Traditionally, creative activities have been used in occupational therapy practice as an intervention with people who have a mental illness. Recent research has explored engagement in creative activities with people living with disabilities, mental illness, retired people and people with cognitive impairment. The findings centred on positive emotions, increase in self-confidence and respite from worrying thoughts. Anecdotal evidence from local occupational therapy practitioners and arts organisations suggested that people in remission of mental illness seemed to use creative activities in their daily lives as a way to keep well, but deeper understanding was missing about this. The first aim of this study was to gain a deeper understanding of the phenomenon of voluntary participation in creative activities by people in remission of mental illness. The second aim was to explore and provide evidence of any relationship between well-being and creative activities as it was perceived by the participants. The research utilised a hermeneutic phenomenological approach. Qualitative data were collected through interviews with participants, transcribed verbatim and analysed within the hermeneutic tradition. Ten participants volunteered and were recruited by mental health NHS staff in central England. All participants had a diagnosis of a mental illness but were in remission from between six months and seven years at the time of the interviews. The data were analysed via my own interpretation of Cohen, Kahn and Steeves’ (2000) approach to hermeneutic phenomenological data analysis. The findings revealed that for all participants, engagement in their chosen creative activity evoked enjoyment and was of particular personal significance and meaning. Their subjective experiences highlighted the possible therapeutic potential of creative occupation, in particular, temporary mental relief from self-referential thoughts through deep immersion into the creative process. Deep engagement in creative occupation encompassed different types of optimal experience and might have a soothing effect on the Default Mode Network. The deliberate engagement in creative activities supports Wilcock’s theory of the use of occupation for self-restoration and keeping healthy. Additionally, the real contact with people and places facilitated a more active lifestyle which impacted also positively on the participants’ sense of well-being. The findings of the study are discussed from an occupational science perspective to extend our understanding of the solitary and group nature and effects of participation in creative activities.

The success of Highly Active Anti-Retroviral Therapy (HAART) requires a high rate of adherence to a complex regimen. Even small variations in adherence compromise treatment efficacy and can lead to viral resistance. Low levels of adherence to HAART continue to pose a major barrier to the success of these treatments. Studies investigating adherence to HAART have focused on practical barriers, yet studies in other illness groups suggest that patients' perceptions of their illness and treatment have a strong influence. This thesis is concerned with furthering our understanding of non-adherence to HAART. It begins with a review of HIV and its treatment. A critical review of the literature was conducted using systematic techniques. This identifies outstanding questions relating to the antecedents of adherence to HAART. The aim of this investigation was primarily to test the Self-Regulatory Model (SRM) and extensions to it to incorporate treatment perceptions (perceptions of personal necessity for HAART and concerns about adverse effects) in predicting adherence to HAART.

Due to the problems associated with local antimicrobial delivery to the oral cavity, such as poor retention times, the use ofbioadhesive polymers within oral healthcare products may significantly improve therapeutic efficacy. In the current study, bioadhesive antimicrobial-polymer complexes were investigated as a formulation strategy to improve the substantivity of antimicrobial compounds within the oral cavity.

Strain differences have previously been observed in the anxiolytic effect of the Angiotensin Type I receptor (AT1 R) antagonist losartan in mice. Structural variation in key binding sites, AT1 receptor binding, AT1 expression, the effect of a microsatellite in the promoter region of the gene and the influence of angiotensin receptor associated protein (ATRAP) were investigated for association with this observed behavioural variation.

β-Carboline derivatives display a wide range of interesting biological activities from intercalation to enzyme inhibition and anticancer to psychological activity. β- Carboline compounds are frequently isolated from natural products in the β- carbolinium form and thus contain a bridgehead quaternary nitrogen.

Soybeans have been in the human diet since the first millennium BC. They contain three major types of isoflavone, genistein, daidzein and glycitein. All three have been shown to have a powerful antioxidant effect and bind to oestrogen receptor beta with high specificity. It has been demonstrated that dietary soybeans favourably impact bone health in postmenopausal women by lowering the incidence of osteoporosis. The literature shows that genistein supplementation reduces marrow stromal cell (MSC) differentiation to an adipocytic pathway and may favourably stimulate osteogenesis. More recently soybean biomaterials (SB) have been developed which contain significant levels of isoflavones and have shown bone regeneration potential in vivo.

