No description available.

No description available.

No description available.

Abstract Fetal alcohol syndrome (FAS) is a common cause of mental retardation and is attributable to the teratogenic effects of alcohol exposure in utero in individuals with genetic susceptibility. The Coloured communities from the Western and Northern Cape regions have some of the highest recorded incidence rates (~70 affected children per 1000 live births) in the world. The candidate genes selected for this study belong to the family of alcohol dehydrogenase genes that code for enzymes which metabolise alcohol. The ADH1B and ADH1C genes have previously been examined in the Western Cape Coloured community and the enzyme encoded by the allele ADH1B*2 was significantly associated with protection against the development of FAS. ADH4, a new candidate gene, was selected due to its role in both the alcohol and retinol metabolic pathways. A case-control genetic association study was performed to examine the potential roles of the ADH1B, ADH1C and ADH4 genes in the etiology of FAS in two Coloured populations from the Northern and Western Cape. Single nucleotide polymorphisms found within the candidate genes were typed by PCR-based methods in samples from the FAS children, their mothers and controls. Significant associations were observed in the Western Cape cohort but were not replicated in the Northern Cape. Allelic association tests revealed that ADH1B*2 may be a protective marker as it occurred more commonly in the controls than the mothers (p= 0.038). The alleles of the polymorphic variant, ADH4.8, have been shown to influence the promoter activity of ADH4 (the ‘A’ allele has been shown to increase the activity of the promoter when compared to the ‘C’ allele as the same position). The alleles of this polymorphic marker were significantly associated with the risk for FAS. The ‘A’ allele was shown to occur more commonly in the mothers and FAS-affected children (p= 0.002 and 0.035 respectively) when compared to the controls, suggesting a role in disease susceptibility while the ‘C’ allele was shown to occur more commonly in the controls. Itwas also observed that ADH1B and ADH4.8 when examined together in a haplotype demonstrated an association with susceptibility to the disease. While the 2-C haplotype (ADH1B-ADH4.8) was shown to be associated with protection against the development of FAS, the 1-A haplotype was associated with increased susceptibility. The results suggest that mothers with the common ADH1B*1 allele and presumably a normal ADH1B function but an increased level of ADH4 (allele ‘A’) as a result of the promoter mutation, will, when the blood alcohol concentration is high, have an increased risk of having a child with FAS. Conversely when the mothers have a faster alcohol metabolising rate due to the allele ADH1B*2 and normal levels of ADH4 protein (allele ‘C’), the circulating alcohol in the blood is removed efficiently resulting in maternal protection against developing the disease. This study has also highlighted the genetic diversity within individuals of the South African Coloured population. Haplotype analysis and logistic regression revealed that the Western and Northern Cape Coloured communities are genetically different and as a result, the samples could not be pooled for analysis. Although the two groups of controls were genetically diverse, haplotype analysis revealed that the sample of mothers and FAS-affected children were not statistically different between the provinces thus possibly suggesting a similar genetic etiology for the disease. The results from this study suggest that the ADH genes do play a role in the pathogenesis of FAS.

Thesis (M.S.)--State University of New York at Binghamton, Department of Psychology, 2008. / Includes bibliographical references.

Thesis (Ph.D.(Social Work and Criminology))-University of Pretoria, 2008. / Includes bibliographical references.

Thesis (Ph. D.)--University of Hawaii at Manoa, 2004. / Includes bibliographical references (leaves 92-105).

The National Institutes of Health defines Fetal Alcohol Syndrome (FAS) as a debilitating collection of birth defects that include craniofacial dysmorphisms, neurological and motor insufficiencies, growth retardation, and behavioral and social discrepancies. Characteristic craniofacial abnormalities, which include smooth philtrum, thin vermillion border, short palpebral fissures, and microcephaly, are used as a diagnostic tool for FAS. There is agreement across the literature that the characteristic craniofacial dysmorphisms are induced as a result of prenatal alcohol exposure in very specific doses, and during very particular time periods during embryonic development. However, ambiguity still exists about the critical time and dose relationship of prenatal alcohol exposure in the production of FAS. In regards to the critical timing, researchers have concluded that prenatal alcohol exposure during the second half of the first trimester, defined as days 43-94 postconception, was found to cause an increased incidence of smooth philtrum, thin vermillion border, microcephaly and reduced birth weight. Conversely, other studies found that prenatal alcohol exposure on day 7 of gestation in mice, which corresponds to week 3 of human gestation, induced craniofacial abnormalities comparable to those seen in humans with FAS. In regards to the critical dose, there is a linear relationship between the dose of prenatal alcohol exposure and the incidence of FAS-related craniofacial abnormalities, with no safe threshold. It was also found that a binge pattern of drinking was more significantly associated with the craniofacial abnormalities seen in FAS than a continuous or less condensed pattern of drinking, even if the binge pattern involved a smaller absolute dose of alcohol. These results regarding both dose and pattern on prenatal alcohol exposure, suggest that binge-drinking patterns are most significantly associated with craniofacial abnormalities if consumed before pregnancy or during late pregnancy, whereas absolute high doses of alcohol in a non-binge pattern were most significantly associated with craniofacial abnormalities in the first trimester. Further research is required for clarification of the critical time and dose relationships involved in the production of the characteristic craniofacial dysmorphisms seen in FAS. A definite conclusion will aid in the public education and prevention programs for FAS if solid information can be provided about the harms of alcohol consumption during pregnancy in regards to timing and dose.

