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Lung transplantation is an established final treatment option for patients with advanced chronic respiratory disease. Despite its success in enhancing pulmonary function and health-related quality of life (HRQoL), limitations in physical and emotional function have been reported to persist in lung transplant recipients. To confirm this notion and to fully understand the level of physical and emotional functioning in these patients, the present thesis compared accelerometry-derived physical activity and HRQoL outcomes between lung transplant recipients and healthy individuals in the UK. Lung transplant recipients displayed significantly lower levels of daily physical activity across a number of parameters, along with significantly lower HRQoL in domains related to physical functioning, highlighting the need for effective interventions to promote physical activity in this population. Physical inactivity in daily life may contribute to impaired recovery of physical functioning following lung transplantation and diminish long-term outcomes. Given the paucity of research into potential interventions to address physical inactivity in lung transplant recipients, the current thesis includes a systematic review of the evidence supporting the benefits of exercise training for lung transplant candidates and recipients. Whilst exercise training appeared to have a positive impact on exercise capacity and HRQoL, the available evidence is low quality and limited by the lack of randomised controlled trials (RCTs). The main study of the present thesis investigated the feasibility, acceptability, and safety of a 3-month behavioural modification physical activity tele-coaching (TC) intervention in lung transplant recipients that has been proof-tested previously in COPD patients. The intervention consisted of a validated, commercially available pedometer that was used as a motivational tool to monitor daily activity, and a smartphone app, allowing transmission of pedometer activity data to a cloud-based platform that provided feedback, activity goals, education, and telephone contact with the researcher when required. The study employed an RCT design to evaluate the potential effect of the intervention, by assessing the short- (3 months) and longer-term (6 months) impact on physical activity, HRQoL, anxiety and depression, compared to usual care (UC). The results showed that key criteria for progressing to a full-scale RCT study were met. Of the 22 patients eligible, 20 were recruited and randomised to TC or UC and 18 completed (67% male; mean ± SD age; 57 ± 10 years; COPD n=5, ILD n=10, CF n=2, PH n=1): TC (n=10) and UC (n=8). TC was well accepted by patients, with 88% indicating that they enjoyed taking part. Usage of the pedometer was excellent, with 80% of patients wearing it for over 90% of days and rating the pedometer and telephone contact as the most vital aspects. There were no adverse events related to the intervention. After 3 months, both TC and UC displayed clinically important improvements in accelerometer steps/day (by 2945±3056 and 1566±1400 steps/day, respectively) and SF-36 physical component summary (PCS) scores, however TC exceeded UC by clinically important margins (by 1379 steps/day and 5 points, respectively). Only the TC group displayed significant improvement in movement intensity (by 138±148 VMU) and time spent in at least light activity (by 43±28 min/day). At 6 months, the TC group maintained improvements gained in physical activity and HRQoL, however the UC group exhibited clinically important declines in daily steps, SF-36 PCS, and anxiety scores. In conclusion, physical activity TC is a feasible, safe, and well accepted intervention in lung transplant recipients. Whilst there is a degree of natural recovery in physical activity and HRQoL following lung transplantation, physical activity TC has the potential to optimise these outcomes. Furthermore, the implementation of behavioural modification strategies resulted in better maintenance of health outcomes beyond the initial intervention period. Therefore, this thesis can inform a full-scale RCT to determine the true short- and long-term effect of physical activity TC in lung transplant recipients, compared to UC.

Inflammation of the ocular surface is required to remove a range of pathogens which come into contact with the anterior surface of the eye, lowering the risk of further pathological complications, such as diminished sight or blindness. The cornea is responsible for refracting light into the eye and must remain clear to ensure functionality. However, unregulated immune responses are associated with corneal tissue damage in a range of inflammatory ocular diseases, which manifests as a loss of visual capability. Previous studies have shown vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25D3) suppresses inflammatory pathways by modulating innate immune responses, including the production of pro-inflammatory mediators and antimicrobial peptides. This research used an in vitro model of corneal inflammation comprising of the human telomerase-immortalized corneal epithelial cell line (hTCEpi) together with various agonists to stimulate toll-like receptors (TLR) which are pattern recognition receptors. The TLR agonists produce inflammatory responses similar to the pathogens they represent. The effects of 10-7M 1,25D3 treatment on these responses were investigated. Using qRT-PCR, the study confirmed that 1,25D3 treatment significantly attenuated the expression of hTCEpi cell TLR3 (p<0.001), TLR5 (p<0.001) and TLR9 (p<0.001) stimulated by their agonists as well as expression of associated inflammatory molecules, including IL-6, IL-8 and IL-1b. Interestingly, IL-1b expression was shown to be significantly attenuated by 4h during TLR3 suppression (p<0.001), which may have suppressed further inflammation. Although there was an overall attenuation in pro-inflammatory cytokine expression following 1,25D3 treatment, 24h of 1,25D3 treatment alongside TLR3 activation led to a significant increase in the expression of cyclooxygenase-2 (COX-2) (p<0.01). This suggested that 1,25D3 is not entirely suppressive towards inflammatory responses, and may exacerbate inflammation. When hTCEpi cells were stimulated with TLR5 ligands, bacterial flagellin from Pseudomonas aeruginosa and Salmonella typhimurium, 1,25D3 treatment reduced the expression of pro-inflammatory mediators IL-6, IL-8 and IL-1b (p<0.001). The study also used various classes of CpG oligodeoxynucleotide (CpG-ODN), TLR9 ligands which possess different levels of unmethylated CpG motifs, where interestingly, increasing CpG motifs led to a weaker pro-inflammatory response by hTCEpi cells. Addition of 1,25D3 to hTCEpi cells stimulated with either CpG-ODN or Escherichia coli (E. coli) DNA significantly decreased expression of a range of pro-inflammatory mediators, including IL-6 (p<0.001) and IL-8 (p<0.001). Micro-RNA (miR), which regulate inflammatory protein expression, were investigated for their role in the mechanism of action of 1,25D3 during its attenuation of responses to TLR3, TLR5 and TLR9 stimulation. Data showed that inhibition of miR-93-5p and miR-181-3p led to a significant increase in the expression IL-6, IL-8 and IL-1b following all TLR3 and TLR5 stimulations, with some TLR9 stimulations. These data implicate a regulatory role for these miR in ocular inflammation. Finally, the study failed to identify significant cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of IFN Gene (STING) activity in hTCEpi cells. In conclusion, this study provides evidence that 1,25D3 inhibits inflammation caused by a range of pathogens, whilst certain miR may regulate pro-inflammatory mediators following a range of TLR activations. Hence both 1,25D3 and miR are candidates for treatment of ocular inflammatory diseases.

