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.
Quantifying changes in thermokarst lake extent is of importance for understanding the permafrost‐related carbon budget, including the potential release of carbon via lake expansion or sequestration ...as peat in drained lake basins. We used high spatial resolution remotely sensed imagery from 1950/51, 1978, and 2006/07 to quantify changes in thermokarst lakes for a 700 km2 area on the northern Seward Peninsula, Alaska. The number of water bodies larger than 0.1 ha increased over the entire observation period (666 to 737 or +10.7%); however, total surface area decreased (5,066 ha to 4,312 ha or −14.9%). This pattern can largely be explained by the formation of remnant ponds following partial drainage of larger water bodies. Thus, analysis of large lakes (>40 ha) shows a decrease of 24% and 26% in number and area, respectively, differing from lake changes reported from other continuous permafrost regions. Thermokarst lake expansion rates did not change substantially between 1950/51 and 1978 (0.35 m/yr) and 1978 and 2006/07 (0.39 m/yr). However, most lakes that drained did expand as a result of surface permafrost degradation before lateral drainage. Drainage rates over the observation period were stable (2.2 to 2.3 per year). Thus, analysis of decadal‐scale, high spatial resolution imagery has shown that lake drainage in this region is triggered by lateral breaching and not subterranean infiltration. Future research should be directed toward better understanding thermokarst lake dynamics at high spatial and temporal resolution as these systems have implications for landscape‐scale hydrology and carbon budgets in thermokarst lake‐rich regions in the circum‐Arctic.
Key Points
Landscape scale assessment of thermokarst lake expansion and drainage rates
Widespread drainage of thermokarst lakes in the continuous permafrost zone
Thermokarst lake dynamics impact the northern high latitude carbon cycle
We have conducted a genotyping study using a custom Illumina Infinium HD genotyping array, the ImmunoChip, in a new UK sample of 1218 bipolar disorder (BD) cases and 2913 controls that have not been ...used in any studies previously reported independently or in meta-analyses. The ImmunoChip was designed before the publication of the Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder Working Group (PGC-BD) meta-analysis data. As such 3106 single-nucleotide polymorphisms (SNPs) with a P-value <1 × 10(-3) from the BD meta-analysis by Ferreira et al. were genotyped. We report support for two of the three most strongly associated chromosomal regions in the Ferreira study, CACNA1C (rs1006737, P=4.09 × 10(-4)) and 15q14 (rs2172835, P=0.043) but not ANK3 (rs10994336, P=0.912). We have combined our ImmunoChip data (569 quasi-independent SNPs from the 3016 SNPs genotyped) with the recently published PGC-BD meta-analysis data, using either the PGC-BD combined discovery and replication data where available or just the discovery data where the SNP was not typed in a replication sample in PGC-BD. Our data provide support for two regions, at ODZ4 and CACNA1C, with prior evidence for genome-wide significant (GWS) association in PGC-BD meta-analysis. In addition, the combined analysis shows two novel GWS associations. First, rs7296288 (P=8.97 × 10(-9), odds ratio (OR)=0.9), an intergenic polymorphism on chromosome 12 located between RHEBL1 and DHH. Second, rs3818253 (P=3.88 × 10(-8), OR=1.16), an intronic SNP on chromosome 20q11.2 in the gene TRPC4AP, which lies in a high linkage disequilibrium region along with the genes GSS and MYH7B.
Abstract FORKMAN, B., A., BOISSY, M.-C., SALAÜN, E., CANALI, AND R.B., JONES. A critical review of fear tests used on cattle, pigs, sheep, poultry and horses. PHYSIOL. BEHAV. 000-000, 2007. Fear is ...arguably the most commonly investigated emotion in domestic animals. In the current review we attempt to establish the level of repeatability and validity found for fear tests used on cattle, pigs, sheep and goats, poultry and horses. We focus the review on the three most common types of fear tests: the arena test (open field), the novel object test, and the restraint test. For some tests, e.g. tonic immobility in poultry, there is a good and broad literature on factors that affect the outcome of the test, the validity of the test and its age dependency. However, there are comparatively few of these well defined and validated tests and what is especially missing for most tests is information on the robustness, i.e., what aspects can be changed without affecting the validity of the tests. The relative absence of standardized tests hampers the development of applied ethology as a science.