Much of the literature on the determinants of health, including alcohol consumption, has focussed on differences in individual socio-economic status as a primary risk factor. However, it has been shown that variation in health between places can be attributed to both the characteristics of the people who live in those places (composition) and also to the characteristics of the places where people live (context). From the 1990s, there has been considerable interest in the role of neighbourhoods, specifically whether their social and physical characteristics are important in explaining inequalities in health. The main aim of this thesis is to determine the influence of ‘place’ effects on alcohol-related behaviour and health and social outcomes in New Zealand. To achieve this, data was obtained for hospitalisation and mortality directly related to alcohol consumption. Age standardised rates of alcohol related hospitalisation and mortality were calculated for different census areas units over time. Secondly, a database of all alcohol outlets including type and category was obtained from the Liquor Licensing Authority and geocoded for all meshblocks in New Zealand. Using ArcGIS road network functionality, least cost distance to nearest alcohol outlets was calculated. In addition, two buffers (800 and 3000 metres) were created around the population weighted centroids of each meshblock. Statistical analysis was undertaken to examine the distribution of alcohol outlets in areas of differing socio-economic status. Thirdly, binary logistic regression was used to examine the relationship between various access measures developed and individual alcohol related behaviour from the New Zealand Health Survey (2006/07). Lastly, Ordinary Least Squares regression was used to establish the association between the density of alcohol outlets and crime, and alcohol related hospitalisation. The results reveal there is increasing geographic inequality of both hospitalisation and mortality between the most and the least deprived areas in New Zealand. Secondly, the results consistently show there is inequity in the availability of alcohol outlets; there are clear social patterns in the distribution of alcohol outlets with disproportionately high numbers in more socially deprived neighbourhoods. Thirdly, at the national level, after controlling for potential confounding factors, there was no association between either hazardous or frequent consumption of alcohol and access to alcohol outlets. However, there was an association for particular sub-populations in regards to hazardous and frequent consumption and access to alcohol outlets. Fourthly, although the explained variance was often quite low in outcome models for crime and hospitalisation, nevertheless most of the variance for crime was predicted by the density of alcohol outlets. A number of important theoretical and policy implications flow from this study. Alcohol outlets are modifiable structures in the environments that are amenable to policy interventions at a community and national level. Interventions could concentrate on three aspects to reduce excess consumption; zoning ordinances, reducing alcohol outlets in deprived areas and increased alcohol taxation. Starting with the first proposed intervention, zoning ordinances provide communities and local governments with the opportunity to regulate outlet numbers and locations as well as their trading hours. This intervention has the potential to reduce opportunities for obtaining alcohol. Secondly, a reduction in the number of alcohol outlets is likely to reduce consumption and consequently improve health and social outcomes. Finally, higher alcohol prices via increased taxation is likely to be a deterrent to excess consumption and related health outcomes. Three priority areas are identified and recommended for future research. Studies using a mixture of both qualitative and quantitative methods, to better understand the association between local purchases of alcohol, consumption and proximity to alcohol outlets would be beneficial. In addition, the use of qualitative methods to examine the influence of social capital and cohesion, culture and norms on alcohol consumption in areas with higher densities of, and better access to alcohol outlets, is imperative. Lastly, longitudinal studies are also recommended to investigate increases or decreases in the number of alcohol outlets over time and the impact of such changes on the consumption patterns of different sub-populations.

It can be useful to discover a person’s chronic drinking consumption in child custody cases and to aid in the diagnosis of diseases like fetal alcohol spectrum disorder. When one alcohol marker in hair is analysed to indicate chronic use false negatives and false positives can occur. When two (ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs)) are analysed false negatives and false positives can be recognized and provide stronger evidence as is underlined statistically in this work. For a combined method, the sample preparation and analytical procedures were optimized. The effect of the decontamination step was difficult to interpret, which shows that addressing issues with external contamination is challenging. Analytes may be extracted from the hair matrix during decontamination and analytes can diffuse into the hair shaft from external contamination. The last is illustrated by the incorporation via excretions of endogenous EtG and FAEEs. A novel and sensitive analytical procedure was developed and validated which saves time and possibly money compared to analysing of both markers separately. The best overall method had a linear calibration curve (r2 > 0:99) and an intra-day (n=3) and inter-day (n=9) accuracy for the quality control samples at three concentration levels between 84–118% with a coefficient of variation of 3–30% for both EtG and the FAEEs. The Bayesian approach was suggested as a new interpretation framework for hair tests, to account for the uncertainties in these tests in a transparent manner. In this work databases were constructed with EtG and FAEEs hair concentrations linked to the subject’s chronic alcohol use, the likelihood ratios were calculated and working examples were provided. This showed that a positive hair test for either EtG or FAEEs may very well be only ’limited’ evidence and therefore should only be used with a high prior odds. This means that a hair test result should not be used in isolation. The large confidence interval in this study also underlines the need for more control data.