The existing literature within the field of trauma care originates primarily from an in-hospital focus. There is no global definition of major trauma or relevant trauma triage tool that can be applied in the prehospital phase of care to help early identification of those older adults at risk of mortality from low energy mechanisms of injury who may benefit from early consultant level assessment and ongoing management. Both of these issues are problematic to prehospital clinicians as well as clinicians who work in the emergency department and this thesis sought to address these questions. An exploratory study to identify prehospital factors associated with outcomes for major trauma patients in a regional trauma network identified candidate variables (Glasgow Coma Score, respiratory rate and age) that provided the foundations of the entire thesis. Critical analysis and synthesis of the existing literature added further domains and issues worthy of critical consideration which included frailty, comorbidities, medications, male gender, injury patterns, ventilatory support, Body Mass Index and acidosis. Subsequently, a series of linked studies applied a mixed-method approach that variously sought to define major trauma from lived experiences of practitioners, gauge the extent to which consensus existed amongst trauma practitioners, and eventually resulted in the tentative formulation of indices for identifying the older adult at risk of mortality from trauma who may benefit from consultant level assessment. A Dynamic Pattern Synthesis analysis accentuated the complexity of trauma in older adults. Collectively, the outcomes of these studies provided an original, elegant and pragmatic definition of major trauma. "Perceived significant injury or injuries that have potential to be life-threatening or life-changing sustained from either high or low energy mechanisms which also considers the complexities encountered by the extremities of age". This thesis concludes by offering a tentative predictive model for use in identifying those older adult trauma patients with a high risk of mortality and a prototype triage tool - the Northumbria Low Energy Trauma Score (NLETS). It is hoped that this model will prove of practical utility to all practitioners operating in a prehospital environment.

Despite continual rising demand for atrial fibrillation ablation, numbers of cases performed have plateaued. One reason for this is a shortage of appropriately skilled sedationists. Administration of sedation by nurses using a protocol is a potential solution, but virtually no research exists on the impact of this on the quality of patient care. This project aimed to evaluate the use of such a protocol in a single NHS Trust in terms of safety and patient experience. By doing so, it was intended that it should ascertain the feasibility of protocol-based sedation by nurses, and identify areas in the practice studied requiring alteration in order to optimise patient outcomes. A two-stage mixed methods project was undertaken. An initial survey phase provided statistical data that allowed comparison between the safety of protocolised nurse-led sedation and other sedation practices. Fuzzy set Qualitative Comparative Analysis (QCA) of the survey data allowed for exploration of patterns of complexity between components determining patient experience, a possibility identified within existing theories of pain such as the 'Gate Control Theory'. Subsequently pathways leading to positive experiences were modelled. These pathways were then tested using a series of case studies to ascertain the existence of causal links between the identified factors and positive outcomes as well as the extent to which protocol-adherence facilitated positive outcomes. This thesis presents findings from both stages. These include the conclusion that nurse-delivered sedation is at least as safe as other methods. It establishes more than one pathway to positive patient experiences may exist, but finds strongest evidence that effective management of patient anxiety leads to a positive outcome. However, it also concludes that creating this outcome depends on the clinical judgement of the individual nurse, and identifies alterations in the status of the protocol and its content to facilitate optimal outcomes.

