No evidence of a significant role for CTLA-4 in multiple sclerosis

Variation in the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene plays a significant role in determining susceptibility to autoimmune thyroid disease and type 1 diabetes. Its role in multiple sclerosis is more controversial. In order to explore this logical candidate more thoroughly, we genotyped 771 multiple sclerosis trio families from the United Kingdom for the 3? untranslated region variable number tandem repeat, the CT60 single nucleotide polymorphism (SNP) and five haplotype-tagging SNPs. No individual marker or common haplotype showed evidence of association with disease. These data suggest that any effect of CTLA-4 on multiple sclerosis susceptibility is likely to be very small

RAS screening in colorectal cancer: a comprehensive analysis of the results from the UK NEQAS colorectal cancer external quality assurance schemes (2009–2016)

Evidence strongly indicates that extended RAS testing should be undertaken in mCRC patients, prior to prescribing anti-EGFR therapies. With more laboratories implementing testing, the requirement for External Quality Assurance schemes increases, thus ensuring high standards of molecular analysis. Data was analysed from 15 United Kingdom National External Quality Assessment Service (UK NEQAS) for Molecular Genetics Colorectal cancer external quality assurance (EQA) schemes, delivered between 2009 and 2016. Laboratories were provided annually with nine colorectal tumour samples for genotyping. Information on methodology and extent of testing coverage was requested, and scores given for genotyping, interpretation and clerical accuracy. There has been a sixfold increase in laboratory participation (18 in 2009 to 108 in 2016). For RAS genotyping, fewer laboratories now use Roche cobas®, pyrosequencing and Sanger sequencing, with more moving to next generation sequencing (NGS). NGS is the most commonly employed technology for BRAF and PIK3CA mutation screening. KRAS genotyping errors were seen in ≤10% laboratories, until the 2014–2015 scheme, when there was an increase to 16.7%, corresponding to a large increase in scheme participants. NRAS genotyping errors peaked at 25.6% in the first 2015–2016 scheme but subsequently dropped to below 5%. Interpretation and clerical accuracy scores have been consistently good throughout. Within this EQA scheme, we have observed that the quality of molecular analysis for colorectal cancer has continued to improve, despite changes in the required targets, the volume of testing and the technologies employed. It is reassuring to know that laboratories clearly recognise the importance of participating in EQA schemes

Tomographic approach to resolving the distribution of LISA Galactic binaries

The space based gravitational wave detector LISA is expected to observe a large population of Galactic white dwarf binaries whose collective signal is likely to dominate instrumental noise at observational frequencies in the range 10^{-4} to 10^{-3} Hz. The motion of LISA modulates the signal of each binary in both frequency and amplitude, the exact modulation depending on the source direction and frequency. Starting with the observed response of one LISA interferometer and assuming only doppler modulation due to the orbital motion of LISA, we show how the distribution of the entire binary population in frequency and sky position can be reconstructed using a tomographic approach. The method is linear and the reconstruction of a delta function distribution, corresponding to an isolated binary, yields a point spread function (psf). An arbitrary distribution and its reconstruction are related via smoothing with this psf. Exploratory results are reported demonstrating the recovery of binary sources, in the presence of white Gaussian noise.Comment: 13 Pages and 9 figures high resolution figures can be obtains from http://www.phys.utb.edu/~rajesh/lisa_tomography.pd

