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The first chapter briefly describes the phenomenology of bipolar disorder, and from this suggests a framework for evaluating psychological approaches to it. Then a broad based review of different psychological models and psychotherapeutic approaches for working with individuals with bipolar disorder are outlined and evaluated using the framework as a guide. The review then briefly explores the wider psychological theory of mood change, focusing specifically upon the example of the cognitive analytical mUltiple self states model as a model of affective instability. This is then related to the current understanding of bipolar disorder, and suggestions are made for how psychologists may work with individuals with such a diagnosis. It concludes with the finding that no single model fully accounts for the phenomenology of bipolar disorder, yet suggests how psychologists may use the current understanding to aid formulation and intervention. There has been little research into the association of shame aOnd other self-conscious emotions in bipolar disorder, although evidence exists linking shame to various psychopathologies, including depression. Chapter two reports on the empirical investigation into the levels of shame in individuals with bipolar disorder in comparison to individuals with unipolar depression and matched non-psychiatric controls. A crosssectional design was used to compare 24 individuals with a diagnosis of bipolar disorder to a clinical control group of 18 individuals with unipolar depression, and 23 age-matched non-psychiatric controls on measures of mood (Beck Depression Inventory and Self Report Manic Inventory) and of self-conscious emotions (Internalized Shame Scale and Test of SelfConscious Affect). In addition a small focus group was carried out investigating the impact of bipolar disorder upon the view of the self across the lifespan. Higher levels of trait (internalised) shame and lower guilt-proneness were found in the bipolar group compared to the unipolar and control groups, and higher levels of shame-proneness in the unipolar group in comparison to the bipolar and control groups.

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This thesis explores the utility of critical care following surgery. In particular, it assesses whether there are differences in how countries provide for critical ca re following surgery and whether these impact on outcomes. A meta-analysis of pre-emptive haemodynamic interventions in surgery was shown to reduce complications and mortality. Many of these interventions required the use of critical care which limited their utility. An analysis of a quality Austrian critical ca re database enabled an understanding of the group of patients admitted to critical care following surgery and the factors that are important in determining outcome. By utilizing these factors in a hierarchical logistic regression model, I demonstrated that outcomes are improving. Unfortunately, the provision of healthcare is not the same throughout Europe. Extrapolating data from Austria to the United Kingdom is therefore difficult. A further study was completed to identify differences in critical care provision between European countries. This study was hampered by inconsistent definitions of what an intensive care bed is, although did find a worryingly wide difference in beds per head of population. This must have implications for the case mix of patients admitted (or refused) to critical ca re and therefore surgical outcomes. A final study was performed to assess whether there were differences in outcomes at a national level. In this large observational study, critical care utilization varied following surgery and mortality rates were higher than expected with significant differences found between individual countries. In conclusion, critical care is a vital part of the surgical pathway for a select group of patients. Unless this group can be understood and quantified, then healthcare providers will be unable to develop systems that are able to cope with the likely demand. Only by matching this demand will optimal ca re be delivered.

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Ovarian cancer commonly relapses after remission and activating tumour-specific T cells with dendritic cells loaded with tumour cells is a promising approach to target residual microscopic tumours. SK-OV-3 cells expressing HER-2/neu and MUC1 ovarian antigens were killed and their immunogenicity enhanced by hypochlorous acid (HOC1) oxidation. Treatment with 60 uM HOC1 for 1 h induced necrosis in all the cells. Oxidised, but not live SK-OV-3 were engulfed by monocyte-derived DCs. Autologous T cells primed with DCs of HLA-A2+ healthy volunteers loaded with oxidised SK-OV-3 (HLA-A2") recognised oxidised SK-OV-3 and HLA-A2-restricted epitopes of MUC1 and HER-2/neu. Responses were absent with heat- or hydrochloric acid (HCl)-killed SK-OV-3, thus HOC1 oxidation and not cell death/necrosis enhanced the immunogenicity of SK-OV-3. Oxidised SK-OV-3 primed T cells did not respond to oxidised melanoma, or vice versa. Next, T cells of ovarian cancer patients in remission, whose tumours overexpressed MUC1 and/or HER-2/neu, were tested using the same model. DCs of HLA-A2+ and A2" patients pulsed with oxidised SK- OV-3 stimulated T cells specific for oxidised SK-OV-3, and HER-2/neu and MUC1 epitopes. Oxidised SK-OV-3 loaded DCs further matured with CD40 agonistic antibody or monophosphoryl lipid A, primed stronger CD4+ and CD8+ responses than immature DCs. T cells stimulated this way also recognised autologous tumour cells from ascites, demonstrating that SK-OV-3 shared significant antigenic repertoire with tumours in patients. Finally, this DC-based vaccination was tested in vivo using the B16.F10 melanoma model. B16.F10 highly expressed tyrosinase-related protein (TRP)-2, and all the cells were necrotic after 1 h treatment with 60uM HOC1. Mice immunised intravenously and not intraperitoneally or subcutaneously with bone- marrow derived DCs loaded with oxidised B16.F10, responded to TRP-2 and oxidised B16.F10. Oxidised and not heat- or HCl-killed B16.F10, primed specific T cells in vivo. DCs were required for efficient delivery for processing and presentation of oxidised B16.F10 in vivo.