Interferences from blood collection tube components on clinical chemistry assays

Improper design or use of blood collection devices can adversely affect the accuracy of laboratory test results. Vascular access devices, such as catheters and needles, exert shear forces during blood flow, which creates a predisposition to cell lysis. Components from blood collection tubes, such as stoppers, lubricants, surfactants, and separator gels, can leach into specimens and/or adsorb analytes from a specimen; special tube additives may also alter analyte stability. Because of these interactions with blood specimens, blood collection devices are a potential source of pre-analytical error in laboratory testing. Accurate laboratory testing requires an understanding of the complex interactions between collection devices and blood specimens. Manufacturers, vendors, and clinical laboratorians must consider the pre-analytical challenges in laboratory testing. Although other authors have described the effects of endogenous substances on clinical assay results, the effects/impact of blood collection tube additives and components have not been well systematically described or explained. This review aims to identify and describe blood collection tube additives and their components and the strategies used to minimize their effects on clinical chemistry assays

Origin of Multikinks in Dispersive Nonlinear Systems

We develop {\em the first analytical theory of multikinks} for strongly {\em dispersive nonlinear systems}, considering the examples of the weakly discrete sine-Gordon model and the generalized Frenkel-Kontorova model with a piecewise parabolic potential. We reveal that there are no $2\pi$-kinks for this model, but there exist {\em discrete sets} of $2\pi N$-kinks for all N>1. We also show their bifurcation structure in driven damped systems.Comment: 4 pages 5 figures. To appear in Phys Rev

The pharmacokinetics and toxicity of morning vs. evening tobramycin dosing for pulmonary exacerbations of cystic fibrosis:A randomised comparison

AbstractBackgroundCircadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity.AimTo investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission.MethodsChildren (age 5–18years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000h. Serum tobramycin levels were drawn at 1h and between 3.5 and 5h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800h in the evening until 1200h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin.ResultsEighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73ng/mg; 95% CI, 0.14 to 1.32; p=0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%).ConclusionsRenal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245)

Chirality Violation in QCD Reggeon Interactions

The appearance of the triangle graph infra-red axial anomaly in reduced quark loops contributing to QCD triple-regge interactions is studied. In a dispersion relation formalism, the anomaly can only be present in the contributions of unphysical triple discontinuities. In this paper an asymptotic discontinuity analysis is applied to high-order feynman diagrams to show that the anomaly does indeed occur in sufficiently high-order reggeized gluon interactions. The reggeon states involved must contain reggeized gluon combinations with the quantum numbers of the anomaly (winding-number) current. A direct connection with the well-known U(1) problem is thus established. Closely related diagrams that contribute to the pion/pomeron and triple pomeron couplings in color superconducting QCD are also discussed.Comment: 52 pages, 29 PS figures in the tex

The environmental stress sensitivities of pathogenic Candida species, including Candida auris, and implications for their spread in the hospital setting

We are grateful to Dr. David Stead, Evelyn Argo and Craig Pattison (Aberdeen Proteomics Core Facility) for their expert identification of Candida isolates by MALDI ToF MS, and to Dr Jill King and our colleagues in the Aberdeen Fungal Group for their helpful advice. AJPB and NARG were supported by a programme grant from the Medical Research Council [www.mrc.ac.uk] (grant number MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (grant number MR/N006364/1). AJPB was also supported by the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk] (grant numbers BB/F00513X/1, BB/P020119/1), and AWW by the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. NARG was also supported by grants from the Wellcome Trust [www.wellcome.ac.uk] (grant numbers 075470, 086827, 093378, 097377, 099197, 101873, 102705, 200208). DMM was supported by National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [www.nc3rs.org.uk] (grant numbers NC/S001557/1 and NC/N002482/1) and the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk] (grant number BB/P02050X/1). HH was supported by the John Duthie Scholarship from the University of Aberdeen’s Development Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Chaperone activity and structure of monomeric polypeptide binding domains of GroEL

The chaperonin GroEL is a large complex composed of 14 identical 57-kDa subunits that requires ATP and GroES for some of its activities. We find that a monomeric polypeptide corresponding to residues 191 to 345 has the activity of the tetradecamer both in facilitating the refolding of rhodanese and cyclophilin A in the absence of ATP and in catalyzing the unfolding of native barnase. Its crystal structure, solved at 2.5 A resolution, shows a well-ordered domain with the same fold as in intact GroEL. We have thus isolated the active site of the complex allosteric molecular chaperone, which functions as a "minichaperone." This has mechanistic implications: the presence of a central cavity in the GroEL complex is not essential for those representative activities in vitro, and neither are the allosteric properties. The function of the allosteric behavior on the binding of GroES and ATP must be to regulate the affinity of the protein for its various substrates in vivo, where the cavity may also be required for special functions

Scaling solution, radion stabilization, and initial condition for brane-world cosmology

We propose a new, self-consistent and dynamical scenario which gives rise to well-defined initial conditions for five-dimensional brane-world cosmologies with radion stabilization. At high energies, the five-dimensional effective theory is assumed to have a scale invariance so that it admits an expanding scaling solution as a future attractor. The system automatically approaches the scaling solution and, hence, the initial condition for the subsequent low-energy brane cosmology is set by the scaling solution. At low energies, the scale invariance is broken and a radion stabilization mechanism drives the dynamics of the brane-world system. We present an exact, analytic scaling solution for a class of scale-invariant effective theories of five-dimensional brane-world models which includes the five-dimensional reduction of the Horava-Witten theory, and provide convincing evidence that the scaling solution is a future attractor.Comment: 17 pages; version accepted for PRD, references adde

“Wax On, Wax Off”: In Vivo Imaging of Plant Physiology and Disease with Fourier Transform Infrared Reflectance Microspectroscopy

Analysis of the epicuticular wax layer on the surface of plant leaves can provide a unique window into plant physiology and responses to environmental stimuli. Well-established analytical methodologies can quantify epicuticular wax composition, yet few methods are capable of imaging wax distribution in situ or in vivo. Here, the first report of Fourier transform infrared (FTIR) reflectance spectroscopic imaging as a non-destructive, in situ, method to investigate variation in epicuticular wax distribution at 25 µm spatial resolution is presented. The authors demonstrate in vivo imaging of alterations in epicuticular waxes during leaf development and in situ imaging during plant disease or exposure to environmental stressors. It is envisaged that this new analytical capability will enable in vivo studies of plants to provide insights into how the physiology of plants and crops respond to environmental stresses such as disease, soil contamination, drought, soil acidity, and climate change