Vibration and Instability of Plate-Assemblies including Shear and Anisotropy (VIPASA) user's guide, addendum

Extensions developed at Langley Research Center to the VIPASA computer program are described including a procedure for simple thermal stress analysis and options for graphical display of output. Input requirements for operation of the modified program are given in detail

Evaluation of a thrice weekly administration of teicoplanin in the outpatient setting; retrospective observational multi-centre study

Introduction: The glycopeptide teicoplanin is commonly utilised to facilitate Outpatient Parenteral Antimicrobial Therapy (OPAT). Licensed for once daily maintenance dosing, teicoplanin’s long half-life allows for less frequent dosing (e.g. thrice weekly) following successful loading. This service evaluation reviews the safety and effectiveness of a novel thrice weekly teicoplanin dosing regimen. Methods A retrospective, observational study was conducted at Chelsea & Westminster hospital (March 2018 – July 2020), evaluating trough serum teicoplanin concentrations for patients receiving >5 days of teicoplanin in the OPAT setting. Teicoplanin dosing and administration (once daily versus thrice weekly), clinical outcomes, and therapeutic levels were analysed for all patients. The project was registered with clinical governance locally. Results A total of 82 patients treated with teicoplanin in the OPAT service where included; 53/82 receiving thrice weekly and 29/82 receiving once daily dosing. Mean teicoplanin trough levels were similar in both groups (26.2mg/L and 25.8mg/L in once daily and thrice weekly groups, p=0.8895). High clinical success rates were recorded in both groups (25/29 [86.2%] versus 50/53 [94.3%]). No correlation with clinical outcomes and initial teicoplanin serum levels was identified. Normal renal function (>90mL/min) was associated with lower teicoplanin serum concentrations (21.4mg/L[±10.1] versus 29.7mg/L[SD±14], p = 0.0178) in the thrice weekly dosed group but not with the once daily dosed group (mean 28.2mg/L[±9.4] versus 23.7mg/L[±9.9], p = 0.2201). Conclusions This study supports thrice weekly teicoplanin as a convenient and effective OPAT for administration in the OPAT setting. Therapeutic drug monitoring is advised to adjust for intra-patient variability

Fragile three-dimensionality in the quasi-one-dimensional cuprate PrBa_2Cu_4O_8

In this article we report on the experimental realization of dimensional crossover phenomena in the chain compound PrBa$_2$Cu$_4$O$_8$ using temperature, high magnetic fields and disorder as independent tuning parameters. In purer crystals of PrBa$_2$Cu$_4$O$_8$, a highly anisotropic three-dimensional Fermi-liquid state develops at low temperatures. This metallic state is extremely susceptible to disorder however and localization rapidly sets in. We show, through quantitative comparison of the relevant energy scales, that this metal/insulator crossover occurs precisely when the scattering rate within the chain exceeds the interchain hopping rate(s), i.e. once carriers become confined to a single conducting element.Comment: 12 pages, 5 figures, published at http://www.iop.org/EJ/article/1367-2630/8/9/172/njp6_9_172.htm

Accelerating Bayesian hierarchical clustering of time series data with a randomised algorithm

We live in an era of abundant data. This has necessitated the development of new and innovative statistical algorithms to get the most from experimental data. For example, faster algorithms make practical the analysis of larger genomic data sets, allowing us to extend the utility of cutting-edge statistical methods. We present a randomised algorithm that accelerates the clustering of time series data using the Bayesian Hierarchical Clustering (BHC) statistical method. BHC is a general method for clustering any discretely sampled time series data. In this paper we focus on a particular application to microarray gene expression data. We define and analyse the randomised algorithm, before presenting results on both synthetic and real biological data sets. We show that the randomised algorithm leads to substantial gains in speed with minimal loss in clustering quality. The randomised time series BHC algorithm is available as part of the R package BHC, which is available for download from Bioconductor (version 2.10 and above) via http://bioconductor.org/packages/2.10/bioc/html/BHC.html. We have also made available a set of R scripts which can be used to reproduce the analyses carried out in this paper. These are available from the following URL. https://sites.google.com/site/randomisedbhc/

Impacts of bromine and iodine chemistry on tropospheric OH and HO2 : Comparing observations with box and global model perspectives

