The operating room (OR) within a hospital environment is one of the most expensive functional areas, yet the use of the OR also provides hospitals with an essential source of income. However, at present, there are variations on how to evaluate the performance of ORs, since there is no clear and full explanation of the concept and methods used for evaluation. The overall aim of this thesis is to develop an evidence based Operating Room Assessment Framework (ORAF) to evaluate Operating Room performance with clear and complete guidelines that can be used by operating room managers, directors or any other medical professionals to evaluate operating room performance, determine OR planning and scheduling efficiency, OR workload and OR utilization. The resulting Operating Room Assessment Framework will assist targeted healthcare professionals in their quest to evaluate, monitor and improve overall Operating Room efficiency. The OR management systems of eight tertiary and teaching hospitals in three countries (Japan, Canada and Saudi Arabia) have been examined from 2010 to 2012, which include more than 98,500 procedures. The Operating Room Assessment Framework (ORAF) involves three important elements of Operating Room performance, namely: OR scheduling level, the type of OR workload, and OR utilization. These elements can simply be read to reach the end result, which includes three types of scheduling levels: under scheduling, ideal scheduling and over scheduling; five types of OR workload: OR total workload (the gross workload), OR actual workload, over workload, unnecessary workload and unexpected workload; and three types of OR utilization: underutilization, ideal utilization, and 100% utilization with over workload. Through the validation process in different hospital contexts, the ORAF has proven its ability to perform satisfactorily, with accuracy, in line within the research’s objectives.

The burden of Diabetes Mellitus (DM) is increasing worldwide and it is estimated to reach indefinite proportions of about 450 million by year 2030. Patients with type 2 diabetes mellitus (T2DM) have a significantly increased risk of developing cardiovascular diseases (CVD). Moreover, CVD is the major cause of mortality and morbidity (75%) in T2DM patients. DM itself has been long recognised as an independent risk factor for several forms of CVD including coronary heart disease (CHD), peripheral arterial disease, cardiomyopathy and congestive heart failure in both men and women. It is well-known that T2DM is associated with several factors including hyperglycaemia, hypertension, dyslipidemia, obesity all of which contribute to CVD. In order to prevent CVD, early intervention on cardiovascular risk factors is vital during clinical assessment of T2DM patients. A major role of inflammation has been well described in the development of CVD in T2DM patients. Inflammatory process and factors which contribute to CVD in T2DM patients have recently become a focus in diabetic research. Elucidation of common patho-physiological mechanisms among T2DM patients might emphasize the role of inflammation in CVD. The main purpose of this study was to investigate any patho-physiological changes in red blood cells (RBC), white blood cells (neutrophils and lymphocytes) and plasma, measuring RBC membrane fragility and proteins, intracellular free calcium concentrations [Ca2+]i and several cations including Na+, Mg2+, Ca2+, Fe2+, Zn2+ and Cu2+, biochemical parameters and inflammatory mediators which normally serve as independent predisposing risk factors for CVD among T2DM patients compared to age-match healthy controls. The results have shown that fura-2 loaded neutrophils and lymphocytes in blood from T2DM patients contain significantly (p<0.05) less [Ca2+]i than neutrophils and lymphocytes from healthy subjects upon stimulation with physiological doses of either fMLP or thapsigargin indicating a derangement in cellular calcium homeostasis during T2DM. Similarly, RBC membranes from T2DM patients contained significantly (p<0.05) more spectrin, ankyrin, band 3, band 4.1, glycophorin etc compared to RBC membranes from age-matched healthy control subjects. The results also show that the RBCs from T2DM patients were more fragile compared to RBC from healthy controls. Measurement of protein glycation in plasma have revealed significantly (p<0.05) more fluorescence in proteins form T2DM patients compared to control. In relation to plasma cations and intracellular markers and mediators, the results show that plasma from T2DM patients contain significantly (p<0.05) more Na+, Mg2+ , Ca2+, Fe2+, Zn2+ and Cu2+ compared to plasma levels from age-match healthy controls. Similarly, the concentrations of kidney and liver function markers such as urea, creatinine, alkaline phosphatase, ALT, AST, GGT, total protein and albumin increased significantly (p<0.05) compared to healthy controls. The same is also true for glucose, total cholesterol, triglycerides, CRP, HBA1C, WBC where the blood from T2DM patients contained elevated concentrations compared to blood from healthy age-matched control patients. Together, the results of this study have clearly demonstrated marked and significant changes in cellular calcium homeostasis in white blood cells, RBC membrane proteins and fragility, plasma protein glycation and in plasma levels of cations, intracellular markers and mediators of T2DM patients compared to healthy controls. Therefore, it is proposed that an early integrated and multi-factorial intervention of risk factors and inflammatory markers must be done in order to reduce the risk of CVD and possible mortality of T2DM patients.

