Aim The aim of this study was to investigate the efficacy of a specific school of acupuncture, Traditional Chinese Medicine Acupuncture (TCMA), as a whole complex intervention, as it operated in a clinic setting, on a wider representation of users and spectrum of diseases than the typical acupuncture user profile, and to explore potential variations in health outcomes. Design and Setting This was a retrospective study that employed a Whole Systems Research (WSR) design that involved outcome evaluation, to determine the efficacy of TCMA, together with process evaluation, to determine patient perceptions of how the intervention worked in practice, with regards to health, wellness, and Quality of Life (QoL). The research focused on a subsidised clinic that was located in a socially deprived area of London. Methods The retrospective study period was February 2007 to March 2008. Scores from Measure Yourself Medical Outcome Profile (MYMOP), an outcome measure used to investigate changes in health outcomes over time, were extracted from individual patient files (N=208) that had fulfilled the inclusion criteria of attendance at six consecutive treatment sessions, delivered from baseline treatment, irrespective of outcome or symptom. MYMOP scores on Symptom, Activity and Wellbeing, that were completed at baseline (treatment 1) follow up (treatment 2), follow up (treatment 3), follow up (treatment 4), follow up (treatment 5) and follow up (treatment 6), were analysed using repeated measures ANOVA to investigate whether a significant difference in QoL, a variable derived from the mean of the nominated MYMOP scores, existed between baseline treatment and outcome for patients over the six week treatment period; statistical analysis was also completed to explore variations in treatment outcomes in relation to patient’s socio-demographic characteristics, age, gender, ethnicity and social grade, and the wide range of health conditions reflected in the sample. Written patient commentaries (N=117), concerning experiences of TCMA, that were provided on patient discharge forms were extracted and analysed using Thematic Analysis. Results Significant differences were found in the direction of better reported MYMOP Symptom, Activity and Wellbeing scores following TCMA treatments and a significant difference in QoL was found between baseline assessment and outcome for TCMA patients over the 6-week course of treatment. Statistical analysis produced no evidence that the perceived benefits of TCMA treatment were associated with patients’ gender, age, ethnicity, social class, or presenting condition; no evidence was found that either demographics or presenting condition operated as outcome modifiers. Thematic analysis resulted in the identification of five themes which together provided insight into, and a way of understanding, both the outcomes and the processes that operated within TCMA. Conclusion Findings from the present study show that TCMA delivered perceived global and multidimensional beneficial changes in health, wellbeing and QoL; furthermore, the perceived positive treatment outcomes, which were unrelated to illness type or severity at the time of initial treatment, were consistent across socio-demographic subgroups and a wide spectrum of challenging cases of both physical and mental pathology. The study’s findings are important because they have advanced understanding of TCMA treatment efficacy and the workings of this particular style of acupuncture (TCMA) in terms of health, wellness and QoL.

