The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC) highlighted 81 single-nucleotide polymorphisms (SNPs) with moderate evidence for association to schizophrenia. After ...follow-up in independent samples, seven loci attained genome-wide significance (GWS), but multi-locus tests suggested some SNPs that did not do so represented true associations. We tested 78 of the 81 SNPs in 2640 individuals with a clinical diagnosis of schizophrenia attending a clozapine clinic (CLOZUK), 2504 cases with a research diagnosis of bipolar disorder, and 2878 controls. In CLOZUK, we obtained significant replication to the PGC-associated allele for no fewer than 37 (47%) of the SNPs, including many prior GWS major histocompatibility complex (MHC) SNPs as well as 3/6 non-MHC SNPs for which we had data that were reported as GWS by the PGC. After combining the new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4, CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained that level of support. In bipolar disorder, we also obtained significant evidence for association for 21% of the alleles that had been associated with schizophrenia in the PGC. Our study independently confirms association to three loci previously reported to be GWS in schizophrenia, and identifies the first GWS evidence in schizophrenia for a further three loci. Given the number of independent replications and the power of our sample, we estimate 98% (confidence interval (CI) 78-100%) of the original set of 78 SNPs represent true associations. We also provide strong evidence for overlap in genetic risk between schizophrenia and bipolar disorder.
Small numbers of monoclonal B cells with the phenotype of chronic lymphocytic leukemia (CLL) were detected by means of high-sensitivity flow cytometry in about 5% of adults with a normal blood count ...and about 14% of subjects with lymphocytosis. In the latter group, frank CLL ultimately developed in 15%. The principal features of these monoclonal B cells and the B cells of CLL were similar.
Small numbers of monoclonal B cells with the phenotype of chronic lymphocytic leukemia (CLL) were detected by means of high-sensitivity flow cytometry in about 5% of adults with a normal blood count and about 14% of subjects with lymphocytosis. In the latter group, frank CLL ultimately developed in 15%.
The incidence of chronic lymphocytic leukemia (CLL) is approximately 6 per 100,000 persons per year in North America.
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The National Cancer Institute–sponsored Working Group guidelines for the diagnosis of CLL require a lymphocyte count of 5000 or more per cubic millimeter and a characteristic cell-surface phenotype of B cells: the presence of CD19, CD5, and CD23, weak expression of CD20 and CD79b, and either kappa or lambda immunoglobulin light chains.
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High-sensitivity flow cytometry allows for the detection of B cells with a CLL phenotype in numbers as low as 1 per 10,000 normal leukocytes.
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With this method, CLL-phenotype cells have . . .
To assess the effects of reading instruction on fMRI brain activation in children with dyslexia.
fMRI differences between dyslexic and control subjects have most often involved phonologic processing ...tasks. However, a growing body of research documents the role of morphologic awareness in reading and reading disability.
The authors developed tasks to probe brain activation during phoneme mapping (assigning sounds to letters) and morpheme mapping (understanding the relationship of suffixed words to their roots). Ten children with dyslexia and 11 normal readers performed these tasks during fMRI scanning. Children with dyslexia then completed 28 hours of comprehensive reading instruction. Scans were repeated on both dyslexic and control subjects using the same tasks.
Before treatment, children with dyslexia showed less activation than controls in left middle and inferior frontal gyri, right superior frontal gyrus, left middle and inferior temporal gyri, and bilateral superior parietal regions for phoneme mapping. Activation was significantly reduced for children with dyslexia on the initial morpheme mapping scan in left middle frontal gyrus, right superior parietal, and fusiform/occipital region. Treatment was associated with improved reading scores and increased brain activation during both tasks, such that quantity and pattern of activation for children with dyslexia after treatment closely resembled that of controls. The elimination of group differences at follow-up was due to both increased activation for the children with dyslexia and decreased activation for controls, presumably reflecting practice effects.
These results suggest that behavioral gains from comprehensive reading instruction are associated with changes in brain function during performance of language tasks. Furthermore, these brain changes are specific to different language processes and closely resemble patterns of neural processing characteristic of normal readers.
ABSTRACT We present Atacama Large Millimeter/submillimeter Array (ALMA) observations from the 2014 Long Baseline Campaign in dust continuum and spectral line emission from the HL Tau region. The ...continuum images at wavelengths of 2.9, 1.3, and 0.87 mm have unprecedented angular resolutions of 0 075 (10 AU) to 0 025 (3.5 AU), revealing an astonishing level of detail in the circumstellar disk surrounding the young solar analog HL Tau, with a pattern of bright and dark rings observed at all wavelengths. By fitting ellipses to the most distinct rings, we measure precise values for the disk inclination ( ) and position angle We obtain a high-fidelity image of the 1.0 mm spectral index ( ), which ranges from in the optically thick central peak and two brightest rings, increasing to 2.3-3.0 in the dark rings. The dark rings are not devoid of emission, and we estimate a grain emissivity index of 0.8 for the innermost dark ring and lower for subsequent dark rings, consistent with some degree of grain growth and evolution. Additional clues that the rings arise from planet formation include an increase in their central offsets with radius and the presence of numerous orbital resonances. At a resolution of 35 AU, we resolve the molecular component of the disk in HCO+ (1-0) which exhibits a pattern over LSR velocities from 2-12 km s−1 consistent with Keplerian motion around a ∼1.3 star, although complicated by absorption at low blueshifted velocities. We also serendipitously detect and resolve the nearby protostars XZ Tau (A/B) and LkH 358 at 2.9 mm.
The SAMI Galaxy Survey: Early Data Release Allen, J. T.; Croom, S. M.; Konstantopoulos, I. S. ...
