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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
This study proposed the application of a novel immersed boundary method (IBM) for the treatment of irregular geometries using Cartesian computational grids for high speed compressible gas flows modelled using the unsteady Euler equations. Furthermore, the method is accelerated through the use of multiple Graphics Processing Units – specifically using Nvidia’s CUDA together with MPI - due to the computationally intensive nature associated with the numerical solution to multi-dimensional continuity equations. Due to the high degree of locality required for efficient multiple GPU computation, the Split Harten-Lax-van-Leer (SHLL) scheme is employed for vector splitting of fluxes across cell interfaces. NVIDIA visual profiler shows that our proposed method having a computational speed of 98.6 GFLOPS and 61% efficiency based on the Roofline analysis that provides the theoretical computing speed of reaching 160 GLOPS with an average 2.225 operations/byte. To demonstrate the validity of the method, results from several benchmark problems covering both subsonic and supersonic flow regimes are presented. Performance testing using 96 GPU devices demonstrates a speed up of 89 times that of a single GPU (i.e. 92% efficiency) for a benchmark problem employing 48 million cells. Discussions regarding communication overhead and parallel efficiency for varying problem sizes are also presented.
Numerous studies have demonstrated that genetic and environmental factors interact to influence alcohol problems. Yet prior research has primarily focused on samples of European descent and little is known about gene–environment interactions in relation to alcohol problems in non-European populations. In this study, we examined whether and how genetic risk for alcohol problems and peer deviance and interpersonal traumatic events independently and interactively influence trajectories of alcohol use disorder symptoms in a sample of African American students across the college years (N = 1,119; Mage = 18.44 years). Data were drawn from the Spit for Science study where participants completed multiple online surveys throughout college and provided a saliva sample for genotyping. Multilevel growth curve analyses indicated that alcohol dependence genome-wide polygenic risk scores did not predict trajectory of alcohol use disorder symptoms, while family history of alcohol problems was associated with alcohol use disorder symptoms at the start of college but not with the rate of change in symptoms over time. Peer deviance and interpersonal traumatic events were associated with more alcohol use disorder symptoms across college years. Neither alcohol dependence genome-wide polygenic risk scores nor family history of alcohol problems moderated the effects of these environmental risk factors on alcohol use disorder symptoms. Our findings indicated that peer deviance and experience of interpersonal traumatic events are salient risk factors that elevate risk for alcohol problems among African American college students. Family history of alcohol problems could be a useful indicator of genetic risk for alcohol problems. Gene identification efforts with much larger samples of African descent are needed to better characterize genetic risk for alcohol use disorders, in order to better understand gene–environment interaction processes in this understudied population.
In our attempt to investigate the basic active galactic nucleus (AGN) paradigm requiring a centrally located supermassive black hole (SMBH), a close to Keplerian accretion disk and a jet perpendicular to its plane, we have searched for radio continuum in galaxies with H2O megamasers in their disks. We observed 18 such galaxies with the Very Large Baseline Array in C band (5 GHz, ~2 mas resolution) and we detected 5 galaxies at 8 σ or higher levels. For those sources for which the maser data is available, the positions of masers and those of the 5 GHz radio continuum sources coincide within the uncertainties, and the radio continuum is perpendicular to the maser disk’s orientation within the position angle uncertainties.
Transcritical flow of a stratified fluid past a broad localised topographic obstacle is studied analytically in the framework of the forced extended Korteweg–de Vries, or Gardner, equation. We consider both possible signs for the cubic nonlinear term in the Gardner equation corresponding to different fluid density stratification profiles. We identify the range of the input parameters: the oncoming flow speed (the Froude number) and the topographic amplitude, for which the obstacle supports a stationary localised hydraulic transition from the subcritical flow upstream to the supercritical flow downstream. Such a localised transcritical flow is resolved back into the equilibrium flow state away from the obstacle with the aid of unsteady coherent nonlinear wave structures propagating upstream and downstream. Along with the regular, cnoidal undular bores occurring in the analogous problem for the single-layer flow modelled by the forced Korteweg–de Vries equation, the transcritical internal wave flows support a diverse family of upstream and downstream wave structures, including kinks, rarefaction waves, classical undular bores, reversed and trigonometric undular bores, which we describe using the recent development of the nonlinear modulation theory for the (unforced) Gardner equation. The predictions of the developed analytic construction are confirmed by direct numerical simulations of the forced Gardner equation for a broad range of input parameters.
