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Background: Heart failure is a common clinical syndrome associated with major adverse symptoms and poor outlook for patients, and high costs for healthcare systems globally. This thesis examines four aspects of the clinical pathway of patients with heart failure in primary care. Methods: Routinely collected GP records are used to estimate the number of newly diagnosed heart failure cases by year. A qualitative interview study explores the patient experience of the diagnostic pathway. Survival analysis is used to determine prognosis of patients following a first diagnostic label. Finally, a screening study examines who develops heart failure over time. Results: The incidence of heart failure has been static at 2.3 cases per 1,000 person-years since 2006. Patients initially normalise their symptoms so delay seeking help, GP access is challenging and communication in secondary care, particularly delivery of diagnosis, could be improved. Survival rates are 81.5%, 51.6% and 29.5% at 1, 5 and 10 years, respectively, and have not changed over time. Screening provides an alternative pathway to identify patients with heart failure. Conclusions: Strategies to reduce the number of new cases of heart failure, enhance patient experience, improve survival and explore new diagnostic pathways should be important priorities for the NHS.

This thesis focuses on paper hangings, an hitherto understudied material in comparison to other components of the Eighteenth century domestic interior. Drawing on recent theories of consumption and the nature of domestic space, the thesis uses study of extant and reconstructed schemes, surviving papers and archival material to illuminate the material's increasingly important role in decoration during the second half of the century. Papers studied include Chinese papers and English papers in the Chinese style, English papers imitating architectural, sculpted and painted ornament and late century English and imported prints and panelled schemes. Three key issues are examined. Firstly, the thesis focuses attention on the structure of the trade, constructing a new model for understanding the way in which the manufacture, retailing, distribution and hanging of papers was organised. Examining the role of imports as well as the rapid expansion of the domestic trade, the thesis argues that control of this trade was contested by both new, and established, trades involved in decoration. Secondly, the role of design is analysed, particularly in terms of the relationship between imitation and innovation. Study of papers' sources further illuminates this issue, for example by examining how far English manufacturers sought to imitate Chinese originals and also how some Chinese papers rework European models. The relationship with other types of wall decoration and three dimensional ornament is also considered; the argument here is that far from merely copying printed designs, papers appropriated design sources from stucco, ceramics and textiles. Thirdly, and finally, aspects of consumption are examined. The thesis investigates how far the selection of paper supports the argument that the period witnessed increased differentiation of space, by gender or function. It questions easy distinctions between the choices of male and female consumers, arguing that both negotiated the materials' positive and negative associations.

This is an investigation by a participant researcher into the 'hidden world' of Further Education (FE). I became interested in how the many innovations, which have occurred in the past twenty years have made FE staff feel and how this effected their work and how they coped with what often felt like the conflicting demands of constant change. This is longitudinal insider research with a political edge as it is an examination of one of New Labour's major inclusion strategies, as it covers almost all of the twelve years they were in power. Over this period I have seen staff concerns change, as have their 'folk devils', and as lecturers and support staff went through different 'moral panics' during a period of massive change and uncertainty in the post compulsory sector. The original grounded theory type emergent categories and my own personal ontology lead me to adopt the position of a 'critical realist' where I have also attempted to incorporate a Feminist stance with some insights from sociological theorists like Bourdieu. Through the Literature Review I looked at the wider social and political issues of 'new managerialism', 'globalisation', 'proletarianisation', 'intensification of labour', the 'audit culture' and the casualisation and 'deprofessionalisation' of academic staff. These and other issues had emerged as possible reasons for the way staff said they felt in my interviews with tutors and my long term participant observations in three colleges and the results from one local stress survey and one national questionnaire of college managers. My conclusions are that many staff who choose to stay in FE are to a degree alienated but not anomic, they still believe in their role despite the changes and take pride and pleasure in their work, especially their interaction with students. The work place and division of labour are gendered both vertically and horizontally. Staff and trainers are unsure of the effectiveness of the new training but recognise that they need more skills to deal with the newer student groups. The different cultural capital, 'habitus' and 'fields' work against a common professionalism developing and these are unlikely to disappear.

Specific and consistent genetic rearrangements have been found to be associated with particular tumours. The observation of these genetic changes highlights areas of the genome which may be involved in tumorigenesis, providing an opening for insights into the molecular mechanisms involved. The presence of a specific genetic aberration may also define the diagnosis in certain tumours, or may be associated with particular prognostic significance in others. Ewing's sarcoma and PNET are members of a group of childhood solid tumours which may be subject to diagnostic difficulty. These tumours are characterised by the presence of a t(11;22) translocation, and the detection of this in a tissue sample allows a firm diagnosis to be made, facilitating appropriate treatment. In this study fluorescence in situ hybridisation (FISH) has been carried out on interphase nuclei using probes flanking the translocation breakpoint on chromosome 22 to visualise the translocation. With proper controls and statistical analysis a test has been established which can be used routinely in the diagnosis of Ewing's sarcoma and PNET. The initial diagnosis of neuroblastoma is not usually difficult, but the natural history of the disease varies greatly depending on whether certain genetic alterations are present. Deletions of chromosome 1p, amplification of N-myc and a near-diploid or near-tetraploid karyotype are associated with a poor clinical outcome, while those with a triploid karyotype have a good prognosis. Knowledge of these genetic data may influence the choice of treatment. In this study FISH techniques have been modified for use on fresh tumour imprints to produce a rapid and reliable method of detecting each of these genetic changes. A large series of patients has been studied and the results correlated with those obtained using conventional methods. The technique is now being used routinely in some centres.

