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Repolarizing potassium currents in working myocardium of Japanese quail: novel translational model for cardiac electrophysiology
No full textBirds developed endothermy and four-chambered high-performance heart independently from mammals. Though avian embryos are extensively studied and widely used as various models for heart research, little is known about cardiac physiology of adult birds. Meanwhile, cardiac electrophysiology is in search for easily accessible and relevant model objects which resemble human myocardium in the pattern of repolarizing currents (I Kr , I Ks , I Kur and I to ). This study focuses on the configuration of electrical activity and electrophysiological phenotype of working myocardium in adult Japanese quails ( Coturnix japonica ). The resting membrane potential and action potential (AP) waveform in quail atrial myocardium were similar to that in working myocardium of rodents. Using whole-cell patch clamp and sharp glass microelectrodes, we demonstrated that the repolarization of quail atrial and ventricular myocardium is determined by voltage-dependent potassium currents I Kr , I Ks and I to – the later was previously considered as an exclusive evolutionary feature of mammals. The specific blockers of these currents, dofetilide (3 μmol l -1 ), HMR 1556 (30 μmol l -1 ) and 4-aminopyridine (3 mmol l -1 ), prolonged AP in both ventricular and atrial myocardial preparations. The expression of the corresponding channels responsible for these currents, in quail myocardium was investigated with quantitative RT-PCR and western blotting. In conclusion, the described pattern of repolarizing ionic currents and channels in quail myocardium makes this species a novel and suitable experimental model for translational cardiac research and reveals new information related to the evolution of cardiac electrophysiology in vertebrates
Parents experiences of care offered after stillbirth: International online survey of high- and middle-income countries
No full textBackground Stillbirth, the death of a baby before birth, is associated with significant psychological and social consequences that can be mitigated by respectful and supportive bereavement care. The absence of high-level evidence to support the broad scope of perinatal bereavement practices means that offering a range of options identified as valued by parents has become an important indicator of care quality. This study aimed to describe bereavement care practices offered to parents across different high- and middle-income countries. MethodsAn online survey of parents of stillborn babies was conducted between December 2014 and February 2015. Frequencies of nine practices were compared between high- and middle-income countries. Differences in proportions of reported practices and their associated odds ratios were calculated to compare high- and middle-income countries.Results Over three-thousand parents (3041) with a self-reported stillbirth in the preceding five years from 40 countries responded. At least 40 responses came from 15 countries.Significant differences in prevalence of offering nine bereavement care practices were reported by women in high-income countries (HICs) compared with women in middle-income countries MICs). All nine practices were reported to occur significantly more frequently by women in HICs, including opportunity to see and hold their baby (OR=4.8, 95%CI 4.0-5.9). Widespread occurrence of all nine practices was reported only for The Netherlands. ConclusionsBereavement care after stillbirth varies between countries. Future research should look at why these differences occur, their impact on parents, and whether differences should be addressed, particularly how to support effective communication, decision-making and follow-up care.<br/
Solving Block Low-Rank Linear Systems by LU Factorization is Numerically Stable
No full textBlock low-rank (BLR) matrices possess a blockwise low-rank property that can be exploited to reduce the complexity of numerical linear algebra algorithms. The impact of these low-rank approximations on the numerical stability of the algorithms in floating-point arithmetic has not previously been analyzed. We present rounding error analysis for the solution of a linear system by LU factorization of BLR matrices. Assuming that a stable pivoting scheme is used, we prove backward stability: the relative backward error is bounded by a modest constant times e, where the low-rank threshold e is the parameter controlling the accuracy of the blockwise low-rank approximations. In addition to this key result, our analysis offers three new insights into the numerical behavior of BLR algorithms. First, we compare the use of a global or local low-rank threshold and find that a global one should be preferred. Second, we show that performing intermediate recompressions during the factorization can significantly reduce its cost without compromising numerical stability. Third, we consider different BLR factorization variants and determine the update–compress–factor (UCF) variant to be the best. Tests on a wide range of matrices from various real-life applications show that the predictions from the analysis are realized in practice
Seismic geomorphology and evolution of the Melville Bugt Trough Mouth Fan, northwest Greenland