The chemistry of the halogen species bromine and iodine has a range of impacts on tropospheric composition, and can affect oxidising capacity in a number of ways. However, recent studies disagree on the overall sign of the impacts of halogens on the oxidising capacity of the troposphere. We present simulations of OH and HO2 radicals for comparison with observations made in the remote tropical ocean boundary layer during the Seasonal Oxidant Study at the Cape Verde Atmospheric Observatory in 2009. We use both a constrained box model, using detailed chemistry derived from the Master Chemical Mechanism (v3.2), and the three-dimensional global chemistry transport model GEOS-Chem. Both model approaches reproduce the diurnal trends in OH and HO2. Absolute observed concentrations are well reproduced by the box model but are overpredicted by the global model, potentially owing to incomplete consideration of oceanic sourced radical sinks. The two models, however, differ in the impacts of halogen chemistry. In the box model, halogen chemistry acts to increase OH concentrations (by 9.8% at midday at the Cape Verde Atmospheric Observatory), while the global model exhibits a small increase in OH at the Cape Verde Atmospheric Observatory (by 0.6% at midday) but overall shows a decrease in the global annual mass-weighted mean OH of 4.5%. These differences reflect the variety of timescales through which the halogens impact the chemical system. On short timescales, photolysis of HOBr and HOI, produced by reactions of HO2 with BrO and IO, respectively, increases the OH concentration. On longer timescales, halogen-catalysed ozone destruction cycles lead to lower primary production of OH radicals through ozone photolysis, and thus to lower OH concentrations. The global model includes more of the longer timescale responses than the constrained box model, and overall the global impact of the longer timescale response (reduced primary production due to lower O3 concentrations) overwhelms the shorter timescale response (enhanced cycling from HO2 to OH), and thus the global OH concentration decreases. The Earth system contains many such responses on a large range of timescales. This work highlights the care that needs to be taken to understand the full impact of any one process on the system as a whole

Cosmology as Geodesic Motion

For gravity coupled to N scalar fields with arbitrary potential V, it is shown that all flat (homogeneous and isotropic) cosmologies correspond to geodesics in an (N+1)-dimensional `augmented' target space of Lorentzian signature (1,N), timelike if V>0, null if V=0 and spacelike if V<0. Accelerating cosmologies correspond to timelike geodesics that lie within an `acceleration subcone' of the `lightcone'. Non-flat (k=-1,+1) cosmologies are shown to evolve as projections of geodesic motion in a space of dimension (N+2), of signature (1,N+1) for k=-1 and signature (2,N) for k=+1. This formalism is illustrated by cosmological solutions of models with an exponential potential, which are comprehensively analysed; the late-time behviour for other potentials of current interest is deduced by comparison.Comment: 26 pages, 2 figures, journal version with additional reference

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

<p>Abstract</p> <p>Background</p> <p>Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose.</p> <p>Methods</p> <p>Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection.</p> <p>Results</p> <p>Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin.</p> <p>Conclusions</p> <p>Lower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.</p

Iodine monoxide at a clean marine coastal site: observations of high frequency variations and inhomogeneous distributions

The first in situ point observations of iodine monoxide (IO) at a clean marine site were made using a laser-induced fluorescence instrument deployed at Mace Head, Ireland in August 2007. IO mixing ratios of up to 49.8 pptv (equivalent to pmol mol&lt;sup&gt;−1&lt;/sup&gt;; 1 s average) were observed at day-time low tide, well in excess of previous observed spatially-averaged maxima. A strong anti-correlation of IO mixing ratios with tide height was evident and the high time resolution of the observations showed IO peaked in the hour after low tide. The temporal delay in peak IO compared to low tide has not been observed previously but coincides with the time of peak aerosol number previously observed at Mace Head. &lt;br&gt;&lt;br&gt; A long path-differential optical absorption spectroscopy instrument (with a 2 × 6.8 km folded path across Roundstone Bay) was also based at the site for 3 days during the point measurement observation period. Both instruments show similar temporal trends but the point measurements of IO are a factor of ~6–10 times greater than the spatially averaged IO mixing ratios, providing direct empirical evidence of the presence of inhomogeneities in the IO mixing ratio near the intertidal region

Qualitative study in Loop Quantum Cosmology

This work contains a detailed qualitative analysis, in General Relativity and in Loop Quantum Cosmology, of the dynamics in the associated phase space of a scalar field minimally coupled with gravity, whose potential mimics the dynamics of a perfect fluid with a linear Equation of State (EoS). Dealing with the orbits (solutions) of the system, we will see that there are analytic ones, which lead to the same dynamics as the perfect fluid, and our goal is to check their stability, depending on the value of the EoS parameter, i.e., to show whether the other orbits converge or diverge to these analytic solutions at early and late times.Comment: 12 pages, 7 figures. Version accepted for publication in CQ

Metric gravity theories and cosmology:II. Stability of a ground state in f(R) theories

A fundamental criterion of viability of any gravity theory is existence of a stable ground-state solution being either Minkowski, dS or AdS space. Stability of the ground state is independent of which frame is physical. In general, a given theory has multiple ground states and splits into independent physical sectors. All metric gravity theories with the Lagrangian being a function of Ricci tensor are dynamically equivalent to Einstein gravity with a source and this allows us to study the stability problem using methods developed in GR. We apply these methods to f(R) theories. As is shown in 13 cases of Lagrangians the stability criterion works simply and effectively whenever the curvature of the ground state is determined. An infinite number of gravity theories have a stable ground state and further viability criteria are necessary.Comment: A modified and expanded version of a second part of the paper which previously appeared as gr-qc/0702097v1. The first, modified part is now published as gr-qc/0702097v2 and as a separate paper in Class. Qu. Grav. The present paper matches the published versio