The purpose of this study was to explore personal accounts of acute non-specific low back pain experiences to gain insights and extend knowledge for physiotherapy practice and research. At present, knowledge of acute low back pain and understandings of the transition from acute to chronic low back problems largely derives from experimental research and population-generated findings developed from self-report questionnaires. Despite extensive research, there remains a limited ability to prevent the transition from acute low back pain problems to chronic pain and long term disability in many individuals. A qualitative study of personal accounts of acute low back pain experiences was undertaken using a theoretical perspective drawn from narrative research and discourse analysis. The approach incorporated narrative theory and perspectives from social constructionism, post-structuralism and theory of language. Nineteen participants with acute non-specific low back pain problems (< 6 weeks) were followed through to recovery or to three months with persisting problems, considered as the transition to `chronicity'. Data was generated through repeated interviews and written personal accounts involving a reflective timeline and a seven day open-format diary. Data analysis applied a narrative-discursive approach, and in particular a combined micro-interactional and macro-social approach drawn from discursive psychology. The nature of personal accounts of acute low back pain experiences has been shown to be significantly more complex than previously described within physiotherapy or low back pain literature. As personal circumstances were characterised so as to be appreciated as a significant problem, the accounts were constructed with qualities to support the credibility of the information. The accounts were also shaped to manage impressions of personal character, moral integrity, and personal accountability. In addition, considerations provided by the broader and situated social context, social relations and the unfolding interaction influenced the nature of the accounts. Finally, time was also an integral feature to the nature of the accounts, as a changing social context, an entity of personal and social significance and for its use as a resource for conveying meanings. This complexity has important implications for the interpretation of accounts and for the kind of knowledge assumed possible. Understanding the complexity also supports a more informed approach to the generation, interpretation and use of personal accounts as a form of information within practice and research contexts. The value of the methodology used in this study and the incorporation of theory and understandings from other disciplines for extending knowledge for physiotherapy practice is also discussed. 2

Changes in health and social care present exciting opportunities for occupational therapists to expand their practice into innovative settings. To prepare graduates for these opportunities, placement experiences must reflect current trends in practice. Role-emerging placements are increasingly being used to help students develop the skills, knowledge and attributes needed to become the therapists of tomorrow. Whilst the literature on role-emerging placements is increasing, studies have tended to be general placement evaluations, with limited studies exploring students' experiences in detail. No studies have explored the influence of role-emerging placements on graduates' professional practice and identity. This study adopted a phenomenological design to gain a deeper understanding of how occupational therapy students experience and ascribe meaning to role-emerging placements and the ways in which such placements influence their professional practice and identity once qualified. In-depth initial interviews were carried out with five MSc pre-registration occupational therapy students within one month of having undertaken a role-emerging placement. Follow-up interviews were carried out six months after the students had graduated and gained employment. Interviews were audio taped, transcribed and analysed using Interpretative Phenomenological Analysis (IPA). Key findings reveal that the role-emerging placements acted as a strong catalyst for the students' ontological development. Through engaging in challenging and autonomous learning experiences, they developed deeper insights of who they were becoming as professionals. This led to a professional identity that was of their own making. Having to continually reflect on and verbalise the core essence and contribution of occupational therapy, students developed clarity of understanding about the uniqueness of the profession. This is an important finding in light of the historical difficulty occupational therapists have had articulating their unique role and professional identity. Once qualified, participants had mixed experiences concerning the extent to which they were able to sustain this identity and enact practice in a way that was meaningful to them. A significant finding was the difficulty that graduates experienced working in NHS settings where the nature of occupational therapy practice restricted their ability to work in a way that was congruent with the professional way of being that they had developed during their placement. Consideration therefore needs to be given to the nature of occupational therapy practice in traditional settings. Recommendation is made for role-emerging placements to be made compulsory for all occupational therapy students to assist them in their ontological development and prepare them more effectively for practice. Further research into the long-term influence of such placements, in particular on graduates' practice and identity, is required.

