949 research outputs found
An index of fatal toxicity for new psychoactive substances
The final, definitive version of this paper has been published in Journal of Psychopharmacology, February 2018, published by SAGE Publishing, All rights reserved.An index of fatal toxicity for new psychoactive substances has been developed based solely on information provided on death certificates. An updated index of fatal toxicity (T f), as first described in 2010, was calculated based on the ratio of deaths to prevalence and seizures for the original five substances (amphetamine, cannabis, cocaine/crack, heroin and 3,4-methylenedioxymethylamphetamine) *. These correlated well with the 2010 index. Deaths were then examined for cases both where the substance was and was not found in association with other substances. This ratio (sole to all mentions; S/A) was then calculated for deaths in the period 1993 to 2016. This new measure of fatal toxicity, expressed by S/A, was well-correlated with the index L n (T f) of the original reference compounds. The calculation of S/A was then extended to a group of new psychoactive substances where insufficient prevalence or seizure data were available to directly determine a value of T f by interpolation of a graph of T f versus S/A. Benzodiazepine analogues had particularly low values of S/A and hence T f. By contrast, γ-hydroxybutyrate/γ-butyrolactone, α-methyltryptamine, synthetic cannabinoid receptor agonists and benzofurans had a higher fatal toxicity.Peer reviewedFinal Accepted Versio
GoPrime: development of an in silico framework to predict the performance of real-time PCR primers and probes using foot-and-mouth disease virus as a model
Real-time PCR (rPCR) is a widely accepted diagnostic tool for the detection and quantification of nucleic acid targets. In order for these assays to achieve high sensitivity and specificity, primer and probe-template complementarity is essential; however, mismatches are often unavoidable and can result in false-negative results and errors in quantifying target sequences. Primer and probe sequences therefore require continual evaluation to ensure they remain fit for purpose. This paper describes the development of a linear model and associated computational tool (GoPrime) designed to predict the performance of rPCR primers and probes across multiple sequence data. Empirical data were generated using DNA oligonucleotides (n = 90) that systematically introduced variation in the primer and probe target regions of a diagnostic assay routinely used to detect foot-and-mouth disease virus (FMDV); an animal virus that exhibits a high degree of sequence variability. These assays revealed consistent impacts of patterns of substitutions in primer and probe-sites on rPCR cycle threshold (CT) and limit of detection (LOD). These data were used to populate GoPrime, which was subsequently used to predict rPCR results for DNA templates (n = 7) representing the natural sequence variability within FMDV. GoPrime was also applicable to other areas of the FMDV genome, with predictions for the likely targets of a FMDV-typing assay consistent with published experimental data. Although further work is required to improve these tools, including assessing the impact of primer-template mismatches in the reverse transcription step and the broader impact of mismatches for other assays, these data support the use of mathematical models for rapidly predicting the performance of rPCR primers and probes in silico
Factors associated with changes of state of foot conformation and lameness in a flock of sheep
The aim of this research was to investigate transitions between foot conformation, lameness and footrot in sheep. Data came from one lowland flock of approximately 700 ewes studied for 18 months. Multilevel multistate analyses of transitions between good and poor foot conformation states in ewes, and lame and non-lame states in ewes and lambs were conducted. Key results were that the longer sheep had feet in good conformation, the more likely they were to stay in this state; similarly, the longer a ewe was not lame the more likely she was not to become lame. Ewes with poor foot conformation were more likely to become lame (OR: 1.83 (1.24-2.67)) and to be > 4 years (OR: 1.50(1.09-2.05)). Ewes with footrot were less likely to move to good foot conformation (OR: 0.48 (0.31-0.75)) and were more likely to become lame (OR: 3.81(2.60-5.59)). Ewes lame for > 4 days and not treated with parenteral antibacterials had a higher risk of developing (OR: 2.00 (1.08-3.61)), or remaining in (OR: 0.49 (0.29-0.95)) poor foot conformation compared with ewes never lame. Treatment of ewes lame with footrot with parenteral antibacterials increased the probability of transition from a lame to a non-lame state (OR: 1.46 (1.05-2.02)) and these ewes, even if lame for > 4 days, were not more likely to develop poor foot conformation. The risk of a ewe becoming lame increased when at least one of her offspring was lame (OR: 2.03 (1.42-2.92)) and when the prevalence of lameness in the group was ≥ 5% (OR: 1.42 (1.06-1.92)). Lambs were at increased risk of becoming lame when they were male (OR: 1.42 (1.01-2.01)), single (OR: 1.86 (1.34-2.59)) or had a lame dam or sibling (OR: 3.10 (1.81-5.32)). There were no explanatory variables associated with lambs recovering from lameness. We conclude that poor foot conformation in ewes increases the susceptibility of ewes to become lame and that this can arise from untreated footrot. Treatment of ewes lame with footrot with parenteral antibacterials leads to recovery from lameness and prevents or resolves poor foot conformation which then reduces the susceptibility to further lameness with footrot
Relating the Lorentzian and exponential: Fermi's approximation,the Fourier transform and causality
The Fourier transform is often used to connect the Lorentzian energy
distribution for resonance scattering to the exponential time dependence for
decaying states. However, to apply the Fourier transform, one has to bend the
rules of standard quantum mechanics; the Lorentzian energy distribution must be
extended to the full real axis instead of being bounded from
below (``Fermi's approximation''). Then the Fourier transform
of the extended Lorentzian becomes the exponential, but only for times , a time asymmetry which is in conflict with the unitary group time evolution
of standard quantum mechanics. Extending the Fourier transform from
distributions to generalized vectors, we are led to Gamow kets, which possess a
Lorentzian energy distribution with and have exponential
time evolution for only. This leads to probability predictions
that do not violate causality.Comment: 23 pages, no figures, accepted by Phys. Rev.
