Pulmonary rehabilitation (PR) is an effective strategy to manage chronic obstructive pulmonary disease (COPD). Self-management is an evolving and under-researched area within PR. The aim of this thesis was to explore the impact of self-management on health outcomes in patients with COPD.

With the incidence of many cancers, including brain tumours, increasing worldwide, the diagnostic pathway and new innovative treatments have often failed to keep pace. The main stay of cancer diagnosis remains at the Histopathologists' microscope, with little change in light microscopy within recent times. Research promises many new diagnostic tools, aiming to improve turn around times and provide instant accurate answers. One such tool is vibrational spectroscopy. This thesis aims to use spectroscopy as a proof of concept within brain tumour diagnostics to demonstrate its abilities within the cancer diagnostic pathway. Proof of concept studies aimed at targeting both biofluid and tissue diagnosis of primary and metastatic brain tumours has been performed, along with involvement of Patients' and Clinicians' to aid development of diagnostic tools. Spectrochemical methods including Raman and attenuated total reflectance- Fourier transform infrared spectroscopy (ATR-FTIR) have shown an ability to diagnose primary and metastatic tumours; with fresh frozen tissue ATR-FTIR proved superior with a classification accuracy of non-tumour brain versus primary brain tumours of 97.2%, though this decreased when comparing tumour types (79% accuracy); when differentiating metastatic brain tumours from formalin fixed tissue accuracy was similar for both spectroscopic techniques at 60% for colorectal adenocarcinomas, 68% for lung adenocarcinomas and 70% for melanoma; finally, with biofluids, using ATR-FTIR to determine a primary versus metastatic tumour and the type of each tumour, accuracy was low at non tumour 85%, high grade glioma 92%, low grade glioma 61%, meningioma 43%, melanoma metastasis 21%, colorectal adenocarcinoma metastasis 50% and lung adenocarcinoma metastasis 24%. The final, novel study, trialled a handheld Raman spectrometer within the histopathology department at Royal Preston Hospital, Lancashire Teaching Hospitals NHS Trust, to determine if the benefits of spectroscopy lay within the intraoperative diagnosis. The final results demonstrate accuracies from 64-94% depending on tumour type, demonstrating that with further training, Raman spectroscopy may provide a clinically useful diagnostic tool within the operating theatre, to replace the need for intraoperative smear preparations and diagnosis by a Neuropathologist. Overall, this thesis highlights the need to involve Patients' and Clinicians' within research to ensure uptake and accurately targeted diagnostic tools. It also demonstrates the potential of spectroscopy, when well targeted within the diagnostic pathway. Moving forward, further work to move Raman spectroscopy into the operating theatre, is likely to prove beneficial to patients.

Background. Influenza and pneumococcal vaccinations are important therapies supported by national and international guidelines for preventing morbidity and mortality from respiratory illnesses in high-risk groups. The responsibility for delivering these vaccinations in the United Kingdom lies with primary care. Little is known about how rates of influenza and pneumococcal vaccination can be increased in high-risk groups in primary care. Aim. To research methods of improving rates of influenza and pneumococcal vaccination in high-risk groups in primary care. Objectives. To investigate the impact of educational interventions for primary care teams on influenza and pneumococcal vaccination rates in high-risk groups. Method. The research had the following components: a. Literature search examining current practice and policy in relation to influenza and pneumococcal vaccination and studies undertaken to improve performance, both in general and specifically in relation to improving adult vaccination rates. b. Pilot study of targeting influenza and pneumococcal vaccination to high-risk groups in a single general practice. c. Effect of audit and feedback with an information pack to primary care teams on influenza and pneumococcal vaccination in primary care: before-and-after multipractice study. d. Effect of audit and feedback with an information pack to primary care teams, as part of a clinical governance programme, on influenza and pneumococcal vaccination in a primary care trust: before-and-after multipractice study. e. Randomised controlled study of an educational outreach intervention partly nested within primary care trust study with audit, feedback and information (passive dissemination of guidelines and recommendations) directed at primary health care teams compared with audit feedback and information alone using multifaceted interventions to increase influenza and pneumococcal vaccine uptake in high-risk groups in primary care. Results. The studies demonstrated significant improvements in influenza and pneumococcal vaccination rate in high-risk groups in primary care, showed the levels of improvement that could be expected from these types of intervention and described how primary care teams responded to direct and indirect educational interventions supported by measurement of performance. Conclusions. Education to multiprofessional teams is an important method for diffusion of innovations in the highly professionalised organisations of primary care and general practice. Educators need to understand the complex nature of primary care organisations and teams, when and how education for teams is likely to be successful, the barriers to implementation of new ideas and how to address these. Education when applied appropriately can have important effects in improving health care. This is more likely to occur when careful assessments are made around the nature of the evidence, clear outcomes are sought and measured and the healthcare intervention is understood from the perspective of the patient, the healthcare team and other stakeholders.

