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Despite the high prevalence of social and performance anxiety, current treatments do not meet the full needs of patients. Development of novel anxiolytics with rapid onset of action for on-demand treatment of social and performance anxiety is an active area of clinical research.
Aims
To examine the anxiolytic effect of VQW-765, an α7-nAChR agonist, in subjects with performance anxiety.
Method
We conducted a randomised, double-blind, placebo-controlled trial of 230 adults with a history of public speaking anxiety. Participants were randomly assigned to receive a single oral dose of 10 mg VQW-765 (n = 116) or placebo (n = 114), followed by a Trier Social Stress Test (TSST). Anxiety levels were assessed by the Subjective Units of Distress Scale (SUDS). Heart rate was monitored during the TSST. Plasma concentration of VQW-765 was measured after the TSST.
Results
Subjects receiving VQW-765 showed a trend of improvement in intensity of anxiety, as measured by the SUDS, during the performance phase of a TSST compared with placebo (P = 0.1443). Females showed a larger magnitude and significant response to VQW-765 (P = 0.034). The pharmacokinetic/pharmacodynamic analysis observed an inverted U-shaped exposure–response relationship. Subjects in the middle 50% quantiles of VQW-765 plasma concentration showed significant improvement in the SUDS rating compared with placebo (P = 0.033); however, subgroup analysis revealed this was true only for females (P = 0.005). VQW-765 was safe and well tolerated.
Conclusions
This is the first study showing anxiolytic effect of an α7-nAChR agonist in humans. VQW-765 is a promising candidate to be developed for on-demand treatment of social anxiety disorder.
This work presents an approach for optimization of window coefficients for 5G user equipment side sensing, using orthogonal frequency division multiplexing radar-based range and velocity estimation, based on the sounding reference signal (SRS) from the 5G New Radio (NR) standard. The signal configuration and the corresponding waveform are generated in compliance with the 3rd Generation Partnership Project (3GPP) standard for 5G. The limitations of conventional signal processing for resources available for sensing with the SRS are highlighted. The proposed approach, which optimizes the window coefficients to improve the sensing capabilities, is implemented through two methods. The first method employs a decoupled optimization strategy for range and velocity, showing high computational efficiency. Our results demonstrate that this method significantly improves the peak sidelobe level (PSL) of the velocity profile by over $\mathrm{15}\,\mathrm{dB}$, although it does not address the issue of diagonally located sidelobes, which occur due to non-uniform resource distribution. The second method adopts a comprehensive full 2D optimization technique. While it requires more computational resources and does not improve the PSL beyond the first method’s achievements, it mitigates the diagonally located sidelobes issue. The level of these have been improved by more than $\mathrm{3}\,\mathrm{dB}$.
With the shift from mechanical value delivery to mechatronic value delivery, development environments are becoming more complex. Intuitive decision-making in development management is becoming increasingly challenging. Meanwhile, the use project management software is spreading, bringing about a new level of project data for development projects, holding to potential to enhance human decision making. To this end, the paper presents an extension to factor analysis of mixed data, which can facilitate usage of exploratory data analysis to improve decision-making in development project planning.
We analysed the coronavirus disease 2019 epidemic curve from March to the end of April 2020 in Germany. We use statistical models to estimate the number of cases with disease onset on a given day and use back-projection techniques to obtain the number of new infections per day. The respective time series are analysed by a trend regression model with change points. The change points are estimated directly from the data. We carry out the analysis for the whole of Germany and the federal state of Bavaria, where we have more detailed data. Both analyses show a major change between 9 and 13 March for the time series of infections: from a strong increase to a decrease. Another change was found between 25 March and 29 March, where the decline intensified. Furthermore, we perform an analysis stratified by age. A main result is a delayed course of the pandemic for the age group 80 + resulting in a turning point at the end of March. Our results differ from those by other authors as we take into account the reporting delay, which turned out to be time dependent and therefore changes the structure of the epidemic curve compared to the curve of newly reported cases.
This chapter comprises the following sections: names, taxonomy, subspecies and distribution, descriptive notes, habitat, movements and home range, activity patterns, feeding ecology, reproduction and growth, behavior, parasites and diseases, status in the wild, and status in captivity.
This issue sees the last Liturgical chant bibliography prepared by Dr Günther Michael Paucker. Having inherited this position from Peter Jeffery in 1996, he has produced, year after year, a total of twenty-one bibliographies, all with an admirably comprehensive coverage of studies on chant across the full range of languages. The journal could not have imagined a more meticulous, thorough and loyal editor. We remain truly thankful to him for all the Herculean efforts he has put into his Liturgical chant bibliographies from 1997 to 2017. They have been tremendously useful to chant scholars and will remain a lasting monument to his generosity of spirit.
