Rapid serodiagnosis of Staphylococcus aureus surgical site infection following median sternotomy

Objectives: To determine the sensitivity and specificity of a novel ELISA for the serodiagnosis of surgical site infection (SSI) due to staphylococci following median sternotomy. Methods: Twelve patients with a superficial sternal SSI and 19 with a deep sternal SSI due to Staphylococcus aureus were compared with 37 control patients who also underwent median sternotomy for cardiac surgery but exhibited no microbiological or clinical symptoms of infection. A further five patients with sternal SSI due to coagulase-negative (CoNS) staphylococci were studied. An ELISA incorporating a recently recognised exocellular short chain form of lipoteichoic acid (lipid S) recovered from CoNS, was used to determine serum levels of anti-lipid S IgG in all patient groups. Results: Serum anti-lipid S IgG titres of patients with sternal SSI due to S. aureus were significantly higher than the control patients (P<0.0001). In addition, patients with deep sternal SSI had significantly higher serum anti-lipid S IgG titres than patients with superficial sternal SSI (P=0.03). Serum anti-lipid S IgG titres of patients with sternal SSI due to CoNS were significantly higher than the control patients (P=0.001). Conclusion: The lipid S ELISA may facilitate the diagnosis of sternal SSI due to S. aureus and could also be of value with infection due to CoNS. © 2005 Published by Elsevier Ltd. on behalf of The Bristish Infection Society

Bayesian inference of agent-based models: a tool for studying kidney branching morphogenesis

The adult mammalian kidney has a complex, highly-branched collecting duct epithelium that arises as a ureteric bud sidebranch from an epithelial tube known as the nephric duct. Subsequent branching of the ureteric bud to form the collecting duct tree is regulated by subcellular interactions between the epithelium and a population of mesenchymal cells that surround the tips of outgrowing branches. The mesenchymal cells produce glial cell-line derived neurotrophic factor (GDNF), that binds with RET receptors on the surface of the epithelial cells to stimulate several subcellular pathways in the epithelium. Such interactions are known to be a prerequisite for normal branching development, although competing theories exist for their role in morphogenesis. Here we introduce the first agent-based model of ex vivo kidney uretic branching. Through comparison with experimental data, we show that growth factor-regulated growth mechanisms can explain early epithelial cell branching, but only if epithelial cell division depends in a switch-like way on the local growth factor concentration; cell division occurring only if the driving growth factor level exceeds a threshold. We also show how a recently-developed method, "Approximate Approximate Bayesian Computation", can be used to infer key model parameters, and reveal the dependency between the parameters controlling a growth factor-dependent growth switch. These results are consistent with a requirement for signals controlling proliferation and chemotaxis, both of which are previously identified roles for GDNF

RAPD for the typing of coagulase-negative staphylococci implicated in catheter-related bloodstream infection

Objectives: A rapid random amplification of polymorphic DNA (RAPD) technique was developed to distinguish between strains of coagulase-negative staphylococci (CoNS) involved in central venous catheter (CVC)-related bloodstream infection. Its performance was compared with that of pulsed-field gel electrophoresis (PFGE). Methods: Patients at the University Hospital Birmingham NHS Foundation Trust, U.K. who underwent stem cell transplantation and were diagnosed with CVC-related bloodstream infection due to CoNS whilst on the bone marrow transplant unit were studied. Isolates of CoNS were genotyped by PFGE and RAPD, the latter employing a single primer and a simple DNA extraction method. Results: Both RAPD and PFGE were highly discriminatory (Simpson's diversity index, 0.96 and 0.99, respectively). Within the 49 isolates obtained from blood cultures of 33 patients, 20 distinct strains were identified by PFGE and 25 by RAPD. Of the 25 strains identified by RAPD, nine clusters of CoNS contained isolates from multiple patients, suggesting limited nosocomial spread. However, there was no significant association between time of inpatient stay and infection due to any particular strain. Conclusion: The RAPD technique presented allows CoNS strains to be genotyped with high discrimination within 4 h, facilitating real-time epidemiological investigations. In this study, no single strain of CoNS was associated with a significant number of CVC-related bloodstream infections. © 2005 Published by Elsevier Ltd on behalf of the British Infection Society

Increasing the detectability of external influence on precipitation by correcting feature location in GCMs

Understanding how precipitation varies as the climate changes is essential to determining the true impact of global warming. This is a difficult task not only due to the large internal variability observed in precipitation but also because of a limited historical record and large biases in simulations of precipitation by general circulation models (GCMs). Here we make use of a technique that spatially and seasonally transforms GCM fields to reduce location biases and investigate the potential of this bias correction to study historical changes. We use two versions of this bias correction—one that conserves intensities and another that conserves integrated precipitation over transformed areas. Focussing on multimodel ensemble means, we find that both versions reduce RMS error in the historical trend by approximately 11% relative to the Global Precipitation Climatology Project (GPCP) data set. By regressing GCMs' historical simulations of precipitation onto radiative forcings, we decompose these simulations into anthropogenic and natural time series. We then perform a simple detection and attribution study to investigate the impact of reducing location biases on detectability. A multiple ordinary least squares regression of GPCP onto the anthropogenic and natural time series, with the assumptions made, finds anthropogenic detectability only when spatial corrections are applied. The result is the same regardless of which form of conservation is used and without reducing the dimensionality of the fields beyond taking zonal means. While “detectability” is dependent both on the exact methodology and the confidence required, this nevertheless demonstrates the potential benefits of correcting location biases in GCMs when studying historical precipitation, especially in cases where a signal was previously undetectable

Stable isotope signatures reveal small-scale spatial separation in populations of European sea bass

Scientific information about European sea bass (Dicentrarchus labrax) stocks in NE Atlantic is limited and a more accurate definition of the stock boundaries in the area is required to improve assessment and management advice. Here we study the connectivity and movement patterns of European sea bass in Wales (UK) using the stable isotope (δ13C and δ15N) composition of their scales. Analysis of fish scale δ13C and δ15N values in the last growing season was performed on 189 adult sea bass caught at nine coastal feeding grounds. Fish >50 cm total length (TL) caught in estuaries had very low δ13C and this is characteristic of fresh water (organic/soil) input, indicating the primary use of estuaries as feeding areas. A random forest classification model was used to test if there was a difference in δ15N and δ13C values between north, mid and south Wales and whether it was possible to correctly assign the fish to the area where it was caught. This analysis was restricted to fish of a similar size range (40-50 cm TL) caught in open coastal areas (n=156). The random forest classification model showed that about 75% of the fish could be correctly assigned to their collection region based on their isotope composition. The majority of the misclassifications of fish were fish from north Wales classifying to mid Wales and vice versa, while the majority of fish from south Wales were correctly assigned (80%). Our findings suggest that two sub-populations of sea bass in Welsh waters use separate feeding grounds (south vs. mid/north Wales), and may need separate management

Proximity-induced screening and its magnetic breakdown in mesoscopic hybrid structures

We derive a general microscopic expression for the non-linear diamagnetic current in a clean superconductor-insulator-normal metal structure with an arbitrary interface transmission. In the absence of electron-electron interactions in the normal metal the diamagnetic response increases monotonously with decreasing temperature showing no sign of paramagnetic reentrance down to T=0. We also analyze the magnetic breakdown of proximity induced Meissner screening. We demonstrate that the magnetic breakdown field should be strongly suppressed in the limit of small interface transmissions while the linear diamagnetic current does not depend on the transmission of the insulating barrier at low enough temperatures.Comment: 7 pages, 2 figure

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure