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Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.
Aims
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
Method
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
Results
No variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
Conclusions
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.
We previously reported an association between 5HTTLPR genotype and outcome following cognitive–behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome.
Aims
To replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2,n = 829).
Method
Logistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed.
Results
There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45,P = 0.014), but not primary anxiety disorder outcomes.
Conclusions
The association between 5HTTLPR genotype and CBT outcome did not replicate. Short-allele homozygotes showed more positive treatment outcomes, but with small, non-significant effects. Future studies would benefit from utilising whole genome approaches and large, homogenous samples.
Trans-oesophageal echocardiographic imaging is valuable in the pre- and post-operative evaluation of children and adults with CHD; however, the frequency by which trans-oesophageal echocardiography guides the intra-operative course of patients is unknown.
Methods
We retrospectively reviewed 1748 intra-operative trans-oesophageal echocardiograms performed between 1 October, 2005 and 31 December, 2010, and found 99 cases (5.7%) that required return to bypass, based in part upon the intra-operative echocardiographic findings.
Results
The diagnoses most commonly requiring further repair and subsequent imaging were mitral valve disease (20.9%), tricuspid valve disease (16.0%), atrioventricular canal defects (12.0%), and pulmonary valve disease (14.1%). The vast majority of those requiring immediate return to bypass benefited by avoiding subsequent operations and longer lengths of hospital stay. A total of 14 patients (0.8%) who received routine imaging required further surgical repair within 1 week, usually due to disease that developed over ensuing days. Patients who had second post-operative trans-oesophageal echocardiograms in the operating room rarely required re-operations, confirming the benefit of routine intra-operative imaging.
Conclusions
This study represents a large single institutional review of intra-operative trans-oesophageal echocardiography, and confirms its applicability in the surgical repair of patients with CHD. Routine imaging accurately identifies patients requiring further intervention, does not confer additional risk of mortality or prolonged length of hospital stay, and prevents subsequent operations and associated sequelae in a substantial subset of patients. This study demonstrates the utility of echocardiography in intra-operative monitoring of surgical repair and highlights patients who are most likely to require return to bypass, as well as the co-morbidities of such manipulations.
In the past, coronary arterial anomalies have been difficult to diagnose by non-invasive methods. Identification of coronary arterial origins is now a routine part of the standard paediatric echocardiogram. Anomalous origin of a coronary artery from the pulmonary trunk is an extremely important diagnosis to make. Many echocardiographic features are not directly related to the visualisation of the coronary arterial origin. Left ventricular dilation and abnormal ventricular performance are common, along with mitral regurgitation and evidence of collateralisation of the flow from the coronary artery that has an aortic origin. In some cases, the anomalous coronary artery can be seen to arise directly from the pulmonary trunk. Congenital atresia of the main stem of the left coronary artery has a similar echocardiographic presentation, except that its aortic origin is not determined. Anomalous aortic origin of the coronary artery has important implications, as the first presenting symptom can be sudden death. With meticulous attention to the origins of the coronary arteries, echocardiographic diagnosis can also be achieved. In contrast to the anomalous origin of a coronary artery from the pulmonary trunk, ventricular performance is usually normal. Whenever there is doubt as to the definition of the origin of the coronary arteries and, indeed, when there is serious clinical concern that a coronary artery has an anomalous origin, other testing, such as cine-computed tomography, magnetic resonance imaging, or cardiac catheterisation may be indicated for confirmation or to provide greater anatomic detail.
Laboratory studies on the embryonic and larval development of Haemonchus contortus under constant temperatures of 0·0°, 7·2°, 11°, 14·4°, 21·7° and 37° C., and varying moisture conditions were carried out. Reports of preliminary studies on Ostertagia spp., Trichostrongylus spp. and Oesophagostomum venulosum are included.
Observations showed that eggs in the same culture may behave in several ways: (1) eggs may develop at different rates; (2) eggs may exhibit intermittent stages of active and inhibited development; and (3) eggs may fail to develop and die at any stage from unknown causes.
We present a case of true facial artery aneurysm with no associated risk factors, which was non-pulsatile on presentation. This case is unique as the lesion was identified using computed tomography scanning, due to the unusual presentation. The vast majority of aneurysms of the head and neck have a traumatic aetiology, giving rise to false aneurysms; true aneurysms are extremely rare. We discuss the implications of such a lesion and its management.
