Global climate change is one of the greatest challenges of the 21st century. Rising ambient temperatures and deterioration of weather patterns are anticipated to result from increased atmospheric concentrations of greenhouse gases caused in part by the use of fossil fuels for electricity generation and domestic heating purposes. The possibility of a global temperature rise of between 1 degree C and 4.5 degree Celsius has led to considerable research efforts into the effects of changes in temperature and other climatic variables. The increasing use of private capital in the energy industry has altered the focus from the provision of a service to the need to make profits from the production and sale of a commodity. Additionally, with respect to Luxembourg, the dependency on imported energy is an important risk factor. This thesis presents biomass as an essential alternative to substitute for some of the fossil fuels in the domain of heat, cooling and power generation. The results presented show an increase in energy utilisation and thus energy efficiency and reduction in emissions when used in combined generation modes as opposed to single generation. These results are gathered through meticulous analytical models, computational fluid dynamics (CFD), and laboratory testing of real life biomass systems. The technologies and analysis investigated here are targeted at those involved in climate change research, providing them with valuable data on the energy analysis of biomass and its associated emissions, highlighting the potential for reduction in pollutions when biomass is used instead of fossil fuels; in energy policy making; investors; engineers; and all others involved in the biomass design and operation of combined generation of biomass applications.

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Previously cloned bacteriophage encoded HyIP 1 from the genome sequenced organism Streptococcus pyogenes SF370 was expressed in Escherichia coli and purified to homogeneity. The protein, previously assigned to glycoside hydrolase family 69 (GH69) was biochemically recharacterised as a polysaccharide lyase and reassigned to family 16 (PL16). The enzyme demonstrated a Km of 1.47 mg m1-1 and a kcat of 7.2 s-1. Biochemically the enzyme had an optimum pH of 6.5 and temperature of 37 °C. The enzyme required no additional divalent ions for catalysis. The enzyme demonstrated strict substrate specificity only degrading hyaluronate and with no activity against related substrates chondroitin 4 sulphate and chondroitin 6 sulphate. HPAEC indicated the HylP1 had an endo mechanism of cleavage producing a range of differently sized oligosaccharides with the smallest being a tetramer. Site directed mutagenesis revealed a role for residues D157 and Y169 with substitution of these residues with alanine resulted in a 88.5% and 91.9 % loss of activity respectively. The location of these residues within the solved structure of HylP1 falls within the triple stranded (3 helix formed by the trimerised protein. This region of the protein was cloned, expressed and characterised and demonstrated similar kinetics as the full length protein (Km of 0.53 mg m1-1 and keat of 11.1 s-1). The activity of the enzyme when compared to other hyaluronate lyases shows it to be relatively inefficient yet when compared to other bacteriophage encoded hyaluronate lyases, HylP 1 was very similar. The proposed role of these bacteriophage encoded hyaluronate lyases is one of degradation of the hyaluronate capsule surrounding the streptococcal cells to allow for penetration of the bacteriophage during infection. Using the sequence of HylP1 the recently completed genome of Streptococcus equi was searched using bioinformatics tool BLAST. This revealed the presence of a protein, SEQ2045, sharing 85 % identity with HylPl. The protein was cloned and expressed in E. colt and biochemically characterised as a hyaluronate lyase. The enzyme demonstrated a Km of 2.05 mg m1-1 and a kcat of 6.2 s-1 which when compared to those of Hy1P 1 is suggestive that the two enzymes are strongly related. The enzyme had an optimum pH of 6.5 and temperature of 37 °C and like Hy1P 1 demonstrated only activity against hyaluronate and had an endo mechanism of cleavage with the smallest product of digestion being a tetramer. Site directed mutagenesis of the same residues as in HylP1 again yielded reduced activity (91.3 % and 87.6 % respectively). Bioinformatic analysis of the genome of S. equi was performed by BLAST searching with the proposed gene sequences of S. equi flanking SEQ2045. This allowed for the production of a prophage map which shows distinct similarities to the prophage map of S. pyogenes suggesting both may be of the same origin. Purified SEQ2045 was used in western blot analysis with S. equi convalescent horse serum. A strong positive reaction demonstrated a possible role for SEQ2045 during an infection suggesting that the bacteria have acquired this enzyme as a potential virulence factor by horizontal gene transfer. This presents a useful opportunity for the study of both S. pyogenes and S. equi infection process and the role of bacteriophage by the use of S. equi as a model for S. pyogenes.

