The progressive loss of cartilage matrix is a major characteristic of arthritic disease, ultimately leading to a loss of joint function. A number of therapeutics are used in the treatment of arthritic disease, with non-steroidal anti-inflammatory drugs used to treat the pain and inflammation seen in osteoarthritis and rheumatoid arthritis, whilst disease modifying anti-rheumatic drugs are used to slow disease progression. However it is not fully understood if and how many of these drugs effect the disease processes in arthritis. The objective of this study is to look at a number of therapeutics and investigate their effect on the breakdown of proteoglycan and collagen, and on the expression of a number of key degradation enzymes, whilst trying to identify the possible mechanisms used by the drugs. Using the bovine nasal cartilage explant model IL-1 + OSM were used to stimulate the release of proteoglycan and collagen from the cartilage. Interleukin-1 (IL-1) and oncostatin M (OSM) together promote the degradation of cartilage by up regulating and activating MMPs that are found within the diseased joint. Treatment of the resorbing cartilage with indomethacin, indomethacin heptyl ester, simvastatin, mevastatin, pravastatin and sulfasalazine produced a variation of findings with many resulting in the inhibition of cartilage degradation. The stimulation of human articular chondrocytes with IL-1 + OSM caused a significant up regulation of MMPs by the cells at both a gene and protein level when measured by TaqMan PCR and ELISA respectively. Again treatment of the stimulated chondrocytes with a number of the drugs showed a significant reduction in the expression of key cartilage degrading enzymes. The investigation of signalling mechanisms affected by one specific drug, namely sulfasalazine by immunoblotting and signalling microarray, showed some interesting results not previously documented. Sulfasalazine is well known to inhibit NF-I(13 activation by blocking the degradation of IicB to the proteosome and data in this study supports these finding. However, study of the MAPK pathway showed that sulfasalazine appears to be able to block the signalling cascade which ultimately leads to AP-1 activation in chondrocytes stimulated with IL-1 + OSM. This study has identified possible chondroprotective properties in a number of the drugs which were screened and whilst the exact mechanisms behind these events still require further investigation, the results highlight the potential of these drugs in being used to prevent further cartilage degradation in arthritis and thus further delaying the possible need for joint replacement operations.

This thesis examines architectural taste and patronage in Newcastle upon Tyne between 1870 and 1914. During this period, the city experienced dramatic expansion as the wealth generated in industry, finance and retail was channelled into commercial and public architecture. The overall aim is to determine whether Newcastle formed a distinctive architectural culture. Newcastle's economic and social profile gave rise to specific patterns of taste and patronage. The thesis explores the cultural networks that shaped the built form of the city, arguing that architectural patronage in Newcastle was dominated by a cultural oligarchy. This group formed an 'architectural culture', a relatively self-contained community in which particular styles and architects were favoured above others. Newcastle was a major centre of industry, finance and retail, and played a significant role in the national economy. The thesis seeks to reposition Newcastle within the context of the dynamic forces that were reshaping Britain's built environment. As the period progressed, the distinctive patterns of taste and patronage within the city were eroded by the increasingly national economy, the influence of the metropolis and the more active role played by the centralised state. The thesis relates the architectural culture under study to the national mainstream, thus shedding light on the relationship between provincial architecture and the metropolis. The thesis employs a range of methodological strategies in order to bring the different facets of architecture into focus. With clearly defined geographical and temporal boundaries, it seeks to clarify the economic, social and cultural factors that underpin architectural production, thus offering a new insight into architectural patronage.

This study used a qualitative method to focus on the perspectives, beliefs and expectations of low back pain sufferers. The research was undertaken within a hospital based pain clinic. In recent years low back pain research has proliferated, and the epidemiological evidence suggests that back pain is an increasing problem. Much attention has been paid to the impact of low back pain on the population, and to the increasing cost in economic and health terms. Biomedical and psychological evidence abounds to shape acute and chronic management of low back pain, but there is a dearth of information about the viewpoint of those suffering pain. This study attempted to bring the understanding of the back pain sufferer to the fore. Issues of quality of life, functional ability and the impact of back pain on their lifestyle were explored, along with the influence of contextual factors in relation to how back pain sufferers perceived themselves and how others perceived them. A narrative method was utilized to illuminate the journey with pain. Nine interviews were conducted, and the interpretation and presentation of the narratives generated was influenced by Ricoeur’s interpretative theory. Thematic analysis revealed that doctorability, agency, control, separation or acceptance of the pain and the concept of future life were key features within the narratives. The analysis highlighted that for the majority in this study pain arrived uninvited following a traumatic accident or incident, and back pain became a chronic condition. It was always unwanted and initially it was unexpected as the usual script for pain is one of a transient incapacity followed by recovery. It was precisely this deviation from the norm that resulted in difficulties for the people suffering the pain. Biographical differences did not appear to be identifiable in the themes discerned in the stories, nor in the overall structure.

This thesis examines the widespread use of bestial imagery in satirical verse, prose and prints published between 1789 – 1820, through a study of Shelley, Spence, Gillray, Gifford, Robinson, Catherine Ann Dorset, Thelwall, Eaton, and Wolcot. The thesis asks why these writers and printers used animal metaphors so frequently, but moreover, what impact the use of this imagery had on the political landscape of satire in the period. Recent criticism has focussed on the historical and political contexts of Romantic-era satire, and this thesis follows that criticism with an historicist methodology, combining literary, historical and political approaches. Furthermore, the thesis analyses verse, prose and pictorial satires as contributing to the same political discourse and as doing so in closely related cultural arenas. This thesis claims originality on the basis that not only the use of animal imagery has a significant impact on how both contemporary and modern readers interpret its political meanings and contexts, but also that this is an argument that has not yet been posited by other critics. In addition, this thesis argues that through bestial metaphors, satirical writers and artists create a community wherein imagery is exchanged, developed and manipulated, and that this practice of cultural exchange significantly shapes those satires’ historical contexts. Each of the thesis’ five chapters focuses on a major satiric animal metaphor, whereby close readings of satires are offered alongside wider political and historical contexts. Consequently, this thesis provides a map of the most common satiric animal metaphors and their concomitant politics, and in doing so creates a new critical framework in which the growing interest in Romantic- period satire can be further developed.

The psychiatric diagnosis of Borderline Personality Disorder (BPD) leads to service users experiencing stigmatising and disempowering attitudes from professional mental health staff. To date, a nursing theory has not been developed to understand mental health nurses’ personal and professional constructions towards service users with this diagnosis. The development of such theory may enable improved service user engagement, collaboration and recovery for this group of individuals. This study answered the questions of determining the nature of mental health nurses’ beliefs towards service users with a diagnosis of BPD and how these beliefs affect their therapeutic relationships with this service user group. An ethnographic approach was used in this study. Data was collected using a combination of observation of the patient assessment and allocation meeting within a community mental health team; and ethnographic interviews with named nurses for service users with a diagnosis of Borderline Personality Disorder. A reflective journal was also kept by the lead researcher. N-Vivo Version 7 was used to aid data analysis and this involved examining the scripts for repetitive patterns or sequences including descriptions, figures of speech, metaphors etc. in order to illuminate differences between different practices and contexts. Findings from the study elicited a model of how CPNs construct BPD categorisations and a potential pathway to alienation is described together with recommendations for the development of CMHTs and CPNs when working with BPD. Development of reflexive practice can be a vehicle for developing alternative constructions of BPD and recovery informed practice can reduce stigmatising practices experienced by service users with BPD.