No full textTrough mouth fans on glaciated margins are a common sedimentary feature that contain a 25 record of ice sheet advance and retreat across the continental shelf. This study uses 2D and 3D seismic reflection data across the Melville Bugt Trough Mouth Fan (MB-TMF), offshore northwest Greenland, to document its stratigraphic architecture, glacigenic landforms, and marine deposits. The MB-TMF stratigraphy is characterised by rapid progradation of the continental shelf (over 100 km since ~2.7 Ma) and heterogeneous truncation or subsidence of topset strata. The variable topset character relates to the repeated growth and retreat of the Greenland Ice Sheet across the shelf since ~2.7 Ma. Seismic geomorphology and facies analysis of the prograding clinoforms show repeated sequences of debris flow deposits and gullies that are taken to infer gravity-driven processes and the presence of meltwater-related hyperpycnal flows in areas proximal to the ice sheet on the outer shelf. Several sets of mega-scale glacial lineations confirm the presence and flow pathways of successive ice streams since ~1.3 Ma. Bottomset contourites provide insights into the evolution of the West Greenland Current in Baffin Bay through the Pleistocene, with deposition starting at ~1.0 Ma, having ceased at the onset of glaciation at ~2.7 Ma. This suggests there was a major reduction in northward oceanographic heat transport during the Early Pleistocene, before an increase during interglacials after ~1.0 Ma. Evolution of the MB-TMF can be summarised into four stages that were controlled by variations in ice sheet erosion, topographic forcing of ice stream flow, and changes in accommodation related to glacigenic deposition and tectonic subsidence. These results show that during the Middle Pleistocene Transition there is an apparent switch from a meltwater-dominated depositional regime, to one with greater emplacement of materials by ice directly at the palaeo-shelf edge. These results provide significant new detail about the large-scale glacigenic and marine depositional processes during the repeated fluctuations of the northwest Greenland Ice Sheet into Melville Bugt since ~2.7 Ma
The effect of low temperature heat treatment on stress corrosion crack initiation in machined 316L stainless steel in high-temperature hydrogenated water
No full textA notable reduction of the stress corrosion cracking (SCC) initiation susceptibility was identified for machined cold-rolled 316L stainless steel that received a 650 °C/10 hours heat-treatment prior to slow strain rate tensile (SSRT) testing in high-temperature hydrogenated water. The cracks per unit area of the machined surface of heat-treated specimens decreased by ~50% compared to as-machined surfaces, and by >70% with respect to polished surfaces. The results were ascribed to recrystallization of the ultrafine-grains present in the outer deformation layer of the machined surface, which resulted in a reduction of the tensile residual stress and nano-indentation hardness
NUC-1031 in combination with cisplatin for the first-line treatment of patients with advanced biliary tract cancer
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The Perceptual Control Model of Psychopathology
No full textPerceptual Control Theory (PCT) states that behaviour controls perception; we act against disturbances in the environment to align hierarchically organised perceived aspects of the self and the world with neurally specified reference values. The diverse symptoms of psychopathology are each examples of loss of control, which are maintained by conflicting control systems, and effective interventions shift and sustain awareness to the source of the conflict to allow trial-and-error changes (reorganisation) in the parameters of the superordinate system to the conflict, until control is restored. Experimental, phenomenological, therapeutic and computational research has examined its mechanisms, and its mode of delivery has extended it from a client-led psychotherapy (Method of Levels) to brief training, group interventions, and computerised modalities
Bounds for an integral of the modified Bessel function of the first kind and expressions involving it
No full textSimple upper and lower bounds are obtained for the integral ∫x0e−γttνIν(t)dt , x>0 , ν>−12 , 0<γ<1 . Most of our bounds for this integral are tight as x→∞ . We apply one of our inequalities to bound some expressions involving this integral. Two of these expressions appear in Stein's method for variance-gamma approximation, and our bounds will allow for a technical advancement to be made to the method
Orientation-selective and Frequency-correlated Light-induced Pulsed Dipolar Spectroscopy
No full textWe explore the potential of orientation-resolved pulsed dipolar spectroscopy (PDS) in light-induced versions of the experiment. The use of triplets as spin-active moieties for PDS offers an attractive tool for studying biochemical systems containing optically-active cofactors. Cofactors are often rigidly bound within the protein structure, providing an accurate positional marker. The rigidity leads to orientation selection effects in PDS, which can be analyzed to give both distance and mutual orientation information. Here we present a comprehensive analysis of the orientation selection of a full set of light-induced PDS experiments. We exploit the complementary information provided by the different light-induced techniques to yield atomic-level structural information. For the first time, we measure a 2D frequency-correlated laser-induced magnetic dipolar spectrum and we were able to monitor the complete orientation dependence of the system in a single experiment. Alternatively, the summed spectrum enables an orientation independent analysis to determine the distance distribution