The main theme of this work is the extremely close connection between British and American humanitarians during the nineteenth century. This age, which is more usually noted for unfriendly relations between the two countries, produced at the same time a generation of Anglo-American reformers bound to each other by many ties. This is exemplified very clearly in the influence of various American reformers who visited Britain at this period. In the first chapter the framework of this connection is discussed, which then leads to a more detailed description of the place of the reform movements in the British scene. In this chap¬ ter the importance of Scotland in the reform world, and its special relations with American reformers is stressed. Throughout the thesis, indeed, special reference is made to Scotland. The work and influence of various American reformers is then considered in detail. For anti-slavery William Lloyd Garrison and certain Negro abolitionists have been selected as best giving an insight into the radical wing of the British anti-slavery movement. For the peace movement, Elihu Burritt was easily the most notable reformer to visit Britain, as was John Gough the most colourful to advocate temperance. The visit of George Cheever does not merely show the continuing interest in anti-slavery but also the close links between British and American churchmen, and in some measure, too, it brings to a close the work of this generation of reformers. The influence of the Americans on working class and democratic movements is considered separately, since it was felt that their influence in this sphere was an important one, if less radical than might be expected. The final chapter contains an overall assessment of the influence of the Americans. That this was often destructive, but always provocative, is clear. The Americans might divide movements, but they always encouraged popular support. Their work, too, might be limited in scope, but it nonetheless had wide indirect repercussions, and sheds an invaluable light on the importance of British humanitarianism. But above all, the visits illustrate the close ties between the two countries, and the value of studying this connection rather than stressing the differences between Britain and America.

Listeria monocytogenes is an intracellular bacterial pathogen that has been responsible for many severe disease outbreaks resulting in multiple fatalities. L. monocytogenes enters the body through contaminated food and is known to contaminate fresh leafy produce such as spinach and lettuce. In the UK there are many stakeholders in the fresh leafy produce supply chain (FLPSC) including growers, processors and retailers, making the FLPSC complex and the management of bacterial contamination in the supply chain difficult. L. monocytogenes is sporadically detected in the FLPSC by routine testing, but currently, little is known about the strains of L. monocytogenes present in the UK FLPSC, their potential pathogenicity and phenotypic characteristics. Furthermore, data on L. monocytogenes survival in environments associated with the FLPSC, like horticultural soils and the leaf surface, is scarce and requires further investigation. Due to the potential risk of the bacterium, source tracking, risk assessment and understanding the ability of L. monocytogenes to survive in the FLPSC should be considered key factors in tackling L. monocytogenes contamination of fresh leafy produce and reducing risk to the consumer. Given the importance of these factors, 15 L. monocytogenes strains isolated from the UK FLPSC were characterised using a range of genotypic (MLST and WGS) and phenotypic (including biofilm formation and rates of swarming motility) methods. WGS revealed a genetically diverse population spanning two lineages but showed some indistinguishable pairs of isolates, suggesting cross contamination may have occurred in the supply chain. Following characterisation, selected isolates (from lineages I and II) were examined for their ability to survive in environments associated with the FLPSC including horticultural soils and spinach leaves. Results showed no differences in soil survival between strains, but strains were detected at a higher level (in sterilised soil) for longer in a clay loam soil compared to other types of soil in the short term (over 70 days). In contrast, L. monocytogenes was detected at higher levels in sandy soil using an illumina based NGS method in the long term. Washing contaminated spinach in chlorine water at operational levels (60ppm) was found to reduce L. monocytogenes number by 1log but electrolysed water (a chlorine alternative) showed lower efficacy at operational free levels of free chlorine, suggesting electrolysed water is not a viable alternative to chlorine wash at these levels. Survival on spinach leaves was influenced by temperature and whether the leaves were subjected to a chlorine wash, or not. L. monocytogenes populations grew to a higher level on contaminated spinach at room temperature vs. when contaminated leaves were refrigerated. This demonstrated the importance of maintaining refrigeration temperatures throughout the supply chain. At both room and refrigeration temperatures, washing spinach leaves in a chlorine wash meant that L. monocytogenes populations grew to a higher level over the shelf life of the spinach. In addition, the endogenous microflora present on ready to eat (washed) spinach was less diverse and abundant than spinach which hadn't been washed. Overall, the results of this work suggest that WGS technology should be phased into L. monocytogenes surveillance programmes in the FLPSC for purposes of source tracking and risk assessment so incidences of L. monocytogenes contamination can be controlled or reduced e.g. by cleaning and sanitation of affected areas. Furthermore, implementing this technology may give customers (retail) and consumers added confidence that growers and processors are informed of the L. monocytogenes risk in their supply chain and demonstrates a precautionary, rather than reactionary approach to consumer safety. Results from soil survival experiments suggest that L. monocytogenes found in the FLPSC can survive for extended periods in horticultural soils and thus, it was concluded that soil is a potential source of contamination in the FLPSC. However, the level of L. monocytogenes in horticultural soil declines quickly and transfer of the bacteria to soil on a large scale (in the field for example) is unlikely, suggesting that this risk of contamination from this source is low. Furthermore, sporadic contamination from this source is hard to prevent due to the intimate nature of the growing environment (soil) with fresh produce products. Results from the final chapter of this work show the chlorine wash at operation levels for the UK FLPSC is an effective sanitiser with regards to L. monocytogenes in a pre-wash contamination scenario. On the other hand, it was shown that chlorine wash may enable L. monocytogenes populations to reach a higher level on spinach leaves when the leaves have been contaminated post-wash by reducing the abundance and diversity of endogenous leaf microflora.