Attention-Deficit/Hyperactivity Disorder (ADHD) is characterised by symptoms of hyperactivity, impulsivity and attentional difficulties. Originally thought to be a condition of childhood, ADHD has now been recognised in adults. One of the main theoretical explanations of ADHD is related to deficits in Executive Functioning (EF). The state of current knowledge regarding the relationship between EF and ADHD was reviewed. Findings suggest that adults with ADHD are likely to exhibit deficits in EF mainly related to response inhibition, set-shifting or working memory. Deficits in EF as shown on neuropsychological tests may help to identify people who are at risk of under achieving in various life domains such as education or occupation. Tests of EF which are more ecologically valid may be more sensitive to EF dysfunction than traditional measures. The experience of having adult ADHD and preferences for support were explored using Interpretative Phenomenological Analysis (IPA). Four super- ordinate themes emerged from five interviews: 'Process of adapting to ADHD', 'Social Appraisal', 'Self-regulation' and 'Coping'. Participants described an adjustment process which impacted on their identity and the impact on self-perception was evident. ADHD was not understood well by others and some participants experienced stigma and bullying. A range of coping strategies were identified and clinical implications and limitations of the study were discussed. Finally, a commentary and reflexive analysis of the research process was offered and factors influential to the research were discussed.

Members of the Mycobacterium abscessus complex (MABSC) are a highly antibiotic-resistant complex of organisms within the genus Mycobacterium, increasingly acknowledged as a significant cause of lung infection in patients with cystic fibrosis (CF) and associated with poor clinical outcomes. Current methods of isolation of MABSC are hindered by the fact that they grow at a slower rate in culture than other microorganisms with many patient samples having to be discarded due to the overgrowth of more rapidly growing species. Decontamination of samples has shown to have an adverse effect upon the viability of MABSC, therefore improvements in the isolation of MABSC are urgently required in order to offer the possibility of a more rapid and accurate diagnosis. A novel medium (RGM) was developed for the isolation of MABSC. Commercially available pre-poured media were compared with RGM and challenged with isolates of rapidly growing mycobacteria and other species. In addition, in a multi-centre study sputum samples collected from patients with CF were inoculated onto RGM medium, BCSA and standard automated liquid culture method and assessed for growth. RGM demonstrated superior sensitivity over currently used methods without any requirement for decontamination and could easily be incorporated into any laboratory alongside routine culture for other CF pathogens. Chromogenic and fluorogenic substrates were investigated for the possibility of differentiating between subspecies within the MABSC complex. However, the results established that these would not provide any additional benefit to RGM. Possible environmental sources were explored in order to establish how patients with CF were acquiring MABSC. Although person-to-person transmission has been suggested, there are very few reports to substantiate this at present and many questions remain unanswered. In this study, MABSC was not isolated from any of the environments screened. Finally, a selection of antimicrobials were investigated against MABSC with the purpose of ascertaining susceptibility and whether any may be used for a more successful treatment outcome. There were no clinically applicable results therefore further work is required in this area. To conclude, RGM is a novel culture medium, which can be embedded alongside routine culture for other CF pathogens without any requirement for decontamination. This means that all respiratory samples submitted from patients with CF can be conveniently cultured for NTM, considerably improving the service offered to clinicians and patients. Furthermore, it is likely that formal AFB culture methods could be replaced by use of such a medium, potentially enabling substantial savings in terms of materials and labour time.

Species relationships of the endemic Elaphoglossum, and the extent and distribution of population genetic diversity were investigated using allozyme analysis in chapter five. As well as supporting the relationships of the taxa in the molecular phylogeny, the allozyme data suggest a hybrid origin of E. dimorphum between E. nervosum and E. bfurcatum. In addition the allozyme data revealed significant genetic differentiation in populations of E. nervosum and E. bfurcatum which should be taken into consideration in any future conservation programme. To conclude, Chapter 5 is a general discussion on the evolution and conservation of island plants, highlighting my research findings from St Helena and comparing it to other studies.