Non-linear regression models for Approximate Bayesian Computation
Approximate Bayesian inference on the basis of summary statistics is
well-suited to complex problems for which the likelihood is either
mathematically or computationally intractable. However the methods that use
rejection suffer from the curse of dimensionality when the number of summary
statistics is increased. Here we propose a machine-learning approach to the
estimation of the posterior density by introducing two innovations. The new
method fits a nonlinear conditional heteroscedastic regression of the parameter
on the summary statistics, and then adaptively improves estimation using
importance sampling. The new algorithm is compared to the state-of-the-art
approximate Bayesian methods, and achieves considerable reduction of the
computational burden in two examples of inference in statistical genetics and
in a queueing model.Comment: 4 figures; version 3 minor changes; to appear in Statistics and
Computin
The floor in the interplanetary magnetic field: Estimation on the basis of relative duration of ICME observations in solar wind during 1976-2000
To measure the floor in interplanetary magnetic field and estimate the time-
invariant open magnetic flux of Sun, it is necessary to know a part of magnetic
field of Sun carried away by CMEs. In contrast with previous papers, we did not
use global solar parameters: we identified different large-scale types of solar
wind for 1976-2000 interval, obtained a fraction of interplanetary CMEs (ICMEs)
and calculated magnitude of interplanetary magnetic field B averaged over 2
Carrington rotations. The floor of magnetic field is estimated as B value at
solar cycle minimum when the ICMEs were not observed and it was calculated to
be 4,65 \pm 6,0 nT. Obtained value is in a good agreement with previous
results.Comment: 10 pages, 2 figures, submitted in GR
Nuclear Structure Functions in the Large x Large Q^2 Kinematic Region in Neutrino Deep Inelastic Scattering
Data from the CCFR E770 Neutrino Deep Inelastic Scattering (DIS) experiment
at Fermilab contain events with large Bjorken x (x>0.7) and high momentum
transfer (Q^2>50 (GeV/c)^2). A comparison of the data with a model based on no
nuclear effects at large x, shows a significant excess of events in the data.
Addition of Fermi gas motion of the nucleons in the nucleus to the model does
not explain the excess. Adding a higher momentum tail due to the formation of
``quasi-deuterons'' makes some improvement. An exponentially falling F_2
\propto e^-s(x-x_0) at large x, predicted by ``multi-quark clusters'' and
``few-nucleon correlations'', can describe the data. A value of s=8.3 \pm
0.7(stat.)\pm 0.7(sys.) yields the best agreement with the data.Comment: 4 pages, 4 figures, 1 table. Sibmitted to PR
A tetragonal-to-monoclinic phase transition in a ferroelectric perovskite: the structure of PbZr(0.52)Ti(0.48)O3
The perovskite-like ferroelectric system PbZr(1-x)Ti(x)O3 (PZT) has a nearly
vertical morphotropic phase boundary (MPB) around x=0.45-0.50. Recent
synchrotron x-ray powder diffraction measurements by Noheda et al. [Appl. Phys.
Lett. 74, 2059 (1999)] have revealed a new monoclinic phase between the
previously-established tetragonal and rhombohedral regions. In the present work
we describe a Rietveld analysis of the detailed structure of the tetragonal and
monoclinic PZT phases on a sample with x= 0.48 for which the lattice parameters
are respectively: at= 4.044 A, ct= 4.138 A, at 325 K, and am= 5.721 A, bm=
5.708 A, cm= 4.138 A, beta= 90.496 deg., at 20K. In the tetragonal phase the
shifts of the atoms along the polar [001] direction are similar to those in
PbTiO3 but the refinement indicates that there are, in addition, local
disordered shifts of the Pb atoms of ~0.2 A perpendicular to the polar axis..
The monoclinic structure can be viewed as a condensation along one of the
directions of the local displacements present in the tetragonal phase. It
equally well corresponds to a freezing-out of the local displacements along one
of the directions recently reported by Corker et al.[J. Phys. Condens.
Matter 10, 6251 (1998)] for rhombohedral PZT. The monoclinic structure
therefore provides a microscopic picture of the MPB region in which one of the
"locally" monoclinic phases in the "average" rhombohedral or tetragonal
structures freezes out, and thus represents a bridge between these two phases.Comment: REVTeX, 7 figures. Modifications after referee's suggestion: new
figure (figure 5), comments in 2nd para. (Sect.III) and in 2nd & 3rd para.
(Sect. IV-a), in the abstract: "...of ~0.2 A perpendicular to the polar
axis.
Developing a high-throughput SNP-based marker system to facilitate the introgression of traits from Aegilops species into bread wheat (Triticum aestivum)
The genus Aegilops contains a diverse collection of wild species exhibiting variation in geographical distribution, ecological adaptation, ploidy and genome organization. Aegilops is the most closely related genus to Triticum which includes cultivated wheat, a globally important crop that has a limited gene pool for modern breeding. Aegilops species are a potential future resource for wheat breeding for traits, such as adaptation to different ecological conditions and pest and disease resistance. This study describes the development and application of the first high-throughput genotyping platform specifically designed for screening wheat relative species. The platform was used to screen multiple accessions representing all species in the genus Aegilops. Firstly, the data was demonstrated to be useful for screening diversity and examining relationships within and between Aegilops species. Secondly, markers able to characterize and track introgressions from Aegilops species in hexaploid wheat were identified and validated using two different approaches
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