Using bioinformatics we have identified stm3071 as a possible regulator of anaerobically induced genes involved in metal homeostasis (Price-Carter et al., 2001) and the aim of this study is to determine the function of stm3071 and define the conditions that induce its expression. Cobalt is required for incorporation into cobalamin (vitamin B12) which is important during S. Typhimurium infection. Vitamin B12 is synthesised de novo under anaerobic conditions and is required for metabolism of 1,2-propanediol and ethanolamine which act as sources of carbon and nitrogen when Salmonella is in the gut (Raux et al., 1996; Thiennimitr et al., 2011). Therefore, sensing Co2+ from the environment, and maintaining Co2+ homeostasis, to avoid metal-mediated toxicity, is required for vitamin B12 biosynthesis. Using λ-red based mutagenesis we have constructed a deletion mutant in order to investigate the function of stm3071. We examined the effect of mutation on the utilisation of 1,2-propanediol under anaerobic conditions and ability to produce vitamin B12. We have also tested the effect of mutation on tolerance to cobalt both aerobically and anaerobically. In order to monitor conditions in which Pstm3071 is switched on, a Pstm3071::lacZ transcriptional fusion was constructed in plasmid pRS415. Levels of β-galactosidase activity were measured in the presence of cobalt in both Δstm3071 and SL1344 (wild type strain) under anaerobic conditions. Anaerobic growth experiments and B12 assays showed that stm3071 is not essential for growth or synthesis of vitamin B12. In addition, cobalt tolerance in both aerobic and anaerobic conditions was unaffected. However, as measured by β-galactosidase assay, our data suggests that Pstm3071 expression is induced in the presence of cobalt in the deletion mutant. In contrast, we observed no difference in expression of Pstm3071 in the presence or absence of cobalt in SL1344.

The food-borne pathogene Listeria monocytogenes has been considered a significant threat to human health worldwide. It mainly infects individuals suffering insuffecint immunity such as pregnant women. During pregnancy, L. monocytogenes is capable of causing a serious damage to the mother and the fetus. It can spread to different organs including the placenta via adaptation to interacellular lifestyle. To maintain pregnancy, the levels of the hormones progesterone and β-estradiol increase and reduction in hormone levels was proposed to be associated with fetal death and abortion. The objectives of this project therefore were to investigate the role of pregnancy hormones on the growth and virulence of L. monocytogenes, and to identify bacterial genes with possible roles in binding to pregnancy hormones. It was obsereved that the growth of L. monocytogenes in the presence of progesterone under anaerobic condition was affected by the action of the hormone and the effect was dose/time-dependent of exposure as increasing concentrations showed greater effect on the bacterial growth. Interestingly, bacterial growth was restored within 24 h of exposure to the hormone. In parallel, a Tn917-LTV3 insertion library was constructed and a number of mutants isolated that had reduced growth in the presence of β-estradiol were identified. However, reduction in growth was not microbiologically significant. Furthermore, bioinformatics analysis was performed to identify listerial genes with possible role in hormones degradation. It was observed that L. monocytogenes encodes for a protein that is possibly involved in steroid degradation; therefore, gene expression and a clear-deletion mutant were performed to test this hypothesis. This revealed no significant role of this protein in the growth restoration observed in the presence of progesterone. Also, the deleted gene was investigated of its ability to reduce NADPH in the presence of a possible substrate (progesterone, β-estradiol). This showed that this gene could possess an enzymatic activity toward pregnancy hormones. An attempt to purify this protein for further investigation was performed and protein expression in a soluble form was unsuccessful. The findings presented in this thesis represent an important view when considering the relation between pregnancy hormones and L. monocytogenes; however, further investigations of hormone-degrading proteins from L. monocytogenes are needed. This knowledge may form the basis of a therapy to protect pregnant individuals.