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Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
UK guidelines recommend routine HIV testing in high prevalence emergency departments (ED) and targeted testing for HBV and HCV. The ‘Going Viral’ campaign implemented opt-out blood-borne virus (BBV) testing in adults in a high prevalence ED, to assess seroprevalence, uptake, linkage to care (LTC) rates and staff time taken to achieve LTC. Diagnosis status (new/known/unknown), current engagement in care, and severity of disease was established. LTC was defined as patient informed plus ⩾1 clinic visit. A total of 6211/24 981 ED attendees were tested (uptake 25%); 257 (4.1%) were BBV positive (15 co-infected), 84 (33%) required LTC. 100/147 (68%) HCV positives were viraemic; 44 (30%) required LTC (13 new, 16 disengaged). 26/54 (48%) HBV required LTC (seven new, 11 disengaged). 16/71 (23%) HIV required LTC (10 new, five disengaged). 26/84 (31%) patients requiring LTC had advanced disease (CD4 <350, APRI (AST-to-Platelet Ratio Index) >1, Fibroscan F3/F4 or liver cancer), including five with AIDS-defining conditions and three hepatocellular carcinomas. There were five BBV-related deaths. BBV prevalence was high (4.1%); most were HCV (2.4%). HIV patients were more successfully and quickly LTC than HBV or HCV patients. ED testing was valuable as one-third of those requiring LTC (new, disengaged or unknown status patients) had advanced disease.
Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.
The magnetic and magnetocaloric properties of Ni45Mn43CoSn11 have been investigated using heat capacity measurements and magnetization with hydrostatic pressure applications. A shift in the martensitic transition temperature by 40 K to higher temperatures was observed with application of pressure P = 1.06 GPa. The magnetic entropy changes significantly increases from 24 to 42 J/kgK at pressure of 0.73 GPa. A large adiabatic temperature change of 4 K was found from specific heat measurements. Also, the density of states and Debye temperature has been estimated from heat capacity measurements. The mixed effects of pressure and magnetic field on the transition temperature are discussed.
Spectral analysis of time series of a c. 17 ± 0.3 year core, calibrated for total ß activity recovered from Sentik Glacier (4908m) Ladakh, Himalaya, yields several recognizable periodicities including subannual, annual, and multi-annual. The time-series, include both chemical data (chloride, sodium, reactive iron, reactive silicate, reactive phosphate, ammonium, δD, δ(18O) and pH) and physical data (density, debris and ice-band locations, and microparticles in size grades 0.50 to 12.70 μm). Source areas for chemical species investigated and general air-mass circulation defined from chemical and physical time-series are discussed to demonstrate the potential of such studies in the development of paleometeorological data sets from remote high-alpine glacierized sites such as the Himalaya.
To improve the interpretation of surface cryospheric albedo from satellite sensor data, diurnal measurements of the spectral bi-directional reflectance of a commonly-found fresh-water ice type were made, from which hemispherical reflectance can be derived. The purpose of this study is to document its clear-sky, bi-directional reflectance characteristics in the visible (650–670 nm) and near-infrared (810–840 nm) region, assess the diurnal nature of the reflectance, and quantify the surface anisotropy. Bi-directional reflectances of the re-frozen slush ice measured show a spectral dependence and change significantly with solar zenith angle. Considerable variation occurs at each view angle and among view angles throughout the day. Although diurnal reflectance patterns were similar in both bands, magnitudes varied greatly, being highest in the visible and lowest in the near-infrared region. With the exception of peak saturated (specular) values in the forward scatter direction, bi-directional reflectance was generally highest in the morning when the surface and the illumination were most diffuse in character. The exitance (πN) computed from nadir radiance (N) is compared to the measured hemispheric exitance (M). The πN/M ratios, an index of anisotropy, reveal an anisotropy that increases with increasing solar zenith angle and is more pronounced in the near-infrared region.