We have investigated 136 Chandra extragalactic sources without broad emission lines, including 93 NELG and 43 ALG. Based on $f_X/f_O$, $L_X$, X-ray spectral hardness and optical emission line diagnostics, we have conservatively classified 36 normal galaxies (20 spirals and 16 ellipticals) and 71 AGNs. Their redshift ranges from 0.01 to 1.2, while normal galaxies are at z=0.01–0.3. Our sample galaxies appear to share similar characteristics with local galaxies in terms of X-ray luminosities and spectral properties, as expected from the X-ray binary populations and the hot ISM. In conjunction with normal galaxies found in other surveys, we found no statistically significant evolution in $L_X/L_B$, within the limited z range ($<$0.1). We have built our log(N)-log(S) relationship of normal galaxies in the flux range, $f_X$ (0.5–8.0) = $10^{-15}$–$10^{-13}$ erg sec$^{-1}$ cm$^{-2}$, after correcting completeness by a series of simulations. The best-fit slope is −1.5 for both soft (0.5–2.0 KeV) and broad (0.5–8.0 KeV) energy bands, which is considerably steeper than that of AGN-dominated cosmic background sources at faint fluxes, but slightly flatter than the previous estimate, indicating normal galaxies will exceed in number over the AGN population at $f_X<10^{-18}$ erg sec$^{-1}$ cm$^{-2}$.
We make use of extensive HST optical and VLA radio observations of the Seyfert galaxy Markarian 78 to analyse the properties of the jet flow. Our starting assumption is that the jet's power can be inferred from the energy stored in the radio lobe, and the jet's momentum flux can be inferred from the momentum of the ionized gas. Using the properties of three regions, we derive a jet flow power of ∼1040.5 erg s−1 and momentum flux of ∼1033.5 dyne. Assuming the jet contains both thermal and relativistic material, we find that the thermal component dominates both the jet's luminosity and its momentum flux. We find the jet to be mildly transonic, with speed only a few times that of the [OIII] velocities. The jet is, however, quite dense, with sufficient ram pressure to accelerate the ionized gas to the observed velocities. Over the region lifetime, the jet can provide the thermal component of the lobes, and likely does this by entraining ISM material en route. These jet properties seem, at least to us, to be eminently plausible, suggesting an approach of this kind may be appropriate for other radio quiet objects.To search for other articles by the author(s) go to: http://adsabs.harvard.edu/abstract_service.html
For the past 10 years there has been an active debate over whether fast shocks play an important role in ionizing emission line regions in Seyfert galaxies. To investigate this claim, we have studied the Seyfert 2 galaxy Mkn 78, using HST UV/optical images and spectroscopy. Since Mkn 78 provides the archetypal jet-driven bipolar velocity field, if shocks are important anywhere they should be important in this object. Having mapped the emission line fluxes and velocity field, we first compare the ionization conditions to standard photoionization and shock models. We find coherent variations of ionization consistent with photoionization model sequences which combine optically thick and thin gas, but are inconsistent with either autoionizing shock models or photoionization models of just optically thick gas. Furthermore, we find absolutely no link between the ionization of the gas and its kinematic state, while we do find a simple decline of ionization degree with radius. We feel this object provides the strongest case to date against the importance of shock related ionization in Seyferts.To search for other articles by the author(s) go to: http://adsabs.harvard.edu/abstract_service.html
Deep submicron CMOS technology for low-power, low-voltage applications requires the use of symmetric n+/p+ poly gate structures. This requirement introduces a number of processing challenges, involving fundamental issues of atomic diffusion over distances of 1Å to ∼30μm. Two of the critical issues are dopant cross-diffusion between P- and NMOS devices with connected gates, resulting in large threshold voltage shifts, and boron penetration through the gate oxide. We show that in devices with W-polycide dual-gat:e structure most of these problems can be alleviated by using rapid thermal annealing, RTA, in combination with a few additional, simple processing steps (e. g., low-temperature recrystallization of a-Si layer and selective nitrogen coimplants). The RTA step, in particular, ensures thai: the boron activation in the p+ poly-Si remains high and negates any effects of arsenic cross-diffusion. CMOS devices with properly processed gates have low gate stack profiles, small threshold voltage shifts (<30mV), and excellent device characteristics.