Monthly notices of the Royal Astronomical Society,
01/2015, Letnik:
446, Številka:
2
Journal Article
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We present the Early Data Release of the Sydney-AAO Multi-object Integral field spectrograph (SAMI) Galaxy Survey. The SAMI Galaxy Survey is an ongoing integral field spectroscopic survey of ~3400 ...low-redshift (z < 0.12) galaxies, covering galaxies in the field and in groups within the Galaxy And Mass Assembly (GAMA) survey regions, and a sample of galaxies in clusters. In the Early Data Release, we publicly release the fully calibrated data cubes for a representative selection of 107 galaxies drawn from the GAMA regions, along with information about these galaxies from the GAMA catalogues. All data cubes for the Early Data Release galaxies can be downloaded individually or as a set from the SAMI Galaxy Survey website. In this paper we also assess the quality of the pipeline used to reduce the SAMI data, giving metrics that quantify its performance at all stages in processing the raw data into calibrated data cubes. The pipeline gives excellent results throughout, with typical sky subtraction residuals in the continuum of 0.9-1.2 per cent, a relative flux calibration uncertainty of 4.1 per cent (systematic) plus 4.3 per cent (statistical), and atmospheric dispersion removed with an accuracy of 0.09 arcsec, less than a fifth of a spaxel.
Abstract
We analyse the velocity dispersion properties of 472 z ∼ 0.9 star-forming galaxies observed as part of the KMOS Redshift One Spectroscopic Survey (KROSS). The majority of this sample is ...rotationally dominated (83 ± 5 per cent with vC/σ0 > 1) but also dynamically hot and highly turbulent. After correcting for beam smearing effects, the median intrinsic velocity dispersion for the final sample is σ0 = 43.2 ± 0.8 km s−1 with a rotational velocity to dispersion ratio of vC/σ0 = 2.6 ± 0.1. To explore the relationship between velocity dispersion, stellar mass, star formation rate, and redshift, we combine KROSS with data from the SAMI survey (z ∼ 0.05) and an intermediate redshift MUSE sample (z ∼ 0.5). Whilst there is, at most, a weak trend between velocity dispersion and stellar mass, at fixed mass there is a strong increase with redshift. At all redshifts, galaxies appear to follow the same weak trend of increasing velocity dispersion with star formation rate. Our results are consistent with an evolution of galaxy dynamics driven by discs that are more gas rich, and increasingly gravitationally unstable, as a function of increasing redshift. Finally, we test two analytic models that predict turbulence is driven by either gravitational instabilities or stellar feedback. Both provide an adequate description of the data, and further observations are required to rule out either model.
It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. As only a small proportion of ...the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among single-nucleotide polymorphisms (SNPs) selected for marginal evidence for association (P<0.5) from genome-wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs, which are also expression quantitative trait loci (eQTLs), should carry more true association signals compared with SNPs that are not marginally associated. To test this, we identified marginally associated (P<0.5) SNPs from two of the largest available schizophrenia GWAS data sets. We assigned eQTL status to those SNPs based upon an eQTL data set derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can, in principle, allow relevant susceptibility eQTLs to be identified.
The opioid system is implicated in the hedonic and motivational processing of food, and in binge eating, a behaviour strongly linked to obesity. The aim of this study was to evaluate the effects of 4 ...weeks of treatment with the mu-opioid receptor antagonist GSK1521498 on eating behaviour in binge-eating obese subjects. Adults with body mass index ≥ 30 kg m(-2) and binge eating scale scores ≥ 19 received 1-week single-blind placebo run-in, and were then randomized to 28 days with either 2 mg day(-1) GSK1521498, 5 mg day(-1) GSK1521498 or placebo (N=21 per arm) in a double-blind parallel group design. The outcome measures were body weight, fat mass, hedonic and consummatory eating behaviour during inpatient food challenges, safety and pharmacokinetics. The primary analysis was the comparison of change scores in the higher-dose treatment group versus placebo using analysis of covariance at each relevant time point. GSK1521498 (2 mg and 5 mg) was not different from placebo in its effects on weight, fat mass and binge eating scores. However, compared with placebo, GSK1521498 5 mg day(-1) caused a significant reduction in hedonic responses to sweetened dairy products and reduced calorific intake, particularly of high-fat foods during ad libitum buffet meals, with some of these effects correlating with systemic exposure of GSK1521498. There were no significant effects of GSK1521498 2 mg day(-1) on eating behaviour, indicating dose dependency of pharmacodynamics. GSK1521498 was generally well tolerated and no previously unidentified safety signals were detected. The potential for these findings to translate into clinically significant effects in the context of binge eating and weight regain prevention requires further investigation.
We present a methodology for the regularization and combination of sparse sampled and irregularly gridded observations from fibre-optic multiobject integral field spectroscopy. The approach minimizes ...interpolation and retains image resolution on combining subpixel dithered data. We discuss the methodology in the context of the Sydney-AAO multiobject integral field spectrograph (SAMI) Galaxy Survey underway at the Anglo-Australian Telescope. The SAMI instrument uses 13 fibre bundles to perform high-multiplex integral field spectroscopy across a 1° diameter field of view. The SAMI Galaxy Survey is targeting ~3000 galaxies drawn from the full range of galaxy environments. We demonstrate the subcritical sampling of the seeing and incomplete fill factor for the integral field bundles results in only a 10 per cent degradation in the final image resolution recovered. We also implement a new methodology for tracking covariance between elements of the resulting data cubes which retains 90 per cent of the covariance information while incurring only a modest increase in the survey data volume.
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