Background: In patients with Chronic Obstructive Pulmonary Disease (COPD) daily physical activity (PA) levels are significantly lower than in healthy age-matched individuals. PA counselling has been employed to address the complex behaviour of PA and was shown via a systematic review and meta-analysis to be effective in improving daily PA levels (steps/day) both as a standalone intervention and alongside pulmonary rehabilitation (PR). However, in patients reporting low baseline levels of PA (≤4000 steps/day), PA counselling alongside PR did not induce clinically important improvements in daily PA levels. A plausible reason involves the concept of a "low functional reserve", indicating that these patients are less likely to become more physically active within their functional limits. Objectives: 1) to perform a systematic review and meta-analysis on PA counselling as a standalone intervention and alongside PR in COPD, 2) to determine the criterion validity and test-retest reliability of a commercially available pedometer used by COPD patients to self-monitor and report daily PA levels, 3) to evaluate daily PA levels, muscle function, anxiety and depression in patients with COPD living in the North East of England in comparison to healthy age-matched individuals from the same region in a cross sectional study design, and 4) to investigate the feasibility, acceptability and efficacy of combining PR, designed to improve exercise capacity, with comprehensive PA behavioural modification interventions, designed to translate PR-induced improvements in exercise capacity into improved daily PA, in COPD patients with low baseline PA levels. Methods: To accomplish the latter objective a prospective, single centre, two parallel-group, RCT, compared the efficacy of a PR programme combined with PA behavioural modification interventions (PR+PA: incorporating motivational interviewing, face-to-face twice weekly goal setting, step count monitoring and feedback) to a PR programme alone in 48 patients with COPD (FEV1: 49±19 % predicted) exhibiting low baseline exercise capacity (6MWT: 289±85m) and daily PA levels (3293±2000 steps/day). In both groups (PR+PA and PA alone) patients with profound anxiety and depression (≥8 HADS score) received sessions of Cognitive Behavioural Therapy (CBT) by a specialist respiratory nurse. Results: Compared to PR alone, PR+PA induced clinically important improvements in both PA levels (by 1016 steps/day; 95% CI 556 to 1474 steps/day, p = 0.001) and patients' PA experiences (by 7 points; 95% CI 4 to 11 points, p= 0.001) that were assessed by the European Medicines Agency qualified Clinical PROactive Physical Activity in COPD instrument (C-PPAC). Importantly, both groups reported clinically important improvements in the 6MWT (≥ 30 m) and CAT questionnaire (≥ -2 points), however improvements in upper and lower muscle strength were significantly greater in the PR+PA compared to PR group. These findings were supported by evidence of adequate PR completion rates (80%) and high patient acceptability of the PA behavioural modification interventions, with 75% of patients indicating that they "liked taking part in the intervention a lot", and 58% of patients claiming that the intervention "helped them a lot" regarding completing more PA outside of PR. Furthermore, patient adherence to the components of the behavioural modification interventions was high, including the weekly use of the pedometer (6.6±0.2 days) and interaction with the PA diary (93±17%) to self-monitor and report daily step counts. Conclusions: The findings suggest that in COPD patients with low baseline exercise capacity and daily PA levels, improvements in exercise capacity following completion of a standard PR programme may translate into clinically important improvements in daily PA levels only when tailored PA behavioural modification interventions are added to PR. In addition, PA behavioural modification interventions were proven to be feasible to incorporate into a standard PR programme and were well accepted by patients with COPD.

Background: Nationally and internationally, evidence indicates that the process of informed consent for clinical research is not fulfilling the purpose for which it was intended, despite efforts by Research Ethics Committees (REC). The reason for this is unknown. Many studies have looked at the views of healthcare professionals on the process of informed consent for participation in clinical research but few focus on the views and overall experiences of real-life clinical research participants. There is a need therefore to gain more insight, particularly from service users' perspectives. Methods & Analysis: Nineteen (19) clinical research participants were interviewed after having taken part in the process of informed consent for participation in clinical research studies. The interviews were conducted face-to-face individually in natural settings and were audio recorded with informed consent. Following verbatim transcription, constructive thematic analysis was conducted, and transcripts were coded to develop categories and themes. Themes were applied to discover theoretical concepts. Findings: Four themes emerged from the data, namely: Trusting Interpersonal Relationships; Researcher Attributes; Study Information; and Personhood. The factors that influenced participants' decision making concerned the involvement of a trusted clinician and the timing of such involvement. The interpersonal attributes of the person seeking consent and how the participants perceived the relevance of the information being shared also influenced engagement and decision making. Other factors that encouraged research participation related to personal interests, the desire to do good and/or the hope for a cure. Perceived barriers to participation included intellectual limitations, lack of research awareness, social, physical, and demographic challenges, transportation, burden of illness, and interference with family life. Conclusion: The findings suggest that the decision to sign up for research was influenced by a range of factors other than the content, size, or layout of written study information. There appears to be a conflict between the perspectives of real-life patients and those of policy makers in relation to the factors influencing decision making for clinical research.

Background: Medulloblastoma is the most common paediatric malignant brain tumour, with heterogeneous clinico-molecular characteristics and survival outcomes. Current WHO classification distinguishes 3 molecular subgroups: WNT, SHH (named after characteristic activation of the WNT/wingless and Sonic Hedgehog signalling pathways) and non-WNT/non-SHH medulloblastoma. Current risk stratification incorporates molecular and clinico-pathological disease correlates. Survival is associated with high-risk factors such as metastasis, large cell/anaplastic histology, MYC/MYCN amplification and subtotal resection; the presence of one or more of these factors defines high-risk disease. High-risk patients receive more intensive therapies at the cost of severe late effects as survivors. Moreover, 20% of standard-risk patients (defined by absence of all high-risk features) will die of their disease. Tumour profiling with genome-wide DNA methylation arrays is the current gold standard for molecular classification of brain tumours. Methylation arrays are also suitable for identifying DNA copy number (CN) changes, enabling simultaneous genomic and epigenomic characterisation. Hypothesis: It was hypothesised that genome-wide Illumina HumanMethylation arrays provide a robust alternative to gold-standard SNP arrays for DNA CN detection and allow for single-platform, integrated genetic and epigenetic assessment, suitable for application to DNA derived from fresh-frozen and formalin-fixed, paraffin embedded tumour materials. Aims: Confirm usability of methylation arrays and develop methods to detect genomic alterations (aneuploidy and focal oncogene amplifications); Showcase application of methylation arrays as a cost-effective single-platform, integrated approach for improved prognostication within medulloblastoma patients. Methods: In this project, methods to detect genomic alterations (aneuploidy and focal oncogene amplifications) using Illumina 450k methylation arrays were developed and validated. These methods were implemented to assess previously published cytogenetic prognostication schemes in medulloblastoma. Next, the GLMnet algorithm was used to identify prognostic methylation loci. These markers were assessed in non-WNT/non-SHH high-risk medulloblastomas and validated in an independent, mixed-risk non-WNT/non-SHH cohort. The previously published cytogenetic prognostic signature for standard-risk, non-WNT/non- SHH medulloblastoma, identified in the PNET4 clinical trial, and its potential for prognostication was assessed in high-risk, non-WNT/non-SHH disease, alone and in conjunction with methylation markers. Results: Easy to use methods with a low barrier to entry were developed to robustly identify genomic copy number and oncogene amplification. These methods were applied to validate two independent, previously published cytogenetic prognostication schemes within medulloblastoma. Two DNA methylation loci, mapping to MYO7A and TRIM72 genes, were identified as independently prognostic markers. A novel prognostication scheme, that combined DNA methylation markers with the PNET4 cytogenetic signature, was devised for non-WNT/non-SHH medulloblastoma. This scheme outperformed the PNET4 signature in the high-risk cohort, reclassifying 21% of high-risk patients to a favourable-risk category. Conclusion: These results demonstrate the potential for routine cytogenetic assessment concurrent with molecular sub-classification using DNA methylation microarrays. Additionally, the integrated genetic and epigenetic stratification from a single platform enabled a more refined prognostication and the identification of a subset of patients, currently classified as high risk, who demonstrate improved outcomes and who may be eligible for reduced intensity treatments that would offer a better quality of life as brain tumour survivors.

