The SUMMIT trial: a field comparison of buprenorphine versus methadone maintenance treatment.

This prospective patient-preference study examined the effectiveness in practice of methadone versus buprenorphine maintenance treatment and the beliefs of subjects regarding these drugs. A total of 361 opiate-dependent individuals (89% of those eligible, presenting for treatment over 2 years at a drug service in England) received rapid titration then flexible dosing with methadone or buprenorphine; 227 patients chose methadone (63%) and 134 buprenorphine (37%). Participants choosing methadone had more severe substance abuse and psychiatric and physical problems but were more likely to remain in treatment. Survival analysis indicated those prescribed methadone were over twice as likely to be retained (hazard ratio for retention was 2.08 and 95% confidence interval [CI] = 1.49-2.94 for methadone vs. buprenorphine), However, those retained on buprenorphine were more likely to suppress illicit opiate use (odds ratio = 2.136, 95% CI = 1.509-3.027, p < .001) and achieve detoxification. Buprenorphine may also recruit more individuals to treatment because 28% of those choosing buprenorphine (10% of the total sample) stated they would not have accessed treatment with methadone

Towards evaluation criteria in participatory flood risk management

Flood risk consists of complex and dynamic problems, whose management calls for innovative ways of engaging with a wide range of local stakeholders, many of whom lack the technical expertise to engage with traditional flood risk management practices. Participatory approaches offer potential for involving these stakeholders in decision-making, yet limited advice is available to users in choosing which techniques to employ and what they might expect them to deliver. Assessing the effectiveness of participatory approaches in local flood risk management is a critical step towards better understanding how community resilience is built. This paper presents a framework for evaluating participatory approaches to flood risk management that covers four evaluation elements (context, process, substantive and social outcomes). Practical success criteria are provided for evaluation, with references indicating where further advice and guidance can be sought. Criteria are tailored to the requirements of flood risk management, and aim to be sufficiently flexible for the framework to be easily transferable

Synthetic Studies of Heterocyclic and Bioactive Agents

This dissertation describes a novel one-pot preparation of bicyclic heterocycles and improved synthetic procedures for the production of compounds possessing established biological activity. A five-component condensation reaction was discovered that follows a mechanistic sequence starting with a Biginelli reaction and ending in a Diels-Alder reaction to form a new class of bicyclic heterocycles. New protocols were developed to synthesize the bioactive compounds Gefitinib and analogs of JP4-039. The FDA approved EGFR inhibitor Gefitinib was synthesized on a pilot-plant scale using a more efficient synthetic sequence and fewer hazardous reagents. A shorter synthetic sequence to ferroptosis inhibitors, JP4-039 and related analogs, was developed with a key vinylogous Mannich reaction utilizing an oxazolidinone auxiliary. The biological activity of new ferroptosis inhibitors was used to generate a structure-activity relationship (SAR) hypothesis

Patients’ perceptions of physical activity before and after joint replacement: A systematic review with meta-ethnographic analysis

Background: It has been perceived that people following hip (THA) or knee arthroplasty (TKA) have the capability, with reduced pain, to increase their levels of physical activity. Objectives: To determine the attitudes and perceptions of people awaiting or having undergone THA or TKA to physical activity post-arthroplasty, and to identify potential facilitators or barriers to engage in active living and physical activity pursuits. Methods: Systematic review of published and unpublished databases was undertaken from their inception to November 2014. Studies exploring the attitudes and perceptions of people awaiting or having undergone THA or TKA to physical activity post-arthroplasty were included. Data was analysed through a meta-ethnography approach. Results: From 528 citations, 13 papers were eligibility, sampling 282 people post-THA or TKA. The literature was judged moderate to high quality. Following THA and TKA, people either wish to return to their pre-pathology level of physical activity or simply be able to engage in less physically demanding activities that are meaningful to them and their lifestyles. Barriers to engaging in higher levels of physical activity were largely related to limited information, which culminated in fear surrounding “doing the right thing” both for individual’s recovery and the longevity of the joint replacement. Conclusions: Whilst many people post-THA or TKA wish to return to pre-pathological physical activity status, there limited interest in actually undertaking greater levels of physical activity post-arthroplasty either for pleasure or health gains. Improvement in education and awareness of this may be key drivers to improve habitualisation of physical activity post-arthroplasty