The crystal structure of a-plane GaN/ZnO heterostructures on r-plane sapphire was investigated by using the XRD and TEM measurment. It was found the formation of (220) ZnGa2O4 and crystal orientation of semipolar (10
3) GaN at GaN/ZnO interface. The epitaxial relation of normal surface direction are the sapphire (1
02) // a-GaN (11
0) and ZnGa2O4 (220) // semi-polar GaN (10
). Beside, the emission peak energy of ZnO appears shift about 60 meV in the GaN/ZnO/GaN heterostructures due to the re-crystallization of ZnO layer with Ga or N atom and the formation of the localized state.
Water vapor megamasers from the center of active galaxies provide a powerful tool to trace accretion disks at sub-parsec resolution and, through an entirely geometrical method, measure direct distances to galaxies up to 200 Mpc. The Megamaser Cosmology Project (MCP) is formed by a team of astronomers with the aim of identifying new maser systems, and mapping their emission at high angular resolution to determine their distance. Two types of observations are necessary to measure a distance: single-dish monitoring to measure the acceleration of gas in the disk, and sensitive VLBI imaging to measure the angular size of the disk, measure the rotation curve, and model radial displacement of the maser feature. The ultimate goal of the MCP is to make a precise measurement of H0 by measuring such distances to at least 10 maser galaxies in the Hubble flow. We present here the preliminary results from a new maser system, Mrk 1419. Through a model of the rotation from the systemic masers assuming a narrow ring, and combining these results with the acceleration measurement from the Green Bank Telescope, we determine a distance to Mrk 1419 of 81 ± 10 Mpc. Given that the disk shows a significant warp that may not be entirely traced by our current observations, more sensitive observations and more sophisticated disk modeling will be essential to improve our distance estimation to this galaxy.
The Hubble constant H0 describes not only the expansion of local space at redshift z ~ 0, but is also a fundamental parameter determining the evolution of the universe. Recent measurements of H0 anchored on Cepheid observations have reached a precision of several percent. However, this problem is so important that confirmation from several methods is needed to better constrain H0 and, with it, dark energy and the curvature of space. A particularly direct method involves the determination of distances to local galaxies far enough to be part of the Hubble flow through water vapor (H2O) masers orbiting nuclear supermassive black holes. The goal of this article is to describe the relevance of H0 with respect to fundamental cosmological questions and to summarize recent progress of the ‘Megamaser Cosmology Project’ (MCP) related to the Hubble constant.
Background: The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NAB) offers information on the clinical diagnosis of Alzheimer's disease (AD) and gives a profile of cognitive functioning. This study explores the effects of age, education and gender on participants' performance on eight subtests in the Chinese-Cantonese version of the CERAD-NAB.
Methods: The original English version of the CERAD-NAB was translated and content-validated into a Chinese-Cantonese version to suit the Hong Kong Chinese population. The battery was administered to 187 healthy volunteers aged 60 to 94 years. Participants were excluded if they had neurological, medical or psychiatric disorders (including dementia). Stepwise multiple linear regression analyses were performed to assess the relative contribution of the demographic variables to the scores on each subtest.
Results: The Cantonese version of CERAD-NAB was shown to have good content validity and excellent inter-rater reliability. Stepwise multiple regression analyses revealed that performances on seven and four out of eight subtests in the CERAD-NAB were significantly influenced by education level and age, respectively. Age and education had significant effects on participants' performance on many tests. Gender also showed a significant effect on one subtest.
Conclusions: The preliminary data will serve as an initial phase for clinical interpretation of the CERAD-NAB for Cantonese-speaking Chinese elders.