The emergence of multidrug resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii has been recognized worldwide and some clinical isolates of these bacteria are now resistant to most of the antibiotics currently available. Unfortunately, there are at present not enough new antimicrobial drugs being produced by the pharmaceutical industry to keep pace with the continuing development of antibiotic resistance. Colistin is an old antibiotic and in the form of colistin methanesulphonate sodium (CMS) has re-emerged as a major treatment for burn patients colonised with Acinetobacter baumannii. However, this antibiotic can lead to profound toxicity and for this reason the blood levels of CMS should be carefully monitored. Unfortunately the methods available for measuring it in serum are not robust and are not able to differentiate between the two forms of colistin i.e. colistin sulphate (CLS) and CMS. In this study the chemical (Thin Layer Chromatography and High Performance Liquid Chromatography) and microbiological methods for CLS and CMS analysis were investigated to develop a methodology for reproducible quantification of CLS and CMS in water or serum. Since CMS in aqueous solution has the potential to hydrolyze to produce a complex mixture of colistin sulphomethylated derivatives as well as colistin base, the optimized chemical and microbiological methods were used to determine the degradation of CLS or CMS in aqueous solution and serum. The bacteriostatic and bactericidal activity of CLS and CMS were probed by calculations of minimum inhibitory concentrations and time survivor studies. Depending on their concentrations, both antibiotics were found to exhibit bacteriostatic and bactericidal properties against a range of Gram-negative bacteria. Membrane damage caused by both forms of colistin was investigated using Acinetobacter lwoffii R46383 anddetennining intracellular potassium leakage and 260nm absorbing materials leakage. CLS was shown to cause substantial membrane damage, indicated by rapid, gross potassium leakage, while the effect of CMS on the membrane appeared to be more subtle, with cells exhibiting a more concentration dependent loss of potassium. Adsorption isotherms ofCLS gave results that were indicative of high affmity isotherm (H- shape), while adsorption isotherms of CMS were indicative of co-operative sorption (S- shape). Investigations into CLS and CMS cytotoxicity were performed using normal rat kidney (NRK-52E) cell line; the investigations revealed that neither forms of colistin has a major adverse effect on the rat renal cells even at concentrations higher than the therapeutic doses.

Ageing is one of the leading health problems faced by society today. An understanding of the fundamental mechanisms of ageing has the potential to provide preventative therapies for multiple degenerative diseases. Drosophila melanogaster is a powerful model organism in which to study the ageing process because the rate of ageing in fly populations is easy to manipulate by either genetic or environmental means. Drosophila are also inexpensive, short lived, easy to collect and can be raised in large numbers (allowing sex and age- specific effects to be determined). Although a large body of data exists m mammals linking ageing and age-related degeneration to the accumulation of molecular cross-links such as advanced glycation end- products (AGEs) prior to the work presented in this thesis only one paper had studied such cross links in Drosophila. Accordingly I hypothesised: [1] That acid stable chemical species existed within Drosophila melanogaster (of which AGE-like entities represent a subset) • .• 1 I,. [2] That such chemical species !represented the stable products of damage to macromolecules within Drosophila' melanogaster and as such had the potential to play either a causal or a correlative role in the ageing process within this organism. To pursue this line of investigation it was first necessary to develop novel analytical methods to investigate the accumulation of damaged compounds in flies. Simple preparative techniques were developed to produce digests of whole Drosophila melanogaster for use in three dimensional (3D) fluorimetry, H NMR spectrometry and mass spectrometry. My initial data clearly indicated the presence of species which either increased or were lost with advancing population age. If they played a role in ageing then interventions that altered the rate of this process would be expected to alter the rates of accumulation or disappearance of these species. Accordingly, environmental (DR and low temperature) and genetic interventions (mutated IIS activity) were used to alter the rates of ageing of multiple cohorts of Drosophila. Populations subject to interventions which slowed ageing rates also showed a reduced rate of accumulation of signals consistent with damage (putative advanced glycation end products) as compared to cohorts under normal conditions. IH NMR spectrometry and mass spectrometry also revealed distinct age associated spectral changes. 3 My recognition that AGE-like molecules had the potential to activate Phase II detoxification mechanisms, together with the body of data on chemical changes within ageing flies that I generated using my novel techniques allowed the first critical test of the broad spectrum detoxification hypothesis of ageing (sometimes known as the "Green Theory" of ageing). The results I obtained were entirely consistent with the predictions of this theory. In conclusion, my work represents the first application of a range of analytical techniques to identify and quantify compounds associated with, and possibly causing, different rates of ageing in Drosophila melanogaster. These techniques will facilitate the identification of novel compounds that either increase or decrease during ageing in this organism and will improve our understanding of the ageing process in this key model system.