Stroke is a medical emergency requiring a rapid response by the public. This thesis aims to explore our current understanding of stroke knowledge and the decision-making processes involved at the onset of stroke symptoms. Using this information, and the results from a focus group, the thesis will go on to describe the development and pilot testing of an information leaflet for those at higher risk of stroke. The thesis consists of four phases: an integrative review; semi-structured interviews; a focus group; pilot testing of an intervention. Phase One is an integrative review of stroke knowledge in stroke patients; relatives; the public and non-stroke patients at risk of stroke. Members of the public frequently state that they would contact the emergency medical services (EMS) if they suspected stroke but few stroke patients reported that they had actually done so. Through qualitative interviews, Phase Two explored the decision-making process in seeking medical help at the onset of stroke symptoms. The decision about what to do at the onset of symptoms was influenced by multiple factors: knowledge of stroke symptoms; perceived seriousness; emotional reaction to the event; help seeking behaviour and previous experience of seeking medical help. The factors informed a theoretical framework describing the decision-making process for seeking help after stroke. In Phase Three, a focus group explored the information that would best encourage people with suspected stroke to seek immediate help from the EMS. It was agreed that information should: be informed by stroke survivors; be suitable for everyone; use pictures and images; describe a range of stroke symptoms; indicate that stroke is a medical emergency for which effective treatments are available. Phase Four was informed by Phases One through Three, and pilot tested an information leaflet, in people at higher risk of stroke. The information leaflet increased the proportions of patients accessing the EMS and reduced time to seeking medical help. This thesis has made a contribution to knowledge through the development of a theoretical framework that reflects the decision-making process for seeking help after stroke. Using this framework, the thesis has further added to knowledge by demonstrating the potential effectiveness of an information leaflet in a higher risk population.

Aim: To explore the lived experience of the relationship between women with anorexia and their care workers in the context of a specialist eating disorder unit. Background The establishment of a positive therapeutic relationship (TR) has been widely acknowledged internationally as an intrinsic part of therapy and caring services; which is healing and restorative in its own right. A TR is crucial when working with patients who are difficult to engage and have high 'drop-out' rates such as those within eating disorder services who are considered to be ‘high risk’, ‘difficult’, ‘defiant’, ‘reluctant to engage in treatment’ and ‘frustrating’ (Fairburn and Harrison, 2003; Pereira et al, 2006). To date there has not been any qualitative exploration of the therapeutic relationship involving women and their care workers. Method/ Methodology This interpretive phenomenological study focuses on women with anorexia and their care workers in both day care and in-patient specialist eating disorder services in the UK. Van Manen's methodological and analytical approach was adopted for this study. Twelve women with anorexia and thirteen of their care workers (nurses, doctors, dieticians and therapists) participated in the study which was conducted in two phases. Phase one was conducted with care workers and women with anorexia in a day care service (between October - November 2009). Phase two was conducted with care workers and women with anorexia within an inpatient care unit (between May – June, 2011). Semi-structured interviews were conducted with all participants to explore their experience of the therapeutic relationship. Phase one data were thematically analysed, following which the full data set (phases one and two) was analysed as a whole, using MAXQDA as a tool for the organisation of the emerging themes. The initial themes were subsequently re-organised into themes and sub-themes through the lens of Merleau-Ponty's existential themes and Heidegger’s concept of ‘authenticity’. Findings The findings illustrate that the experience of the therapeutic relationship for women with anorexia and their workers cannot be viewed without fully acknowledging the impact of the anorexia, the anorexic identity, the context (the therapeutic landscape) in which this exists and the effect of time. Hence Merleau Ponty's existential lens provided a very suitable framework for the findings. Corporeality, the bodily experience, is integral to the lifeworld of both women and workers and reflects the primary goal of eating disorder services. Its associated sub-themes of 'identity', 'externalisation' and 'recovery measured in kilos' highlight how anorexia is integrated within the women’s perception of their identity , as well as the care workers focus on weight restoration. ‘Spatiality’ reflects the significance of ‘space’ in the creation and experience of a TR; the sub-themes of 'lived space', 'the therapeutic landscape' and 'rules and regulations’ consider the contextual basis of care. The theme relationality focusses on the person-to-person encounters and included the sub-themes 'conflicting perspectives' and 'maternalism'. Finally, the time spent together was considered to be fundamental to the connection made between the women and the workers and so, within temporality, 'the gift of time' and 'availability' emerged as sub themes within the data. The fifth theme, 'authenticity' is pivotal to both the therapeutic relationship and also phenomenology and reflects Heidegger’s perception that authenticity is 'being one's self', for which honesty and truthfulness are essential components. Hence this last theme includes the sub-themes of 'the power and uniqueness of the individual', 'empathy for the worker' and 'trust'. Both the women and the care workers valued the relationship but the externalisation of the disorder created difficulties in the authenticity of the relationship. A temporary, maternalistic, nurturing approach was highly valued and recognised as only transitory. Contribution to knowledge of the subject This study offers new knowledge and understanding about the experience of the relationship that occurs between women with anorexia and their care workers. Overall, the findings suggest that a whilst a relationship that has therapeutic effects existed between the women with anorexia and their care workers, some fundamental features of the therapeutic relationship that have been previously accepted as pre-requisites in other contexts (e.g. mutuality and reciprocity) were not identified as crucial to the instrumental nature of the relationship. Care workers should re-consider the assumptions of mutuality for this client group and thus construct their relationship differently. A meaningful connection can be made between the care workers and the women which is based upon a 'tear and repair' model, but it is only therapeutic if the patient perceives it to be therapeutic for them. A fractured relationship is inevitable when the woman's sense of self is split, that is, divided into the authentic ('real') self and the anorexic self. Hence, in order to gain an authentic connection, it is suggested that the care worker focus on the 'real' woman in order to establish a relationship with the part of the person that has the capacity for an authentic relationship. Thus, a two-fold intervention takes place; the relationship is potentiated and the woman's battle remains between her and her anorexia, rather than with her care workers.

Treatment guidelines for low back pain (LBP) advocate the use of cognitive behavioural approaches, typically delivered by physiotherapists. This thesis explores the role of physiotherapist competence in the delivery of these approaches. A systematic review of the literature found an absence of tools appropriate for the assessment of competence in delivering cognitive behavioural (CB) approaches in LBP. A consensus study was undertaken with experts and a new competency tool was developed with good psychometric properties. This competency tool was then used to explore the relationship between competency and clinical outcome in a cohort of LBP patients. New insights into the role of experience on competence and patient outcome were found. Competence in delivering a CB intervention varied within the cohort. Specific previous experience of delivering similar interventions predicted competence score but not patient outcome. Years since qualification did not predict competence but negatively predicted patient outcome. Overall competence was not found to predict patient outcome in delivering a structured, manualised, cognitive behavioural approach for LBP and possible reasons for this finding are discussed. Competence was further explored through a qualitative interview study which found interesting patterns in beliefs and behaviours of the physiotherapists. The most competent physiotherapists consistently discussed aspects of reflective learning on their practice. Physiotherapists reported most difficulty with switching from a didactic stance to one of a questioning approach. Overall physiotherapists valued the structure of the manualised CB approach they delivered in the study. Physiotherapists reported the CB approach was most difficult to apply to the patient group that the skills are advocated for, i.e. those with poor coping skills and high psychosocial risk factors. The thesis concludes with suggestions on how training in a CB approach may be enhanced for physiotherapists working with a LBP patient population.

