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Neuromesodermal progenitors (NMPs) are bipotent progenitors, located at the caudal end of the embryo and are essential for axis formation. These stem cell-like progenitors possess the ability to self-renew and differentiate to both mesodermal and neural lineages, such as skeletal muscle and spinal cord derivatives. These progenitors arise at E8.5 and are localised in the caudal lateral epiblast (CLE), a posterior region of the embryo near the primitive streak. Later in development, they reside in the tail bud until cessation of axial elongation at E13.5. Throughout these stages NMPs are characteristically marked by co-expression of T(Bra) (Brachyury) and Sox2. This characteristic is also present in in vitro NMPs, which can be derived from Epiblast Stem Cells (EpiSCs) through treatment with Wnt/β-catenin signalling agonists and Fgf2, which simulates their in vivo environment. Protein and mRNA profiling of NMPs and mutant phenotypes in vivo supports the hypothesis that a non-canonical Wnt pathway, the Wnt/Planar Cell Polarity pathway (PCP) could be involved in NMP fate decision and/or maintenance. This thesis focuses on understanding more about the role of PCP by aiming to identify the spatio-temporal profile of Wnt/PCP pathway components in NMP regions during axial elongation, as well as determining its role in NMP behaviour through manipulation of this pathway via in vivo and in vitro assays Employing in situ hybridisation and immunohistochemistry techniques, key Wnt/PCP components, including Pk1, Vangl2 and Ptk7, were confirmed to be present in in vivo and in vitro NMPs, thus, providing strong evidence that Wnt/PCP may be involved regulating NMP behaviour. Disruption of Wnt/PCP signalling through overexpression of Wnt/PCP components was tested in refined in vivo and in vitro assays. Overexpression of Vangl2 and Ptk7, but not Pk1 in NMPs regions in vivo resulted in loss of contribution to neural lineages, as well as lower contribution to NMP regions themselves. Similarly, Wnt/PCP components were disrupted in vitro through generation of dox-inducible overexpression cells lines for Wnt/PCP components. These lines were used to generate NMPs from an optimised novel alternative source Epiblast-Like Cells (EpiLCs), however no clear affect to lineage was observed. Overall this work has successfully advanced our knowledge of Wnt/PCP mediated control of NMP differentiation and maintenance, and provided a finer grained description of the relationships between them.

Sign language has become increasingly popular as a means of language intervention for the mentally handicapped. Much research has centred on various aspects of single sign acquisition, but there is a lack of detailed and systematic research on the acquisition of more complex levels of sign use. The majority of work in this area fails to use or report the specific methods employed. One study, however, by Karlan et al. (1982) did introduce a potentially useful technique, derived from Miniature Linguistic Systems research, that was specifically aimed at establishing the use of generalised, recombinable, two-sign combinations. The aim of the research in this thesis is to investigate aspects of the technique, termed 'matrix training', with special emphasis on areas of generalisation. The research involved a series of five, long-term, school-based teaching programmes using children classified as 'Severe Learning Difficulties'. A single-subject, multiple baseline/probe methodology was employed. Training and testing sessions were alternated in order to follow the emergence of any generalised responses. Each separate study examined specific areas of generalisation associated with the technique. Results indicated that matrix training was successful, within certain conditions, in establishing the use of productive, expressive, two-sign combinations over a heterogenous group of children, and using three differnet forms of combination. There was also evidence for generalisation beyond the original training situation, and of generalisation which enabled the children to incorporate novel elements into their productive responses. Consideration was also given to the children's comprehension of relationships encoded within two-sign combinations in the form of word/sign order information. In the reversible object-location combinations used, it seemed unlikely that the children used sign order to identify object or location items, but rather used their own 'nongrammatical' strategies. Consideration was also given to how, or if, matrix training procedures could be used to establish the use of sign order in this manner. Overall, mentally hadicapped children, who do not typically use expressive sign (or word) combinations, can under certain circumstance be brought to use productive sign combinations by systematic teaching procedures of the kind described. These need to be highly contrived if they are to be effective, and what is learned may be sensitive to the precise characteristics of the matrices used. The potential role of matrix training within language intervention is seen as only a part of a more general sign programme. Discrete-trial matrix training procedures could be used to establish the structure of the two-sign combination, while incidental learning could develop the use of combination within the child's natural environment. Evidence from this research is favourable for this type of combined approach within sign language intervention.

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The aim of this dissertation is to explain how elective surgery patients choose between the public and private hospital sectors in the United Kingdom, and to analyze government policy changes which affect this choice. First the choice between the public and private sectors is modeled for the case where there is no private insurance available. The model takes into account the different rationing mechanisms used by National Health Service (NHS) and private hospitals to allocate surgery among patients. Private hospitals charge a price and ration on the basis of willingness to pay , while NHS hospitals , which face budget limits, ration on the basis of clinical need and require patients to wait for surgery. Consequently, a patient's choice of sector depends on her income and her level of clinical need. A simulation model is used to compare the efficiency and equity of two policy measures designed to raise the number of people receiving elective surgery : an increase in NHS funding and a subsidy to the price of private surgery. The subsidy is shown to be more efficient and the NHS funding increase more equitable. Within the same framework an expected utility model of the demand for private health insurance is developed. Two cases are analyzed: the case where individuals have no information about their future need for elective surgery and the case where they have partial information. In each case it is shown that for a given insurance premium there is a threshold level of income above which people buy insurance. It is also shown by simulation that in each case the insurance company can set a premium that allows it to break even. Finally the two models are combined. This enables the efficiency and equity of an increase in NHS funding, a subsidy to private care and a subsidy to private insurance to be compared in a situation where some private patients have insurance to cover the cost of their surgery. The NHS funding increase is shown to be most equitable , and depending on the definition of efficiency chosen, one of the two subsidies is most efficient.