Molecular genetic analysis offers opportunities to advance our understanding of the nosological relationship between psychiatric diagnostic categories in general, and the mood and psychotic disorders ...in particular. Strong evidence (P=7.0 × 10(-7)) of association at the polymorphism rs1006737 (within CACNA1C, the gene encoding the α-1C subunit of the L-type voltage-gated calcium channel) with the risk of bipolar disorder (BD) has recently been reported in a meta-analysis of three genome-wide association studies of BD, including our BD sample (N=1868) studied within the Wellcome Trust Case Control Consortium. Here, we have used our UK case samples of recurrent major depression (N=1196) and schizophrenia (N=479) and UK non-psychiatric comparison groups (N=15316) to examine the spectrum of phenotypic effect of the bipolar risk allele at rs1006737. We found that the risk allele conferred increased risk for schizophrenia (P=0.034) and recurrent major depression (P=0.013) with similar effect sizes to those previously observed in BD (allelic odds ratio ∼1.15). Our findings are evidence of some degree of overlap in the biological underpinnings of susceptibility to mental illness across the clinical spectrum of mood and psychotic disorders, and show that at least some loci can have a relatively general effect on susceptibility to diagnostic categories, as currently defined. Our findings will contribute to a better understanding of the pathogenesis of major psychiatric illness, and such knowledge should be useful in providing an etiological rationale for shaping psychiatric nosology, which is currently reliant entirely on descriptive clinical data.
In 1928, Dirac published an equation
that combined quantum mechanics and special relativity. Negative-energy solutions to this equation, rather than being unphysical as initially thought, represented ...a class of hitherto unobserved and unimagined particles-antimatter. The existence of particles of antimatter was confirmed with the discovery of the positron
(or anti-electron) by Anderson in 1932, but it is still unknown why matter, rather than antimatter, survived after the Big Bang. As a result, experimental studies of antimatter
, including tests of fundamental symmetries such as charge-parity and charge-parity-time, and searches for evidence of primordial antimatter, such as antihelium nuclei, have high priority in contemporary physics research. The fundamental role of the hydrogen atom in the evolution of the Universe and in the historical development of our understanding of quantum physics makes its antimatter counterpart-the antihydrogen atom-of particular interest. Current standard-model physics requires that hydrogen and antihydrogen have the same energy levels and spectral lines. The laser-driven 1S-2S transition was recently observed
in antihydrogen. Here we characterize one of the hyperfine components of this transition using magnetically trapped atoms of antihydrogen and compare it to model calculations for hydrogen in our apparatus. We find that the shape of the spectral line agrees very well with that expected for hydrogen and that the resonance frequency agrees with that in hydrogen to about 5 kilohertz out of 2.5 × 10
hertz. This is consistent with charge-parity-time invariance at a relative precision of 2 × 10
-two orders of magnitude more precise than the previous determination
-corresponding to an absolute energy sensitivity of 2 × 10
GeV.
Background
X-ray imaging addresses many challenges with visible light imaging in extreme environments, where optical diagnostics such as digital image correlation (DIC) and particle image velocimetry ...(PIV) suffer biases from index of refraction changes and/or cannot penetrate visibly occluded objects. However, conservation of intensity—the fundamental principle of optical image correlation algorithms—may be violated if ancillary components in the X-ray path besides the surface or fluid of interest move during the test.
Objective
The test series treated in this work sought to characterize the safe use of fiber-epoxy composites in aerospace and aviation industries during fire accident scenarios. Stereo X-ray DIC was employed to measure test unit deformation in an extreme thermal environment involving a visibly occluded test unit, incident surface heating to temperatures above 600
o
C, and flames and soot from combusting epoxy decomposition gasses. The objective of the current work is to evaluate two solutions to resolve the violation of conservation of intensity that resulted from both the test unit and the thermal chamber deforming during the test.
Methods
The first solution recovered conservation of intensity by pre-processing the path-integrated X-ray images to isolate the DIC pattern of the test unit from the thermal chamber components. These images were then correlated with standard, optical DIC software. The second solution, called Path-Integrated Digital Image Correlation (PI-DIC), modified the fundamental matching criterion of DIC to account for multiple, independently-moving components contributing to the final image intensity. The PI-DIC algorithm was extended from a 2D framework to a stereo framework and implemented in a custom DIC software.
Results
Both solutions accurately measured the cylindrical shape of the undeformed test unit, recovering radii values of
R
=
76.20
±
0.12
mm compared to the theoretical radius of
R
theor
=
76.20
mm. During the test, the test unit bulged asymmetrically as decomposition gasses pressurized the interior and eventually burned in a localized jet. Both solutions measured the heterogeneous radius of this bulge, which reached a maximum of approximately
R
=
91
mm, with a discrepancy of 2–3% between the two solutions.