Glucose homeostasis is regulated by the opposing actions of insulin and glucagon; insulin facilitates rapid glucose uptake from the blood stream to muscle and adipose cells. These tissues express the facilitative glucose transporter (GLUT4), which in response to insulin is translocated from intracellular compartments to the plasma membrane (PM) allowing glucose entry to cells. GLUT4 undergoes a complex intracellular trafficking itinerary, including recycling to and from the PM, but in the absence of insulin is mainly stored in GLUT4 storage vesicles (GSVs). When insulin binds its receptor, a complicated signalling cascade is initiated which results in the tethering, docking and fusion of GSVs to the PM. Fusion of the GSVs with the plasma membrane is mediated by SNARE proteins. The formation of a SNARE complex composed of Syntaxin4 (Sx4) and SNAP23 localised to the PM and VAMP2 on GSVs is a key event; the formation of this complex is in turn regulated by the Sec1/Munc18 protein, Munc18c. It has been shown that insulin stimulation leads to phosphorylation of Sx4 at two sites (Y115 and Y251) and Munc18c at Y521. The stoichiometry and order of phosphorylation are not yet known, and the biological consequences of this action to be uncovered. Therefore, the current study sought to ascertain the functional consequences of SNARE protein phosphorylation on GLUT4 trafficking. The approaches used include in vitro assessment of recombinant SNARE proteins and studies in vivo using 3T3-L1 adipocytes. The results of this study confirmed that tyrosine 115 and 251 of syntaxin4 are phosphorylated in response to insulin in 3T3-L1 adipocytes; however, phosphorylation of Munc18c was ambiguous. Subsequently, phosphomimetic recombinant SNARE proteins were expressed and ternary SNARE complex formation was successfully recapitulated in vitro and the complex found to be SDS and heat resistant. Phosphomimetic syntaxin4 mutants showed increased formation of SNARE complexes, notably double phosphomimetic mutant. Moreover, binary interactions with other SNAREs (SNAP23 and VAMP2) revealed tighter binding and higher affinity of the double phosphomimetic syntaxin4 compared to wild-type syntaxin4. Additional spectroscopic evidences suggest these differences are due to conformational changes and syntaxin4 mutants are more likely to be in the open form especially the double phosphomimetic mutant. In order to translate in vitro findings into cell models, in vivo intervention tools were generated including phospho-specific antibodies against phosphorylated residues in syntaxin4 and lentivirus particles for 3T3-L1 adipocytes infection. Antibodies validated on recombinant proteins phosphorylated using recombinant insulin receptor tyrosine kinase indicated they are functional and specific. Efforts dedicated towards optimizing working conditions for phospho-specific antibodies using adipocyte lysates were extensively examined, yet signals detected were generally found to be non-specific. A non-intrusive protein-protein interaction protocol, proximity ligation assay, was used to detect insulin-stimulated phosphorylation in adipocytes. A positive signal was detected confirming antibodies functionality in this assay; further work will be required to optimize this. Lentiviruses were used to over-express phosphomimetic mutants of syntaxin4 in 3T3-L1 adipocytes and Hela cells. The functionality of the transfected syntaxin4 mutants was assessed by measuring basal and insulin-stimulated glucose uptake. Infected native 3T3-L1 adipocytes showed a trend towards an increase in glucose uptake under basal conditions with no effect observed on the maximal insulin-stimulated rate of glucose transport. We speculate this may reflect the presence of the endogenous Sx4 molecules masking any effects of mutant over-expression thus Sx4 knockout cell lines was considered as an alternative experimental system. Sx4 overexpression rescued insulin-stimulated glucose uptake in Sx4 knockout 3T3-L1 cells and was significantly enhanced in cells expressing the double phosphomimetic mutant. Finally, our work showed that the native Munc18c native mouse gene sequence expressed poorly in bacteria; hence we used a gene-enhanced sequence that was found to express well and purify effectively. CD spectroscopy showed similar structures of expressed Munc18c using either sequences. Phosphomimetic Munc18c (Y521E) binds with higher affinity both wild type and double phosphomimetic syntaxin4 compared to wild type Munc18c. The data presented in this study suggest strongly that phosphorylation influences GLUT4 trafficking by altering the frequency and affinity of SNARE protein interactions. Such findings enrich knowledge about the mechanism of GLUT4 trafficking thus ultimately could help in understanding type 2 diabetes.

The chaperonin proteins form a ubiquitous family of molecular chaperones and are absolutely required for correct folding or assembly of a subset of proteins in the cell. They are divided into two groups based on phylogeny: Group 1 found in bacteria and eukaryotic-organelles and Group 2 found in eukaryotic-cytoplasma and archaea. The two groups share a significant degree of conservation but differ in structure and mechanism and are believed to have evolved to serve specific client proteins. Using archaeal chaperonin from M. maripaludis (MmCCT) as a representative, we report here for the first time that a Group 2 chaperonin can partially replace the function of a Group 1 chaperonin from E. coli (GroEL). We have also identified and characterized two functional variants of MmCCT that show better GroEL complementation and have utilized them for a preliminary mutational analysis of potential client binding residues of MmCCT. We further demonstrate an initiative using a tagging approach for identification of bacterial proteins that interact with MmCCT in vivo. We suggest that our findings provide a novel platform for genetic dissection of MmCCT using a comparatively simple host, E. coli, which in turn can help identify properties of this archaeal chaperonin and provide insights for structure-function co-relations of Group 2 chaperonins in general.