Developing the implicit association test to uncover hidden preferences for sustainable drainage systems

Understanding public perceptions of Sustainable Drainage Systems (SuDS) is critical for addressing barriers to their implementation. Perceptions are typically evaluated using explicit measures (e.g. questionnaires) that are subject to biases and may not fully capture attitudes towards SuDS. A novel image-based application of the Implicit Association Test (IAT) is developed to investigate unconscious perceptions of SuDS in public greenspace, and combined with explicit tests to evaluate perceptions of greenspace with and without SuDS, focussing on a sample population in Newcastle-upon-Tyne. Greenspace with or without SuDS is perceived positively by the sample population. Overall, respondents implicitly and explicitly prefer greenspace without SuDS, and perceive greenspace without SuDS as more attractive, tidier and safer. The wide distribution of scores for SuDS, nonetheless, suggests a range of opinions and illustrates the complex nature of preferences for the use of greenspace. That the strongly negative explicit scores were not reflected in the implicit tests may suggest that explicit attitudes towards tidiness and safety may not be deep-rooted and are subject to social bias. Combined explicit and implicit tests may help us to understand any disconnect between expressed positive attitudes to natural spaces and behaviours around them, and inform SuDS design to increase public acceptance

Using Learning and Action Alliances to build capacity for local flood risk management

Learning and Action Alliances (LAAs) are becoming an increasingly popular method for overcoming the challenges associated with participatory forms of governance, where decision making requires collaboration between stakeholders. In flood risk management, LAAs provide a mechanism through which institutional participants can come together, share knowledge, innovate, and devise solutions to ‘wicked’ problems. While the social learning generated at LAAs is now well understood, the mechanism by which this learning is translated into action is less so. In this paper, we argue that in order to maximise the potential for action, LAAs must attend to different elements of capacity building, in order that action can diffuse outwards, from the individual members of the LAA, to their organisations and society beyond. By investigating two UK case study examples, we illustrate how different elements might be utilised in combination, to maximise the potential for longer-term, longer-lasting change. We conclude that the architects of participatory processes, including LAAs, should attend to different elements of capacity building, and consider those best suited to their individual contexts and objectives

Educational and psychosocial interventions to prevent uptake of smoking by young people

Introduction: More than 200,000 UK children aged 11–15 years start smoking each year and up to 50% of children who try smoking will become regular smokers within 2–3 years. Given the high personal, social and economic cost of smoking, intervening to prevent children and young people from beginning to smoke is an important public health goal. Whilst rates of smoking uptake have decreased significantly in recent years, the social gradient in young people taking up smoking remains marked, contributing to health inequalities. Methods: Using National Institute for Health Research (NIHR) Research Capability Funding (RCF) from a pooled fund contributed to by the Norfolk and Waveney Clinical Commissioning Groups, a team at the University of East Anglia undertook a comprehensive literature review and programme of public and patient involvement (PPI) in order to gather current evidence about the educational and psychosocial interventions that are effective in preventing smoking uptake, and improve understanding of current smoking prevention practice. The aim was both to provide evidence to inform commissioning decisions and to facilitate the development of an application for research funding for a trial of an intervention to support young people to choose not to start smoking. Results of review: The literature review identified a large number of educational and psychosocial interventions that have been found to be effective in reducing smoking uptake. Most of the identified interventions are universal, classroom-based interventions, designed to be delivered in mainstream schools. There is evidence that approaches to smoking prevention that combine elements designed to help young people refuse offers to smoke by improving general social competence, with elements aimed at increasing awareness of the social influences that promote smoking, may be most effective. However, it is important that smoking prevention interventions are tailored to the developmental stage of the age group targeted: interventions effective in one group may be ineffective, or even detrimental, in other populations. The ASSIST approach, involving training influential children to encourage their peers not to smoke, was the only approach identified with recent, UK evidence of both effectiveness and cost-effectiveness. Despite a clear rationale for targeting smoking prevention at high-risk groups, few interventions specifically targeting such groups have been trialled to-date. Results of PPI work: The PPI work carried out suggests that teaching in science lessons and/or Personal Social and Health education are the most common approaches to smoking prevention in Norfolk secondary schools. Providing information about the health threats of smoking was perceived by both teachers and pupils to be the most effective means of preventing smoking uptake. Given that research findings suggest that simply providing information about smoking is not the most effective means of preventing young people from taking up smoking, this may point to the need to provide schools with evidence-based information about optimum smoking prevention strategies. The use of peers to discourage smoking initiation was rarely reported as a currently used strategy in Norfolk, but most teachers and pupils responded that they believed this to be a good idea when specifically asked about this approach. Whilst all teachers and majority of pupils reported that their school had a policy in place in the event that pupils are found to be/suspected of smoking, fewer had a similar policy for pupils found to be/suspected of vaping (using e-cigarettes). Teachers reported awareness of school policies to also support smoking cessation where applicable (e.g. referral to specialist services), but pupils were generally unaware of such policies. Conclusions/recommendations: A range of evidence-based educational/psychosocial interventions for preventing uptake of smoking by young people are available, most of which are designed to be delivered within the school environment. The implementation of these interventions within schools has the potential to significantly reduce smoking prevalence, contributing to improvements in public health. However, it appears that many Norfolk schools may not be implementing these evidence-based interventions at present. Schools should be provided with information about the most effective strategies for preventing uptake of smoking by children and young people and encouraged to implement evidence-based smoking prevention initiatives. Equally, further research is needed to identify interventions that are effective in targeting groups of young people at high-risk of smoking uptake

