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The analysis of the geographical variation of disease has been part of the subject of epidemiology since its beginnings. However, it has not been the subject of much statistical research until the late 1980s when it became computationally feasible to examine the spatial structure. In thesis three problems of geographical epidemiology are examined, namely: 1. A simulation study which examines how different models used for disease mapping perform under various 'true' relative risk surfaces. 2. A new model for disease mapping is proposed which is based on the spatial variation being split into two different types of autocorrelation. These different types of spatial autocorrelation can be used in order not to over smooth any rural/urban divide which might exist in the dataset. 3. A new model is proposed for the examination of clustering in the spatio-temporal domain. Although a number of different tests exist for the detection of clustering in spatio-temporal domain, to date, very little has been done on the modelling of the clustering.

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The object of this thesis is to present an epidemiological study of maladjustment in children drawn from a sample population. The work has been carried out as part of a more extensive longitudinal study of morbidity in childhood which has come to be known as the Newcastle Thousand Families Survey. Before describing the work upon which this thesis is based I would like to desoibe briefly the historical development of the present concepts of maladjustment and the approach to its study and treatment. In order to appreciate the background of the present work it will also be necessary to give some account of the City of Newcastle, from which the sample was drawn, and of the development of the Thousand Families Survey.

The cross-linked PhD study dataset comprises information on blood component use within a subset of Scottish hospitals that received approximately 48% of the red blood cell units delivered by the Scottish National Blood Transfusion Service in the year 2000. The dataset contains 41,431 transfusion day records of used units that represent 21,309 transfused patients and 60,130 used red blood cell units, 4,795 used platelet units, 9,446 used fresh frozen plasma units, and 1,7598 used cryoprecipitate units. For red blood cell, platelet and plasma use, few patients were intensely transfused with a large proportion of blood component units. 13,894 (23%) red blood cell units were attributed to 4,664 clinical events defined as red blood cell-using procedures; 7,286 (12%) red blood cell units were attributed to 726 patients with a diagnosis of haematological disease. The remaining 65% of red blood cell units were attributed to case groups which, though not fully classified, include patients with multiple transfusion day records and/or multiple SMR01/cancer/death records, patients with malignant neoplasms (other than those defined for haematological case group), patients with markers for gastrointestinal bleeding, and elderly patients. The data was also used to describe blood component use by age, and further, used to model the effect of the aging population on the demand for blood. Other potential applications of the study dataset relating to blood use modelling are also described. The results can be used for future planning and to inform guidelines and policy, with the aim of changing practice and promoting the appropriate use of blood.

Objectives: (i) Describe the geographical distributions of three indicators of male reproductive health in Scotland (i.e. testicular cancer, cryptorchidism and hypospadias); (ii) Describe the conjoint geographical distribution of the three indicators specified in (i); and (iii) Identify explanatory factors that might account for the geographical distribution of male reproductive health in Scotland. Methods: An epidemiology study modelling the geographical distributions using routinely collected data of the three indicators. Results: There are similarities in the spatial pattern of the cryptorchidism and hypospadias relative risks, with both conditions having clusters of high relative risks in the East and South-West of Scotland. The spatial variation of the testicular cancer relative risks is not similar to the other two conditions nor is it conclusive that it, has a distinct spatial pattern. The relative risks of the postcode sectors for all the indicators are associated with radon measurements and the rural/urban indicator. The spatial analysis of individual information concerning the cryptorchidism cases indicate that the spatial variation of the relative risks might also be explained by individual information; namely maternal age and co-morbidity with hypospadias. Conclusions; There does appear to be geographically varying risk factors associated with these three conditions. Furthermore, as the spatial variation of cryptorchidism and hypospadias is similar it is likely that they have some common aetiology. As the same risk factors were found to be associated with testicular cancer and the congenital malformations, then this carcinoma appears to share some aetiology with cryptorchidism and hypospadias. Therefore there are geographically varying risk factors whose exposure occurs <i>in utero, </i>that are associated with all three conditions, providing some evidence to support the proposed hypothesis. Further studies are required to investigate the associations between all the disease/conditions of male reproductive health and the various potential risk factors.

