The HLA System and Primary Open-Angle Glaucoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66382/1/j.1399-0039.1978.tb01313.x.pd

Harnessing software development contexts to inform software process selection decisions

Software development is a complex process for which numerous approaches have been suggested. However, no single approach to software development has been met with universal acceptance, which is not surprising, as there are many different software development concerns. In addition, there are a multitude of other contextual factors that influence the choice of software development process and process management decisions. The authors believe it is important to develop a robust mechanism for relating software process decisions and software development contexts. Such an approach supports industry practitioners in their efforts to implement the software development processes vital for a particular set of contextual factors. In this paper, the authors outline a new tool-based framework for relating the complexity of software settings with the various aspects of software processes. This framework can extract the key software process concepts from process repositories, for example, from CMMI-DEV or ISO/IEC 15504-5 (a.k.a. SPICE – Software Process Improvement and Capability dEtermination). A team of software development experts then collaborates in order to identify and validate the strength and nature of the relationship between the key process concepts and the contextual factors that are known to affect the software development process. The result of this collaboration is a prototype of a flexible model, which can be extended over time into a broader process consideration, for example, where agile processes or further specific situational factors could be added to the framework. The authors contend that a model such as the one proposed in this paper can serve as a valuable tool, assisting software developers in making decisions regarding the selection of software best practices, as well as providing general guidance for process improvement initiatives

Planned Reduction in Electrical Energy Use in Nashville - Davidson County, Tennessee: A Preliminary Assessment

An assessment was carried out of the impacts of the various alternative strategies designed to reduce the rate of electrical energy use in the Nashville-Davidson County area, in the light of a potential crisis in supply. Seven strategies were identified among the major categories of voluntary reduction, price regulation, and mandatory reduction. Thirty-three sub-sectors were identified among residential, commercial and industrial users, and the consequences of imposing the strategies were assessed using a cross-impact matrix. The value of the methodology as an aid to public policy formulation lies in its possible extension to allow direct participation of various affected publics

Investigation of Founder Effects for the Thr377Met Myocilin Mutation in Glaucoma Families from Differing Ethnic Backgrounds

Purpose: The aim of this study was to determine if there is a common founder for the Thr377Met myocilin mutation in primary open angle glaucoma (POAG) families with various ethnic backgrounds. Methods: Genomic DNA of 24 POAG-affected individuals from nine pedigrees with the Thr377Met mutation and 104 unaffected family members was genotyped with six microsatellite markers and four single nucleotide polymorphisms. The families were from Greece, India, Finland, the USA, and Australia. To assess the degree of linkage disequilibrium across MYOC in the general population we also investigated data generated from the HapMap consortium. Results: Three distinct haplotypes associated with the Thr377Met myocilin mutation were identified. The families from the USA and Greece, as well as the three Australian families originating from Greece and the former Yugoslavian Republic of Macedonia had one common haplotype. Interestingly, however, HapMap data suggest that linkage disequilibrium across MYOC was not strong. Conclusions: The Thr377Met myocilin mutation has arisen at least three separate times. Evidence for genetic founder effects in this prevalent age-related, yet heterogeneous, disease has important implications for future gene identification strategies

GALC Deletions Increase the Risk of Primary Open-Angle Glaucoma: The Role of Mendelian Variants in Complex Disease

DNA copy number variants (CNVs) have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG) is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC). This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1.) (p = 0.017, fisher's exact test). It was validated with array comparative genomic hybridization (arrayCGH) and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio) = 3.5, 95% CI −1.1–12.0). Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6–16.4). Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG

Work, love, and death thought accessibility: a terror management investigation

Terror management theory suggests that following culturally derived scripts for valued behaviour protects people from death concerns, and conversely, not meeting standards for cultural value can weaken this protection, heightening mortality concerns. Using this conceptual framework we examine (1) how considerations of loss of employment, a source of cultural value for many, relates to the accessibility of death-related cognition, and (2) the moderating role of job market health and (3) involvement in close relationships. Study 1 found that writing about being unemployed (vs. a control topic) led to greater mortality-related cognition. Study 2 found that considering unemployment heightened death-cognition, but only when participants were led to perceive the job market as unhealthy. Finally, Study 3 found that considering unemployment led to greater death-cognition, but not for those involved in a close relationship. Findings offer insight into a previously overlooked consequence of unemployment, and factors that may serve a protective function

The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a β cell phenotype

types: JOURNAL ARTICLEMutation specific effects in monogenic disorders are rare. We describe atypical Fanconi syndrome caused by a specific heterozygous mutation in HNF4A. Heterozygous HNF4A mutations cause a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Autosomal dominant idiopathic Fanconi syndrome (a renal proximal tubulopathy) is described but no genetic cause has been defined.This article presents independent research supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The research is funded by a Wellcome Trust Senior Investigator Award, (grant number 098395/Z/12/Z).Wellcome Trus