Avian pathogenic Escherichia coli (APEC) is one of the most
economically damaging diseases affecting the poultry industry. This group of
extra-intestinal E. coli causes a variety of clinical
conditions including air-sacculitis and cellulitis. The economic impact of APEC
is mainly due to mortality, slower growth rates and carcass downgrading. In
commercial broiler operations, APEC infections are controlled indirectly by
vaccination against other respiratory diseases and minimising stress conditions,
and directly by administration of antimicrobial agents to suppress symptoms in
infected flocks. Several studies have demonstrated that the most common
virulence factors studied in APEC are rarely present in the same isolate,
showing that APEC strains constitute a heterogeneous group. Different isolates
may harbour different associations of virulence factors, each able to induce
colibacillosis. Despite its economical relevance, the pathogenesis of
colibacillosis is poorly understood. The O antigen, a component of the surface
lipopolysaccharide, has been identified as a promising vaccine target. With the
availability of a novel bioconjugation technology it is expected that
multivalent O antigen conjugate vaccines can be produced on an industrial scale.
Despite the potential for developing an efficacious vaccine to combat this
economically important poultry disease, several obstacles hinder such efforts.
These include cost, vaccine delivery method and timing of vaccination. The
present discusses current knowledge on APEC virulence, host response to
infection and various attempts to develop an effective vaccine
We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Methods Eighty seven people with 1-3 brain metastases were enrolled on this Phase II trial of WBRT (30Gy/10)+simultaneous FSRT, (60Gy/10). Results Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to<27) ranged from 26-38% for KPS, 32-59% for FACT-Br and 0-16%for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (<6months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. Conclusions The effects on function and quality of life of this integrated treatment of WBRT+simultaneous FSRT were similar to other published series combining WBRT+SRS.
Avian influenza viruses have become endemic in land-based domestic poultry and have crossed species barriers. Turkeys are an important host in influenza virus ecology because they are susceptible to infection with these viruses and are often involved in inter species transmission. Several previous studies reveal that waterfowl-origin influenza viruses can be more easily transmitted to domestic turkeys than to chickens. Studies indicate turkeys to be better hosts for low pathogenic avian influenza viruses isolated from commercial poultry operations and live bird markets in comparison to chickens. Moreover, turkeys require low, 50% infectious-dose titres from wild bird as well as poultry adapted viruses, suggesting their high susceptibility for infection following a low dose exposure. Additionally, interspecies transmission of swine influenza viruses to turkeys occurs frequently, thus turkeys may be considered as a bridge species between poultry and wildlife. These findings suggest that turkeys can be easily infected with influenza viruses of different origins and highlight the potential role of turkeys in the transmission and maintenance of influenza viruses between premises.
We studied the prevalence of Helicobacter pylori virulence markers, e.g. cytotoxin associated gene (cagA), cagA promoter, vacuolating associated cytotoxin A (vacA) alleles induced by contact with epithelium (iceA type), and outer membrane protein Q (hopQ) in expatriates and compared them with those in local residents. Gastric biopsies were obtained at endoscopy for culture, histology and PCR for virulence marker and hopQ. Of 309 patients, 236 (76%) were males with a mean age of 45 years. A total of 102 patients were expatriates. hopQ type 1 was present in 98 (47%) local residents compared to 88 (86%) expatriates (P < 0·001), while hopQ type 2 was present in 176 (85%) local residents, compared to 60 (59%) expatriates (P < 0·001). H. pylori virulence marker cagA was positive in 97 (47%) local residents compared to 86 (84%) expatriates (P < 0·001) while cagA-P was positive in 72 (35%) local residents compared to 87 (85%) expatriates (P < 0·001). iceA type 1 was positive in 157 (76%) local residents compared to 45 (44%) expatriates (P < 0·001), while iceA type 2 was positive in 81 (39%) local residents compared to 86 (84%) expatriates (P < 0·001). Distribution of H. pylori cagA, cagA promoter, iceA and hopQ type in local residents and expatriates was different. H. pylori virulence markers were associated with severe pathology in expatriates.