The treatment of menopausal symptoms by combined hormone replacement therapy (HRT) utilises drug formulations whereby a progestii1 is added to the oestrogen component to decrease the risk of endometrial carcinoma prnduced by the oestrogen. However, administration of large doses of progestins can increase low density lipid cholesterol, as well as reduce some of the beneficial effects of oestrogens. Local administration of progestins to the uterus may allow a much smaller dose to be used reducing the antagonism produced by progestins on desired oestrogenic effects. The simplest way to administer drugs to the uterus is by inserting a device through the cervix, however, this procedure may be associated with bacterial contamination of the uterus leading to pelvic infection. This study has therefore set out to develop a device for the delivery of antimicrobial agents to the uterus to reduce microbial contamination associated with transcervical insertion, and also the delivery of progestins which could be used as an adjunct to oestrogen HRT by targeting the progestin locally to the endometrium.

Background: UK ambulance clinicians are able only to terminate resuscitation attempts that have resulted in an asystolic (flat line) cardiac rhythm, following twenty minutes of advanced life support. All other attempted resuscitations must be transported to hospital for further treatment. Despite this, there are still large numbers of patients transported to hospital who do not survive. Thirteen studies were identified that purported to validate termination of resuscitation guidelines. This evidence could not be used to reduce the number of futile transportations to hospital of adult cardiac arrests of presumed cardiac aetiology within the geographical area of interest, due the variances in emergency medical systems. Methods: Binominal logistic regression identified variables associated with outcomes in a dataset of 4,870 adult cardiac arrests of presumed cardiac aetiology (Phase 1). The clinical decision rule was validated retrospectively against an independent dataset of 2139 patients (Phase 2). It was then validated prospectively (Phase 3). Finally, the financial benefit of introducing the guideline was assessed. Assumptions were made on the potential resources required to treat each patient and the impact from an acute care perspective was assessed as the difference in cost when applying the guideline, compared to current practice. Results: The clinical decision rule (terminate on scene if the initial rhythm was not shockable and there is no return of circulation) was shown in Phase 1 to have a specificity of 99.0% (95% CI: 97.7% to 99.7%) and sensitivity of 53.1% (95% CI: 51.6% to 54.6%). The transport rate was 52.4%. There were five (0.2%) unexpected survivors. This compared favourably with existing guidelines. In Phase 2 the guideline recommended termination for 832 patients. Of these, 829 (99.6%) died and three (0.4%) survived (Specificity = 99.1%, 95% CI: 97.4% to 99.8%, Sensitivity = 46.5%; 95% CI: 44.1% to 48.8%). The transportation rate was 60.7%, which was lower than for existing guidelines when applied to the same dataset. Of 656 patients in Phase 3, the guideline recommended termination of 162 patients. None of these survived to hospital discharge (Specificity = 100%, 95% CI: 95.6% to 100%, sensitivity = 29.3%, 95% CI: 25.6% to 33.4%). The transportation rate during this phase was 75.3%. When plotted on a ROC space, the guideline showed better predictive power, when compared to existing guidelines. The minimum cost saving was shown to be £33,739 per 1000 adult OHCA patients currently transported to hospital. Conclusion: Introducing the decision rule to the trust in question would reduce the number of transportations to hospital of adult patients suffering cardiac arrest of presumed cardiac aetiology. Further research is needed to apply the findings to other locations or emergency medical systems. In order to strengthen the validity of the tool, it should be assessed prospectively in either one large prospective study or several smaller studies, but within different settings. Ideally, to prevent bias, such a validation would be performed by a different research group.

Osteoarthritis is common with radiographic features practically universal in at least some joints in people aged over 60 years. One of the main therapeutic interventions used in the management of osteoarthritis is the injection of corticosteroid and hyaluronan (Gossec 2006). However, there exist few studies that seek to explore possible factors that influence outcome following injection. This study examined the factors that may influence the outcomes following injection of either corticosteroid or hyaluronan in the management of osteoarthritis of the knee.

The Drosophila gene pacman encodes a 5’-3’ exoribonuclease, which is involved in RNA degradation. pacman mutants were created by P-element excision. These mutants have phenotypes including dull and blistered wings, kinked legs and thoracic closure defects. Also, pacman mutant embryos show a dorsal closure defect. The thorax and dorsal closure phenotypes in pacman mutants closely resemble those observed in flies mutant for genes of the highly conserved JNK signalling pathway, for example hemipterous (JNKK), basket (JNK) and kayak (Dfos). These similarities suggest pacman may be involved in regulating the JNK pathway. The JNK signalling pathway is known to regulate morphological processes such as dorsal closure during Drosophila development and wound healing. The phenotypes of our pacman mutants suggest pacman may have a role in these processes possibly through interactions with the JNK signalling pathway.