Four focus groups were carried out with 27 11-13 and 16-17 year olds and analysed using deductive thematic analysis. The findings from this study show that young people in this sample were able to clearly describe the characteristics of social images (i.e. prototypes) in relation to alcohol. Step Three: The results of an online questionnaire completed by 182 young people supported the application of the PWM in an alcohol misuse intervention aimed at UK adolescents. The results indicated the intervention should use behaviour change techniques (BCTs) that target prototype perceptions with a focus on characteristics related to sociability. Step Four: The intervention was developed drawing the findings of steps one to three. Four BCTs reflecting the processes in the PWM were incorporated into an intervention in the format of an online quiz. Step Five: Fifteen expert participants gave feedback on the planned intervention in a Delphi study that took place in two questionnaire rounds. Findings suggested support for the content and mode of delivery and suggestions were made for improvements to the intervention. Step Six: Results of a questionnaire completed by 102 teachers and parents, and 16 think aloud interviews with young people found favourable responses to the format and content of the intervention. Feedback suggested that further development may be needed in terms of challenging coolness and peer pressure and in how plans to avoid drinking might be enacted. Step Seven: The findings were integrated and five intervention development priorities were identified from the studies with experts, teachers, parents and young people. In addition, nine overarching meta-themes were identified across all studies, which are discussed in light of their implications for interventions and future research. Conclusion: Drawing on these findings, a plan for intervention based on the social reaction pathway of the PWM, named the Alcohol Smart Quiz (ASQ) is presented. Strengths and weaknesses of the ASQ and the guiding framework used to develop it are discussed. The project highlighted the benefits of taking a clearly stated mixed methods approach, and shows the importance of early qualitative work in exploring theoretical constructs in intervention design

Feasibility of the Prototype Willingness Model as the basis for school-delivered alcohol misuse prevention: A qualitative think aloud study to explore acceptability of 'The Alcohol Smart Quiz’ with adolescents and teachers.

This study sought feedback from teachers and adolescents on a novel intervention to reduce alcohol misuse based on the Prototype Willingness Model. A qualitative, think aloud interview study was conducted with 17 adolescents aged 11-14 and nine teachers. Transcripts were analysed using thematic analysis. Adolescents found the content of the intervention appealing and credible. Teachers welcomed the content and format of as a means of generating discussion. ‘Moderate’ drinking appeared to be an acceptable message, although difficult to define. Enacting ‘if-then’ plans in real social situations might be challenging and representations of drinking on social media should be considered

"The monster of the month": Teachers’ views about alcohol within personal, social and health education (PSHE) in schools

Purpose: There is a lack of evidence for effective school based prevention programmes to reduce alcohol misuse in adolescents. This study sought to explore teacher’s views about alcohol education in secondary schools in order to inform the subsequent development of new educational and intervention measures. Methodology: Semi structured interviews were conducted with nine female teachers from a range of schools who had responsibility for designing and delivering Personal Social and Health Education (PSHE). Findings: Three main themes were identified in a thematic analysis of the interview transcripts. The themes demonstrated the importance of PSHE to these teachers, who faced challenges in delivering a comprehensive enough curriculum. Alcohol unit knowledge and responsible drinking were priorities for the teachers. However, given the many pressures faced by young people, alcohol could be viewed as just one challenge amongst many. Research Implications: Interventions may be seen as too compartmentalised by teachers if they fail to address the wider concerns of adolescents. Intervention developers should consider gaining input from teachers on the content of their programmes prior to running a trial to enhance feasibility and acceptability. Originality/Value: There are few studies that have explored what teachers think about alcohol education in general or about the content of specific interventions prior to their implementation. This study adds their voice to the literature, and highlights the importance of considering the views and first hand experiences when developing new alcohol interventions aimed at adolescents

L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease

Cell therapy is a promising treatment for Parkinson’s disease (PD), however clinical trials to date have shown relatively low survival and significant patient-to-patient variability. Glucagon Like Peptide-1 receptor (GLP-1R) agonists have potential neuroprotective effects on endogenous dopaminergic neurons. This study explores whether these agents could similarly support the growth and survival of newly transplanted neurons. 6-OHDA lesioned Sprague Dawley rats received intra-striatal grafts of dopaminergic ventral mesencephalic cells from embryonic day 14 Wistar rat embryos. Transplanted rats then received either saline or L-dopa (12 mg/kg) administered every 48 h prior to, and following cell transplantation. Peripheral GLP-1R agonist administration (exendin-4, 0.5 μg/kg twice daily or liraglutide, 100 μg/kg once daily) commenced immediately after cell transplantation and was maintained throughout the study. Graft survival increased under administration of exendin-4, with motor function improving significantly following treatment with both exendin-4 and liraglutide. However, this effect was not observed in rats administered with L-dopa. In contrast, L-dopa treatment with liraglutide increased graft volume, with parallel increases in motor function. However, this improvement was accompanied by an increase in leukocyte infiltration around the graft. The co-administration of L-dopa and exendin-4 also led to indicators of insulin resistance not seen with liraglutide, which may underpin the differential effects observed between the two GLP1-R agonists. Overall, there may be some benefit to the supplementation of grafted patients with GLP-1R agonists but the potential interaction with other pharmacological treatments needs to be considered in more depth

"It's just in that sea of things that I never cared about" : Perception of hepatitis B amongst university students in Aberdeen, North East Scotland

Acknowledgements: We would like to acknowledge the contribution of Elaine Adam (MA, PhD) who was involved in the data collection and analysis. Funding: This study was funded through NHS Endowments. The funding body had no role in the design of the study or the collection, analysis and interpretation of data or writing the manuscript. Availability of data and materials: The audio recordings and transcripts are held in the Institute of Applied Health Sciences, University of Aberdeen. They are not publicly available as they contain potentially participant identifiable information.Peer reviewedPublisher PD