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The formation of new blood vessels; physiological function of quiescent vasculature; and remodelling of vasculature after injury, is regulated by a wide variety of complex and overlapping signalling pathways. The endothelial cell monolayer, vascular smooth muscle cells and adventitial tissue which constitute blood vessels are influenced by multiple circulating and locally secreted factors, with each tissue type exerting effects on the other; especially in the context of angiogenesis and in the pathophysiological response to vascular injury. Insulin-like growth factor binding protein-2 (IGFBP-2) has been considered an important factor in tumour angiogenesis and cellular proliferation, but little is known about its effects on vascular function, vascular remodelling, and its effects on the individual cell types within the vascular environment. In this work, we describe the effects of IGFBP-2 on vascular physiological and pathophysiological processes. We achieved this predominantly through the use of two transgenic murine models: of conditional endothelial specific IGFBP-2 overexpression, and conditional global IGFBP-2 overexpression. We demonstrate that endothelial specific IGFBP-2 overexpression has no effect on ex vivo aortic vasomotor function, whilst global overexpression of IGFBP-2 causes significant aortic hypocontractility, but without any change in endothelium-dependent vasodilatation, and without altering nitric oxide bioavailability. No change for in vivo blood pressure was evident, with increased aortic distensibility seen with global overexpression of IGFBP-2. We also demonstrate that global overexpression of IGFBP-2 leads to reduced re-endothelialization after vascular injury, but does not affect neointimal quantity, although possible changes in neointima composition were observed. Finally, increased exposure to IGFBP-2 caused an increase in sprouting angiogenesis across multiple endothelial cell types. In conclusion, increased expression of IGFBP-2 may exert multiple effects on murine vasculature in the setting of vascular vasomotor function, vascular injury and angiogenesis. More work is required to further understand the effects IGFBP-2 exerts in vascular biology, and the signalling mechanisms through which these occur.

In this thesis I develop novel methods and datasets, based on the processing of CryoSat-2 satellite radar altimeter data, to improve the understanding of retrieving measurements of surface elevation and elevation change over the Antarctic and Greenland ice sheets. First, I used 6 years of CryoSat-2 altimetry to create a model of the surface height of the Antarctic Ice Sheet and ice shelves. Posted at a resolution of 1 km, 94 % of the grounded ice sheet and 98 % of the floating ice shelves are observed, and the remaining grid cells North of 88 ° S are interpolated using ordinary kriging. Taking into account slope-dependent errors and the distribution of slopes across the ice sheet, I estimated the average accuracy of the DEM to be 9.5 m - a value that is comparable to, or better than that of other models derived from satellite radar and laser altimetry. Next, I developed a new technique to retrieve estimates of the depth distribution of radar backscatter from CryoSat-2 altimeter waveforms using a backscatter model. I then applied this model to chart spatial and temporal variatibility in radar backscatter and, for the first time, explicitly estimate radar penetration depth across the interior of the Greenland Ice Sheet. I then used this information to correct for artefacts in elevation trends derived from Cryosat-2 pulse-limited altimetry resulting from an episodic melt event which reset the radar scattering horizon. Incorporating the penetration depth into the surface height retrieval, I find improved agreement when compared to independent airborne laser altimeter data recorded over the same time period. Finally, I used CryoSat-2 altimetry to estimate seasonal elevation changes in the Greenland Ice Sheet. Using regional climate model simulations of height fluctuations due to surface process alone, I demonstrate that CryoSat-2 observations track elevation changes driven by melting and snowfall accumulation in the ice sheet ablation zone. I then mapped spatial and temporal variations in seasonal elevation change, demonstrating the ability of CryoSat-2 to monitor changes in Greenland which arise due to its meteorology.

The aim of this thesis is to investigate the methodology of three dimensional chemical imaging of nanoparticles through the use of scanning transmission electron microscope (STEM) – energy dispersive X-ray (EDX) spectroscopy. In this thesis, an absorption correction factor is derived for spherical nanoparticles that can correct X-ray absorption effects. Quantification of EDX spectra of nanoparticles usually neglects X-ray absorption within the nanoparticle but may lead to erroneous results, thus an absorption correction is important for accurate compositional quantification. The absorption correction presented is verified through comparison with experimental data of Au X-ray peaks in spherical Au nanoparticles and is found to agree excellently. This absorption correction allows accurate compositional quantification of large ( > 100 nm) particles with STEM-EDX.Three dimensional chemical mapping is achievable through the use of EDX spectroscopy with electron tomography. Here, the methodology of STEM-EDX tomography is fully explored, with a focus on how to avoid artefacts introduced through detector shadowing and low counts per pixel. A varied-time acquisition scheme is proposed to correct for detector shadowing that is shown to provide a more constant intensity over a series of projections, allowing a higher fidelity reconstruction. The STEM-EDX tomography methodology presented is applied to the study of AgAu nanoparticles synthesized by the galvanic replacement reaction. The elemental distribution as a function of the composition of the as-synthesized nanoparticles is characterised and a reversal in the element segregated to the surface of the nanoparticles is found. The composition at which the reversal takes place is shown to correlate with a peak in the catalytic yield of a three component coupling reaction. It is hypothesized that a continuous Au surface results in the optimum catalytic conditions for the reaction studied, which guides the use of galvanically prepared AgAu nanoparticles as catalysts.

This thesis explores the role of social workers in suicide prevention. Using a mixed methods approach the research examines how social workers understand, and work with, suicidal individuals in multi-agency and interdisciplinary settings. In my first empirical chapter (chapter five) a secondary analysis of the Adult Psychiatric Morbidity Survey (2007) (n=7,403) explores the circumstances under which social workers come into contact with suicidal individuals. Using a multinomial logistic regression it has been possible to establish that substance misuse is associated with social worker contact. This suggests that social workers are having contact with a group at elevated risk of suicide. The second part of the thesis is based on a series of semi-structured interviews with statutory social workers (n=17) (chapters six and seven), service users with a history of suicide attempts (n=3) and Community Psychiatric Nurses (CPNs) (n=3) (chapter eight). A thematic analysis of the interviews found that although statutory social workers had little or no training in assessing suicide, both service users and CPNs believed that social workers have a vital role in supporting suicidal individuals. Social workers found peer learning to be important as both a source of knowledge and learning, and as a support network. The findings of this research indicate that social workers have particular expertise in taking a holistic approach to suicide assessment and prevention. The Approved Mental Health Professional (AMHP) role is also felt to give social workers a strong knowledge of the legal issues that underpin working with this vulnerable group. However further research into the contact between social workers and suicidal service users and the assessment of suicide is necessary. The findings of this thesis have implications for practitioners, policy makers and researchers.

This study examined the impact of the 1984 Alternatives to Incarceration legislation on jail overcrowding in New York State from an interorganizational network perspective. A literature review was undertaken that reflects the nature of the jail overcrowding problem just prior to the passage and implementation of the Alternatives to Incarceration Legislation in 1983-84. Jail use patterns were analyzed as well as certain process and demographic variables thought to be associated with incarceration practices. The analysis of jail use patterns indicated that, overall, the legislation did not have the desired impact on jail overcrowding. While crime, arrest and conviction rates were static, jail use increased. The study also revealed that the use of advisory boards, composed of criminal justice network actors, coupled with the nature of the mandated criminal justice network, provided ample opportunity for the networks to blunt efforts at change and reinforce domain consensus. The study has implications for change efforts directed at local criminal justice networks. Society's seeming infatuation with incarceration makes a shift toward non-incarcerative sanctions nearly impossible without major system battles. [ABSTRACT FROM AUTHOR]