Although mature seeds of the monogeneric conifer family Cephalotaxaceae sensu stricto have underdeveloped embryos, no definitive studies have been done to classify dormancy in this family. Our primary purpose was to determine the kind of dormancy in seeds of Cephalotaxus wilsoniana and to put the results into a broad phylogenetic context for gymnosperms. The species is of horticultural and medicinal value, and information is needed on how to propagate it efficiently from seeds. Embryo growth and germination were monitored for seeds at warm, cold and warm plus cold temperatures, and germination was monitored for seeds subjected to: (1) cold → warm → cold → warm; and (2) warm → cold → warm → cold → warm temperature sequences. The effects of gibberellic acids GA3 and GA4 were tested on radicle emergence in ungerminated seeds and on shoot emergence in root-emerged seeds. Germination was promoted by ≥ 36 weeks of warm stratification followed by ≥ 8 weeks of cold stratification, but only if seeds were returned to high temperatures. The underdeveloped embryo must increase in length by >120% before the radicle emerges. Neither GA3 nor GA4 was effective in promoting radicle emergence; however, both plant growth regulators increased rate (but not percentage) of shoot emergence in root-emerged seeds. We conclude that seeds of C. wilsoniana have the deep simple level of morphophysiological dormancy (MPD), C1b-C3-B1b; thus, warm stratification followed by cold stratification and then warm-temperature incubation are required for germination. In gymnosperms, MPD is known in cycads, Ginkgo and now in three families of conifers.
Pavement roughness causes pavement stress fluctuation along the road. However, the dynamic effects were not taken into account in most pavement design and studies. To investigate the influences of roadway roughness on pavement stresses, this study developed a coupled system consisting of a quarter-car model and an equivalent lump pavement model. The coupled system also incorporated measured road profiles. By means of transfer function in frequency domain, the deflections and stresses of pavements were computed in seconds. The results were validated with Westergaard's solutions satisfactorily. It was found that the critical roughness, which might cause extreme responses, is related to the vehicle speed and suspension of vehicles. The maximum tension at the bottom of pavements also depends on the size of bump. In addition, the study demonstrates the correlation between roughness index, IRI, and ISO roughness classifications. It was also found that disturbance due to model boundary affects simulation results significantly.
The present study aimed to (a) characterize 10-year trajectory patterns of depressive symptoms and (b) investigate the association between depressive trajectory and subsequent obesity, metabolic function and cortisol level.
In a prospective study of Taiwanese adults aged ⩾60 years (n=3922) between 1989 and 1999, depression was assessed using a 10-item short-form of the Center for Epidemiologic Studies Depression Scale and information on body mass index (BMI) was collected by self-report. A subsample (n=445) of the original cohort in 1989 was drawn to assess metabolic variables and cortisol levels in a 2000 follow-up. After trajectory analyses were performed, multinomial logistic regression analyses were used to estimate the association estimates.
We identified four distinctive trajectories of depressive symptoms: class 1 (persistent low, 41.8%); class 2 (persistent mild, 46.8%); class 3 (late peak, 4.2%); and class 4 (high-chronic, 7.2%). The results from both complete cases and multiple imputation analyses indicated that the odds of obesity were lower in the class 2, 3 or 4 elderly, as compared with those in class 1, while the odds of underweight were higher. The classes of older adults with more and persistent depressive symptoms showed a trend toward having both a lower BMI (p=0.01) and a higher cortisol level (p=0.04) compared with those with low depressive symptoms.
Incremental increases in depressive symptoms over time were associated with reduced risk of obesity and higher cortisol levels.
We report on a measles outbreak originating in an anthroposophic community in Austria, 2008. A total of 394 (94·9%) cases fulfilled the outbreak case definition including 168 cases affiliated to the anthroposophic community. The source case was a school pupil from Switzerland. The Austrian outbreak strain was genotype D5, indistinguishable from the Swiss outbreak strain. A school-based retrospective cohort study in the anthroposophic school demonstrated a vaccine effectiveness of 97·3% in pupils who had received a single dose of measles-containing vaccine and 100% in those who had received two doses. The vaccination coverage of the cases in the anthroposophic community was 0·6%. Of the 226 outbreak cases not belonging to the anthroposophic community, the 10–24 years age group was the most affected. Our findings underline the epidemiological significance of suboptimal vaccination coverage in anthroposophic communities and in older age groups of the general population in facilitating measles virus circulation. The findings of this outbreak investigation suggest that the WHO European Region is unlikely to achieve its 2010 target for measles and rubella elimination.
The coupling of hydromagnetic Alfvén waves is studied numerically in a dipolc-field model of the magnetosphere. The two coupled hydromagnetic equations derived by Radoski are solved as an implicit boundary-value problem, namely the boundary conditions at the magnetopause are determined self-consistently. Thus the calculated wave-field distribution inside the magnetosphere can match all known linear characteristic features of the stormtime Pc5 waves observed on 14/15 November 1979 from satellites. A set of proper boundary conditions is found, excellent agreement between the numerical results and observations is demonstrated. Based on the very limited spatial coverage (L ≈ 6·6 and within a latitudinal region ( −10°, 10°)), of the data provided by the satellites, the theoretical model can successfully reconstruct the global micropulsations in the magnetosphere and identify the source regions of hydromagnetic waves.