Anomalies noticed in midwifery practice prompted a review of literature around progress in labour after Loop Excision of the Transformation Zone (LETZ). The previous research was equivocal. This study investigates the pattern and progress of women's labours following LETZ, and the effect of the experience on women. It also explores the basis of clinical decisions made by midwives. It takes place in North East England and involves women giving birth in 2004-2005. The case study strategy brings together quantitative retrospective case control results, qualitative analysis of semi-structured interviews from women and midwives, and guidelines and protocols surrounding assessment and management of labour. The quantitative data is from 111 women after LETZ and 214 controls, reducing to 94 and 150 respectively after removal of cases with confounding variables. Interviews are from four women, three individual midwives caring for one of the women and a focus group of four midwives. In the interviews, women gave no thought to how their births may be affected by LETZ, as no one had discussed the possibility with them. Women having their second baby after LETZ take less time to reach full dilatation; a result related to grade of Cervical Intraepithelial Neoplasia. Women having their first baby after LETZ are 1.8 times more likely to be admitted later in their labours, an important emergent issue that needs further research. Women having their first or second baby after LETZ are 2.3 times more likely to have a premature birth, confirming indications in previous research. This study for the first time reveals important differences in pattern and progress of labour after LETZ. It adds to our knowledge of premature birth after LETZ. Midwives, obstetricians and colposcopists need to incorporate the study results into counselling of women before LETZ and during any pregnancy after LETZ.

Innovations in cancer care requiring intensive support, and improved cancer patient survival in and out of critical care, have led to greater numbers of cancer patients than ever accessing critical care. Of these, however, a fair proportion will die. Current research points to around one in six patients dying in general critical care units and even higher numbers for cancer patients. End-of-life care (EOLC) for critically ill patients is problematic and rarely addressed beyond satisfaction or chart review studies, while palliative care is an established domain in cancer. It is not known whether dying, critically ill cancer patients experience good EOLC. In the context of a cancer critical care unit, this thesis explores the provision of EOLC for cancer patients in a critical care unit. Exploring measures for comfort care and palliative principles of care helped identify what is important for patients and families, and what those measures meant for all participants. The diagnosis of cancer and how it impacts on EOLC provision for critically ill cancer patients was also explored from the perspective of patients, families, doctors and nurses. A Heideggerian phenomenological interview approach was undertaken, in order to gain personal experiences. Families of those patients who died after decisions to forgo life-sustaining treatment (DFLSTs) were interviewed. Patients who have experienced critical care were also interviewed, since patients‘ views about EOL care provision are very rarely explored. Doctors and nurses also contribute their vision for, and experiences of, EOL care in a cancer critical care unit. Thirty one interviews with 37 participants were carried out. Cancer prognosis together with critical illness prognosis contributed to difficulties in deciding to move to, and enact EOLC. The nursing voice in DFLSTs was minimal and their role in EOLC depended on experience and confidence. Achieving a good death was possible through caring activities that made best use of technology to prevent prolonged dying. EOLC was an emotive experience. Decision-making and EOLC could be difficult to separate out which, in turn, affects prospects for EOLC. A continuum of dying in cancer critical illness is presented with different participants‘ experiences along that continuum. Three main themes included: Dual Prognostication; The Meaning of Decision-Making; and Care Practices at EOL: Choreographing a Good Death with two organising themes: Thinking the Unthinkable and Involvement in Care. These themes outlined the essence of moving along a continuum toward patients‘ deaths and the impact that had on opportunities for care and a good death. Nurses could use the care of patients dying in critical care as an opportunity to develop specialist knowledge and lead in care, but this requires mastery and reconciliation of both technology and EOLC. This work builds on Seymour‘s (2001) theory of a negotiated and natural death related to achieving a good death in critical care. Trajectories of dying, part of Seymour‘s (2001) theory, are extrapolated on with reference to Glaser and Strauss (1965) and Lofland (1978)‘s theories on dying trajectories. Nursing theory is developed through examination of Falk Rafael‘s (1996) and Locsin‘s (1998) theories of empowered caring. Implications and propositions are presented for nursing and wider practice around EOL care for critically ill cancer patients.

