Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia.

BACKGROUND: In first-episode schizophrenia, longer duration of untreated psychosis (DUP) predicts poorer outcomes. AIMS: To address whether the relationship between DUP and outcome is a direct causal one or the result of association between symptoms and/or cognitive functioning and social functioning at the same time point. METHOD: Symptoms, social function and cognitive function were assessed in 98 patients with first-episode schizphrenia at presentation and 1 year later. RESULTS: There was no significant clinical difference between participants with short and long DUP at presentation. Linear regression analyses revealed that longer DUP significantly predicted more severe positive and negative symptoms and poorer social function at 1 year, independent of scores at presentation. Path analyses revealed independent direct relationships between DUP and social function, core negative symptoms and positive symptoms. There was no significant association between DUP and cognition. CONCLUSIONS: Longer DUP predicts poor social function independently of symptoms. The findings underline the importance of taking account of the phenomenological overlap between measures of negative symptoms and social function when investigating the effects of DUP

Inaccuracies in plasma oxytocin extraction and enzyme immunoassay techniques

Numerous studies have reported extensive associations between plasma oxytocin (OXT) concentrations and various human physiological and neurobehavioral processes. Measurement of OXT is fraught with difficulty due to its low molecular weight and plasma concentrations, with no consensus as to the optimal conditions for pre-analytical sample extraction, standards for immunoassay validation or the ideal protease inhibitors to prevent OXT degradation. Previous attempts at determining the efficacy of various purification techniques such as solid phase extraction (SPE) or ultrafiltration have only utilized human plasma samples, making it difficult to dissect out whether the effect of interference comes from the extraction process itself or cross-reactivity with other proteins. By testing these on pure OXT solutions, we demonstrate poor recovery efficacy and reliability of reversed phase SPE (maximum 58.1%) and ultrafiltration (<1%) techniques, and the potential for the former to introduce interference into enzyme immunoassay (EIA) measurements. The clonality of antibodies used in EIA kits also potentially contributes to the differences in the readings obtained, and we validate an EIA kit which did not require pre-analytical sample extraction with low cross-reactivity and high reliability (intraclass correlation coefficient 0.980 (95% CI 0.896–0.999). Biochemical techniques used for measuring plasma OXT concentrations must therefore be internally validated prior to translation into clinical studies

Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing

What's in your next-generation sequence data? An exploration of unmapped DNA and RNA sequence reads from the bovine reference individual.

BackgroundNext-generation sequencing projects commonly commence by aligning reads to a reference genome assembly. While improvements in alignment algorithms and computational hardware have greatly enhanced the efficiency and accuracy of alignments, a significant percentage of reads often remain unmapped.ResultsWe generated de novo assemblies of unmapped reads from the DNA and RNA sequencing of the Bos taurus reference individual and identified the closest matching sequence to each contig by alignment to the NCBI non-redundant nucleotide database using BLAST. As expected, many of these contigs represent vertebrate sequence that is absent, incomplete, or misassembled in the UMD3.1 reference assembly. However, numerous additional contigs represent invertebrate species. Most prominent were several species of Spirurid nematodes and a blood-borne parasite, Babesia bigemina. These species are either not present in the US or are not known to infect taurine cattle and the reference animal appears to have been host to unsequenced sister species.ConclusionsWe demonstrate the importance of exploring unmapped reads to ascertain sequences that are either absent or misassembled in the reference assembly and for detecting sequences indicative of parasitic or commensal organisms

Predicting air-borne droplet drift from agricultural areas

Non-Peer Reviewe

Validity of Ligand Efficiency Metrics

A recent viewpoint article (Improving the plausibility of success with inefficient metrics. ACS Med. Chem. Lett. 2014, 5, 2-5) argued that the standard definition of ligand efficiency (LE) is mathematically invalid. In this viewpoint, we address this criticism and show categorically that the definition of LE is mathematically valid. LE and other metrics such as lipophilic ligand efficiency (LLE) can be useful during the multiparameter optimization challenge faced by medicinal chemists