Clinicians are continually looking for effective treatments for multiple sclerosis (MS)- fatigue, but this has been hampered by unclear definitions of fatigue and studies of heterogeneous people with MS, including those who are highly-fatigued (MS-HF) and those who are less-fatigued (MS-LF). By directly comparing neuromuscular and transcranial magnetic stimulation measures between MS-HF and MS-LF, more light could be shed on the underpinning mechanisms of MS fatigue, and this could serve as a stronger foundation for therapeutic interventions. In addition, progressive resistance exercise has shown potential as an accessible exercise intervention for alleviating MS fatigue, but most studies have not recruited MS-HF or did not include MS fatigue as a primary outcome measure. In addition to positively impacting a range of other functional and mental health outcomes in PwMS, an individually tailored progressive resistance exercise (PRE) intervention has the potential to improve symptoms of fatigue and fatigability by helping to promote the development of new neural pathways (neuroplasticity). Thus, the overarching aim of this thesis was to establish whether neurophysiological differences between MS-HF and MS-LF could be reliably distinguished, and to investigate the feasibility and potential of PRE as a therapeutic exercise intervention for ameliorating perceived MS-fatigue in MS-HF. The series of investigations that set out to address this aim have led to many novel and interesting findings. Firstly, study 1 was the first systematic review and meta-analysis to synthesis the current evidence base comprising studies which used a dichotomised model (MS-HF versus MS-LF) to provide insights into structural and neurophysiological correlates of MS-fatigue. Secondly, Study 2 reports on the good to excellent test-retest reliability for a range of neuromuscular and transcranial magnetic stimulation measures assessed in the upper- and lower-limb muscles in MS-HF and MS-LF. Thirdly, based on the test-retest reliability findings of study 2, study 3 presents data for the differences between MS-HF compared to MS-LF and HC on a range of neuromuscular measures, including an isometric fatiguing exercise task in the upper- and lower-limb (performance fatigability measure). Finally, Study 4 presents important feasibility data regarding the utility of PRE as a therapeutic exercise option for MS-HF. In addition, this study provides preliminary evidence of the efficacy of PRE for ameliorating perceived MS-fatigue, a range of other patient-reported health outcomes and indices of neuromuscular function.

Introduction: Integrating interprofessional working (IPW) as a contemporary response to the ever changing needs of the UK population is a 'gold standard' healthcare strategy (including in a stroke care setting). However, difficulties in collaboration remain despite the ubiquity and the barriers being well understood. Aim & Methodology: Effective relationships are important for IPW, yet an in-depth understanding on how relationships are perceived, formed and sustained is limited. This study aimed to address this area of limited knowledge by exclusively exploring interprofessional relationships through the individuals who work within a stroke care MDT context. A constructivist grounded theory methodology influenced by the theoretical perspectives of symbolic interactionism and social constructivism was used to address the study's aim. The constructivist methodology, investigates social behaviour by its ability to interactively link the researcher and the participants under study, while acknowledging that knowledge and reality are not fixed, but are multiple and occur in the social contexts which the participant interacts in. The sample population was selected through purposive sampling, followed by the theoretical sampling strategy. In total, 14 stroke care professionals were recruited. Thirteen of these participants were observed in practice, and out of the 13, 12 were individually interviewed, resulting in data saturation from 25 data collection episodes. Data was analysed using the constant comparative analysis process. Findings: Four interrelated categories emerged from analysis; Developing a sense of belonging, Rewards and recognition, Inclusive working and learning and Interprofessional compassion. The grounded theory model of experiencing growth through interprofessional relationships: a stroke care MDT setting was constructed to reflect the MDT stroke care participants' relationship perceptions and to support the discussion of the findings. The original model proposes a process for which IPW relationships can be understood, with three overarching theoretical perspectives providing insight into the social process, functions and motives of interprofessional relationships in stroke care. This new theoretical insight offers an original contribution to practice, education and theoretical knowledge, by providing a comprehensive and multi-dimensional interpretation, for understanding the IPW relationships that exist and the process in which they can be developed and sustained. It additionally contributed new research opportunities which includes an interprofessional application of the IOS tool.