The central argument in this thesis is that the workplace environment has an impact upon users and that perceptions of the environment are related to overall satisfaction with the workplace, stimulation and perceived productivity. In addition, it is proposed that changing the environment can influence users’ perceptions and stimulation levels. To test this argument a methodology was developed to allow the collection of both objective and subjective data relating to a range of aspects of the workplace environment. A questionnaire was developed to test users’ attitudes towards aspects of the workplace environment including the internal climate, spatial layout, interior design and workplace features. These user perceptions were analysed in relation to corresponding objective measures of these workplace aspects. Data was collected in 16 workplaces and analysed to determine the relationship between user perceptions and objective measurements of the workplace and establish how these were related to overall satisfaction, stimulation and perceived productivity. The results revealed that users were satisfied with the more quantitative aspects of the workplace: internal climate and spatial layout, but were not satisfied with the qualitative aspects of the workplace: decoration, furniture, personal control and choice, window provision and break areas. All aspects of the workplace were significantly correlated with satisfaction with the workplace and stimulation. There was also an effect on perceived productivity. The findings of the workplace evaluations were tested to determine whether changing the environment in the afternoon could affect stimulation. The results revealed some evidence of a positive impact upon stimulation levels through variation of the workplace environment. Implications for the design of future workplaces and further research in light of the findings are discussed.

Introduction: Pigeon fanciers’ lung (PFL) is one of the most common forms of hypersensitivity pneumonitis (HP) in the UK. Generally it is considered that PFL is caused by immune complexes, however, this does not explain why some fanciers are asymptomatic despite the presence of high levels of anti-avian antigen antibodies in their serum. Pigeon intestinal mucin (PIM) is considered to be an important antigen in PFL. Thus this study was designed in order to understand the role of specific antibodies and T cells in the pathogenesis of PFL. Methods: Anti-avian IgG and IgG subclass responses among 50 symptomatic and 50 asymptomatic pigeon fanciers were determined by ELISA and the functional affinity of IgG1 and IgG2 against a range of pigeon antigens was determined by inhibition ELISA and microcalimetry. Mucin-specific T cell clones were also generated from pigeon fanciers and T cell phenotypes and cytokine profile of these cells were identified. Results: The median titres of IgG1 and IgG2 against all the pigeon antigens tested was always higher in asymptomatic than symptomatic fanciers and these differences were significant for anti-PS IgG1 (P=0.04), anti-PDF IgG2 (P=0.028), anti-PDO IgG2 (P=0.04) and anti-PIS IgG2 (P=0.03). The functional affinity of IgG1 and IgG2 against PDO was higher in symptomatic individuals as compared to asymptomatic fanciers (P=0.006 and P=0.002, respectively) whilst the functional affinity of anti-PDF IgG2 was also significantly higher in these patients (P≤0.001). Symptomatic fanciers were also significantly more likely to have high ΔH and thus had higher avidity antibodies against PDO (P=0.044). 12 T cell clones specific for t mucin also were generated from an asymptomatic fancier and 90-96% of clone 04, 22, 23 were CD4-CD8- double negative (DN). Conclusion: The data suggests that the magnitude of the serum antibody response cannot determine the development of the disease and as symptomatic fanciers had higher IgG antibody avidities and therefore immune complexes in individuals with PFL may have a stronger composition and bonds. In addition, this is the first demonstration of the use of ITC to measure antibody avidity in a clinical situation. This is a rapid and simple method of measuring antibody avidity and has a diagnostic potential in PFL. Finally t mucin-specific T cell clones with double negative phenotype may have a crucial role in immune regulation in asymptomatic fanciers and can be one of the reasons why these individuals do not have any symptoms in spite of having high antibody responses.

Although parents’ involvement has been identified as important for interventions for their children and young people, little research is conducted to explore parental management strategies for anxiety in children and young people with mild to moderate learning disabilities (LD) and autism. Given that children and young people with LD and autism are more vulnerable to experience anxiety, the overall purpose of this thesis was to identify the prevalence rates of anxiety and explore management strategies for anxiety in children and young people with LD and autism. Three studies were conducted to identify prevalence of anxiety and develop and implement a parental programme of management strategies for anxiety in children and young people with LD and autism. In the first study of this research “Screening study”, 150 children and young people with LD and autism were screened for anxiety using Reiss Scale and Glasgow Anxiety Scale. Results from the screening indicated that children and young people with LD and autism have high prevalence rates of anxiety (32.6%). The second study of this research “Developing a programme” was to develop a programme of management strategies for anxiety from parents’, carer’s, teachers’ and health professionals’ views. In this study parents and teachers were interviewed regarding the management strategies they use to manage their children’s / young people’s anxiety. Results from 34 interviews revealed that sixteen different management strategies were identified by parents and teachers of children and young people with LD and autism. Following this, the management strategies identified by parents, carers and teachers were discussed with an expert panel of health professionals to develop a parental programme “Calm Child Programme” of the most useful and appropriate strategies for those children and young people. The Calm Child Programme was developed using Delphi method to identify a consensus approach with professionals. This consisted of ten useful management strategies for parents to manage their children’s and young people’s anxiety. Finally, the third study of this research “Implementing the calm child programme” was a pilot study of the implementation for the Calm Child Programme. This programme of parental management strategies for anxiety was piloted with seven parents of children and young people with LD and autism. The results from the pilot study indicate reduction in the children’s and young people’s anxiety after its use by parents. Parents reported that the developed strategies were useful in managing their children’s and young people’s anxiety. This research has two key contributions to knowledge. Firstly, this research highlighted the theme of anxiety of children and young people with LD and autism. The identification of high prevalence of anxiety in this population indicates the need for management strategies. Secondly, this research aimed to improve the paucity of autism specific research as it relates to anxiety management strategies in children and young people with autism. This research explored a new programme of parental management strategies for anxiety in children and young people with LD and autism. This research has contributed to our understanding of using systematic and evidence based management approaches in supporting and involving parents.

Complementary and Alternative Medicine (CAM) has long been used in the Far East to aid in the recovery and prevention of illness. Ginseng, an over-the-counter herbal product in the UK, is amongst these herbal CAMs currently available to the general public. Ginseng is renowned for its rejuvenating properties and its purported ability to aid cognitive function and well-being. Despite the huge global market for ginseng there is little in the way of human research, utilising standardised ginseng extracts and well controlled methodology to support many of these claims. Additionally, ginseng's underlying mechanisms of action are poorly understood. The present thesis documents 5 double-blind, placebo-controlled, cross-over trials investigating the effects of Panax ginseng, following acute and chronic ingestion, on behaviour, mood and indices of glucose regulation in young healthy volunteers. The results of the five studies making this thesis suggest that both acute and chronic dosing with Panax ginseng is capable of modulating mood and cognitive performance in healthy young volunteers. Chapters 2 and 3 also demonstrate, for the first time, Panax ginseng's ability to modulate blood glucose levels following a single acute dose in overnight fasted healthy volunteers. In chapters 2 and 3, significant reductions in blood glucose levels and concomitant improvements in mental arithmetic (working memory) performance were reported. Chapter 4 revealed for the first time Panax ginseng's positive effects on traditional measures of working memory, thus posing the suggestion that previous failures to report working memory effects (using traditional working memory tasks) may have been due to poor task selection. Chapter 5 revealed an unexpected superimposed relationship between chronic and acute ingestion of Panax ginseng. The pattern of results suggests that following chronic dosing, an acute dose can further modulate cognition and mood (suggestive of a psychological dependence). The final chapter documents a different profile of cognitive and mood effects following a non-standardised Panax ginseng extract, thus highlighting the need for caution when generalising results across ginseng types and beyond the specific parameters of the methodologies utilised in any given study. Methodological differences between studies may go some way in explaining the inconsistent data patterns reported between studies, research groups and ginseng extracts. These data further highlight the need for well-controlled studies utilising standardised ginseng extracts and the need for the integration of 'theory driven' research in order to fractionate any behavioural effect. Such methodologies will inevitably lead to greater consistency between behavioural studies, at least in the first instance within the restricted population of volunteers utilised in the present thesis.

Examination of the literature suggests that relationships between psychiatric staff and the families of service-users are often characterized as unsatisfactory, and that psychiatric hospitals provide an unconducive environment for the implementation of family and network-orientated approaches. This research focused upon the development in an adult psychiatric admissions unit of family- staff network meetings, that occurred when a person entered hospital. These network meetings, or 'reception meetings', were strongly influenced by the Finnish social network approach (Seikkula, Alakare & Aaltonen 2001), which focuses upon the creation of open dialogue between the service-user, family members and professionals. An overall aim of the study was to generate a body of practice-based narrative accounts which might act as a catalyst to practice developments in this field. Drawing upon a postmodern methodological framework, a range of methods were employed to engage with the multiple voices of service-users, family members and staff in the research site. Data sources included semi-structured interviews, participant observation, secondary data, and material from a research diary that was maintained as a reflexive tool in relation to the practitioner research process. A 'voice-centred relational method' (Brown and Gilligan 1992) provided a heuristic device for guiding data interpretation which facilitated multiple readings from different perspectives. A subsequent stage of data-analysis entailed developing more general connecting themes from across the data-set. A number of themes are developed in the research, which principally relate to the tensions associated with the introduction of a relationally orientated, reflective approach to practice within an individually-based medico-psychiatric organizational context. Practice approaches are discussed which appeared to facilitate an ethos of 'safe uncertainty' (Mason 1993) within network meetings, which is a necessary condition for dialogue. Connections are also drawn between themes generated in this study and the broader contexts of government policy, professional and organizational development, and practice-based research.