Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor

Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023

AGU hydrology days 2003

Includes bibliographical references.23rd annual AGU hydrology days was held on March 31 - April 2, 2003 at Colorado State University.SAMS is a software for stochastic analysis, modeling, and simulation of hydrologic time series such as streamflows. It has been written in MS Visual C++ and Fortran. The package consists of many menu option windows that focus on three primary application modules - Statistical Analysis of Data, Fitting of a Stochastic Model (including parameter estimation and testing), and Generating Synthetic Series. SAMS has the capability of analyzing single site and multisite annual and seasonal data such as monthly and weekly streamflows based on a number of single site and multisite models, and aggregation and disaggregation modeling schemes. Results can be presented in graphical and tabular forms and, if desired, saved to an output file. The purpose of the paper is to summarize and update on the current capabilities of SAMS. Some illustrations are made to demonstrate the improved technical capabilities of the program using flow data of the Colorado River system

'People in this country have had enough of experts': Brexit and the paradoxes of populism

In June 2016, the United Kingdom voted to leave the European Union, creating massive political turmoil and controversy. Our aim in this paper is to contribute to a discussion about how to analyze such critical moments in policy and politics. Rather than searching for one ‘real’ cause (whether the micro-politics of the Conservative Party or popular disaffection from neo-liberalism), we offer a form of conjunctural analysis that highlights issues of multiplicity and heterogeneity. We sketch this approach and then explore two puzzles that have particular pertinence for Critical Policy Studies. One is the puzzle of populism: how new imaginings and representations of the ‘British people’ were constructed. The second is the puzzle of expertise; how antipathy to ‘expert’ knowledge was shaped to challenge British and European ‘elites’. Conjunctural analysis, we argue, offers a vital means of engaging with such puzzles, and of grasping the heterogeneous and contradictory forces, tendencies, and pressures that enabled Brexit

Post-stroke epilepsy and antiepileptic drug use in men and women

Evidence-based recommendations for choice of antiepileptic drug (AED) in post-stroke epilepsy (PSE) are lacking. The aim of this study was to describe the use and persistence of AEDs when initiating treatment in men and women with PSE. An observational study based on individual-level patient data from a regional healthcare register in Stockholm, Sweden, was conducted. Adults (>= 18 years) with a stroke diagnosis 2012-2016, a dispensed prescription of any AED within two years after the stroke, and with an epilepsy-related diagnosis were identified. Multinomial logistic regression and logistic regression were used to identify factors associated with choice of AED and discontinuation within 90 days, respectively. Of 9652 men and 9844 women with a stroke diagnosis, 287 men and 273 women had PSE and were dispensed AED. More than 60% of both men and women with PSE were treated with levetiracetam. Carbamazepine was the second most common drug followed by lamotrigine and valproic acid. There were significant differences in AED choice depending on for instance sex, age and renal impairment. Levetiracetam had the highest persistence in both men and women. Choice of AED, oral anticoagulant use and percutaneous endoscopic gastrostomy (PEG) showed an association with the persistence to therapy. We conclude that in both men and women with PSE, levetiracetam was the most used AED for initiation of treatment and also had the highest persistence