Breathlessness is the dominant symptom that limits exercise tolerance in patients with COPD. Several ergogenic approaches have been employed to improve exercise tolerance in this population including bronchodilators, oxygen and heliox supplementation, intermittent exercise and non-invasive ventilation (NIV). Although application of NIV during exercise is beneficial for increasing exercise capacity in patients with COPD, there are several disadvantages that limit its wider application during exercise, including lack of compliance with the equipment, and the time required to set up and supervise the equipment in the setting of pulmonary rehabilitation. Recent advances in technology have facilitated the development of portable non-invasive ventilation (pNIV) devices aiming to alleviate breathlessness during activities of daily living. The VitaBreath (Philips, Respironics) was developed in 2016 as a portable, handheld, battery powered, bi-level, NIV device, providing fixed positive inspiratory and expiratory airway pressure support (IPAP:18 and EPAP: 8 cmH2O, respectively). Accordingly, this dissertation aimed to investigate the physiological effects of pNIV application during controlled laboratory exercise conditions and activities of daily living, in patients with advanced COPD. As the VitaBreath device is no longer commercially available, but similar devices may come to market, the present dissertation provides proof of concept on how pNIV can be applied intermittently during exercise in patients with COPD, and how to select patients most likely to respond to pNIV. This in turn may encourage the development of more suitable devices. Intermittent exercise was chosen to evaluate the effects of pNIV in comparison to the commonly adopted pursed lip breathing (PLB) technique, as this type of exercise allowed regular application of the pNIV device or the PLB technique during recovery periods. Patients retained the device for 3 months to investigate the acceptability, comfort and usability of the device during activities of daily living. Twenty-four COPD patients were randomised to perform two intermittent exercise protocols sustained at different work intensities (60% WRpeak for 6-min and 80% WRpeak for 2-min) alternated with 2-min rest periods. Within each intermittent exercise modality, patients performed two identical exercise tests using either pNIV or the PLB technique in a balanced order sequence, during the recovery phases of intermittent exercise. The findings of this study showed that with both intermittent protocols average endurance time was greater when pNIV was applied compared to PLB. Improvements in exercise tolerance were due to lower degrees of dynamic hyperinflation (DH) and breathlessness with pNIV compared to PLB. An important finding of the aforementioned study was that a subgroup of patients (8/24) failed to show a clinical important improvement in DH with pNIV compared to PLB and did not improve exercise tolerance. Analysis identified that these 8 patients experienced greater resting lung hyperinflation, greater exercise-induced DH and breathlessness, secondary to the adoption of a tachypnoeic breathing pattern with pNIV compared to PLB. Interestingly, these patients also reported less benefit from using the device at home, in terms of anxiety around breathlessness and recovery time from breathlessness. Considering the variation of response reported in the present thesis it is important that clinicians assess the response to pNIV on an individual basis. As with any new method, it was important to appreciate the physiological consequences of the acute application of pNIV on thoracoabdominal volume regulation and respiratory muscle recruitment (assessed by optoelectronic plethysmography), and central hemodynamic responses. Compared to PLB, acute application of pNIV was associated, in the majority of patients, with increased end-inspiratory and end-expiratory rib cage volumes and greater rib cage muscle recruitment, as well as decreased end-expiratory abdominal volumes reflecting reduced expiratory abdominal recruitment. Measurement of cardiac output revealed no adverse circulatory responses with the application of positive airway pressures provided by pNIV during the recovery periods. However, the pattern of thoracoabdominal volume regulation and respiratory muscle kinematics confirmed the findings of the original studies, thereby identifying responders and non-responders to pNIV. Interestingly, responders to pNIV exhibited greater recruitment of the expiratory abdominal muscles compared to non-responders, thereby facilitating them to combat end-expiratory rib cage dynamic hyperinflation effectively. When patients used the VitaBreath device during their daily physical activities, the majority of patients felt less anxious about becoming breathless and felt that their breathlessness recovered faster when using the device at home for 3 months. Moreover, almost all patients used the device at least weekly and all patients rated the ease of VitaBreath use to be between good and excellent. Additionally, most patients felt that using the device had benefited them and that they would recommend the device to other patients. The main disadvantage of the device was reported to be the high cost and its portability. The pNIV method provided fixed IPAP and EPAP. This represents a very important disadvantage of this particular pNIV device, which clearly mitigated the beneficial impact it had on some patients. Future research into pNIV devices should examine how best to identify patients who benefit from a pNIV method in everyday life. On-going development of auto-adjusted ventilators would facilitate a larger fraction of COPD patients to be physically active and experience a better quality of life.

The assessment and management of surgical pain are paramount to good quality perioperative care. Regrettably, patients still declare inadequate satisfaction levels within this important area of practice. Holistic preoperative pain planning and education is a useful strategy to address this issue which has never been fully studied in day case surgery. This thesis has used a critical ethnographic research approach to explore and examine preoperative cultural practices and provide insight into what influences and shapes pain planning, management strategies and interactions with day surgical patients. This methodology observed healthcare interactions in the day case unit through a critical lens, underpinned by critical social theory and a transformative paradigm. Using Carpspecken’s (1996) analytical enquiry framework, the preoperative practice of one department was investigated over nine months. Both qualitative and quantitative data collection methods were used, including observations, interviews and timings of interactions. One hundred and twenty-four patients and thirty-three healthcare professionals took part in the study, one hundred and thirty hours of practice were observed, and twenty in-depth interviews with healthcare professionals took place. Data were analysed using reconstructive and statistical analysis, and four main themes were identified as having an impact on preoperative interactions. These four themes were: • The prioritisation of patient safety over pain management. • A production line culture which negatively impacted on holistic practice. • The existence of paternalism and power that affected staff and patient autonomy. • Unconscious gender and surgery bias, which had a direct impact on the levels and depth of preoperative pain conversations and management strategies. These were explored further in relation to Bourdieu's (1977) sociological theory of habitus and capital, in an attempt to raise awareness of practice culture and increase transparency, in order to challenge the status quo.