The personality characteristic locus of control internality is widely-accepted as a trait possessed by women entrepreneurs. Recent research also suggests the presence of a coexisting attribute of similar strength, characterized as influence of a significant other. The presence of one personality characteristic implying perception of self-directed capability, together with indication of need for external assistance, poses a theoretical paradox. The study's purpose was to determine the nature and extent of direct and interactive effects which these and related variables had on entrepreneur return on investment. It was hypothesized that dimensions of significant other, as operationalized for this research, would support internality of locus of control and also modify constraining effects of educational and experiential disadvantage which the literature cites as pertinent to women entrepreneurs. This was nonexperimental, exploratory research of correlational cross-sectional design which examined hypothesized variable linkages. A convenience sample from a women's entrepreneur networking group was surveyed. Significant other elements were derived from factor analysis, resulting in four common dimensions. These factors, together with Rotter's Locus of Control instrument scores, reports on levels of education and experience, and hypothesized interactions, were independent variables. Hierarchial multiple regression was used to test a proposed path model. Two interpretable four-factor solutions derived from significant other variables were tested in two models. Although neither model attained overall significance, individual variables were directionally as hypothesized, and locus of control and certain factoral dimensions attained bivariate significance. Significant other factors appear to influence locus of control through statistical suppression as they interact with other variables. Results point toward a possibility that significant others who most affect female entrepreneur performance are those who give specific advice and aid, rather than moral support. Further research to explore what seems a strong relationship between return on investment and locus of control internality is recommended.

The aim of this thesis is to address the contextual and harmony issues in shape grammar (SG) by applying knowledge from the field of natural language processing (NLP). Currently shape grammars are designed for static models (Ilčík et al., 2010), limited domain (Chau et al., 2004), time-consuming process (Halatsch, 2008), high user skills (Lee and Tang, 2009), and cannot guarantee aesthetic results (Huang et al., 2009). The current approaches to shape grammar produce infinite design and often meaningless shapes. This thesis addresses this problem by proposing a harmonised shape grammar framework which involves applying five levels of analysis namely morphological, lexical, syntactic, semantic, and pragmatic levels to enhance the overall design process. In satisfying these semantically well-formed and pragmatically well-formed shapes, the generated shapes can be contextual and harmonious. The semantic analysis level focuses on the character’s anatomy, body function, and habitat in order to produce meaningful design whereas the pragmatic level achieves harmony in design by selecting relevant character’s attributes, characteristics, and behaviour. In order to test the framework, this research applies the five natural language processing levels to a set of 3D humanoid characters. To validate this framework, a set of criteria related to aesthetic requisites has been applied to generate humanoid characters; these include the principles of design (i.e. contrast, emphasis, balance, unity, pattern, and rhythm) and aspects of human perception in design (i.e. visceral, behavioural and reflective). The framework has ensured that the interrelationships between each design part are mutually beneficial and all elements of the humanoid characters are combined to accentuate their similarities and bind the picture parts into a whole.

Samuel Bourne (1834-1912), one of the most prestigious Victorian English commercial photographers to have worked in British India, is best known for his photographs of the Himalayas. Bourne's work features in general studies of photography of the period; his representations of the Indian landscape have been the object of studies and several exhibitions. Bourne was in India initially from 1863 to 1870 thereby establishing his career as a professional photographer. Soon after his arrival he started a business with the experienced photographer Charles Shepherd. Within a few years, the firm of Bourne & Shepherd became recognised as being a directing influence over British-Indian photography. The photographs were taken either in studio or on location, and included individual and group portraits of both the British and Indians, topographical images in which peoples were incidental, as well as a range of representations of Indian life, customs and types. These images were informed by, and in turn contributed to, an expanding body of photographic practice that mixed, to varying degrees, authenticity and aesthetic style. Whilst Bourne's work was significant and influential in the representation of Indian peoples, no substantial study has been undertaken until now. The aim of this thesis is to redress this imbalance. The central focus highlights the specific character of the images portraying Indian people. This specificity was determined by a combination of technical and 'authorial' factors, by the audience to which they were addressed — ranging from the general public in Britain to the family circle of wealthy Indians — by commercial considerations, and by current and evolving notions of authority, race and gender. The first two chapters seek to frame Bourne's work by first examining the political and cultural context of photography in India during the mid-nineteenth century, then by focusing on the context of the photographer's own production. The following three chapters are concerned with the study of the photographs themselves regarding what they depict and the questions they raise such as gender, racial identities and imperialism. The last chapter is an attempt to assess the significance of these photographs by comparing them with the work of Lala Deen Dayal, and highlighting different perspectives on Bourne's work regarding British India and Western societies. Placed in the context of the development of photography as a medium of record and representation, this thesis aims to show that Bourne's work is a significant historical source for understanding British cultural presence in post-Mutiny India.

