No description available.

No description available.

This thesis considers how informational imperfections may give rise to advantages for those born to relatively rich parents. The first chapter focuses on the separation of some societies into different classes. Within the model, classes provide greater advantages to those from privileged backgrounds and, even in the absence of legal barriers preventing the lower classes from accessing skilled jobs, the skilled amongst them are still de facto denied access to high paying jobs through statistical discrimination. This chapter shows that there can be a net benefit from class discrimination, versus a classless state, when it creates information relating to the abilities of the upper class. This theme is expanded on in chapter two where a signalling model more explicitly describes the statistical discrimination suffered by some members of society. The advantage conferred on those from privileged backgrounds generates income dispersion, which in turn reinforces the advantages of the rich. If this feedback is strong enough, the model may exhibit multiplicity of steady states. This multiplicity of steady states is backward looking: the income dispersion today depends on the extent to which firms use the information available to them, which in turn depends on the income dispersion in the previous generation. The model of chapter two also demonstrates why societies with more "meritocratic" institutions may exhibit less intergenerational income mobility: the income dispersion that meritocracy creates increases the value of a privileged upbringing. The final chapter adds parental investment to the model. In doing so it brings the model more squarely in line with the statistical discrimination literature, although the model does not exhibit a multiplicity of equilibria. There is a unique optimal investment rule for parents. Exogenous shocks to meritocracy are again examined. Meritocracy increases income variance and hence, from behind the veil of ignorance, creates greater uncertainty over the income an individual will receive. The model describes how a risk averse person might prefer to be born into an economy where they expect to be poorer but avoid this increased uncertainty, and so despite raising incomes, meritocracy may make agents, on average, more unhappy.

No description available.

No description available.

No description available.

Inherited retinal and corneal dystrophies represent a group of disorders with great genetic heterogeneity. Over 250 genes are associated with retinal diseases and 16 genes are causative of corneal dystrophies. This thesis is focused on finding the genetic causes of corneal dystrophy, Leber congenital amaurosis (LCA), Stargardt disease and retinitis pigmentosa in families from northern Sweden.  By whole exome sequencing a novel mutation, c.2816C>T, p.Thr939Ile, in Collagen Type XVII, Alpha 1 chain, COL17A1, gene was identified in several families with epithelial recurrent erosion dystrophy (ERED). We showed that the COL17A1 protein is expressed in the basement membrane of the cornea, explaining the mutation involvement in the corneal symptoms. We could link all the families in this study to a couple born in the late 1700s confirming a founder mutation in northern Sweden. Our finding highlights role of COL17A1 in ERED and suggests screening of this gene in patients with similar phenotype worldwide. Furthermore the genetic causes in several retinal degenerations were identified. In one family with two recessive disorders, LCA and Stargardt disease, a novel stop mutation, c.2557C>T, p.Gln853Stop, was detected in all LCA patients. In the Stargardt patients two intronic variants, the novel c.4773+3A>G and c.5461-10T>C, were detected in the ABCA4 gene. One individual was homozygous for the known variant c.5461-10T>C and the other one was compound heterozygote with both variants present. Both variants, c.4773+3A>G and c.5461-10T>C caused exon skipping in HEK293T cells demonstrated by in vitro splice assay, proving their pathogenicity in Stargardt disease. Finally, in recessive retinitis pigmentosa, Bothnia Dystrophy (BD), we identified a second mutation in the RLBP1 gene, c.677T>A, p.Met226Lys. Thus, BD is caused not only by common c.700C>T variant but also by homozygosity of c.677T>A or compound heterozygosity. Notably, known variant, c.40C>T, p.R14W in the CAIV gene associated with a dominant retinal dystrophy RP17 was detected in one of the compound BD heterozygote and his unaffected mother. This variant appears to be a benign variant in the population of northern Sweden. In conclusion, novel genetic causes of retinal dystrophies in northern Sweden were found demonstrating the heterogeneity and complexity of retinal diseases. Identification of the genetic defect in COL17A1 in the corneal dystrophy contributes to understanding ERED pathogenesis and encourages refinement of IC3D classification. Our results provide valuable information for future molecular testing and genetic counselling of the families.

No description available.