The past two decades has seen an increased interest in, and awareness of, the ways in which cancer and concomitant treatments effects individuals and couples in terms of their expressions of sexuality and sexual health (incorporating psychosexual health) (Sadovsky & Bassoon et al, 2010, Greenwald &McCorkle, 2008, De Vocht, 2011). However, the research studies found focused on the impact on heterosexual individual's and couples, with a dearth of literature pertaining to the impact on lesbian and bisexual women affected by cancer. Although, the health care needs of individuals from sexual minority groups has begun to be recognised and addressed by practitioners (Stonewall, 2010, Davey, 2012), the lack of available literature to help guide practice in this area means that they often fail to recognise the needs of the lesbian women in their care. The aims of this study were therefore twofold, firstly to explore the sexuality, sexual health (incorporating psychosexual health) and relationship experiences of lesbian and bisexual women who have been diagnosed and received treatment for cancer. Secondly to use the outputs from the first aim, to develop a conceptual framework and model for practitioners working with lesbian and bisexual women in the fields of cancer care in regards to these areas. This study was designed with a research design which enabled the 'voices' of both the lesbian and bisexual women, and the cancer practitioners to be heard. The overarching research methodology was descriptive phenomenology, however, it became evident that the traditional approach taken in descriptive phenomenological studies (Giorgi, 1985, 2009, Rutherford & McIntyre et al, 2012) would not yield the breadth and depth of data needed to develop the conceptual framework. Therefore, as suggested by Mayoh & Onwegbuzie (2013) the concept of applying the steps that underpin action research throughout the phenomenologically inspired journey were used. As a starting point for the study, and to assess the readiness and preparation of practitioners in cancer care the views and experiences of both an expert panel and focus groups of specialist practitioners were sought on four occasions. The face to face interactions were supplemented with paper and online questionnaires. A documentary analysis of the United Kingdom (UK) government and healthcare professional organisations documents pertaining to the place of sexuality and sexual health within practice and education was undertaken to explore the actual practice situation. This was followed by review of undergraduate nursing and medical curriculum with a focus on the holistic assessment and management of sexuality and sexual health needs. In addition, the UK governmental and professional body Lesbian, Gay, Bisexual and Transgender (LGBT) specific directives for good patient care practice, together with the LGBT specific content within undergraduate nursing and medical curriculum were systematically analysed. The voices of lesbian and bisexual women affected by cancer - both survivors and partners provided a wealth of in-depth information through the individual interviews and online qualitative questionnaires. This gave new insights into and increased understanding of the issues faced by participants. It highlighted similarities and differences with and from the findings from the heterosexual studies, and provided the baseline from which the conceptual framework and model were developed. It was seen as essential that these had a theoretical basis that practitioners could accept and utilise and that it was incremental to recognise the longevity of the support and guidance sought by participants. When shared with practitioners the conceptual framework and model were well received and only minor refinements were needed. It does enable cancer care practitioners to offer more tailored care to the lesbian and bisexual women in their care. Especially in regards to the women's sexuality, sexual health (incorporating psychosexual health) and relationships, and has led to links and work with both Macmillan Cancer Support and Relate the UK's largest provider of relationship support.

Introduction: Cancer risk assessment tools are novel tools that combine risk factors and symptoms to predict an individual's risk of developing cancer. Little is known about the views of service users and primary care practitioners on how cancer risk assessment tools should be used in primary care. Following a scoping review of the literature, the qualitative study explored perspectives of service users and primary care practitioners about how best cancer risk information can be communicated to patients during primary care consultations. The study also explored the enablers (facilitators) and barriers to the implementation of cancer risk assessment tools from the perspectives of both service users and practitioners. Methods: The scoping review followed the framework proposed by Arksey and O'Malley for conducting scoping reviews. The scoping review resulted in the statement of two research questions: (i) How best can cancer risk information be communicated to patients? (ii) What do service users and practitioners perceive as enablers and barriers to the implementation of cancer risk assessment tools in primary care? The next phase was the qualitative study, which involved the use of individual and focus group interviews with service users recruited from the public and primary care practitioners (GPs and nurses) recruited from general practices in Lincolnshire, a large rural county in the East of England. The qualitative data were transcribed verbatim and analysed using the framework approach. Results: Thirty-six participants (19 service users and 17 primary care practitioners) were interviewed before practitioners used cancer risk assessment tools in patient consultations. Some of the practitioner participants were interviewed again after they had used the tools in patient consultations. Participants suggested ways to best communicate cancer risk information to patients in primary care consultations. Before using the tools with patients, participants emphasised the importance of: tailoring visual representation of risk; being open and honest; informing and involving patients in use of cancer risk assessment tools; and providing time for listening, explaining and reassuring in the context of a professional approach. After using the tools in patient consultations, primary care practitioners maintained these perceptions. These findings add to our knowledge and understanding of how best to communicate cancer risk information to patients when using cancer risk assessment tools in general practice consultations. Before using the tools with patients, both service users and practitioners agreed on the following as potential enablers to the implementation of cancer risk assessment tools: aiding decision making; improving speed and processes of diagnosis and treatment of cancer; identifying and raising awareness for modifying health risk behaviours; and personalising care. After using the tools, primary care practitioners mentioned 'ease of use' in addition to the enablers already cited. Barriers to the uptake of cancer risk assessment tools were also identified by participants, which included: the additional time required; worry and anxiety generated by referral for investigations; the potential for over-referral; practitioner scepticism about using the new tools; and the need for evidence of effectiveness before introducing cancer risk assessment tools in general practice consultations. These barriers were perceived before the use of the tools. After using the tools, practitioners identified the following barriers in addition to those already mentioned: the need to integrate the tools into general practice IT systems; the need to involve secondary care specialists (consultants) in the implementation of the tools; and the need for training of practitioners on how to use cancer risk assessment tools in patient consultations. Conclusion: Ways to best communicate cancer risk information during patient consultations were identified in this study, adding to existing knowledge. Enablers and barriers to the implementation of cancer risk assessment tools were also identified by participants in this study.