Mathematical models have been applied to biology and health to gain a better understanding of physiological systems and disease, as well as to improve levels of treatment and care for certain conditions. This thesis will focus on two different methodologies to investigate models of health, namely delay differential equations andBayesian based data mining. The first approach uses delay differential equations to model the glucose-insulin regulation system. Many models exist in this area, typically including four exponential functions, and take a number of different forms. The model used here is a system of two delay differential equations with two time delays. The one delay form of this model has previously been widely studied, but less is known about the two delay system from an analytical view point. This work improves upon the existing models by incorporating Hill functions instead of exponential functions. The new model presented is studied for its appropriateness and robustness to changing parameters such as glucose infusion rate and insulin degradation. A local and global stability of the two-delay system is presented both in general terms and explicitly using Lyapunov functionals and linear matrix inequalities. The second method employs data mining techniques including a robust and transparent naïve Bayes classifier for classification and prediction of aspects of health. A study into prediction of post-stroke mortality is made on a data set of stroke patients. Interesting results are obtained for the classification of naturally arising mortality periods and an investigation into the role of age as a risk factor for post-stroke mortality. A wide range of risk factors are then investigated for significance which are used to build new predictive models. These two approaches have the joint aim of improving the understanding of aspects of health through mathematical modelling techniques. A new model of the glucose-insulin regulatory system is developed and for the first time an analysis of the global stability of the two-delay model by use of a Lyapunov functional is provided. The second approach sees typical and robust data mining techniques used to analyse medical data. New models for stroke mortality and prediction of diabetes and obesity are created, which review risk factors and also illustrate the benefit of data mining techniques for analysing medical data.

This thesis explores the impact of changes in health policy introduced by Conservative administrations in the period 1987 to 1995 on the definition, management and control of professional work within general medical practice. The research underpinning this work combined secondary analysis, large-scale primary fieldwork and qualitative research with clinicians and managers. The first stage of primary fieldwork was conducted during the period September 1994 to June 1995 and consisted of a postal survey of 750 practices across England and Wales. This was followed up with a second phase of research involving depth interviews with managers and clinicians, delivered in the period July to November 1995. This pluralist methodology sought to connect micro and macro levels of analysis in exploring the relationship between the state, professions and managers in primary care. The research explores the extent to which a number of professional freedoms have been challenged by policy change including political, economic and technical autonomy and the extent to which this had changed the position and rewards of managers in general practice. Employing a multi-dimensional approach to the analysis of power this thesis suggests that prevailing theories of a decline in professional power, based primarily on economic relations at the macro level cannot account for the complexity of relations found in UK general practice. Further, studies focusing at the collective level of bargaining between the state and the medical profession in the UK have over-estimated the impact of policy change due to a neglect of study at the micro level. Rather this study has revealed a complex picture of both continuity and change in which general practitioners have lost, retained and in some cases extended their power as a result of policy initiatives. Whilst professional freedoms have remained relatively intact, the impact of policy change on the occupation of Practice Management has been more significant, with prevailing discourses of `managerialism' creating gendered struggles over the definition and meaning of management in primary care. This work therefore calls for a multi-dimensional account of social life which can explain the complex interaction of differing sites of power, within which a wide range of power resources are deployed. Further this work would endorse a dynamic concept of power in which 'patterns of interaction' (Bradley 1999) are fluid and changeable rather than fixed and self-sustaining systems. It is argued here that constraints on social action are created by the history of past agency, embedded in institutions and social practices that both shape, and are shaped by the agency of individuals.