Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Panel Discussion: Judicial Elections

Examines the ethical and professionalism issues that arise in the context of judicial elections. The panelists will discuss and evaluate the efficacy of the various models of judicial elections, as well as the ethical challenges presented by campaigning and campaign finance. In addition, the panel will consider the potential effect of the election process on judicial decision-making, including possible influence on actual outcomes and the necessity for recusal. Special attention given to recent judicial elections in Florida, Iowa, and Wisconsin

Synthesis of monthly natural flows for selected sites in the Musselshell River Basin, Montana, base period 1929-89 /

Chiefly tables."June 1996."Shipping list no.: 96-0314-P.Includes bibliographical references (p. 9).Mode of access: Internet

Identification of Patients for Adjuvant Therapy After Resection of Carcinoma of the Extrahepatic Bile Ducts: A Propensity Score-Matched Analysis

BACKGROUND: Resectability rates for extrahepatic cholangiocarcinoma have increased over time, but long-term survival after resection alone with curative intent remains poor. Recent series suggest improved survival with adjuvant therapy. Patient subsets benefiting most from adjuvant therapy have not been clearly defined. METHODS: Patients with extrahepatic cholangiocarcinoma who underwent resection with curative intent and received adjuvant therapy (chemotherapy \ub1 radiotherapy) or surgery alone (SA) were identified in the U.S. National Cancer Data Base (2004-2014). Cox regression identified covariates associated with overall survival (OS). Adjuvant therapy and SA cohorts were matched (1:1) by propensity scores based on the survival hazard in Cox modeling. Overall survival was compared by Kaplan-Meier estimates. RESULTS: Of 4872 patients, adjuvant chemotherapy was used frequently for 2416 (49.6%), often in conjunction with radiotherapy (RT) (n = 1555, 64.4%). Adjuvant chemotherapy with or without RT was used increasingly for cases with higher T classification [reference: T1-2; T3: 1.36; 95% confidence interval (CI), 1.19-1.55; T4: 1.77; 95% CI 1.38-2.26], nodal positivity [odds ratio (OR), 1.26; 95% CI 1.01-1.56], lymphovascular invasion (OR 1.21; 95% CI 1.01-1.46), or margin-positive resection (OR 1.85; 95% CI 1.61-2.12), and was associated with significant improvements in OS for each high-risk subset in the propensity score-matched cohort. Adjuvant therapy was associated with improved median OS for hilar tumors (40.0 vs 30.6 months; p = 0.025) but not distal tumors (33.0 vs 30.3 months; p = 0.123). Chemoradiotherapy was associated with superior outcomes compared with chemotherapy alone in the subset of margin-positive resection [hazard ratio (HR), 0.63; 95% CI 0.42-0.94]. CONCLUSIONS: Adjuvant multimodality therapy is associated with improved survival for patients with resected extrahepatic cholangiocarcinoma and high-risk features

Mode-Locking and Regional Business Cycle Synchronization

Business cycles in different regions of the United States tend to synchronize. This study investigates the reasons behind this synchronization of business cycles and the consequent formation of a national business cycle. Trade between regions may not be strong enough for one region to "drive" business cycle fluctuations in another region. This study suggests that regional business cycles synchronize due to a nonlinear "mode-locking" process in which weakly coupled oscillating systems (regions) tend to synchronize. There is no definitive test for mode-lock. However, simulations, correlations, Granger causality tests, tests for nonlinearities, vector autoregressions, and spectral analysis reveal modest econometric support for the regional mode-locking hypothesis of business cycle synchronization. Copyright Blackwell Publishers, 2005