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To examine the pathophysiological consequences of autoimmunity to TAG-1, CD4⁺ T cells and autoantibodies specific for TAG-1 were generated and their potential to induce EAE was investigated in a rat model. An adoptive transfer of T cells specific for the first two immunoglobulin domains of TAG-1 initiates an intense inflammatory response in both the cortex and spinal cord in the Dark Agouti and Lewis rats. This is particularly interesting as conventional models of EAE are of little help in investigating the pathomechanisms responsible for cortical tissue damage, as the cortex is only rarely targeted by myelin-specific autoimmune responses in this animal model of Multiple Sclerosis (MS). Moreover, when a demyelinating antibody like Z2 (anti-MOG) antibody was co-transferred with TAG-1-specific T cells it resulted in demyelination not only in the spinal cord white matter but also the grey matter and triggered demyelination coupled with macrophage infiltration in the perivascular areas of the cortex. This new model of cortical demyelination is exciting as it bears some resemblance with chronic progressive MS. However, two different monoclonal antibodies (4D7/TAG1) and 3.1C12) specific to TAG-1, when co-transferred with TAG-1 specific T cells, failed to mediate tissue damage in the CNS. Although the role of TAG-1-specific antibodies in EAE remained inconclusive from the preliminary experiments, this study clearly demonstrates TAG-1-specific T cells as a new tool to mediate EAE highlighting cortical pathology which can be exploited further to investigate the factors that control regional differences in the pathogenesis of inflammatory demyelinating lesions in the CNS. This new model might provide novel insights into the development of cortical pathology in MS patients and will ultimately guide to design therapeutic approaches in MS.

Background: Multiple sclerosis (MS) is a common, disabling neuro-inflammatory disorder, whose prevalence seems to be increasing. Objectives: The main aims of this thesis were to: (i) systematically review good quality MS prevalence studies and assess heterogeneity in prevalence rates; (ii) conduct a new prevalence study in Aberdeen, Orkney and Shetland to assess temporal trends, compare rates to other areas and describe demographic, clinical and disability data in prevalent MS patients. Methods: The systematic review used defined search strategies to identify references that satisfied inclusion criteria. The influence of time, latitude, diagnostic criteria, quality of case ascertainment and methods of classifying patients on age-gender standardised prevalence rates and sex ratios were analysed by uni- and multivariate regression. The new prevalence study identified all MS patients alive on 24/9/09 from defined general practices through multiple sources. Primary and secondary care records were used to confirm the diagnosis. Prevalence rates were standardised to 2009 Scottish population. A postal questionnaire survey was conducted to gain additional data, which allowed a randomised factorial trial of the effect of envelope colour/address labelling on response rates to be performed. Results: The review identified marked heterogeneity (I2 99.7%) in prevalence rates, partially explained by latitude (p<0.0001), prevalence date (p=0.009) and number of ascertainment sources (p=0.04). High and rising prevalence was recorded in Orkney [402/100,000 (95% CI 319-500)], the highest worldwide, Shetland [295/100,000 (95%CI 229-375)] and Aberdeen city [229/100,000 (95%CI 208-250)]. Male-to-female ratio was 1:2.55 (95%CI 2.26-2.89). Postal response rates to brown/white envelopes were not different [OR 1.17 (95% CI 0.81 to 1.68)] but hand-written address labels had a higher response than computer-generated labels [OR 1.22 (95% CI 1.06-1.40)]. Conclusions: This research showed that MS prevalence remains very high in northern Scotland and confirmed international observations of rising prevalence. Explanations include increased survival, improved diagnosis and probably increasing incidence.

This study was designed to explore the acceptability of social, business, and romantic relationships in counselor-client, professor-student, and supervisor-supervisee relationships. In addition, the study sought to determine whether professors and doctoral students in CACREP-accredited counseling programs responded differently to ethical boundary issues, and whether the differences in relationships between professor-student, supervisor-supervisee, or counselor-client influenced their responses. The study examined and compared the responses of participants to boundary issues on three different surveys. The results of the study revealed that personal relationships between counselors and clients were perceived to be less acceptable than relationships between professors and students and supervisors and supervisees. Personal relationships between professors and students were perceived acceptable at the same level as relationships between supervisors and supervisees with relationships between counselors and clients perceived as least acceptable. This research study revealed a significant difference between perceptions of participants regarding the social, business, and romantic relationships. Participants perceived the social relationships to be most acceptable, the business relationships to be more acceptable at a moderate level, and the romantic relationships to be least acceptable. Counselor educators and counseling doctoral students agreed regarding personal relationships in counseling in all but one of the six areas that were studied. A significant difference was found between counselor educators and counseling doctoral students in relation to the perceptions of personal social relationships. Counselor educators perceived personal social relationships between counselors and clients, professors and students, and supervisors and supervisees to be more acceptable than did counseling doctoral students. This study found that, among counselor educators, as their ages increased, their mean score on the Counselor-Client Survey increased. This suggests that as the counselor educators' age increased, their perceptions that counselor-client personal relationships were acceptable increased as well. In addition, older counselor educators perceived romantic relationships to be more acceptable between counselors and clients, professors and students, and supervisors and supervisees. This study provided information regarding the perceptions counselor educators and counseling doctoral students hold regarding the acceptability of persona l relationships in counselor-client, professor-student, and supervisor-supervisee relationships. Additional research is needed to determine where the limits should be set for personal relationships (social, business, and romantic) between counselors and clients, professors and students, and supervisors and supervisees.

There are many multiple-model (MM) target-tracking algorithms that are available but there has yet to be a comparison that includes all of them. This work compares seven of the currently most popular MM algorithms in terms of performance, credibility, and computational complexity. The algorithms to be considered are the autonomous multiple-model algorithm, generalized pseudo- Bayesian of first order, generalized pseudo-Bayesian of second order, interacting multiple-model algorithm, B-Best algorithm, Viterbi algorithm, and reweighted interacting multiple-model algorithm. The algorithms were compared using three scenarios consisting of maneuvers that were both in and out of the model set. Based on this comparison, there is no clear-cut best algorithm but the B-best algorithm performs best in terms of tracking errors and the IMM algorithm has the best computational complexity among the algorithms that have acceptable tracking errors.