Service evaluation to establish the sensitivity, specificity and additional value of broad-range 16S rDNA PCR for the diagnosis of infective endocarditis from resected endocardial material in patients from eight UK and Ireland hospitals

Infective endocarditis (IE) can be diagnosed in the clinical microbiology laboratory by culturing explanted heart valve material. We present a service evaluation that examines the sensitivity and specificity of a broad-range 16S rDNA polymerase chain reaction (PCR) assay for the detection of the causative microbe in culture-proven and culture-negative cases of IE. A clinical case-note review was performed for 151 patients, from eight UK and Ireland hospitals, whose endocardial specimens were referred to the Microbiology Laboratory at Great Ormond Street Hospital (GOSH) for broad-range 16S rDNA PCR over a 12-year period. PCR detects the causative microbe in 35/47 cases of culture-proven IE and provides an aetiological agent in 43/69 cases of culture-negative IE. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the 16S rDNA PCR assay were calculated for this series of selected samples using the clinical diagnosis of IE as the reference standard. The values obtained are as follows: sensitivity = 67 %, specificity = 91 %, PPV = 96 % and NPV = 46 %. A wide range of organisms are detected by PCR, with Streptococcus spp. detected most frequently and a relatively large number of cases of Bartonella spp. and Tropheryma whipplei IE. PCR testing of explanted heart valves is recommended in addition to culture techniques to increase diagnostic yield. The data describing the aetiological agents in a large UK and Ireland series of culture-negative IE will allow future development of the diagnostic algorithm to include real-time PCR assays targeted at specific organisms

Orbital and stochastic far-UV variability in the nova-like system V3885 Sgr

Highly time-resolved time-tagged FUSE satellite spectroscopic data are analysed to establish the far-ultraviolet (FUV) absorption line characteristics of the nova-like cataclysmic variable binary, V3885 Sgr. We determine the temporal behaviour of low (Ly_beta, CIII, NIII) and high (SIV, PV, OVI) ion species, and highlight corresponding orbital phase modulated changes in these lines. On average the absorption troughs are blueshifted due to a low velocity disc wind outflow. Very rapid (~ 5 min) fluctuations in the absorption lines are isolated, which are indicative of stochastic density changes. Doppler tomograms of the FUV lines are calculated which provide evidence for structures where a gas stream interacts with the accretion disc. We conclude that the line depth and velocity changes as a function of orbital phase are consistent with an asymmetry that has its origin in a line-emitting, localised disc-stream interaction region.Comment: Accepted for publication in MNRA

Homotopy on spatial graphs and generalized Sato-Levine invariants

Edge-homotopy and vertex-homotopy are equivalence relations on spatial graphs which are generalizations of Milnor's link-homotopy. Fleming and the author introduced some edge (resp. vertex)-homotopy invariants of spatial graphs by applying the Sato-Levine invariant for the constituent 2-component algebraically split links. In this paper, we construct some new edge (resp. vertex)-homotopy invariants of spatial graphs without any restriction of linking numbers of the constituent 2-component links by applying the generalized Sato-Levine invariant.Comment: 16 pages, 13 figure

Stories tell us? Political narrative, demes, and the transmission of knowledge through culture

This paper compares two institutions of storytelling, mainstream national narratives and self-represented digital storytelling. It considers the centenary of World War 1, especially the Gallipoli campaign (1915) and its role in forming Australian ‘national character’. Using the new approach of cultural science, it investigates storytelling as a means by which cultures make and bind groups or ‘demes’. It finds that that demic (group-made) knowledge trumps individual experience, and that self-representation (digital storytelling) tends to copy the national narrative, even when the latter is known not to be true. The paper discusses the importance of culture in the creation of knowledge, arguing that if the radical potential of digital storytelling is to be understood – and realised – then a systems (as opposed to behavioural) approach to communication is necessary. Without a new model of knowledge, it seems we are stuck with repetition of the same old story

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

Stochastic Tachyon Fluctuations, Marginal Deformations and Shock Waves in String Theory

Starting with exact solutions to string theory on curved spacetimes we obtain deformations that represent gravitational shock waves. These may exist in the presence or absence of sources. Sources are effectively induced by a tachyon field that randomly fluctuates around a zero condensate value. It is shown that at the level of the underlying conformal field theory (CFT) these deformations are marginal and moreover all \a'-corrections are taken into account. Explicit results are given when the original undeformed 4-dimensional backgrounds correspond to tensor products of combinations of 2-dimensional CFT's, for instance SL(2,R)/R \times SU(2)/U(1).Comment: 26 pages, harvmac, no figures. Very minor modifications, and in addition conditions (B.3) and (B.4) were also obtained using beta-function equations. Version to appear in Phys. Rev.

Resonance line-profile calculations based on hydrodynamical models of cataclysmic variable winds

We present synthetic line profiles as predicted by the models of 2-D line- driven disk winds due to Proga, Stone & Drew. We compare the model line profiles with HST observations of the cataclysmic variable IX Vel. The model wind consists of a slow outflow that is bounded on the polar side by a fast stream. We find that these two components of the wind produce distinct spectral features. The fast stream produces profiles which show features consistent with observations. These include the appearance of the P-Cygni shape for a range of inclinations, the location of the maximum depth of the absorption component at velocities less than the terminal velocity, and the transition from absorption to emission with increasing inclination. However the model profiles have too little absorption or emission equivalent width. This quantitative difference between our models and observations is not a surprise because the line-driven wind models predict a mass loss rate that is lower than the rate required by the observations. We note that the model profiles exhibit a double-humped structure near the line center which is not echoed in observations. We identify this structure with a non-negligible redshifted absorption which is formed in the slow component of the wind where the rotational velocity dominates over expansion velocity. We conclude that the next generation of disk wind models, developed for application to CVs, needs to yield stronger wind driving out to larger disk radii than do the present models.Comment: LaTeX, 19 pages, to appear in Ap

Computational Methods for HSCT-Inlet Controls/CFD Interdisciplinary Research

A program aimed at facilitating the use of computational fluid dynamics (CFD) simulations by the controls discipline is presented. The objective is to reduce the development time and cost for propulsion system controls by using CFD simulations to obtain high-fidelity system models for control design and as numerical test beds for control system testing and validation. An interdisciplinary team has been formed to develop analytical and computational tools in three discipline areas: controls, CFD, and computational technology. The controls effort has focused on specifying requirements for an interface between the controls specialist and CFD simulations and a new method for extracting linear, reduced-order control models from CFD simulations. Existing CFD codes are being modified to permit time accurate execution and provide realistic boundary conditions for controls studies. Parallel processing and distributed computing techniques, along with existing system integration software, are being used to reduce CFD execution times and to support the development of an integrated analysis/design system. This paper describes: the initial application for the technology being developed, the high speed civil transport (HSCT) inlet control problem; activities being pursued in each discipline area; and a prototype analysis/design system in place for interactive operation and visualization of a time-accurate HSCT-inlet simulation