Between 1950 and 1999 the Scottish death rate, standardised to the 1950 population, declined from 13.1 per 1000 to 7.8 for men and from 12 per 1000 to 6.3 for women. The main aim of this thesis has been to establish the key influences on this doctrine. Thomas McKeown examined the decline of mortality in an earlier time period (up to the 1970s) and concluded that: falls in deaths from infectious diseases were responsible for the majority of the decline in mortality rate; and the main influence on their decline was standards of living, in particular diet. The causes of death which contributed most to the decline in mortality rates 1950-1999 were established by digitising GRO(S) mortality records and calculating ‘potential lives saved’ . This method allows an estimate to be made of the number of deaths which would be expected to occur in 1999, taking into account changing age structure, if the death rates from 1950 still applied. Tuberculosis (TB), stomach cancer (SC), ischemic heart disease (IHD) and stroke were selected as case studies; these accounted for over 70% of the decline of male and female mortality. The trajectory of decline in these causes of death was then considered in detail and set in social and medical context. The thesis has reached an alternative conclusion from that of Thomas McKeown. It is argued that improving standards of living were responsible for some of the decline in SC and haemorrhagic stroke mortality, and the pre-1950 decline of TB; however, the main influence on the decline of TB, IHD and ischemic stroke mortality post-1950 was medicine. Using the wider definition of the influence of medicine adopted in this study, medicine is considered to account for the majority of the decline in the identified causes of mortality. Medicine has, at last, delivered important contributions to the life expectancy of the Scottish population.

Prevalence rates of type 2 diabetes and impaired fasting glyceamia (IFG) in Sri Lanka are high and an increasing number of people are succumbing to disease. Identifying people at risk of developing complications is a healthcare priority of the county to prevent morbidity and mortality. Type 2 diabetes is familiarly aggregated and maternal influence for disease transmission has been observed in European countries but not in South India. The severity of periodontitis is reported to be high when diabetes control decreases but data relating to periodontitis as a complication of diabetes is not present in this population. Periodontal associated genotype (PAG), presence of allele 2 of both {ILIA (+4845) & IL1B (+3954)}) is positively associated with periodontal disease in some populations but ruled out in other populations. Heightened levels of TNF-? level have been observed in both patients with type 2 diabetes and periodontitis. This study aimed to determine familial aggregation of type 2 diabetes and parental influence of disease transmission in the Sri Lankan population. The project also aimed to investigate periodontal status in diabetic patients and the effect of glycaemic control on periodontal status. The final aim of the project was to investigate the role of cytokine polymorphisms PAG and TNFA (-308) in association with periodontitis in people with type 2 diabetes. Family history data for one thousand patients was collected and analyzed. Subjects with established diabetes were recruited to the periodontal study (n=285) with an age and sex matched control population (n=72). All subjects underwent both periodontal and general health examination. Their periodontal parameters and metabolic parameters were measured including blood pressure, TG and LDL values. Patients were genotyped by PCR/RFLP method. The results of the study indicated that 59.4% of the diabetic subjects had at least one affected first degree relative in the family. It was also observed that 15.6% of mothers transfer the disease compared to (12.5%) of fathers (p < 0.001). When both parents had diabetes the early age of onset of diabetes is observed among offspring compared to offspring of maternal, paternal and no parental history of diabetes respectively (p < 0.05). 16.67% (12/72) of the control patients were identified as IFG and 66.67% (8/12) of this group were diagnosed with periodontitis. Systolic BP, diastolic blood pressure and LDL values were significantly lower in patients than controls (P < 0.05). Triglyceride levels were significantly higher in patients with diabetes than controls (p=0.001). A higher number of diabetic subjects were affected with chronic periodontitis (33.3%) compared to the non diabetic population (21.7%) (p=0.077). People with diabetes had significantly higher mean recession, percent bleeding on probing (BOP), maximum Probing depth (PD), PD > 4mm, PD >5mm and maximum loss of attachment (LOA) scores than the non diabetic population (p0.05). Subjects with periodontitis were significantly older than those with gingivitis or periodontally healthy (p < .01). Only FBG values were significantly higher in subjects with chronic periodontitis compared to periodontally healthy subjects (p < .01). Population frequency analysis of allele 1 vs. allele 2 were 0.9 & 0.1 for IL1B (+3954), 0.74 and 0.26 for ILIA (+4845) and 0.91 and 0.09 for TNFA (-308) respectively. The TNFA (-308) polymorphism deviates from the frequencies observed in North British Caucasians but similar to that observed in Taiwan and Japan. PAG had no significant effect on periodontal status in diabetes and controls (p>0.05). The percentage of PAG (12.5%) is low compared to Caucasians but higher compared to Chinese population. TNFA (-308) allele distribution had no significant effect on periodontal status. TNFA (-308) genotypes were significantly correlated with HDL.The results of the present study indicate that type 2 diabetes is familiarly aggregated in the Sri Lankan diabetic population and maternal excess is observed in the transmission pattern. There is a trend towards periodontital status to be higher in the diabetic population. Severity of periodontitis is higher in people with diabetes than those without and there is an indication that periodontitis may induce hyperglycaemia. PAG distribution shows population variation and the TNFA (-308) polymorphism may be associated with diabetes.