The concept of autonomy has acquired paramount status in English medical law, medical ethics and philosophy. Using the methodology of grounded theory, and three iterative cycles of enquiry of the medical law reports and the literature, this thesis investigates how and why judges use and interpret autonomy in ethically-contentious medical law cases. Each cycle of enquiry reveals its internal limitations, prompting further engagement with the data in order to overcome those limitations and deepen the level of understanding and explanation. The first cycle of empirical enquiry describes variation in judicial usage of the autonomy concept in the law reports but gives way to a second cycle of hermeneutical enquiry in order to advance understanding of what judges mean in their use of it. Concurrent analysis of the literature on autonomy reveals a progressive development from a partial view of autonomy as body and mind towards an emerging holistic concept as the identity and capability of the person. The failure of hermeneutical enquiry to explain judicial variations in meaning and interpretation leads to a third cycle of enquiry based on critical realist analysis, examining the underlying social structures and traditions that may influence judicial variations in usage. Using MacIntyre’s concept of tradition, and Brandom’s tools of inferential analysis, the thesis explores whether the law reports reveal the influence on judicial usage of traditions of legal rationality – common law, statute law, and European human rights law – and whether these legal traditions are influenced by wider traditions of moral and political order. The emergent theory of the research, developed through the iterative cycles of enquiry of the data is that judges have developed a community of practice which has over time elaborated a sophisticated ethical language of autonomy to mediate the influence of different legal traditions and, in so doing, has constituted a new practice of medical jurisprudence.

The effectiveness of mild hyperthermia in improving the outcome of radiotherapy and chemotherapy treatment is well established for surface tumours (e.g. an average improvement of 20% in the 5 years survival rate using mild hyperthermia in conjunction with radiotherapy). However, to apply this technique to deep body solid tumours clinically, a non-invasive thermometry method is needed. Several approaches have been proposed for non-invasive thermometry in the past but none were capable of providing 3D temperature distributions in-vivo with the required accuracy. In this thesis, the potential for determining the temperature in a deep body solid tumour during mild hyperthermia by combining ultrasound propagation velocity and electrical impedance measurement techniques has been investigated. Simultaneous ultrasound propagation velocity and electrical impedance measurements were made in-vitro on liver, fat and layered fat-liver samples as the temperature was increased to mild hyperthermia levels (45°C max.). From the ultrasound measurements a linear correlation was found between the percentage of fat in the sample and the change in ultrasound propagation velocity with temperature (-0.12ms-1°C-1%-1, r2 = 0.93). Analysis of the data from the multi-frequency electrical impedance measurements showed that the magnitude of the electrical impedance measured at 256kHz normalised to the magnitude of the electrical impedance measured at 8kHz gave a linear correlation with the percentage of fat in the sample (0.003 %-1, r2 = 0.72) but no statistically significant correlation between the fat content and the temperature coefficient at 256kHz (r2 = 0.007, p >0.05). These results support an approach of using high to low frequency impedance ratios to determine the percentage of fat in the tissue and then this together with an ultrasound propagation velocity measure to detect the change in the temperature of the tissue. Application of this technique is limited by the variation in the change in ultrasound propagation velocity with temperature between tissue samples found in this study but the origins of this are unclear. In addition, further improvements in the spatial sensitivity of the tetrapolar impedance measurements are necessary to ensure an adequate spatial determination of fat content.

It is generally accepted that the use of compulsory powers in the treatment of mental health difficulties may be required to prevent harm to self or others. Exploring the experiences of patients and staff in relation to the use of coercive measures can offer a meaningful insight into how clinical settings might best meet the needs of their clients. Chapter 1 consists of a systematic review of the literature exploring inpatient experiences of coercion by asking 'what are patients' emotional experiences of psychiatric inpatient care?' and 'what can be done to help minimise the negative impact of patients' experiences of coercion?' Negative experiences were found to impact upon prognosis, engagement and later attitudes to accessing care; core emotions experienced included fear, anger and sadness. Suggestions for ways of minimising the negative impact of coercion have been discussed in depth. Chapter two presents an empirical study conducted in an Assertive Outreach Team (AOT) which explored staff experiences of working with Community Treatment Orders (CTOs). Eight multidisciplinary team members participated in interviews. Following the use of Interpretative Phenomenological Analysis, three superordinate themes emerged from the data. The findings emphasise the individual way in which clients were perceived to respond to the implementation of the CTO and explore the tension that staff experience between the use of engagement and coercion. Clinical implications were discussed as well as suggestions for further research. The final paper offers a reflective account of the research process. It is structured around the three superordinate themes which emerged from the empirical data and considers the way in which the researcher’s own experiences were closely related to issues arising from the research. Methodological limitations and ethical issues are discussed as well as an exploration of the way that personal style has influenced the process and facilitated future self-development.

