Summary of Aims. The aim of this project was to test the hypothesis that there are genetic risk factors separate from SOD1 gene mutations which can lead to ALS or modify phenotype, in sporadic and familial disease, in a population which was well defined clinically. To achieve this, the population attending the King’s MND clinic was chosen as the primary group to be studied. All those attending who consented, had clinical details entered into a database, and blood taken for genotyping. Statistical analysis of the database helped to define the clinical characteristics of the population. The number of potential genes which could be studied to test the hypothesis of disease causation or phenotype modification is vast. For this reason, three different studies were performed, each approaching the problem in a different way, and each testing specific genes in a hypothesis-led manner. The first study was an association study to test the hypothesis that the APOE4 allele is associated with bulbar onset ALS. This was chosen because ALS does not just involve the motor system, and with evidence of cognitive impairment in pseudobulbar palsy, and the association between the APOE4 allele and Alzheimer’s disease, this allele might be a phenotype modifier. An association study is not sensitive or specific and yields associations with low relative risk genes, but is comparatively simple to perform. The second study was a candidate gene study to test the hypothesis that mutations in the heavy neurofilament subunit tail are associated with the development of ALS. Pathological and animal studies implicate neurofilaments in the disease process, and the repeat domain of NFH would be expected to be prone to mutation. Candidate gene studies are problematic because unless the correct gene and disease are chosen, the study will be negative. They are specific but not sensitive. The final study used linkage techniques and haplotyping to test the hypothesis that a founder effect can explain the apparently recessive inheritance of a specific mutation of SOD1, Asp90Ala, when all other SOD1 mutations are dominant. All the major molecular genetic and statistical techniques were therefore used in various stages of the thesis to test the overall hypothesis, and the study has provided a unique opportunity to combine clinical and genetic data in a meaningful way.
Summary of Aims. Looking at the literature on this topic, we can see that there are a number of different theories on what has the strongest effect on an individual’s eating habits, and the main themes that emerge as barriers to healthy nutrition in low-income communities are cost and accessibility. There is with a noticeable gap in information regarding long-term behavior change following implemented interventions, and also, what specifically the individuals in these communities are looking for when it comes to improving their health through nutrition. Further complicating the issue is that every community is different. Where one type of program or intervention might be effective in a specific region in the northeast, might not work as well for low-income communities in the south. It is important to understand the big picture of what communities face when it comes to accessing healthy food, and the impact that has on their health status.
Summary of Aims. To investigate what the essential components of routine services in the community should be for people with intellectual disabilities and severe mental health problems. • To investigate whether some people with intellectual disabilities and severe mental health problems might need more intensive community services. If this was considered to be the case, then a further objective would be to investigate the characteristics of those service users. • To investigate what the essential components of more intensive community services should be for people with intellectual disabilities and severe mental health problems. • To investigate expert opinions regarding how some of the key community service components could be implemented and delivered. • To carry out a feasibility study of a particular service component for people with intellectual disabilities and severe mental health problems that had been identified as essential from the preceding studies. * See also Appendix I, for a flowchart of the overall MD (Res) Programme.
