Possible mechanisms of action of the anti-ulcerogenic properties of the hormone calcitonin and some related peptides have been investigated. The hypocalcaemic actions and the actions on indomethacin-induced gastric erosions of calcitonin, icatacalcin and calcitonin gene-related peptide (CGRP) were found to be very different. Whilst calcitonin was shown to have both hypocalcaemic and anti-ulcerogenic actions, katacalcin demonstrated only an hypocalcaemic action, and CGRP showed neither of these actions. The results indicate that anti-ulcerogenic activity is a property of the calcitonin molecule alone and cannot be explained solely by the hypocalcaemic activity of calcitonin. Methodology was developed to measure the glycoprotein content of the whole stomach as an index of changes in the gastric mucus. Indomethacin significantly reduced the glycoprotein content of the stomach, whilst calcitonin reversed this reduction to near normal levels and carbenoxolone sodium to significantly higher than normal levels. Despite this reversal, carbenoxolone sodium failed to reduce the ulceration produced by indomethacin. In contrast, calcitonin significantly inhibited the indomethacin-induced ulceration. An increase in mucus production alone is therefore insufficient to account for the anti-ulcerogenic effect observed. Of the several methods of measuring gastric blood flow evaluated, none proved successful under the experimental conditions imposed. Intracerebroventricular injection of low doses of calcitonin produced greater inhibition of indomethacin-induced ulceration than administration of the same dose by the subcutaneous route. The results suggest that following intracerebroventricular calcitonin administration, part of the anti-gastric erosive action must be mediated via the central nervous system, possibly by an action on gastric acid secretion. Isolated rat stomach studies demonstrated that calcitonin reduced basal hydrogen ion output and also that induced by indomethacin, and pentagastrin in the presence of indomethacin or bile salts. A calcitonin-stimulated increase in bicarbonate secretion may be suggested to explain these results. A mechanism for the gastrointestinal action of calcitonin is postulated.

Ongoing research has identified a potential disconnect in academic and pedagogic expectation between academic staff and students. At the same time a context of higher tuition fees and changing student expectations renders this relationship even more important to the success of higher education institutions. This research investigated the sources of student expectations for the pedagogic relationship, the alignment between staff and student expectations and the potential impact of expectation fulfilment and frustration on the student experience. The study used the Psychological Contract as a theoretical framework, responding to recent calls for the further use of psychological contracts in education. The author has taught business in both secondary and university contexts for a number of years. This experience informed the phenomenological positioning of the thesis, its focus, its location in a large post -’92 business school, its mixed methods and an analytical method (template analysis) which has enabled both anticipated and emergent themes to be explored. Data was collected from a sample of students at regular intervals throughout their first year of study and from staff. Both exploratory statistical analysis of survey data and template analysis of interviews suggested that staff and students’ initial expectations broadly concur. However the practical implications of such notions as ‘independent learning’ develop significantly over the first year and it is contended that pre-entry expectations are significantly influenced by students’ experience of the pedagogic relationship at tertiary education level. The initial pedagogic psychological contract changes significantly over the first year as post entry experiences (or the ‘reality shock’) reshapes and reconfigures their expectations. The research developed a series of recommendations to both secondary schools and universities to improve the management of expectations.

No description available.

This thesis explored the factors contributing to the employability and identity development of occupational psychology graduates at various career stages. A mixed methods approach was taken to achieve three broad aims of the professional doctorate: 1) raising awareness of employability within the occupational psychology (OP) profession; 2) improving theoretical understanding of employability applied to a domain specific occupational sample; and finally 3) enhancing the professional practice of the thesis author. A qualitative study using focus group methodology (N=6) and thematic analysis identified barriers and facilitators to OP employability culminating in six core themes of ‘identity, ‘continuing professional development’, ‘making a difference’, ‘adaptability’, ‘evidence-based practice’ and ‘external environment’ (study 1). These themes were translated into an Occupational Psychologists Facilitators to Employability Scale (OPFES) which was assessed for its psychometric properties (N=88) using exploratory factor analysis. This study also detailed the development of a Subjective Career Satisfaction Scale (SCSS) (study 2). A revised version of the OPFES and measures of employability antecedents (Competence and Psychological Capital) and career success were distributed to the OP community (N=185). An analysis of the demographic data detailed the variety of OP careers. This study emphasised the potential challenges in creating a strong professional identity (study 3). Structural Equation Modelling determined the relationship between employability and career success (objective and subjective) where final models suggested different relationships between employability antecedents and objective and subjective career success (study 4). Finally, a narrative thematic analysis of OP stories (N=20) concluded the thesis (study 5). This study revealed the presence of five identity types: ‘learners’, ‘networkers’, ‘compromisers’, ‘achievers’ and ‘career builders. Each type was present in the career stories adding further support for the concept of ‘career identity complexity’. Overall, findings indicated that the career of an OP graduate was varied, that multiple employability antecedents could enhance career success and that a diversity of strategies were utilised in identity formation. Support was provided for Career Construction Theory and the influence of human capital and personal resources in employability. Reflections on how the research outcomes have impacted on the thesis author’s professional development are discussed throughout. The research programme contributes an evidence base for interventions that can inform MSc curriculum and the ongoing career and professional development of OccPsychs.

