An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100kb), rare copy number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1,564 cases and 1,748 controls all from Ireland, and further extended the analysis to include an additional 5,196 UK controls. We found association with duplications at chr20p12.2 (P=0.007) and evidence of replication in large independent European schizophrenia (P=0.052) and UK bipolar disorder case-control cohorts (P=0.047). A combined analysis of Irish/UK subjects including additional psychosis cases (schizophrenia and bipolar disorder) identified 22 carriers in 11,707 cases and 10 carriers in 21,204 controls (meta-analysis CMH P value=2x10(-4) (odds ratio (OR)=11.3, 95% CI=3.7, ∞)). Nineteen of the 22 cases and 8 of the 10 controls carried duplications starting at 9.68Mb with similar breakpoints across samples. By haplotype analysis and sequencing we identified a tandem ∼149kb duplication overlapping the gene p21 Protein-Activated Kinase 7 (PAK7, also called PAK5) which was in linkage disequilibrium with local haplotypes (P=2.5x10(-21)), indicative of a single ancestral duplication event. We confirmed the breakpoints in 8/8 carriers tested and found co-segregation of the duplication with illness in two additional family members of one of the affected probands. We demonstrate that PAK7 is developmentally co-expressed with another known psychosis risk gene (DISC1) suggesting a potential molecular mechanism involving aberrant synapse development and plasticity.

Banished to the Barn - John Doherty and 'Bonnie Kate'

John Doherty (1900-1980) was one of the most influential Irish musicians of the twentieth century. His music has had a lasting impact on Irish traditional music making around the globe. This paper traces the development of his setting of the canonical reel 'Bonnie Kate'. Using transcription historical investigation Doherty's style is examined in comparison to his contemporaries.

Python PSS/E Simulation to Test Efficacy of Proposed PMU Based WAMS and Potential WAMPAC Applications

A PSS/E 32 model of a real section of the Northern Ireland electrical grid was dynamically controlled with Python 2.5. In this manner data from a proposed wide area monitoring system was simulated. The area is of interest as it is a weakly coupled distribution grid with significant distributed generation. The data was used to create an optimization and protection metric that reflected reactive power flow, voltage profile, thermal overload and voltage excursions. Step changes in the metric were introduced upon the operation of special protection systems and voltage excursions. A wide variety of grid conditions were simulated while tap changer positions and switched capacitor banks were iterated through; with the most desirable state returning the lowest optimization and protection metric. The optimized metric was compared against the metric generated from the standard system state returned by PSS/E. Various grid scenarios were explored involving an intact network and compromised networks (line loss) under summer maximum, summer minimum and winter maximum conditions. In each instance the output from the installed distributed generation is varied between 0 MW and 80 MW (120% of installed capacity). It is shown that in grid models the triggering of special protection systems is delayed by between 1 MW and 6 MW (1.5% to 9% of capacity), with 3.5 MW being the average. The optimization and protection metric gives a quantitative value for system health and demonstrates the potential efficacy of wide area monitoring for protection and control.

Strangers in a strange land: How Afghanistan changed our lives:How Afghanistan changed our lives

This half hour audio documentary for BBC Northern Ireland examined the connections between the different people in Northern Ireland who have forged links with Afghanistan.

The British conservative party and Europe:The choosing of John Major

This article provides an empirical analysis of voting behaviour in the second ballot of the 1990 Conservative leadership contest that resulted in John Major becoming party leader and prime minister. Seven hypotheses of voting behaviour are generated from the extant literature relating voting to socio-economic variables (occupational and educational background), political variables (parliamentary experience, career status, age and electoral marginality) and ideological variables (drawn from survey data on MPs' positions on economic, European and moral issues). These hypotheses are tested using data on voting intentions gathered from published lists of MPs' declarations, interviews with each of the leadership campaign teams, and correspondence with MPs. Bivariate relationships are presented, followed by logistic regression analysis to isolate the unique impact that each variable had on voting. This shows that educational background, parliamentary experience and (especially) attitudes to Europe were the key factors determining voting. The importance of Europe in the contest is particularly instructive: the severe problems for Major's leadership which were caused by the issue can be attributed to, and understood in the context of, the 1990 contest in which he became leader.