Colorectal cancer is the fourth most common cancer in the UK. The advances in cancer care are such that the longevity of this group has extended well beyond the five years through which the NHS follows them. The diagnosis of a colorectal cancer and a permanent colostomy for the patient causes challenges in terms of the diagnosis and treatment, and also in the need to adapt to the permanently changed bodily functions and body image they have to live with. Healthcare professionals are aware of the impact of care on patients and their relatives and carers, but research shows that there is little support guidance or help for them once discharged from follow up services. They report being told to 'go off and enjoy life' but say they feel 'cast adrift' with no recourse to further help and advice when they experience physical, psychological and psychosocial problems.

As a result of perceived insufficient non-acute care provision, the Government is making efforts to extend primary care hours to reduce the inappropriate utilisation of 999 and A&E services (NHS England, 2013c, 2014b; Kings Fund, 2017). The case management programme was implemented to reduce acute care use in the ageing and multimorbid demographic who are high-intensity service users (DOH, 2005a). However, case management typically has restricted hours of service delivery, which could place unnecessary burden on emergency and acute services during the out-ofhours period. The aim of this study was to understand the patterns of case-managed patients' use of 999 emergency services and presentations at A&E, and hospital admissions, as well as to explore what factors were perceived as influencing patterns of service interaction. Within a pragmatic paradigm, a sequential explanatory mixed methods study was deployed, delivered in five studies. Two cross-sectional observational studies analysed 999 callout (n=2,930, study one) and A&E attendance and hospital admission data (n=16,495, study two). Descriptive statistics were applied, and inferential statistics conducted according to data type. Key stakeholders were interviewed (patients n=19, study three, carers n=19, study four) and three focus groups conducted (case managers n=18, study five). Transcripts were analysed via an analysis spiral using both deductive and inductive approaches (Creswell, 2007). Using a pluralistic framework and previously unexploited flagged patient-level quantitative datasets produced a novel understanding of when, why and how casemanaged patients interact with services. Despite no out-of-hours emergency service burden within studies one and two, twenty-four-hour case management service provision may be required to align with acute services. Quantitative data highlighted that integration and digital interoperability across systems are required to aid admission avoidance and to improve patient experience. Qualitative investigation revealed service contact was seen in places where several parts of the system were seen to be under strain. Person-centred care and shared decision making may also need to be improved when conveyance and admission decisions are made. Case management as a model for admission prevention to manage the ageing and multimorbid population was valued in studies three to five. The inclusion of elderly and housebound participants brought the lived experience of older people to the forefront, highlighting the negative impact of the media in delaying service interactions. This research could be used to inform policy and service-level decisions at the macro- and meso-levels of healthcare. A conceptual model of the factors that contribute to service interaction presents a holistic infographic guide for case management admission prevention.

Background: The efficacy of UK National Health Service (NHS) multidisciplinary pain management programmes (PMPs) is currently measured using self-report questionnaires. Whilst subjective measurements provide important information about personal experiences, they cannot reveal underlying changes in cortical activity related to pain that may also accompany PMP treatment. There is no objective measurement of treatment efficacy currently available. This thesis contains studies of two NHS PMPs that differ in their psychological approach. The effect of these treatments was assessed using self-report questionnaire measures, and a newly developed neurophysiological assessment technique. Methods: Studies examined the effect of a cognitive-behavioural therapy (CBT) based PMP, and an acceptance and commitment therapy (ACT) based PMP, upon questionnaire measures of psychological, physical, and social health, as well as measures of coping and acceptance. Further studies examined pre- to post-treatment changes in patients' cortical pain processing measured using electroencephalography (EEG), as well as in healthy and patient (waiting list/treatment as usual) control groups. The effect of treatment on contact heat evoked potentials (CHEPs), and on changes in power spectral density (PSD) following exposure to medium duration tonic pain (90s cold pressor test) was investigated. Results: Small but significant (p < .05) improvements in self-report measures of mental health, coping, and acceptance were found in patients following both CBT- and ACT-based PMPs. There were differences in the effect of PMPs on measures of anxiety, depression and catastrophising, with the ACT-based programme data showing slightly larger effect sizes. Neurophysiological testing revealed no pattern of effect upon CHEPs, however there were pre- to post-treatment differences in the effect of tonic pain upon PSD. Alpha (α) and theta (θ) rhythms were significantly (p < .05) reduced pre-treatment in the CBT group (n=12); post-treatment this effect was not iv observed. There were no pre- to post-treatment differences in the ACT group (n=4) and there were also no changes in either healthy (n=14) or waiting list (n=13) control groups between test sessions. Conclusion: Both PMPs studied brought about small but significant improvements in patients' perceived mental and physical health. Despite their differences both programmes were clinically beneficial to patients in terms of self-report measures. Measurable change was observed in the cortical response to pain pre- to post-treatment with a CBT-based PMP, most likely due to a change in cognitive appraisal of painful signals brought about by taking part in the PMP. Results imply the possible use of neurophysiological assessment to identify patients who may benefit most from treatment, to match treatments to patients' individual psychological and neurophysiological profile, and to more closely monitor treatment efficacy.