Partnership is a dominant theme of public policy and service provision in England and in other western countries. It is also a concept that remains relatively under-researched and under-theorised, especially with respect to conceptualising underlying relational processes that can shape conflict and consensus within partnerships. This thesis draws on a richly textured ethnographic study, using an in-depth casestudy of a voluntarily-founded, network-like, cross-sectoral partnership, which aimed to develop and implement a community learning centre in the village parish of Broadley, located in the English Midlands. The research sees fieldwork conducted over twenty-four months, using multiple methods of qualitative data-generation including the observation of partnership meetings and activities, semi-structured interviews and the collection of partnership artefacts (meeting minutes, funding bid document, emails). It presents an ethnographic view of the inner workings of one partnership and follows its entire lifecycle. This partnership was not sustained and did not realise the vision to which it aspired. A central concern of this thesis is to investigate the development of conflict and consensus within partnership practice. The contribution of the thesis is to tease out how these elements are understood. This study challenges naive texts that prescribe simplistic, recipe-based formulas for achieving partnership success. Instead, it illustrates what can happen when partners do not develop sufficiently strong and balanced sets of social ties between one another. Consequently, this thesis sets up a new research agenda focusing more specifically on issues of community overlaps, identities and social ties. This thesis has value in terms of providing a deeply relational account of challenges facing the development of one cross-sectoral, network-like partnership. It draws together insights from partnership literature, community literature and fieldwork,and provides a strong basis from which further research can be developed.

The Maptaphut Industrial Estate is located on the Gulf of Thailand, Rayong Province. The area, which has been designated as a main centre for the petrochemical industry currently occupies 16 sq km and comprises petrochemical plants, chemical and fertilizer plants, refineries, construction plants, and steel industry; there are also residential and commercial areas (IEAT, 2004). There is a significant population around the site, with 24,000 inhabitants in the immediate vicinity according to Jadsri et a/ (2006). The estate has been held responsible for deaths and hospital admissions due to leaks and accidents dating back as far as 1997. Whilst the environmental and health and safety performance of the estate as a whole has significantly improved over recent years, there are still significant outpatient admission rates to Maptaphut hospital for respiratory illness, as recently reported by Jadsri et al. (2006), raising the question of whether local emissions are significantly contributing to ill health, or whether general background concentrations of pollutants from nearby road sources and from Rayong City are the main contributions. The main aim of this research, therefore, was to accurately model the dispersion of pollutants from the estate, and to attempt to quantify the health impacts of these emissions. The specific objectives of this study were to (a) to characterise meteorological conditions in the Maptaphut area; (b) to develop a multiple linear regression statistical model to characterise and predict atmospheric pollutant concentrations in Maptaphut; (c) to investigate the relationship between air pollution and ill health in Maptaphut using a multiple linear regression statistical model; (d) to evaluate the effectiveness of Gaussian and Computational Fluid Dynamics atmospheric dispersion modelling software packages in predicting ground level pollutant concentrations at points around the industrial estate and (e) to use the results of the dispersion modelling studies to assess the contribution of the industrial estate to the overall atmospheric pollutant load in the Maptaphut area, and from published health impact factors, to assess the overall health impact of the estate. The first objective was to characterise the environmental status, trend, and impacts of air pollution during the period 1998 to 2007. The estate is located in the coastal area; thus, the role of the sea-land breeze has a significant role in the dispersion of air pollutants harmfulness. Data collected for the Maptaphut Industrial Estates area, including regional, temporal and spatial considerations included: meteorological data from 100-metres tall meteorological mast; ambient air quality data from three ambient air quality monitoring stations; industrial emissions data; traffic volume on nearby major roads; and outpatient admissions data at the Maptaphut and Rayong hospitals. Comparisons with the ambient air quality in the Bangkok area were made, and the daily and yearly trends in concentrations of the main air pollutants were analysed. Multiple linear regression models correlating pollutant concentrations with respiratory outpatient admissions rates showed that 03, PMio and NO were statistically significant determinants. The overall correlation had a coefficient of Determination (R2) of 41.4% for one week average data, increasing to 51.2% when air temperature and %RH were included. Accumulation effect of pollutants up to four weeks period exposure does not appear to have an effect. A basic health impact analysis study using the ADMS modelled concentrations and the WHO AirQ tool, along with default risk factors, showed that emissions from the Maptaphut industrial estate account for almost all of the NO2 and SO2 related respiratory illness and between 10 and 27% of the PMio related admissions; this actually represents less than 2% of the total respiratory admissions for this area.