The behavioural, metabolic and proteomic effects of temperature stress on bold and shy beadlet anemones (Actinia equina)

Environmental change caused by human activity is an ever-increasing threat to global biodiversity. A key determinant of the survival of animal populations under climate change is intraspecific phenotypic variation. This variation occurs at multiple levels, including between-individual differences in behavioural phenotypes (personalities), varied metabolic rates, and contrasting patterns of proteomic expression. Furthermore, an animal’s behavioural phenotype is split into two levels of its own, such that individuals vary consistently both in their mean level behaviours, and in the residual variation, or unpredictability, that they show around those means. Studies indicate that these different phenotypic levels could often be associated with one another: unpredictability may be constrained, or act as a constraint on, mean level personality; metabolic rate could be positively or negatively correlated with an animal’s propensity to take risks, termed their boldness; and proteomic expression under stress may differ between personality-types. All of these phenotypic levels provide important mechanisms for animals to mitigate against or cope with climate change, but few investigations have yet explored the relationships between them in the context of phenotypic flexibility during environmental shifts, termed plasticity. In this thesis, I explore how acute thermal perturbation, which is predicted to increase in frequency under continued climate change, affects the relationships between behavioural, metabolic, and proteomic phenotypes. Using the beadlet anemone (Actinia equina), a common intertidal species living in a thermally heterogeneous environment, I examine plasticity in two boldness-related behaviours: startle response-time (SRT), defined as the time it takes an anemone to re-extend its tentacles after a threatening stimulus; and immersion response-time (IRT), defined as the time to re-extend tentacles after simulated tidal immersion. In my first and second data chapters, I show that both behaviours exhibit between-individual variation in temperature-driven plasticity at the mean level, and that this extends to the level of unpredictability for IRT. I also show behaviour-dependent associations between temperature-driven behavioural plasticity, genotypic differences, and environmental history. In my third and fourth data chapters, I expand my investigations of each behaviour to encompass temperature-driven plasticity at other phenotypic levels. I find directionally unexpected associations between IRT and metabolic rate, and clear relationships between proteomic expression under thermal stress and SRT. The data presented here provide strong evidence for multi-level associations in temperature-driven phenotypic plasticity, and indicate that several strategies for dealing with thermal perturbation exist in A. equina. They advocate taking account of physiological and molecular correlates when investigating behavioural plasticity in a changing climate, and suggest that some individuals living in intertidal populations are likely to be more at risk from climate change-induced mortality than others. Overall, this thesis reveals the remarkable complexity of intraspecific variation in phenotypic plasticity, and drives home the need for ecologists and conservationists to consider this variation when assessing organismal vulnerability to climate change