Common data elements for pediatric traumatic brain injury: Recommendations from the working group on demographics and clinical assessment

The Common Data Elements (CDEs) initiative is a National Institutes of Health (NIH) interagency effort to standardize naming, definitions, and data structure for clinical research variables. Comparisons of the results of clinical studies of neurological disorders have been hampered by variability in data coding, definitions, and procedures for sample collection. The CDE project objective is to enable comparison of future clinical trials results in major neurological disorders, including traumatic brain injury (TBI), stroke, multiple sclerosis, and epilepsy. As part of this effort, recommendations for CDEs for research on TBI were developed through a 2009 multi-agency initiative. Following the initial recommendations of the Working Group on Demographics and Clinical Assessment, a separate workgroup developed recommendations on the coding of clinical and demographic variables specific to pediatric TBI studies for subjects younger than 18 years. This article summarizes the selection of measures by the Pediatric TBI Demographics and Clinical Assessment Working Group. The variables are grouped into modules which are grouped into categories. For consistency with other CDE working groups, each variable was classified by priority (core, supplemental, and emerging). Templates were produced to summarize coding formats, guide selection of data points, and provide procedural recommendations. This proposed standardization, together with the products of the other pediatric TBI working groups in imaging, biomarkers, and outcome assessment, will facilitate multi-center studies, comparison of results across studies, and high-quality meta-analyses of individual patient data

Infall, Outflow, Rotation, and Turbulent Motions of Dense Gas within NGC 1333 IRAS 4

Millimeter wavelength observations are presented of NGC 1333 IRAS 4, a group of highly-embedded young stellar objects in Perseus, that reveal motions of infall, outflow, rotation, and turbulence in the dense gas around its two brightest continuum objects, 4A and 4B. These data have finest angular resolution of approximately 2" (0.0034 pc) and finest velocity resolution of 0.13 km/s. Infall motions are seen from inverse P-Cygni profiles observed in H2CO 3_12-2_11 toward both objects, but also in CS 3-2 and N2H+ 1-0 toward 4A, providing the least ambiguous evidence for such motions toward low-mass protostellar objects. Outflow motions are probed by bright line wings of H2CO 3_12-2_11 and CS 3-2 observed at positions offset from 4A and 4B, likely tracing dense cavity walls. Rotational motions of dense gas are traced by a systematic variation of the N2H+ line velocities, and such variations are found around 4A but not around 4B. Turbulent motions appear reduced with scale, given N2H+ line widths around both 4A and 4B that are narrower by factors of 2 or 3 than those seen from single-dish observations. Minimum observed line widths of approximately 0.2 km/s provide a new low, upper bound to the velocity dispersion of the parent core to IRAS 4, and demonstrate that turbulence within regions of clustered star formation can be reduced significantly. A third continuum object in the region, 4B', shows no detectable line emission in any of the observed molecular species.Comment: LateX, 51 pages, 9 figures, accepted by Ap

QTL global meta-analysis: are trait determining genes clustered?

Background: A key open question in biology is if genes are physically clustered with respect to their known functions or phenotypic effects. This is of particular interest for Quantitative Trait Loci (QTL) where a QTL region could contain a number of genes that contribute to the trait being measured. Results: We observed a significant increase in gene density within QTL regions compared to non-QTL regions and/or the entire bovine genome. By grouping QTL from the Bovine QTL Viewer database into 8 categories of non-redundant regions, we have been able to analyze gene density and gene function distribution, based on Gene Ontology (GO) with relation to their location within QTL regions, outside of QTL regions and across the entire bovine genome. We identified a number of GO terms that were significantly over represented within particular QTL categories. Furthermore, select GO terms expected to be associated with the QTL category based on common biological knowledge have also proved to be significantly over represented in QTL regions. Conclusion: Our analysis provides evidence of over represented GO terms in QTL regions. This increased GO term density indicates possible clustering of gene functions within QTL regions of the bovine genome. Genes with similar functions may be grouped in specific locales and could be contributing to QTL traits. Moreover, we have identified over-represented GO terminology that from a biological standpoint, makes sense with respect to QTL category type.Hanni Salih and David L Adelso

A comparative analysis of algorithms for somatic SNV detection in cancer

Motivation: With the advent of relatively affordable high-throughput technologies, DNA sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are the simplest class of mutation, yet their identification in DNA sequencing data is confounded by germline polymorphisms, tumour heterogeneity and sequencing and analysis errors. Four recently published algorithms for the detection of somatic SNV sites in matched cancer–normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer–normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterized and compared to investigate the strengths and weaknesses of each SNV calling algorithm. Results: Comparing the candidate SNV sets returned by VarScan, SomaticSniper, JointSNVMix2 and Strelka revealed substantial differences with respect to the number and character of sites returned; the somatic probability scores assigned to the same sites; their susceptibility to various sources of noise; and their sensitivities to low-allelic-fraction candidates.Nicola D. Roberts, R. Daniel Kortschak, Wendy T. Parker, Andreas W. Schreiber, Susan Branford, Hamish S. Scott, Garique Glonek and David L. Adelso

