Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Total phenolic contents and antioxidant activities of Prangos Lindl. (Umbelliferae) species growing in Konya province (Turkey)

Prangos species are widely used as medicinal plants in Turkey, and 14 species of this genus grow naturally in Anatolia. In the present study, the phenolic contents and antioxidant activities of the water and methanol (MeOH) extracts obtained from the root, herb, and fruits of 4 species of Prangos (Prangos ferulacea, P. heyniae, P. meliocarpoides var. meliocarpoides, and P. uechtritzii) collected in Konya province were compared. The phenolic contents of the samples were determined using Folin-Ciocalteu's phenol reagent. Antioxidant activities of the extracts were studied by qualitative DPPH (1,1-diphenyl-2-picrylhydrazyl radical) assay to detect the free radical scavenging activity and by thiobarbituric acid (TBA) assay to detect their liposome lipid peroxidation. Total phenolic contents of the MeOH extracts were found to range from 77.99 to 140.29 mg/g and the water extracts ranged from 37.53 to 97.29 mg/g in dry weight expressed as gallic acid equivalents (GAE). All extracts showed a slightly antioxidant activity with the DPPH(center dot) test. High activity was observed in the MeOH extracts when compared to the water extracts in the TBA test

New types of toxin A-negative, toxin B-positive strains among clinical isolates of Clostridium difficile in Australia

A total of 817 human clinical isolates of Clostridium difficile from all Australian states were screened for A-B+ strains by toxin gene PCR assays. Nine (1.1%) strains were confirmed to be A-B+ by enzyme immunoassay for toxin production. Of these, six (66.7%) were binary toxinpositive by PCR. Using PCR ribotyping and toxinotyping, the A-B+ strains could be grouped into seven ribotypes and three toxinotypes. Only one of the ribotypes had been reported previously (017). The prevalence of ribotype 017 was low in this study with only two strains detected. Two new A-B+ toxinotypes were also defined (XXX, XXXI). Toxinotype XXX had a toxin B gene similar to that of toxinotype IV (A+B+) but with a novel cytopathic region. Toxinotype XXXI was similar to other A-B+ types (X, XVII), but had a larger deletion to the toxin A gene than in either of those types. The types of A-B+ strains identified in this study differed markedly from those described in other regions

Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology

Objective: To establish evidence-based recommendations for the molecular analysis of lung cancers that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed. Participants: Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies. Evidence: Three unbiased literature searches of electronic databases were performed to capture published articles from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation. Consensus Process: Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4). Conclusions: The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines