293 research outputs found
Influence of Polymorphisms in Innate Immunity Genes on Susceptibility to Invasive Aspergillosis after Stem Cell Transplantation
The innate immune system plays a pivotal role in the primary defence against invasive fungal infection. Genetic variation in genes that regulate this response, initiated by pulmonary macrophages, may influence susceptibility to invasive aspergillosis in patients at risk. We investigated in a clinical setting whether common polymorphisms in Toll-like receptor (TLR) and cytokine genes involved in macrophage regulation are associated with susceptibility to invasive aspergillosis. Forty-four allogeneic stem cell transplantation recipients diagnosed with probable or proven IA according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group, were enrolled. The control group consisted of 64 allogeneic stem cell transplantation recipients without invasive aspergillosis. The TLR4 1063A>G single nucleotide polymorphism was associated with invasive aspergillosis when present in donors of allogeneic stem cell transplantation recipients (unadjusted OR 3.77 95%CI 1.08–13.2, p = 0.03). In a multivariate analysis, adjusted for occurrence of graft-versus-host-disease, Cytomegalovirus serostatus and duration of neutropenia, paired presence of the TLR4 1063A>G and IFNG 874T>A single nucleotide polymorphisms showed a trend towards increased susceptibility to invasive aspergillosis (p = 0.04). These findings point to the relevant immunological pathway involved in resistance to invasive aspergillosis and warrant further study of the effects of TLR and cytokine polymorphisms and their interaction, which may occur on different levels of the complex biological interplay between the immunocompromised host and Aspergillus sp
Analytical and experimental characterization of a miniature calorimetric sensor in pulsatile flow
The behaviour of a miniature calorimetric sensor, which is under
consideration for catheter-based coronary artery flow assessment, is
investigated in both steady and pulsatile tube flow. The sensor is composed of
a heating element operated at constant power, and two thermopiles that measure
flow-induced temperature differences over the sensor surface.
An analytical sensor model is developed, which includes axial heat conduction
in the fluid and a simple representation of the solid wall, assuming a
quasi-steady sensor response to the pulsatile flow. To reduce the mathematical
problem, described by a two-dimensional advection-diffusion equation, a
spectral method is applied. A Fourier transform is then used to solve the
resulting set of ordinary differential equations and an analytical expression
for the fluid temperature is found. To validate the analytical model,
experiments with the sensor mounted in a tube have been performed in steady and
pulsatile water flow with various amplitudes and Strouhal numbers. Experimental
results are generally in good agreement with theory and show a quasi-steady
sensor response in the coronary flow regime. The model can therefore be used to
optimize the sensor design for coronary flow assessment
Modelling regulation of vascular tone following muscle contraction: model development, validation and global sensitivity analysis
In this study the regulation of vascular tone inducing the blood flow increase at the onset
of exercise is examined. Therefore, our calf circulation model was extended with a regulation
model to simulate changes in vascular tone depending on myogenic, metabolic
and baroreflex regulation. The simulated blood flow corresponded to the in vivo response
and it was concluded that metabolic activation caused the flow increase shortly
after muscle contraction. Secondly, the change in baseline flow upon tilt was a result of
myogenic and baroreflex activation. Based on a sensitivity analysis the myogenic gain
was identified as most important parameter
The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity
Open Access funded by Wellcome Trust: Under a Creative Commons license Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. Acknowledgments We would like to thank S. Hardison, P. Redelinghuys, J. Taylor, C. Wallace, A. Richmond, S. Hadebe, A. Plato, F. Abbass, L. Fick, N. Allie, R. Wilkinson, K. Wilkinson, S. Cooper, D. Lang, and V. Kumar for reagents and assistance, and the animal facility staff for the care of our animals. This work was supported by the MRC (UK) and Wellcome Trust (G.D.B.); MRC (South Africa) and Sydney Brenner Fellowship (M.J.M.); Vici (M.G.N.), Vidi (R.v.C.), and Veni grants (T.S.P.) from the Netherlands Organization for Scientific Research; the Royal Netherlands Academy of Arts and Sciences (T.H.M.O.); EC FP7 projects (NEWTBVAC, ADITEC; T.H.M.O.); Carnegie Corporation and CIDRI (J.C.H.); and the University of Aberdeen (B.K.).Peer reviewedPublisher PD
3D fusion of intravascular ultrasound and coronary computed tomography for in-vivo wall shear stress analysis: A feasibility study
Wall shear stress, the force per area acting on the lumen wall due to the blood flow, is an important biomechanical parameter in the localization and progression of atherosclerosis. To calculate shear stress and relate it to atherosclerosis, a 3D description of the lumen and vessel wall is required. We present a framework to obtain the 3D reconstruction of human coronary arteries by the fusion of intravascular ultrasound (IVUS) and coronary computed tomography angiography (CT). We imaged 23 patients with IVUS and CT. The images from both modalities were registered for 35 arteries, using bifurcations as landmarks. The IVUS images together with IVUS derived lumen and wall contours were positioned on the 3D centerline, which was derived from CT. The resulting 3D lumen and wall contours were transformed to a surface for calculation of shear stress and plaque thickness. We applied variations in selection of landmarks and investigated whether these variations influenced the relation between shear stress and plaque thickness. Fusion was successfully achieved in 31 of the 35 arteries. The average length of the fused segments was 36.4 ± 15.7 mm. The length in IVUS and CT of the fused parts correlated excellently (R2= 0.98). Both for a mildly diseased and a very diseased coronary artery, shear stress was calculated and related to plaque thickness. Variations in the selection of the landmarks for these two arteries did not affect the relationship between shear stress and plaque thickness. This new framework can therefore successfully be applied for shear stress analysis in human coronary arteries
- …