A purely growing instability characterized by a four-wave interaction has been analysed in a uniform, magnetized plasma. Up-shifted and down-shifted upper-hybrid waves and a non-oscillatory mode can be excited by a pump wave of ordinary rather than extraordinary polarization in the case of ionospheric heating. The differential Ohmic heating force dominates over the ponderomotive force as the wave–wave coupling mechanism. The beating current at zero frequency produces a significant stabilizing effect on the excitation of short-scale modes by counterbalancing the destabilizing effect of the differential Ohmic heating. The effect of ionospheric inhomogeneity is estimated, showing a tendency to raise the thresholds of the instability. When applied to ionospheric heating experiments, the present theory can explain the excitation of field-aligned plasma lines and ionospheric irregularities with a continuous spectrum ranging from metre-scale to hundreds of metre-scale. Further, the proposed mechanism may become a competitive process to the parametric decay instability and be responsible for the overshoot phenomena of the plasma line enhancement at Arecibo.
The fundamental process of acceleration of charged particles by large-amplitude electromagnetic waves is investigated. Exact analytical solutions can be derived from the nonlinear equations that govern the motion of charged particles in wave fields. It is found that circularly polarized electromagnetic waves can act on the charged particles via α d.c. Lorentz force imposed by the wave fields. This process can effectively energize charged particles that may initially have low energies.
This work is intended to explain why the resonant response of the magnetosphere prefers to have discrete frequencies. Using a cylindrical model for the outer magnetosphere with a plasma density profile proportional to 1/r, we show that the eigenequation characterizing the eigenmodes of the hydromagnetic waves in this model has two turning points along the radial axis. The locations of the turning points depend upon the values of the eigenperiod and the associated east-west wavenumber of the eigenmode. The energy spectrum of the excited cavity modes is seen to have sharp peaks at discrete frequencies when the surface perturbations have a uniform spectrum in the frequency range of interest. We, therefore, have also shown that only the discrete set of the magnetospheric cavity eigenmodes can efficiently couple the perturbations excited on the boundary of the magnetosphere to the field-line resonant mode excited inside the inner turning point of the cavity eigenmode. The most likely values of east-west wavenumbers and wave period range are determined.
A thermal instability is studied as an explanation of the anomalous electron density depletion observed during the electron-cyclotron resonance (ECR) heating of plasma in a tokamak device for an impurity study experiment (ISXB). Considering the fact that the background plasma has an elevated electron temperature and a localized heat source located near the ECR layer, we show that density striations having scale length 10 cm and larger can be excited via the thermal instability. The amplitude of the striations can grow by more than one e-folding during the ECR pulse period of 10 ms, which causes about 50% electron temperature elevation. A 0·1% temperature fluctuation excited by the thermal instability leads to about 50 V m-1 field fluctuation. Such a large electrostatic field can effectively cause anomalous plasma diffusion via the E ′ B drift and account for the observed 15% electron density depletion.
The theory of resonant electron diffusion as an effective saturation process of the auroral kilometric radiation has been formulated. The auroral kilometric radiation is assumed to be amplified by the synchrotron maser instability that is driven by an electron distribution of the loss-cone type. The calculated intensity of the saturated radiation is found to have a significantly lower value in comparison with that caused by the quasi-linear diffusion process as an alternative saturation process. This indicates that resonant electron diffusion dominates over quasi-linear diffusion in saturating the synchrotron maser instability.
This work explores the sound transmission loss provided by the orthotropic multi-layers to elucidate the sound insulation of FRP (Fiber Reinforced Plastics). Mat is the major material considered in the numerical works. The transfer matrices of a single layer of the orthotropic laminate and the fluid are determined. Further, the boundary conditions on the various interface planes are arranged into matrix form. Combining the transfer matrixes and the boundary conditions and applying the transfer matrix method (TMM) yields the surface impedance and the sound transmission loss. The sound-propagation characteristics are studied. Additionally, the STC (Sound Transmission Class) of FRP and steel are compared and discussed.