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Previously the GABA(A) receptor beta-2 subunit gene GABRB2 was found to be associated with schizophrenia (SCZ). for SNPs and haplotypes in GRBRB2, the associations with bipolar disorder (BPD), the functional consequences on GABRB2 expression and their relationship to demographic and clinical characteristics in BPD and SCZ remain to be elucidated.
Case-control analysis was performed for association study of GABRB2 with BPD, and its mRNA expression in postmortem BPD brains was examined using quantitative real-time PCR. Quantitative trait analysis was subsequently employed to assess the covariate effects of demographic and clinical characteristics on genotypic correlation of GABRB2 expression in SCZ and BPD.
Significant association of GABRB2 with BPD and reduction in GABRB2 mRNA expression in BPD brains were observed in the present study. Duration of illness (DOI) was found to be a significant covariate for the correlation of the disease-associated SNPs rs1816071, rs1816072 and rs187269 with GABRB2 expression in both SCZ and BPD. for individuals with homozygous major genotypes of these SNPs, while GABRB2 expression increased with age in the controls, it decreased with DOI and age in SCZ, and with DOI in BPD. with age of onset as covariate, these three SNPs were significantly correlated with antipsychotic dosage in SCZ.
These results have thus revealed correlations of GABRB2 SNPs and expression not only with the occurrence of SCZ and BPD, but also with the clinical characteristics of patients, therefore providing support for a shared etiological role played by the gene in both diseases.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
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.
Many accretion disks surrounding supermassive black holes in nearby AGN are observed to host 22 GHz water maser activity. We have analyzed single-dish 22 GHz spectra taken with the GBT to identify 32 such “Keplerian disk systems,” which we used to investigate maser excitation and explore the possibility of disk reverberation. Our results do not support a spiral shock model for population inversion in these disks, and we find that any reverberating signal propagating radially outwards from the AGN must constitute <10% of the total observed maser variability. Additionally, we have used ALMA to begin exploring the variety of sub-mm water megamasers that are also predicted, and in the case of the 321 GHz transition found, to be present in these accretion disks. By observing multiple masing transitions within a single system, we can better constrain the physical conditions (e.g., gas temperature and density) in the accretion disk.
We made dynamical black hole mass measurements from nineteen Seyfert 2 galaxies which host sub-parsec H2O maser disks using the H2O megamaser technique. The nearly perfect Keplerian rotation curves in many of these maser systems guarantee the high accuracy and precision of the black hole mass measurements. With the stellar velocity dispersion (σ∗) of the galaxy bulges measured with the Dupont 2.5 m telescope at Las Campanas Observatory in the South and the Apache Point Observatory (APO) 3.5m telescope in the North, we found that H2O maser galaxies, most of which host pseudo bulges rather than classical bulges, do not all follow the MBH–σ∗ relation shown in the literature. This result is well consistent with the latest findings by Kormendy & Ho (2013) that only early type galaxies and galaxies with classical bulges follow a tight MBH–σ∗ relation. Such a tight correlation may not exist in pseudo bulge galaxies.
The Millimetre Astronomy Legacy Team 90 GHz (MALT90) survey aims to characterise the physical and chemical evolution of high-mass star-forming clumps. Exploiting the unique broad frequency range and on-the-fly mapping capabilities of the Australia Telescope National Facility Mopra 22 m single-dish telescope1, MALT90 has obtained 3′ × 3′ maps towards ~2 000 dense molecular clumps identified in the ATLASGAL 870 μm Galactic plane survey. The clumps were selected to host the early stages of high-mass star formation and to span the complete range in their evolutionary states (from prestellar, to protostellar, and on to
regions and photodissociation regions). Because MALT90 mapped 16 lines simultaneously with excellent spatial (38 arcsec) and spectral (0.11 km s−1) resolution, the data reveal a wealth of information about the clumps’ morphologies, chemistry, and kinematics. In this paper we outline the survey strategy, observing mode, data reduction procedure, and highlight some early science results. All MALT90 raw and processed data products are available to the community. With its unprecedented large sample of clumps, MALT90 is the largest survey of its type ever conducted and an excellent resource for identifying interesting candidates for high-resolution studies with ALMA.
Singularity-free workspace is a very important criterion for the design of manipulators, especially for parallel manipulators which are well known for their limited workspace and complex singularities. This paper studies geometric parameters and dexterity measures that affect the size of a singularity-free joint space and proposes methods for the development of 6-DOF Stewart–Gough parallel manipulators that have better singularity-free joint space. With a local dexterity measure as the objective function, a systematic method is employed to search for the design with a maximal singularity-free joint space. The related workspaces are also investigated. It is shown that the workspace is not proportional to the size of the joint space and that manipulators with a larger singularity-free workspace usually have relatively poor dexterity.
A survey of the Milky Way disk and the Magellanic System at the wavelengths of the 21-cm atomic hydrogen (H i) line and three 18-cm lines of the OH molecule will be carried out with the Australian Square Kilometre Array Pathfinder telescope. The survey will study the distribution of H i emission and absorption with unprecedented angular and velocity resolution, as well as molecular line thermal emission, absorption, and maser lines. The area to be covered includes the Galactic plane (|b| < 10°) at all declinations south of δ = +40°, spanning longitudes 167° through 360°to 79° at b = 0°, plus the entire area of the Magellanic Stream and Clouds, a total of 13 020 deg2. The brightness temperature sensitivity will be very good, typically σT≃ 1 K at resolution 30 arcsec and 1 km s−1. The survey has a wide spectrum of scientific goals, from studies of galaxy evolution to star formation, with particular contributions to understanding stellar wind kinematics, the thermal phases of the interstellar medium, the interaction between gas in the disk and halo, and the dynamical and thermal states of gas at various positions along the Magellanic Stream.
To constrain models of dark energy, a precise measurement of the Hubble constant, H0, provides a powerful complement to observations of the cosmic microwave background. Recent, precise measurements of H0 have been based on the ‘extragalactic distance ladder,’ primarily using observations of Cepheid variables and Type Ia supernovae as standard candles. In the past, these methods have been limited by systematic errors, so independent methods of measuring H0 are of high value. Direct geometric distance measurements to circumnuclear H2O megamasers in the Hubble flow provide a promising new method to determine H0. The Megamaser Cosmology Project (MCP) is a systematic effort to discover suitable H2O megamasers and determine their distances, with the aim of measuring H0 to a few percent. Based on observations of megamasers in UGC 3789 and NGC 6264, and preliminary results from Mrk 1419, the MCP has so far measured H0 = 68.0 ± 4.8 km s−1 Mpc−1. This measurement will improve as distances to additional galaxies are incorporated. With the Green Bank Telescope, we recently discovered three more excellent candidates for distance measurements, and we are currently acquiring data to measure their distances.
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.
Four thousand and one hospital staff were screened for hepatitis B virus (HBV) markers in a vaccination programme in Hong Kong. The seropositivity rate for HBsAg, anti-HBs and anti-HBc were significantly higher in the 3160 existing hospital staff than in 841 new recruits. Of the subjects negative for HBV markers, 605 were randomized to receive three doses of either 10 or 20 μg of the Merck Institute vaccine (HB-VAX). Compared with the 20 μg dose, vaccination with the 10 μg dose results in equal immunogenicity and efficacy at the completion of the three injections but induced a slower response rate and lower anti-HBs titres with the first two doses. The commonest side-effect of local soreness was less with the 10 μg dose. We conclude that (1) hospital staff working in high endemic areas should be vaccinated on recruitment and (2) the 10 μg dose of HB-VAX can replace the recommended 20 μg dose for adults, being cheaper and as efficacious.
The objective of this study was to address the impact of heterogeneity of infectious period and contagiousness on Salmonella transmission dynamics in dairy cattle populations. We developed three deterministic SIR-type models with two basic infected stages (clinically and subclinically infected). In addition, model 2 included long-term shedders, which were defined as individuals with low contagiousness but long infectious period, and model 3 included super-shedders (individuals with high contagiousness and long infectious period). The simulated dynamics, basic reproduction number (R0) and critical vaccination threshold were studied. Clinically infected individuals were the main force of infection transmission for models 1 and 2. Long-term shedders had a small impact on the transmission of the infection and on the estimated vaccination thresholds. The presence of super-shedders increases R0 and decreases the effectiveness of population-wise strategies to reduce infection, making necessary the application of strategies that target this specific group.
A determination of the Hubble Constant (H0) to better than 3% would be the best complement to cosmic microwave background (CMB) data to constrain the equation of state of Dark Energy. Water vapor megamasers provide perhaps the best opportunity for measuring direct distances to galaxies out to about 200 Mpc. We have formed a team of astronomers in the Megamaser Cosmology Project to pursue the ambitious goal of making a precise measurement of H0 by measuring such distances using the techniques pioneered on the disk maser in NGC 4258 by Herrnstein et al (1999). In recent surveys we have made significant progress identifying new maser systems analogous to that in NGC 4258, but more distant. Once the appropriate candidates are identified, two types of observations are necessary to ultimately measure a distance: single-dish monitoring to measure the acceleration of gas in the disk, and sensitive VLBI imaging in order to measure the angular size of the disk, measure the rotation curve, and model radial displacement of the systemic maser features. We have recently obtained preliminary VLBI maps of the masers in two systems, NGC 6323 and UGC 3789. The maser disks in both galaxies were discovered and monitored with the Green Bank Telescope (GBT) and subsequently imaged with the High Sensitivity Array (VLBA + GBT + Effelsberg). In this contribution we present a map of the maser distribution in one of those systems, NGC 6323. The map demonstrates that pc-scale maser disks as distant as ~ 100 Mpc can be imaged with existing telescopes. Results on UGC 3789 will be presented in a later publication.
We present an atlas of extragalactic water vapor masers. As of 2007, one hundred galaxies have been detected as sources of water vapor maser emission, two thirds of them discovered since 2003. Extragalactic water masers fall in at least three categories: those associated with nuclear jets or winds, those in starbursts or star-forming regions, and those in AGN accretion disks. While all maser systems offer the possibility of unique investigations into their physical environments, it is the disk masers that have been most aggressively sought because of their potential for use as precision distance indicators. Type 2 Seyfert and LINER galaxies are hosts to such disk masers. Insingle-dish spectra, disk masers are often revealed by the presence of high-velocity emission features (defined roughly by having anomalous velocities in excess of 200 km s−1). About one third of the extragalactic water masers detected to date show evidence of disk origin. Only a few galaxies are currently identified as jet-type or star-forming type. The remaining systems show only a few narrow doppler components, usually near the systemic velocity, and are difficult to categorize. These unclassified systems are detected toward AGNs and are also possibly associated with disks or winds near the nucleus. Detection rates in large maser surveys are typically 5% or less, but the observing efficiency and sensitivity of the Green Bank Telescope (GBT) allow for short integration times (typically 10 minutes to detect a narrow 30 mJy line) so many galaxies can be searched. Recently, GBT surveys targeting type 2 Seyfert galaxies identified by the SDSS have been the most productive, identifying 17 systems in surveys observed during 2006.
Objectives: We aimed to conduct a retrospective analysis of patients treated with radiotherapy for laryngeal carcinoma at a single institution.
Methods: We analysed data from 202 consecutive patients treated with primary or post-operative radiotherapy for laryngeal carcinoma over a 10-year period.
Results: Sixty-nine patients had a T1, 65 a T2, 39 a T3 and 29 a T4 lesion. Forty-one patients were node-positive. The clinical stage was I in 67 patients, II in 53, III in 36 and IV in 46. Primary radiotherapy was given to 152 patients. The median follow up was 60 months. The five-year overall local control rate was 86 per cent, the ultimate local control rate was 93 per cent, the five-year regional control rate was 96 per cent, the five-year relapse-free survival rate was 82 per cent and the five-year overall survival rate was 69 per cent.
Conclusions: Patients with laryngeal carcinoma treated with primary or post-operative radiotherapy had a five-year overall survival rate of 69 per cent.
Twenty-one Candida albicans isolates from three HIV-infected patients were collected over a period of 3 years and characterized for fluconazole susceptibility, infectivity and genetic relatedness. Fluconazole resistance was found in five isolates, four exhibited dose-dependent susceptibility and the remainder were fully susceptible to this agent. Pulsed-field gel electrophoresis of SfiI restriction digests of the genomic DNA from the isolates revealed that isolates from the same swab specimen were identical despite differences in susceptibility to fluconazole and isolates recovered over time from the three patients retained clonally related DNA fingerprints within each patient. This small-scale study confirms the persistence of oral colonization of C. albicans strains in HIV-infected patients. Clinical data also suggests that the primary infecting strain may become a persistent colonist in the oral cavity once the immune function of the patient has been restored.