Disability has a profound impact on a person's quality of life (QOL). Rehabilitation, a process by which measures are taken to improve the QOL of people with disability (PWD) uses several approaches. Community Based Rehabilitation (CBR) is one such approach, which evolved because of the magnitude of the problems of PWD in the community, the limited availability and poor access of rehabilitation services. Research in CBR is limited and hence there is lack of evidence on outcomes in CBR. Considering the need for more information on current practice and research in CBR, the researcher studied the effectiveness of an integrated model of CBR set up in the Christian Medical College, Vellore, South India (VCBR). The objectives of this study were to generate theory on the value of an `integrated model' that uses an educational strategy and to explore the value of secondary and tertiary care services for PWD in a community based rehabilitation programme for the improvement of their quality of life. A 'Case Study' design was used. The practitioner role of the researcher added an important component to this study. An in depth study of 20 PWD, their immediate family members, concerned trained volunteers (LS) and others who were involved in VCBR was undertaken in addition to observation and reference of documents. Qualitative Analysis was undertaken based on the Framework Technique. The quality of life of PWD and the role of secondary and tertiary care centres in VCBR were studied. In this study the realist approach, which takes note of the contextual elements in the evaluation of case study materials, showed that overall QOL of PWD will not improve to its full potential if solutions are mooted from polarized viewpoints. The study found that an integrated model of CBR that uses an educational strategy, has good links with secondary/tertiary care centres and makes use of social network/capital, which is available in the community, improved the overall QOL of PWD.

Acute lymphoblastic leukaemia (ALL) is the commonest of the childhood cancers, but thankfully responds well to chemotherapeutic agents, with 80% of children achieving long-term survival. However, for the remaining 20% who relapse, outcome is bleak. Increasing knowledge and understanding of pharmacogenetics indicates that constitutive or acquired resistance to the drugs used in the treatment of cancer contribute to relapse. Methotrexate (MTX) is one of the most important drugs used in the treatment of ALL and the work presented here contributes to the body of knowledge relevant to the understanding of resistance to this drug. The aim of this research is to determine if changes in genes involved in folate metabolism contribute to methotrexate resistance and subsequent relapse of childhood ALL. The reduced folate carrier (RFC) is required to transport methotrexate into the cell where it competitively inhibits dihydrofolate reductase (DHFR) and other key enzymes of folate and 1-carbon metabolism. Following the design of primers and optimisation of PCR amplification, the entire coding regions of both RFC and DHFR were screened for novel SNPs or mutations using denaturing high performance liquid chromatography (DHPLC) on genomic DNA from 40 normal and 40 relapse childhood ALL patients. Ethical approval for use of the samples was granted under WCRLEC no347 and reference 2002/111 for normal and relapse samples respectively. The relapse group was made up of 29 males and 11 females with an average age of 6.59 years (range 0.8-14.1) and was made up of 5 T-cell; 30 B-cell; 4 mixed lineage; and 1 null classification. The screening method was shown to be sufficiently sensitive to detect single base changes. Several of the exons in both genes have a high G-C content and required destabilisation agents and/or use of a new DNA polymerase (OptimaseTM) to achieve sufficient PCR amplification. Dimethyl sulphoxide (DMSO) and betaine were shown to be effective agents which did not interfere with subsequent DHPLC. The results show that somatic mutations in the coding sequences of RFC and DHFR are rare in relapsed ALL and that while it is recognised as a mechanism of methotrexate resistance in vitro, it is unlikely to contribute to relapse in children with ALL. However, for one patient who suffered multiple relapses, a novel acquired mutation was identified in the 5'-UTR of the RFC-1 gene (C-37T). The significance of the C-37T mutation on RFC transcription requires further study, but it may decrease RFC mRNA quantity or stability and thus protein levels. DHPLC analysis also detected common SNPs. In terms of frequency, there were no significant differences between relapse and normal samples for the genotypes; RFC G80A (38.3% G/G; 49.4% G/A; 12.3% A/A in 81 normal samples; 31.8%; 56.8%; 11.4% respectively in 44 relapse samples; x2 p = 0.656); RFC C696T (97.8% C/C; 2.2% C/T; 0% T/T in 45 normal samples; 92.5%; 5%; 2.5% respectively in 40 relapse samples; x2 p = 0.458). However, there was a significant difference in the 5'-UTR -19 base pair deletion in the DHFR gene between the normal and relapse groups (0% WT/WT; 100% WT/-19 or -19/-19 in 45 normals; 26.7% and 73.3% respectively in 15 relapse samples; Fisher's exact probability p = 0.017) and needs to be confirmed in a larger cohort. Estimated copy number and the probability of loss of heterozygosity (LOH) were generated from the Affymetrix 50K SNP microarray for the RFC, DHFR and other genes involved in folate metabolism using gDNA from 73 presentation and 20 relapse childhood ALL cases. Mann-Whitney non-parametric comparison of the presentation and relapse data showed that for estimated copy number, statistically significant differences were seen for MTHFR (p = 0.0072), MS (0.0025), FPGS (0.00048), TS (0.00046), CBS (0.0002) and RFC (0.0001). When the data at the nearest SNP location to the gene was presented as a scatterplot, the difference in each case was due to a bimodal distribu...