NAMPT (nicotinamide phosphoribosyltransferase) is a universally expressed protein elevated in the serum and synovial fluid of rheumatoid arthritis (RA) sufferers. NAMPT is a rate-limiting enzyme in the biosynthesis of (nicotinamide adenine dinucleotide) NAD+, an essential cellular coenzyme, and has also been shown to exert cytokine-like activities as a mediator of innate immunity. However little is currently known of the role of NAMPT in cartilage metabolism. In this thesis, the role and regulation of NAMPT was studied in a variety of model systems. Addition of exogenous (e)NAMPT to fibroblasts in vitro increased MMP-3 release, an effect attenuated by APO866. In vivo studies in a murine arthritis model showed APO866 treatment reduced arthritis index, with a slight reduction in synovial hyperplasia, inflammatory infiltrate and cartilage degradation. In vivo imaging with MMP activatable fluorescent probes showed a reduction in MMP activity in APO866-treated animals compared with placebo. Analyses of archived tissue indicated that APO866 reduced MMP gene expression in affected limbs in a time and dose dependent manner. In a cartilage explant culture system, APO866 significantly attenuated cytokine-mediated proteoglycan (PG) depletion and MMP-2 and -9 release. This was associated with a dose-dependent loss of cell viability. These effects were reversed by co-incubation with NAD+ metabolites NMN and NA, suggesting that cell survival was highly NAD+-dependent, and that cytokine-induced MMP expression could be NAMPT independent. Finally, in vitro studies in RA synovial fibroblasts revealed that intracellular (i)NAMPT is upregulated by cytokine stimulation, with concurrent upregulation of MMPs -1 and -3. The data emphasise the pleiotropic function of NAMPT in health and disease, and suggest a role for extracellular (but not intracellular) NAMPT in cartilage catabolism. Finally, NAMPT inhibition is highlighted as a promising therapeutic strategy for RA.

Nucleic acid therapies may have significant potential for effectively treating genetic, hyper-proliferative or malignant skin conditions caused by aberrant gene expression. To be effective, the restorative pDNA or inhibitive siRNA must access the viable skin layers and cells in a stable and functional form, preferably without painful administration. Microneedles are able to penetrate the stratum corneum skin barrier in a minimally invasive manner to allow targeted delivery of therapeutic macromocules. To date, there are limited studies reporting the delivery of nucleic acids, particularly siRNA, to the skin using microneedle devices. A range of in vitro, ex vivo and in vivo skin models was developed to characterise nucleic acid delivery and functional response. In vitro studies conducted in both continuous and primary keratinocyte cultures provided proof-of-concept of efficient and non-toxic cell uptake and gene silencing with siRNA and moderately efficient gene expression with pDNA. In initial studies, pDNA and siRNA was pre-complexed with lipid-based transfection reagents, however, in the case of siRNA, coating of the lipoplexes onto microneedles resulted in a reduction in functionality. Hence, modified self-delivery (sd) siRNA formulations were used in subsequent microneedle delivery experiments. Stainless steel microneedles coated with reporter pDNA or sd-siRNA were successful in penetrating the stratum corneum barrier of ex vivo viable human breast skin. It was difficult to demonstrate equivocally both plasmid gene expression and functional gene silencing in the skin explants, which only remain viable for short periods. Delivery of pDNA and sd-siRNA to in vivo mouse skin however, resulted in demonstrable gene expression and gene silencing, particularly evident at the protein level, in an established transgenic reporter mouse skin model. Overall, these investigations generally support the use of the coated steel microneedles for the simple and potentially self-administrable delivery of nucleic acids to the skin.