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.

Smoking, excessive alcohol consumption and illicit drug use are prevalent within the Cystic Fibrosis population, with these behaviours having adverse health effects upon patients regardless of their treatment adherence. Previous quantitative research highlighting the incidence, prevalence and effects of these behaviours within the Cystic Fibrosis population demonstrates the need for more effective health promotion measures to be integrated into Cystic Fibrosis care. Therefore, attempting to reduce occurring risky health behaviours specifically within the Cystic Fibrosis population, this doctoral research aimed to identify influential factors associated with these behaviours. This research utilised qualitative methods to explore beliefs associated with risky health behaviours within the adult Cystic Fibrosis population. This first phase of data collection was followed by another qualitative study exploring Cystic Fibrosis adolescents' understanding of, and beliefs about risky health behaviours. Both phases of data collection highlight that a desire to be normal, acceptance of Cystic Fibrosis and awareness of risks are influential in initiation and engagement of risky health behaviours. Both adult and paediatric participants reported a lack of awareness regarding adverse health effects of risky behaviours, demonstrating the need for more effective health promotion and encouragement of healthier lifestyles. Accordingly, to create a corresponding intervention, the researcher has listened to how Cystic Fibrosis Specialist Nurses perceive the issue of risky health behaviours within the population, along with gaining Cystic Fibrosis health care professionals' views on what interventions are needed to reduce the occurrence of such behaviours. The researcher presently plans to collaborate with health care professionals to design an intervention, which would consist of continuous professional development for health care professionals to improve awareness on risky health behaviours within the Cystic Fibrosis population, and would inform patients regarding the Cystic Fibrosis-specific adverse effects of risky health behaviours via interdisciplinary collaboration and scholarship between psychology and technology. Overall this research has provided practical insight into policy change for the prevention and reduction of risky health behaviours within the Cystic Fibrosis population nationally and internationally by informing current advice and practice.

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.

For women with anorexia nervosa, control and routine are important in managing distress and maintaining a sense of self in challenging situations. The transition to motherhood is characterised by change and uncertainty. Women may struggle to integrate the demands of anorexia alongside the challenges of motherhood. The aim of this thesis was to review the literature regarding the experiences of pregnancy and motherhood for women with eating disorders and develop a grounded theory of the transition to motherhood for women with anorexia nervosa. The literature regarding experiences of pregnancy and motherhood with an eating disorder was reviewed. The findings suggested a trend for remission of eating disorder symptoms in pregnancy followed by relapse during the postpartum period. Women with eating disorders were most likely to experience depression and anxiety during the later stages of pregnancy and postpartum. The review highlighted how eating disorders impacted on women's ability to embrace motherhood and bond with their children. There was a paucity of research exploring the lived experience of motherhood for women with specific eating difficulties, most notably anorexia. A grounded theory was informed by the experiences of eight mothers with anorexia. A core process of breaking the cycle highlighted how women were attempting to make lasting positive changes. They achieved this by protecting their children from anorexia, exploring new perspectives, setting a good example to their children and battling temptation to succumb to anorexia. This study provides a unique insight into the experiences of mothers with anorexia. In the final chapter the research process is reflected upon. It is hoped that these findings will influence clinical practice and help professionals to better understand women's experiences.

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.

Background: In the UK, South Asian and Black Caribbean communities are more at risk of developing vascular dementia and experience a higher rate of young onset dementia (under age 65 years), compared with the majority ethnic population (Seabrooke & Milne, 2004). Despite this, Black and Minority Ethnic (BME) persons with dementia are underrepresented in health services, receive diagnoses later in disease progression and are less likely to access anti-dementia medication or partake in research trials (Cooper, Tandy, Balamurali et al., 2009). An emerging theme in culture and dementia research is the impact of religion on dementia in terms of perceiving the illness, accepting the illness, coping with the illness and accessing services (Milne & Chryssanthopoulou, 2005). Religious beliefs and practices offer one explanation for BME underrepresentation in mainstream health and social care services (MHSCS). MHSCS appear ill-equipped to respond to the religious needs of ethnic minority individuals (Bowes & Wilkinson, 2003). Aim: To conduct an investigation of the influence of religion on access to - and experiences of - dementia care services, for South Asians from the Sikh, Hindu and Muslim communities in the West Midlands. Method: An exploratory, qualitative study employing Critical Realist Grounded Theory methodology (Strauss & Corbin, 1990) utilising a multimethods approach of semi-structured interviews and observations informing a three-phase data collection and data analysis model with five service user and service provider cohorts. Results: A two-stage model: “Existing Service Provision” and “Service Improvements” demonstrates religious beliefs influence low knowledge of dementia, stigma of mental illness, isolation and family duty of care. This led to ill-informed care choices and carer burden. Persons with dementia were also under-identified within their religious communities. Regular outreach in to South Asian religious communities is vital to educate and identify underrepresented persons, allow informed dementia care choices and relieve carer burden. Scripture-influenced dementia training is required to dispel stigma and improve care options. Investment in face to- face communication with translators and a shift away from paper resources is required. Conclusion: The full potential of religious communities in dementia care provision is yet to be realised. Utilising this resource as a symbiotic channel – firstly, to identify persons with dementia and educate the congregation about dementia - and secondly, to utilise the existing congregation to meet the psycho-social needs of the person with dementia, offers a holistic care package, leading to informed care choices.

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.

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.

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.