Spiritual matters lie at the heart of a good dying. However, the shape and focus of spiritual care in palliative care has, I believe, shifted away from the original vision of hospice pioneers, such as Cicely Saunders. Assessing the value of spiritual care has become a priority to those who value a 'scientific' evidence-based practice. The issue this thesis addresses is whether there is a better 'artistic' way to evaluate the care given to dying people. This thesis describes the current landscape of care and then argues for spiritual artistry, as a way to reclaim 'inner space' and 'deep silences' as sites of sacred encounters. This radical move takes the focus of spiritual care away from both evaluative endeavours and also beyond the alternative meaning-making and narrative models, which are currently offered. I hope to shift the focus towards a relational spirituality in which greater attention is given to spiritual awakenings. Dying and grieving can both be viewed as the space of spiritual quests. The challenge is to discover a new way of seeing these complex and sometimes chaotic spiritual contexts in which important things occur which sometimes are beyond measurement and communication. An innovative methodology, spiritual autoethnography, which integrates creative arts, autoethnography and theology, is chosen to pursue this research. In the process of interrogating the silences enounterered in spiritual care at the end of life new insights and understandings are generated. I illustrate the deep silences that occur in times of trauma, shame, cognitive impairment, betrayal and grief, and how understanding these sheds light on marginalised areas rarely the focus of current models of spiritual care. However, the radically new insights gleaned from this research come from the construction of inner space and deep silences as a locus of the sacred. These heuristic constructs, offer a new framework to shape the role of hospice chaplain, and the delivery of spiritual care. In conclusion, spiritual artistry, founded on a poetics, is presented as enabling chaplains to inhabit 'inner space' and 'deep silences'; to say the unsayable and delight in the gifts that accompany griefs. This new understanding of the role of the hospice chaplain, and of the delivery of spiritual care, benefits all those confronting their mortality and their grief.

Long-haul optical fiber communication system is an important infrastructure to support the latest broadband communication in the world. It is important to study a technology to improve the performance of such system, and the Return-to-Zero Differential Phase Shift Keying (RZ-DPSK) modulation attracts much attention because of its improved long distance transmission performance. One important technology of the current long-haul optical fiber communication system is the dispersion map, and it is widely deployed for already installed undersea optical fiber communication system in the world. Recently, a new dispersion map that was totally different from the map used for already deployed system was proposed, and it demonstrated advantageous performance of the long-haul RZ-DPSK transmission. Even though, the reason of the performance improvement is not investigated, and it is important to clarify the physical mechanism of the performance improvement, because it will contribute to improve the system design of the long-haul optical fiber communication systems in near future. In this master thesis, the performance of the RZ-DPSK format in the long-haul transmission system is studied. Both computer simulations and experiments are conducted to confirm the effects of various factors in the long-haul RZ-DPSK transmission system. From the theoretical study, it is pointed out that the Self-Phase Modulation (SPM) played a significant role to degrade the transmission performance of the conventional map, while it does not cause so significant degradation in the new map. The effects of the SPM and the Cross-Phase Modulation (XPM) with the conventional map are investigated through the experimental study.

This study aimed to investigate any difference between the attributions parents made about their child’s sleep problem, in parents of children with an Autism Spectrum Disorder and parents of children with Down Syndrome. Seventy-six parents of children with an Autism Spectrum Disorder and fifty-two parents of children with Down Syndrome completed a series of questionnaires on-line, regarding their child’s sleep problem, their beliefs about their child’s sleep problem and the parent’s level of anxiety and depression. A significant difference was found between the groups on four of the causal items; other health problem, child’s emotional state, child’s personality and diet. Parents of children with Down Syndrome showed a higher level of agreement that their child’s sleep problem could be attributed to another health problem compared to parents of children with an Autism Spectrum Disorder. Parents of children with an Autism Spectrum Disorder showed a higher level of agreement that their child’s sleep problem could be attributed to their child’s personality, their child’s emotional state and their child’s diet compared to parents of children with DS. There was a high level of agreement across all parents that their child’s disability was a causal factor to their sleep problem and differences in attributions may reflect characteristics of the child’s diagnosis. The results are consistent with previous findings that parents view disability as an important causal factor to their child’s sleep problem and suggest a possible overlap in parent’s views of their child’s sleep problem and views of their disability.