The purpose of this research is to assess the function, form and content of knowledge sharing in communities of practice, social networks and the use of collaborative technologies in Third Sector community networks in the North East of England. This is a significant area worthy of detailed examination due to the acknowledged relationship between communities of practice, social networks and the use of collaborative technologies. These three domains have been examined separately by others and suggestions have been made as to relationships between them but few, if any, studies appear to have used case-based evidence to explore how these relationships add value to knowledge sharing. The research addresses the following research question: To what extent does the use of collaborative technologies in communities of practice and social networks, in the Third Sector of the North East region, add value to face- to-face knowledge sharing and how may this be measured? In order to answer the research question a qualitative holistic case study approach based upon three case studies in Newcastle upon Tyne, South Tyneside and Sunderland has been utilised and grounded theory is used to formulate theory from the observed and analysed practice of the case studies under investigation. The conclusion is drawn that when value is added to knowledge sharing it is relative to the strength of several key variables, including, reciprocity, trust, the strength of network ties and the ability to integrate the use of collaborative technologies into ongoing activities. To aid analysis of the presence and strength of these variables a working paradigm has been designed and developed. Case studies are analysed through this paradigm leading to the development of a theory of knowledge sharing in the Third Sector.

The last fifty years has seen an increase in the production of synthetic or artificial enzyme substrates used to identify and quantify enzymes. These substrates have found applications in a range of biomedical science disciplines. Used in biochemistry and clinical chemistry to identify and measure enzymes, some of these substrates have been adapted for use in microbiology, particularly bacterial diagnosis and, in more recent years, molecular biology. The use of artificial chromogenic and fluorogenic enzyme substrates to identify certain bacteria is now common place in medical laboratories worldwide. Not all bacteria can be identified with existing and commercially available artificial substrates. Some of these can be slow to yield results, imprecise, expensive or require a technical method too complicated to provide a viable laboratory test. Therefore, the search for new, more efficient, biochemical tests has progressed, with novel substrates and inventive applications being developed continually. In this study, core compounds were synthesised by various condensation reactions and their characteristics evaluated with respect to colouration/fluorescence and possible enhancement of these properties by metal chelation. Promising candidates were selected for glycosidation, via modified Koenigs-Knorr reactions, in an attempt to synthesise artificial substrates. Several commercially available core molecules were also subjected to glycosidation. The more successful substrates included glycosides of alizarin, nitrosalicylaldehyde and 3- hydroxyflavone. The galactoside of nitrosalicylaldehyde was evaluated in solid agar media and found to be selective for certain Gram-negative bacteria. When similarly investigated, the 3- hydroxyflavone-β-D-glucoside showed the possibility of being used in a procedure for the isolation of the clinically significant pathogens including Listeria monocytogenes. The enzyme kinetics of β-glucosidase with this substrate were also determined in a novel fluorescence assay and compared favourably to the well documented 4-methylumbelliferyl-β-D-glucopyranoside. Alizarin-2-yl-β-D-galactoside and p-naphtholbenzein-β-D-galactoside were successfully utilized for the screening of recombinant and non-recombinant Escherichia coli transformants produced routinely in molecular biology. Aminopeptidase substrates have been shown to be useful for the detection of enzymes which hydrolyse peptides that are specific to certain bacteria. To allow the evaluation of novel aminopeptidase substrates, that were to be subsequently synthesised, a cost effective, large scale source of recombinant leucyl aminopeptidase enzyme was developed via gene cloning techniques. Consequently, the products of this study may serve a beneficial purpose in future enzymatic investigations, medical diagnosis and molecular biology.