USDA Stakeholder Workshop on Animal Bioinformatics: Summary and Recommendations

An electronic workshop was conducted on 4 November–13 December 2002 to discuss current issues and needs in animal bioinformatics. The electronic (e-mail listserver) format was chosen to provide a relatively speedy process that is broad in scope, cost-efficient and easily accessible to all participants. Approximately 40 panelists with diverse species and discipline expertise communicated through the panel e-mail listserver. The panel included scientists from academia, industry and government, in the USA, Australia and the UK. A second ‘stakeholder’ e-mail listserver was used to obtain input from a broad audience with general interests in animal genomics. The objectives of the electronic workshop were: (a) to define priorities for animal genome database development; and (b) to recommend ways in which the USDA could provide leadership in the area of animal genome database development. E-mail messages from panelists and stakeholders are archived at http://genome.cvm.umn.edu/bioinfo/. Priorities defined for animal genome database development included: (a) data repository; (b) tools for genome analysis; (c) annotation; (d) practical application of genomic data; and (e) a biological framework for DNA sequence. A stable source of funding, such as the USDA Agricultural Research Service (ARS), was recommended to support maintenance of data repositories and data curation. Continued support for competitive grants programs within the USDA Cooperative State Research, Education and Extension Service (CSREES) was recommended for tool development and hypothesis-driven research projects in genome analysis. Additional stakeholder input will be required to continuously refine priorities and maximize the use of limited resources for animal bioinformatics within the USDA

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): study protocol for a pilot randomized controlled trial.

BACKGROUND: Trauma is the leading cause of morbidity and mortality in children in the United States. The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage, however, the drug has not been evaluated in a clinical trial in severely injured children. We designed the Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) trial to evaluate the feasibility of conducting a confirmatory clinical trial that evaluates the effects of TXA in children with severe trauma and hemorrhagic injuries. METHODS: Children with severe trauma and evidence of hemorrhagic torso or brain injuries will be randomized to one of three arms: (1) TXA dose A (15 mg/kg bolus dose over 20 min, followed by 2 mg/kg/hr infusion over 8 h), (2) TXA dose B (30 mg/kg bolus dose over 20 min, followed by 4 mg/kg/hr infusion over 8 h), or (3) placebo. We will use permuted-block randomization by injury type: hemorrhagic brain injury, hemorrhagic torso injury, and combined hemorrhagic brain and torso injury. The trial will be conducted at four pediatric Level I trauma centers. We will collect the following outcome measures: global functioning as measured by the Pediatric Quality of Life (PedsQL) and Pediatric Glasgow Outcome Scale Extended (GOS-E Peds), working memory (digit span test), total amount of blood products transfused in the initial 48 h, intracranial hemorrhage progression at 24 h, coagulation biomarkers, and adverse events (specifically thromboembolic events and seizures). DISCUSSION: This multicenter trial will provide important preliminary data and assess the feasibility of conducting a confirmatory clinical trial that evaluates the benefits of TXA in children with severe trauma and hemorrhagic injuries to the torso and/or brain. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT02840097 . Registered on 14 July 2016

Manager- und transaktionsspezifische Determinanten der Performance von Arbitrage CLOs

Der vorliegende Beitrag untersucht die Determinanten der Performance europäischer Arbitrage Collateralized Loan Obligations für das Jahr 2009. Der Fokus liegt dabei auf der Bedeutung der performanceabhängigen Vergütung des CLO-Managers, den Eigenschaften des CLO-Managers und der Transaktionscharakteristika als mögliche Einflussfaktoren der Rating Performance. Es wird gezeigt, dass Transaktionen, bei denen dem CLO-Manager eine Incentive Management Fee gewährt wird, mit einer höheren Wahrscheinlichkeit herabgestuft werden als Transaktionen ohne Incentive Fee. Dieser Befund bestätigt die Hypothese, dass durch die Incentive Fee Risikoanreize für CLO-Manager geschaffen werden. Des Weiteren wird ein positiver Zusammenhang zwischen der Erfahrung bzw. der Größe eines CLO-Managers und der Rating Performance festgestellt. Der Einfluss des Managers auf die Performance einer CLO-Transaktion wird auch an den weiteren in der Studie herangezogenen managerspezifischen Charakteristika wie Typ und Unternehmenssitz bestätigt. Für die Transaktionscharakteristika wird hingegen im betrachteten Untersuchungszeitraum kein signifikanter Einfluss auf die Rating Performance nachgewiesen

Multiple horizontal transfer events of a DNA transposon into turtles, fishes, and a frog

Horizontal transfer of transposable elements (HTT) has been reported across many species and the impact of such events on genome structure and function has been well described. However, few studies have focused on reptilian genomes, especially HTT events in Testudines (turtles). Here, as a consequence of investigating the repetitive content of Malaclemys terrapin terrapin (Diamondback turtle) we found a high similarity DNA transposon, annotated in RepBase as hAT-6_XT, shared between other turtle species, ray-finned fishes, and a frog. hAT-6_XT was notably absent in reptilian taxa closely related to turtles, such as crocodiles and birds. Successful invasion of DNA transposons into new genomes requires the conservation of specific residues in the encoded transposase, and through structural analysis, these residues were identified indicating some retention of functional transposition activity. We document six recent independent HTT events of a DNA transposon in turtles, which are known to have a low genomic evolutionary rate and ancient repeats