Objectives: This study explores the relationships between challenging behaviour, emotional recognition, alexithymia and cognitive emotional regulation strategies in a population of people with learning disabilities. The Emotional Recognition Questionnaire was developed to measure an individual’s ability to identify the emotions they would feel in a given situation. One objective of this study was to assess the validity and reliability of the tool. Methodology: Cross-sectional data was collected from 96 participants with a learning disability and 95 of their carers. The service user participants completed the Emotional Recognition Questionnaire (ERQ), and adapted versions of the Alexithymia Questionnaire for Children (AQC) and the Cognitive Emotion Regulation Questionnaire for Children (CERQ-k). Carer participants completed the Checklist for Challenging Behaviour (CBC) and the Observer Alexithymia Scale (OAS). Correlational analyses were computed to identify relationships between the variables and linear regression was used to identify the predictive value of variables in relation to the main outcome variables of challenging behaviour frequency, management difficulty and severity. Finally, a between group analysis was conducted to compare the emotional recognition abilities of people with high frequency challenging behaviour with those with low or no challenging behaviour. Analyses were conducted to test the hypotheses. Results: No relationship was found between the ERQ and the AQC so the construct validity of the ERQ was not supported. The results highlighted significant negative associations between emotional recognition abilities and challenging behaviour frequency and management difficulty. Significant differences in emotional recognition abilities were found between people with high frequency challenging behaviour and those with low or no challenging behaviours. Observer rated alexithymia was significantly related to challenging behaviour frequency, management difficulty and severity. Cognitive emotional regulation strategies and service user measured alexithymia were not, however, related to challenging behaviour. Other relationships were found between service user rated alexithymia and the cognitive emotional regulation strategies of Catastrophizing and acceptance, and emotional recognition was negatively related to self-blame. Conclusions: Overall, the study suggests that emotional recognition and observer related alexithymia are important in understanding challenging behaviour presented by people with a learning disability. This has implications for clinical practice and further research. Additional research needs to be conducted to evaluate the construct validity and test-retest reliability of the Emotional Recognition Questionnaire.

Diabetes Mellitus (DM) has become one of the most important metabolic diseases that reduces one’s quality of life and doubles the risk of early death. Amongst the major complications linked to DM, diabetic retinopathy (DR) leads to gradual loss of vision and blindness. DR is now the second cause of certifiable blindness among the working age adults in the UK. The lifetime costs to the UK government are calculated to be up to £327,000 per person, with almost 50% of these costs being attributed to loss of productivity caused by visual impairment and blindness. The UK is one of the leading countries in the implementation of DR screening programmes. The latter rely heavily on fundus imaging and grading using trained experts and subsequent referral to hospital for further clinical examination and evaluation depending on the grade of retinopathy. It is now known that subtle, structural changes in the retina that are linked to diabetes can precede detectable vascular changes. The former can affect one’s colour vision and this offers the potential of using changes in chromatic sensitivity as an early biomarker of retinal disease. The first part of this thesis focuses on measuring chromatic sensitivity using the colour assessment and diagnosis (CAD) test in diabetic subjects with varying degrees of retinopathy. The severity of colour vision loss is graded in comparison to other factors that are normally linked to diabetes, such as the type, grade, control methods and duration. The results of this study reveal losses of both red/green and yellow/blue chromatic sensitivity in patients with diabetes, but the correlation with factors, normally associated with high risk of diabetes is low. The results from this study do, however, show that the magnitude of chromatic sensitivity losses correlates with the severity of diabetic retinopathy. The second, related study examines the effectiveness of intravitreal injection of a dexamethasone implant (Ozurdex) in patients with diabetic macular oedema (DMO) in stabilising and reducing loss of visual function and in particular the reduction in chromatic sensitivity up to 24 weeks. This treatment demonstrated efficacy in the treatment of chronic DMO and DMO which is resistant to anti-VEGF treatment. The results show that intravitreal treatment with Ozurdex causes improvement is visual acuity, central retinal thickness and significant improvement in red/green chromatic sensitivity.

Spinal cord injury (SCI) has a dramatic effect on the function and appearance of the body. The first chapter of this thesis is a literature review which focuses on studies with participants who have incurred an alteration to their appearance due to a health condition. The implications of these studies for the likely impact of Body Image (BI) in men with SCI are considered. Cognitive and disfigurement models of BI are reviewed and research evidence evaluated. Results reveal that whilst the extent of appearance change is an important predictor of BI dissatisfaction, further variation is explained by the strategies individuals use to cope with the alteration in their appearance. BI dissatisfaction appears to impact upon the psychosocial wellbeing of both men and women and can also affect physical health. Further research is therefore needed in order to explore the links between appearance change, methods of coping and BI dissatisfaction, particularly in men with SCI. The second chapter reports on a cross sectional study of 102 male participants with SCI, which revealed group differences in BI dissatisfaction between inpatients and outpatients, who are established in the community. BI investment was found to moderate the effect of BI evaluation on low mood. The use of maladaptive coping strategies was also found to moderate the relationship between BI dissatisfaction and BI quality of life. Evidence suggests that BI should be assessed and BI dissatisfaction monitored after discharge from rehabilitation hospitals. Clinical intervention could focus upon reducing the use of maladaptive coping strategies, in order to reduce the impact of BI dissatisfaction upon quality of life.

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