Homeostasis in C. elegans sleep is characterized by two behaviorally and genetically distinct mechanisms

Biological homeostasis invokes modulatory responses aimed at stabilizing internal conditions. Using tunable photo- and mechano-stimulation, we identified two distinct categories of homeostatic responses during the sleep-like state of Caenorhabditis elegans (lethargus). In the presence of weak or no stimuli, extended motion caused a subsequent extension of quiescence. The neuropeptide Y receptor homolog, NPR-1, and an inhibitory neuropeptide known to activate it, FLP-18, were required for this process. In the presence of strong stimuli, the correlations between motion and quiescence were disrupted for several minutes but homeostasis manifested as an overall elevation of the time spent in quiescence. This response to strong stimuli required the function of the DAF-16/FOXO transcription factor in neurons, but not that of NPR-1. Conversely, response to weak stimuli did not require the function of DAF-16/FOXO. These findings suggest that routine homeostatic stabilization of sleep may be distinct from homeostatic compensation following a strong disturbance. DOI: http://dx.doi.org/10.7554/eLife.04380.00

The First Provenance Challenge

The first Provenance Challenge was set up in order to provide a forum for the community to help understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a Functional Magnetic Resonance Imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the challenge, and submitted their inputs. In this paper, we present the challenge workflow and queries, and summarise the participants contributions

Assessment of the multidisciplinary education for a major change in clinical practice; a prospective cohort study

Background: New approaches are often introduced to the neonatal intensive care unit (NICU) and other areas of the health service in either a haphazard or cataclysmic fashion. The needs of staff education are often addressed incompletely or too late. Rarely is education assessed after the introduction of a major change. We changed the basis of our NICU respiratory support. We conducted a major educational and support program before this intervention. This study documented and assessed the educational components of this change in our health service provision. Methods: Senior medical and nursing staff attended training abroad and an education program was applied for one year prior to the change. Multidisciplinary educational support for doctors, nurses and allied health was continued after the change. Assessment was by anonymous questionnaire, prior to change, at one and at nine months. Our hypothesis was that dissatisfaction with education would be greatest at one month. Results: Both theory education and practical education aspects of the new approach were rated as good to very good and this did not change with time. Difficulty of applying the technique was rated as ambivalent initially but decreased significantly over 9 months until it was rated easy to very easy (p < 0.001). Over all, the change was rated by staff as beneficial, both at the end of the education period and at nine months, with no decrease at one month. Conclusion: If education and training reaches all staff, with a system of mutual and continued support, even large changes in clinical practice can be achieved without the dissatisfaction with the educational process that is often otherwise seen

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

Contains fulltext : 169719.pdf (publisher's version ) (Open Access)The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services

Reporting to Improve Reproducibility and Facilitate Validity Assessment for Healthcare Database Studies V1.0.

PURPOSE: Defining a study population and creating an analytic dataset from longitudinal healthcare databases involves many decisions. Our objective was to catalogue scientific decisions underpinning study execution that should be reported to facilitate replication and enable assessment of validity of studies conducted in large healthcare databases. METHODS: We reviewed key investigator decisions required to operate a sample of macros and software tools designed to create and analyze analytic cohorts from longitudinal streams of healthcare data. A panel of academic, regulatory, and industry experts in healthcare database analytics discussed and added to this list. CONCLUSION: Evidence generated from large healthcare encounter and reimbursement databases is increasingly being sought by decision-makers. Varied terminology is used around the world for the same concepts. Agreeing on terminology and which parameters from a large catalogue are the most essential to report for replicable research would improve transparency and facilitate assessment of validity. At a minimum, reporting for a database study should provide clarity regarding operational definitions for key temporal anchors and their relation to each other when creating the analytic dataset, accompanied by an attrition table and a design diagram. A substantial improvement in reproducibility, rigor and confidence in real world evidence generated from healthcare databases could be achieved with greater transparency about operational study parameters used to create analytic datasets from longitudinal healthcare databases

Loss of Expression and Promoter Methylation of SLIT2 Are Associated with Sessile Serrated Adenoma Formation.

Serrated adenomas form a distinct subtype of colorectal pre-malignant lesions that may progress to malignancy along a different molecular pathway than the conventional adenoma-carcinoma pathway. Previous studies have hypothesised that BRAF mutation and promoter hypermethylation plays a role, but the evidence for this is not robust. We aimed to carry out a whole-genome loss of heterozygosity analysis, followed by targeted promoter methylation and expression analysis to identify potential pathways in serrated adenomas. An initial panel of 9 sessile serrated adenomas (SSA) and one TSA were analysed using Illumina Goldengate HumanLinkage panel arrays to ascertain regions of loss of heterozygosity. This was verified via molecular inversion probe analysis and microsatellite analysis of a further 32 samples. Methylation analysis of genes of interest was carried out using methylation specific PCR (verified by pyrosequencing) and immunohistochemistry used to correlate loss of expression of genes of interest. All experiments used adenoma samples and normal tissue samples as control. SSA samples were found on whole-genome analysis to have consistent loss of heterozygosity at 4p15.1–4p15.31, which was not found in the sole TSA, adenomas, or normal tissues. Genes of interest in this region were PDCH7 and SLIT2, and combined MSP/IHC analysis of these genes revealed significant loss of SLIT2 expression associated with promoter methylation of SLIT2. Loss of expression of SLIT2 by promoter hypermethylation and loss of heterozygosity events is significantly associated with serrated adenoma development, and SLIT2 may represent a epimutated tumour suppressor gene according to the Knudson “two hit” hypothesis

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version