We investigate the low-frequency (by comparison with the ion Larmor frequency) electrostatic solitary structures in a spatially non-uniform electron–positron–ion (e–p–i) magnetoplasma with non-Maxwellian electrons. A linear dispersion relation for the obliquely propagating ion acoustic drift wave is derived and it is shown that the non-Maxwellian electron population modifies the dispersion characteristics of the wave under consideration. We also carry out a nonlinear analysis and derive the modified Zakharov–Kuznetsov (MZK) equation for the coupled drift acoustic wave in a non-uniform magnetized plasma. We highlight the differences between the MZK equation and its homogeneous counterpart. We also find the solution of the MZK equation using the tangent hyperbolic method. It is observed that the electron spectral index
, positron concentration, and propagation angle
alter the structure of the ion acoustic drift solitary waves. The results obtained in this paper may be beneficial to understanding the propagation characteristics of electrostatic drift solitary structures in the interstellar medium and in laboratory experiments where electron–positron plasmas have recently been created by impinging ultra-intense laser pulses on a solid density target at the Lawrence Livermore National Laboratory (LLNL).
We aimed to reparameterize and validate an existing dengue model, comprising an entomological component (CIMSiM) and a disease component (DENSiM) for application in Malaysia. With the model we aimed to measure the effect of importation rate on dengue incidence, and to determine the potential impact of moderate climate change (a 1 °C temperature increase) on dengue activity. Dengue models (comprising CIMSiM and DENSiM) were reparameterized for a simulated Malaysian village of 10 000 people, and validated against monthly dengue case data from the district of Petaling Jaya in the state of Selangor. Simulations were also performed for 2008-2012 for variable virus importation rates (ranging from 1 to 25 per week) and dengue incidence determined. Dengue incidence in the period 2010–2012 was modelled, twice, with observed daily weather and with a 1 °C increase, the latter to simulate moderate climate change. Strong concordance between simulated and observed monthly dengue cases was observed (up to r = 0·72). There was a linear relationship between importation and incidence. However, a doubling of dengue importation did not equate to a doubling of dengue activity. The largest individual dengue outbreak was observed with the lowest dengue importation rate. Moderate climate change resulted in an overall decrease in dengue activity over a 3-year period, linked to high human seroprevalence early on in the simulation. Our results suggest that moderate reductions in importation with control programmes may not reduce the frequency of large outbreaks. Moderate increases in temperature do not necessarily lead to greater dengue incidence.
In this paper, we demonstrate deposition methods and conditions that allow the control of the electrical properties of doped ZnTe grown by RF magnetron sputtering using both nitrogen and copper as dopants. The carrier density of the films was characterized using a van der Pauw Hall effect measurement method. We demonstrate how the concentration of nitrogen in the plasma during the growth of the film impacts the conductivity of the ZnTe films. Films with hole concentrations in excess of 1018 cm-3 and a high degree of crystallinity were successfully grown. Similarly, we demonstrate that the hole concentration in the Cu-doped ZnTe can be varied by varying the amount of copper introduced in the films. We also observe that annealing the copper doped ZnTe films increases the carrier density, whereas annealing the nitrogen doped ZnTe films causes a decrease in carrier concentration and conductivity.
The Ultra-Fast Flash Observatory (UFFO) is a space observatory for optical follow-ups of
gamma ray bursts (GRBs), aiming to explore the first 60 seconds of GRBs optical emission.
UFFO is utilized to catch early optical emissions from GRBs within few sec after trigger
using a Gimbal mirror which redirects the optical path rather than slewing entire
spacecraft. We have developed a 15 cm two-axis Gimbal mirror stage for the UFFO-Pathfinder
which is going to be on board the Lomonosov satellite which is to be launched in 2013. The
stage is designed for fast and accurate motion with given budgets of 3 kg of mass and 3
Watt of power. By employing stepping motors, the slewing mirror can rotate faster than 15
deg/sec so that objects in the UFFO coverage (60 deg × 60 deg) can be targeted in
~1 sec. The obtained targeting resolution is better 2 arcmin using a close-loop
control with high precision rotary encoder. In this presentation, we will discuss details
of design, manufacturing, space qualification tests, as well as performance tests.