We report on the EPICA Dronning Maud Land (East Antarctica) deep drilling operation. Starting with the scientific questions that led to the outline of the EPICA project, we introduce the setting of sister drillings at NorthGRIP and EPICA Dome C within the European ice-coring community. The progress of the drilling operation is described within the context of three parallel, deep-drilling operations, the problems that occurred and the solutions we developed. Modified procedures are described, such as the monitoring of penetration rate via cable weight rather than motor torque, and modifications to the system (e.g. closing the openings at the lower end of the outer barrel to reduce the risk of immersing the drill in highly concentrated chip suspension). Parameters of the drilling (e.g. core-break force, cutter pitch, chips balance, liquid level, core production rate and piece number) are discussed. We also review the operational mode, particularly in the context of achieved core length and piece length, which have to be optimized for drilling efficiency and core quality respectively. We conclude with recommendations addressing the design of the chip-collection openings and strictly limiting the cable-load drop with respect to the load at the start of the run.
In this paper we introduce high dimensional tensor product interpolation for the combination technique. In order to compute the sparse grid solution, the discrete numerical subsolutions have to be extended by interpolation. If unsuitable interpolation techniques are used, the rate of convergence is deteriorated. We derive the necessary framework to preserve the error structure of high order finite difference solutions of elliptic partial differential equations within the combination technique framework. This strategy enables us to obtain high order sparse grid solutions on the full grid. As exemplifications for the case of order four we illustrate our theoretical results by two test examples with up to four dimensions.
We study a novel class of numerical integrators, the adapted nested force-gradient schemes, used within the molecular dynamics step of the Hybrid Monte Carlo (HMC) algorithm. We test these methods in the Schwinger model on the lattice, a well known benchmark problem. We derive the analytical basis of nested force-gradient type methods and demonstrate the advantage of the proposed approach, namely reduced computational costs compared with other numerical integration schemes in HMC.
The Liturgical chant bibliography 25 retains the traditional format: (1) Editions and facsimile editions, (2) Books and reprints, (3) Congress reports, (4) Chant journals, (5) Colections of essays and dictionaries, (6) Articles in periodicals and Festschriften. Additions to the bibliographies of previous years (mostly reviews) are listed directly after this introduction.
Modern computer-aided techniques foster the availability and quality of 3D visualization and reconstruction of extinct and extant species. Moreover, animated sequences of locomotion and other movements find their way into motion pictures and documentary films, but also gain attraction in science. While movement analysis is well advanced in vertebrates, particularly in mammals and birds, analyses in arthropods, with their much higher variability regarding general anatomy and size, are still in their infancies and restricted to a few laboratory species. These restrictions and deficient understanding of terrestrial arthropod locomotion in general impedes sensible reconstruction of movements in those species that are not directly observable (e.g., extinct and cryptic species). Since shortcomings like over-simplified approaches to simulate arthropod locomotion became obvious recently, in this review we provide insight into physical, morphological, physiological, behavioral, and ecological constraints, which are essential for sensible reconstructions of terrestrial arthropod locomotion. Such concerted consideration along with sensible evaluations of stability and efficiency requirements can pave the way to realistic assessment of leg coordination and body dynamics.
The Liturgical chant bibliography 24 retains the traditional format: (1) Editions and facsimile editions, (2) Books and reprints, (3) Congress reports, (4) Chant journals, (5) Colections of essays and dictionaries, (6) Articles in periodicals and Festschriften. Additions to the bibliographies of previous years (mostly reviews) are listed directly after this introduction. This year's bibliography opens with five Cantus planus databases and indexes, which were introduced in a detailed review published in the Journal of the American Musicological Society, 67 (2014), 267–85 (24001).
In the frame of the EXPOSE-R mission outside the Russian Zvezda Module of the International Space Station (ISS) passive thermoluminescence dosimeters were applied to measure the radiation exposure of biological samples. The detectors were located beneath the sample carriers to determine the dose levels for maximum shielding. The dose measured beneath the sample carriers varied between 317 ± 10 and 230 ± 2 mGy, which amount to an average dose rate of 381 ± 12 and 276 ± 2 μGy d−1. These values are close to those assessed for the interior of the ISS and reflect the high shielding of the biological experiments within the EXPOSE-R facility. As a consequence of the high shielding (several g cm−2), the biological samples were predominantly exposed to galactic cosmic heavy ions and trapped protons in the Earth's radiation belts, whereas the trapped electrons did not reach the samples.
X-ray surveys provide us with one of the least biased samples of Active Galactic Nuclei (AGNs) against obscuration. Here we present the most up-to-date AGN X-ray luminosity function (XLF) and absorption function over the redshift range from 0 to 5, using the largest, highly complete sample ever available obtained from surveys of various depth, depth, and energy bands. We utilize a maximum likelihood method to reproduce the count-rate versus redshift distribution for each survey, by taking into account the evolution of the absorbed fraction, contribution from Compton-thick AGNs, and AGN broad band X-ray spectra including reflection components from tori based on the luminosity and redshift dependent unified scheme. We find that the shape of the XLF at z ~ 1–3 is significantly different from that in the local universe, for which the luminosity dependent density evolution (LDDE) model gives the best description. These results establish the standard population synthesis model of the X-Ray Background (XRB), which well reproduces the source counts in both soft and hard bands, the observed fractions of Compton-thick AGNs, and the spectrum of the XRB.