A Gross Anatomy Ontology for Hymenoptera

Hymenoptera is an extraordinarily diverse lineage, both in terms of species numbers and morphotypes, that includes sawflies, bees, wasps, and ants. These organisms serve critical roles as herbivores, predators, parasitoids, and pollinators, with several species functioning as models for agricultural, behavioral, and genomic research. The collective anatomical knowledge of these insects, however, has been described or referred to by labels derived from numerous, partially overlapping lexicons. The resulting corpus of information—millions of statements about hymenopteran phenotypes—remains inaccessible due to language discrepancies. The Hymenoptera Anatomy Ontology (HAO) was developed to surmount this challenge and to aid future communication related to hymenopteran anatomy. The HAO was built using newly developed interfaces within mx, a Web-based, open source software package, that enables collaborators to simultaneously contribute to an ontology. Over twenty people contributed to the development of this ontology by adding terms, genus differentia, references, images, relationships, and annotations. The database interface returns an Open Biomedical Ontology (OBO) formatted version of the ontology and includes mechanisms for extracting candidate data and for publishing a searchable ontology to the Web. The application tools are subject-agnostic and may be used by others initiating and developing ontologies. The present core HAO data constitute 2,111 concepts, 6,977 terms (labels for concepts), 3,152 relations, 4,361 sensus (links between terms, concepts, and references) and over 6,000 text and graphical annotations. The HAO is rooted with the Common Anatomy Reference Ontology (CARO), in order to facilitate interoperability with and future alignment to other anatomy ontologies, and is available through the OBO Foundry ontology repository and BioPortal. The HAO provides a foundation through which connections between genomic, evolutionary developmental biology, phylogenetic, taxonomic, and morphological research can be actualized. Inherent mechanisms for feedback and content delivery demonstrate the effectiveness of remote, collaborative ontology development and facilitate future refinement of the HAO

Tissue accumulation of cephalothin in burns: A comparative study by microdialysis of subcutaneous interstitial fluid cephalothin concentrations in burn patients and healthy volunteers

Burn tissue sites are a potential source of bacteremia during debridement surgery. Burn injury is likely to affect the distribution of antibiotics to tissues, but direct evidence of this is lacking. The aim of this study was to directly evaluate the influence of burn trauma on the distribution of cephalothin to peripheral tissues. We used subcutaneous microdialysis techniques to monitor interstitial fluid concentrations of cephalothin in the burnt and nonburnt tissues of adult patients with severe burns following parenteral administration of 1 g cephalothin for surgical prophylaxis. Analogous simultaneous studies conducted with healthy adult volunteers provided reference tissue concentration data. Equivalent tissue exposures were seen for burn and nonburn sites, giving overall median interstitial cephalothin concentrations (from 0 to 240 min) of 2.84 mg/liter and 3.06 mg/liter, respectively. A lower overall median interstitial cephalothin concentration of 0.54 mg/liter was observed for healthy individuals, and the patient nonburnt tissue and volunteer control tissue cephalothin concentrations exhibited significantly different data distributions (P < 0.001; Kolmogorov-Smirnov nonparametric test). The duration of tissue residence for cephalothin was longer for burn patients than for healthy volunteers. The results demonstrate the potential fallibility of using healthy population models to extrapolate tissue pharmacodynamic predictions from plasma data for burn patients

Quantum reconstruction of an intense polarization squeezed optical state

We perform a reconstruction of the polarization sector of the density matrix of an intense polarization squeezed beam starting from a complete set of Stokes measurements. By using an appropriate quasidistribution, we map this onto the Poincare space providing a full quantum mechanical characterization of the measured polarization state.Comment: 4 pages, 4 eps color figure

Normal and abnormal tissue identification system and method for medical images such as digital mammograms

A system and method for analyzing a medical image to determine whether an abnormality is present, for example, in digital mammograms, includes the application of a wavelet expansion to a raw image to obtain subspace images of varying resolution. At least one subspace image is selected that has a resolution commensurate with a desired predetermined detection resolution range. A functional form of a probability distribution function is determined for each selected subspace image, and an optimal statistical normal image region test is determined for each selected subspace image. A threshold level for the probability distribution function is established from the optimal statistical normal image region test for each selected subspace image. A region size comprising at least one sector is defined, and an output image is created that includes a combination of all regions for each selected subspace image. Each region has a first value when the region intensity level is above the threshold and a second value when the region intensity level is below the threshold. This permits the localization of a potential abnormality within the image

The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear.

The vestibular maculae of the inner ear contain sensory receptor hair cells that detect linear acceleration and contribute to equilibrioception to coordinate posture and ambulatory movements. These hair cells are divided between two groups, separated by a line of polarity reversal (LPR), with oppositely oriented planar-polarized stereociliary bundles that detect motion in opposite directions. The transcription factor EMX2 is known to establish this planar polarized organization in mouse by regulating the distribution of the transmembrane receptor GPR156 at hair cell boundaries in one group of cells. However, the genes regulated by EMX2 in this context were previously not known. Using mouse as a model, we have identified the serine threonine kinase STK32A as a downstream effector negatively regulated by EMX2