The UFFO (Ultra-Fast Flash Observatory) is a GRB detector on board the Lomonosov
satellite, to be launched in 2013. The GRB trigger is provided by an X-ray detector,
called UBAT (UFFO Burst Alarm & Trigger Telescope), which detects X-rays from the GRB
and then triggers to determine the direction of the GRB and then alerts the Slewing Mirror
Telescope (SMT) to turn in the direction of the GRB and record the optical photon fluxes.
This report details the calibration of the two components: the MAPMTs and the YSO crystals
and simulations of the UBAT. The results shows that this design can observe a GRB within a
field of view of ±35° and can trigger in a time scale as short as 0.2 – 1.0 s
after the appearance of a GRB X-ray spike.
The Ultra-Fast Flash Observatory (UFFO) aims to detect the earliest moment of Gamma-Ray
Bursts (GRBs) which is not well known, resulting into the enhancement of GRB mechanism
understanding. The pathfinder mission was proposed to be a scaled-down version of UFFO,
and only contains the UFFO Burst Alert & Trigger Telescope (UBAT) measuring the
X-ray/gamma-ray with the wide-field of view and the Slewing Mirror Telescope (SMT) with a
rapid-response for the UV/optical photons. Once the UBAT detects a GRB candidate with the
position accuracy of 10 arcmin, the SMT steers the UV/optical photons from the candidate
to the telescope by the fast rotatable mirror and provides the early UV/optical photons
measurements with 4 arcsec accuracy. The SMT has a modified Ritchey-Chrètien telescope
with the aperture size of 10 cm diameter including the rotatable mirror and the image
readout by the intensified charge-coupled device. There is a key board called the UFFO
Data Acquisition system (UDAQ) that manages the communication of each telescope and also
of the satellite and the UFFO overall operation. This pathfinder is designed and built
within the limited size and weight of ~20 kg and the low power consumption up to
~30 W. We will discuss the design and performance of the UFFO-pathfinder, and its
integration to the Lomonosov satellite.
The Ultra-Fast Flash Observatory (UFFO) Pathfinder for Gamma-Ray Bursts (GRBs) consists
of two telescopes. The UFFO Burst Alert & Trigger Telescope (UBAT) handles the
detection and localization of GRBs, and the Slewing Mirror Telescope (SMT) conducts the
measurement of the UV/optical afterglow. UBAT is equipped with an X-ray detector, analog
and digital signal readout electronics that detects X-rays from GRBs and determines the
location. SMT is equipped with a stepping motor and the associated electronics to rotate
the slewing mirror targeting the GRBs identified by UBAT. First the slewing mirror points
to a GRB, then SMT obtains the optical image of the GRB using the intensified CCD and its
readout electronics. The UFFO Data Acquisition system (UDAQ) is responsible for the
overall function and operation of the observatory and the communication with the satellite
main processor. In this paper we present the design and implementation of the electronics
of UBAT and SMT as well as the architecture and implementation of UDAQ.
The Ultra-Fast Flash Observatory (UFFO), which will be launched onboard the
Lomonosov spacecraft, contains two crucial instruments: UFFO Burst
Alert & Trigger Telescope (UBAT) for detection and localization of Gamma-Ray Bursts
(GRBs) and the fast-response Slewing Mirror Telescope (SMT) designed for the observation
of the prompt optical/UV counterparts. Here we discuss the in-space calibrations of the
UBAT detector and SMT telescope. After the launch, the observations of the standard X-ray
sources such as pulsar in Crab nebula will provide data for necessary calibrations of
UBAT. Several standard stars will be used for the photometric calibration of SMT. The
celestial X-ray sources, e.g. X-ray binaries with bright optical sources
in their close angular vicinity will serve for the cross-calibration of UBAT and SMT.