Conclusions
Two solutions that resolve the violation of conservation of intensity for path-integrated X-ray images were developed. Both were successfully employed in a stereo X-ray DIC configuration to measure deformation of an aluminum-skinned, fiber-epoxy composite test unit in a fire accident scenario.
Precipitation downscaling improves the coarse resolution and poor representation of precipitation in global climate models and helps end users to assess the likely hydrological impacts of climate ...change. This paper integrates perspectives from meteorologists, climatologists, statisticians, and hydrologists to identify generic end user (in particular, impact modeler) needs and to discuss downscaling capabilities and gaps. End users need a reliable representation of precipitation intensities and temporal and spatial variability, as well as physical consistency, independent of region and season. In addition to presenting dynamical downscaling, we review perfect prognosis statistical downscaling, model output statistics, and weather generators, focusing on recent developments to improve the representation of space‐time variability. Furthermore, evaluation techniques to assess downscaling skill are presented. Downscaling adds considerable value to projections from global climate models. Remaining gaps are uncertainties arising from sparse data; representation of extreme summer precipitation, subdaily precipitation, and full precipitation fields on fine scales; capturing changes in small‐scale processes and their feedback on large scales; and errors inherited from the driving global climate model.
Sinh-arcsinh distributions JONES, M. C.; PEWSEY, ARTHUR
Biometrika,
12/2009, Letnik:
96, Številka:
4
Journal Article
Recenzirano
Odprti dostop
We introduce the sinh-arcsinh transformation and hence, by applying it to a generating distribution with no parameters other than location and scale, usually the normal, a new family of sinh-arcsinh ...distributions. This four-parameter family has symmetric and skewed members and allows for tailweights that are both heavier and lighter than those of the generating distribution. The central place of the normal distribution in this family affords likelihood ratio tests of normality that are superior to the state-of-the-art in normality testing because of the range of alternatives against which they are very powerful. Likelihood ratio tests of symmetry are also available and are very successful. Three-parameter symmetric and asymmetric subfamilies of the full family are also of interest. Heavy-tailed symmetric sinh-arcsinh distributions behave like Johnson SU distributions, while their light-tailed counterparts behave like sinh-normal distributions, the sinh-arcsinh family allowing a seamless transition between the two, via the normal, controlled by a single parameter. The sinh-arcsinh family is very tractable and many properties are explored. Likelihood inference is pursued, including an attractive reparameterization. Illustrative examples are given. A multivariate version is considered. Options and extensions are discussed.
The discovery of an M4+T8.5 binary system Burningham, Ben; Pinfield, D. J.; Leggett, S. K. ...
Monthly Notices of the Royal Astronomical Society,
05/2009, Letnik:
395, Številka:
3
Journal Article
Recenzirano
Odprti dostop
We report the discovery of a T8.5 dwarf, which is a companion to the M4 dwarf Wolf 940. At a distance of 12.50+0.75−0.67 pc, the angular separation of 32 arcsec corresponds to a projected separation ...of 400 au. The M4 primary displays no Hα emission, and we apply the age–activity relations of West et al. to place a lower limit on the age of the system of 3.5 Gyr. Weak Hα absorption suggests some residual activity, and we estimate an upper age limit of 6 Gyr. We apply the relations of Bonfils et al. for V−Ks and to determine the metallicity, Fe/H=−0.06 ± 0.20 for Wolf 940A, and by extension the T8.5 secondary, Wolf 940B. We have obtained JHK NIRI spectroscopy and JHKL′ photometry of Wolf 940B, and use these data, in combination with theoretical extensions, to determine its bolometric flux, Fbol= 1.75 ± 0.18 × 10−16 W m−2, and thus its luminosity log (L*/L⊙) =−6.07 ± 0.04. Using the age constraints for the system and evolutionary structural models of Baraffe et al., we determine Teff= 570 ± 25 K and log g= 4.75 − 5.00 for Wolf 940B, based on its bolometric luminosity. This represents the first determination of these properties for a T8+ dwarf that does not rely on the fitting of T dwarf spectral models. This object represents the first system containing a T8+ dwarf for which fiducial constraints on its properties are available, and we compare its spectra with those of the latest very cool BT–Settl models. This clearly demonstrates that the use of the (WJ, K/J) spectral ratios (used previously to constrain Teff and log g) would have overestimated Teff by ∼100 K.