Lateral dopant diffusion is a well known problem in dual-gate W-polycide CMOS devices. We have recently demonstrated that RTA processing helps to alleviate this problem and at the same time ensures sufficient dopant activation. However, due to the complex micro-structural changes in both poly-Si and WSix (x˜2.5) layers during the RTA process, the time dependence of the diffusion processes and dopant distribution are difficult to predict. Consequently, the process optimization and device simulations are rather unreliable. We describe a new experimental technique to measure lateral dopant diffusion and 2-dimensional dopant distribution in RTA processed W-polycide structures using conventional SIMS analysis of lithographically defined test structures. Our experiments show that the technique is capable of measuring lateral dopant diffusion over distances between one and tens of microns without losing the vertical resolution of conventional SIMS profiling. The technique can be used to study diffusion processes in a variety of materials and multi-layer structures.
Electrical characterization of MOS structures and device modeling require accurate information about dopant concentration, particularly at the poly-Si/SiO2 interface. We compare four experimental techniques (secondary ion mass spectrometry SIMS, resonant ion mass spectrometry RIMS, differential Hall effect profiling, and spreading resistance analysis) to measure boron and free carrier concentrations in poly-Si, SiO2 and crystalline Si. We find that no single technique completely characterizes the entire MOS structure, and that spreading resistance analysis in particular substantially underestimates the free carrier concentration at the poly-Si/SiO2 interface. We conclude that in most cases of technological interest the magnitude of the poly depletion effect scales with the average carrier concentration at some distance away from the interface and that the interfacial effects, such as dopant segregation, are of only secondary importance. These findings are supported by theoretical modeling of capacitance-voltage behavior of boron-doped MOS capacitors.
This paper seeks to define and explain financial reinsurance, a type of reinsurance growing rapidly in the general insurance market. It provides criteria for underwriters and actuaries to understand the degree of risk transfer involved and the limitations on that risk transfer. It seeks to set out criteria, applicable to both insurer and reinsurer, for estimating reserves where financial reinsurance covers are involved and for compliance with supervisory requirements. Several examples are given of typical financial reinsurance contracts currently in use.
We report Hall mobilities (at T = 4.2K) as high as 180,000cm2V−1 s−1 in modulation-doped Si layers in Si1−x Gex heterostructures grown by Molecular-Beam Epitaxy. These mobilities reflect dramatic improvements in the quality of relaxed Si1−xGex buffer layers (with x'30%) grown by gradual grading of composition at high temperature. The resulting moderate threading dislocation densities (< 106 cm−2 ) appear to cause no mobility degradation. The strong damping of Shubnikov de Haas oscillations, as well as the increase of mobility with carrier density, indicate predominantly small-angle scattering. This suggests that residual Coulomb scattering from background impurities limit the mobility, rather than interface-roughness scattering as for the Si/SiO2 interface. The reduced interfacial scattering, as well as the strain-induced splitting of the valley degeneracy to select the two low-effective-mass valleys, significantly enhance room-temperature transport as well, with μHall ' 2,100cm2 V−1 s−1. We also observe a small splitting of the remaining twofold valley degeneracy using the integral quantized Hall effect. As a further indication of the high sample quality, measurements to 17T at 0.3K show indications of the v = 2/3 fractional quantum Hall effect.
Let K be an algebraic number field and f(X) ∈ K[X]. The Diophantine problem of describing the solutions to equations of the form
has attracted considerable interest over the past 60 years. Siegel [12], [13] was the first to show that under suitable non-degeneracy conditions, the equation (+) has only finitely many integral solutions in K. LeVeque[7] proved the following, more explicit, result. Let
where a ∈ K* and αl,…,αk are distinct and algebraic over K. Then (+) has only finitely many integral solutions unless (nl,…,nk) is a permutation of one of the n-tuples
In 1930, Miss Zarita Nahón recorded for the Departments of Anthropology and Spanish at Columbia University, at the suggestion of Prof. Franz Boas, nineteen examples of Judeo-Spanish traditional songs from Tangier (Morocco). The informant was her sister, Suzanne (Simy) Toledano. During the previous year, Miss Nahón brought together an extensive collection of Sephardic folk literature in her native Tangier as part of a graduate studies project under the direction of Prof. Boas (see Armistead/Silverman 1977). The examples, which were beautifully sung at Columbia University and recorded on aluminum discs, significantly supplement, both musically and textually, the corpus gathered in Tangier. The original recordings were subsequently deposited at the Indiana University Archives of Folk and Primitive Music under the direction of Prof. George Herzog.
Sylvester [7] proposed the following question in 1893. If a finite set of points in a plane is such that on the line determined by any two points of the set there is always a third point of the set, is the set collinear? Equivalently, given a finite planar set of non-collinear points, does there exist a line containing exactly two of the points?
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