Yes / Fundus-controlled perimetry (FCP, also called 'microperimetry') allows for spatially-resolved mapping of visual sensitivity and measurement of fixation stability, both in clinical practice as well as research. The accurate spatial characterization of visual function enabled by FCP can provide insightful information about disease severity and progression not reflected by best-corrected visual acuity in a large range of disorders. This is especially important for monitoring of retinal diseases that initially spare the central retina in earlier disease stages. Improved intra- and inter-session retest-variability through fundus-tracking and precise point-wise follow-up examinations even in patients with unstable fixation represent key advantages of these technique. The design of disease-specific test patterns and protocols reduces the burden of extensive and time-consuming FCP testing, permitting a more meaningful and focused application. Recent developments also allow for photoreceptor-specific testing through implementation of dark-adapted chromatic and photopic testing. A detailed understanding of the variety of available devices and test settings is a key prerequisite for the design and optimization of FCP protocols in future natural history studies and clinical trials. Accordingly, this review describes the theoretical and technical background of FCP, its prior application in clinical and research settings, data that qualify the application of FCP as an outcome measure in clinical trials as well as ongoing and future developments.

ABSTRACT INTRODUCTION: Cancer is one of the most common diseases in the developed world and both genetic and environmental factors play a role in the development of cancer. About 5-10% of all cancers are due to predisposing genes. Some of the more common inherited cancer syndromes are hereditary breast and ovarian cancer (HBOC) and two colorectal cancer syndromes, familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). Recognition of cancer susceptibility can allow “at risk” individuals and families to participate in cancer risk assessment, genetic testing, and various cancer prevention strategies. As the public is becoming more aware of inherited cancers, it is expected that there will be an increasing demand for genetic services and testing. For this reason more GP involvement is required to assess patients and families at risk and refer them appropriately. Since the Clinical and Counselling Section, Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, Johannesburg is establishing a cancer genetics service it woud be of great value to assess the GPs’ practice, knowledge and attitudes with regards to cancer genetics and this was therefore the aim of this study. METHODOLOGY: A quantitative, exploratory research design was chosen and GPs in the Johannesburg area were selected as subjects. After the completion of a pilot study a research package was mailed to 196 GPs. This package was sent out twice and both times the GPs were asked to respond within 3-4 weeks. The final sample consisted of 61 GPs and the data were analysed using descriptive statistics. RESULTS: Of the 61 participants more male GPs (42, 69%) than female GPs (19, 31%) responded and there were about an equal number of GPs practicing alone (29, 48) and in a multiple practice (32, 52%). Twenty two (33%) of the GPs had never had personal experience of cancer. Practices: The GPs made use of several cancer screening procedures but obtained limited information on cancer history from their patients particularly from second degree relatives and about age of onset. Very few subjects (15, 25%) reported that they assess patients’ risk for inherited cancer susceptibility and only 22 (36%) reported that they refer patients to other facilities for risk assessment and genetic testing. Knowledge: Only 32 (52%) of the GPs were aware of genetic testing facilities and 54 (86%) reported never having received advertising material to promote genetic testing for cancer susceptibility services. They also are not aware of genetic counselling facilities but do feel patients should have genetic counselling by a genetic counselor, clinical geneticist or oncologist before genetic testing. Even though genetic testing for inherited cancer susceptibility is only available at some academic institutions, mostly on a research basis, the GPs seem to be unaware of the availability of genetic testing in South Africa for colorectal cancer genes (8, 13% and 9, 15%) but 28 (46%) knew about breast cancer genes. They were not aware of the autosomal dominant inheritance of hereditary breast cancer and the percentage of individuals with breast cancer who carry the BRCA1/2 gene nor did they know the penetrance of HNPCC genes. Attitudes: The subjects’ attitudes to genetic testing for inherited cancer susceptibility were positive although they reported that they were unaware of several general factors regarding cancer genetic testing. The GPs had limited knowledge about inherited cancers and do not take an active part in cancer genetic management. However, 53 (87%) of the GPs reported interest in learning about these services and expected to play a role in cancer genetics in the future. CONCLUSION: The findings of this study suggest that there is a need to educate GPs about the basic cancer genetic concepts so that they can identify patients at risk for an inherited cancer syndrome. They need to be informed about the genetic tests currently available for the inherited cancer syndromes, and about genetic counselling and testing facilities.