Altered Na/Ca exchange distribution and activity in ventricular myocytes from failing hearts

In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocytes isolated from rat hearts ∼18 wk after coronary artery ligation (CAL) or corresponding sham operation (Sham). NCX current (I(NCX)) and l-type Ca current (I(Ca)) were recorded using the whole cell, voltage-clamp technique in intact and detubulated (DT) myocytes; intracellular free Ca concentration ([Ca](i)) was monitored simultaneously using fluo-4. I(NCX) was activated and measured during application of caffeine to release Ca from sarcoplasmic reticulum (SR). Whole cell I(NCX) was not significantly different in Sham and CAL myocytes and occurred predominantly in the T tubules in Sham myocytes. CAL was associated with redistribution of I(NCX) and I(Ca) away from the T tubules to the cell surface and an increase in t-tubular I(NCX)/I(Ca) density from 0.12 in Sham to 0.30 in CAL myocytes. The decrease in t-tubular I(NCX) in CAL myocytes was accompanied by an increase in the fraction of Ca sequestered by SR. However, SR Ca content was not significantly different in Sham, Sham DT, and CAL myocytes but was significantly increased by DT of CAL myocytes. In Sham myocytes, there was hysteresis between I(NCX) and [Ca](i), which was absent in DT Sham but present in CAL and DT CAL myocytes. These data suggest altered distribution of NCX in CAL myocytes

Ion currents, action potentials and noradrenergic responses in rat pulmonary vein and left atrial cardiomyocytes

The electrophysiological properties of pulmonary vein (PV)-cardiomyocytes, and their responses to the sympathetic neurotransmitter, noradrenaline (NA), are thought to differ from those of the left atrium (LA) and contribute to atrial ectopy. The aim of this study was to examine rat PV-cardiomyocyte electrophysiology and responses to NA in comparison with LA-cells. LA- and PV-cardiomyocytes were isolated from adult male Wistar rat hearts, and membrane potentials and ion currents recorded at 36 °C using whole-cell patch-clamp techniques. PV- and LA-cardiomyocytes did not differ in size. In control, there were no differences between the two cell-types in zero-current potential or action potential duration (APD) at 1 Hz, although the incidence of early afterdepolarisations (EADs) was greater in PV- than LA-cardiomyocytes. The L-type Ca2+ current (ICaL) was ~×1.5-smaller (P=0.0029, Student’s t-test) and the steady-state K+ current (IKss) was ~×1.4-larger (P=0.0028, Student’s t-test) in PV- than in LA-cardiomyocytes. PV-cardiomyocyte inward-rectifier current (IK1) was slightly smaller than LA-cardiomyocyte IK1. In LA-cardiomyocytes, NA significantly prolonged APD30. In PV-cells, APD30 responses to 1 μM NA were heterogeneous: while the mean percentage-change in APD30 was not different from 0 (16.5±9.7%, n cells/N animals=12/10, P=0.1177, one-sample t-test), 3 cells showed shortening (-18.8±6.0%) whereas 9 showed prolongation (28.3±10.1%, P=0.008, Student’s t-test). NA had no effect on IK1 in either cell-type but inhibited PV IKss by 41.9±4.1% (n/N=23/11 P<0.0001), similar to LA-cells. NA increased ICaL in most PV-cardiomyocytes (median ×2.2-increase, P<0.0001, n/N=32/14, Wilcoxon-signed-ranks-test), although in 7/32 PV-cells ICaL was decreased following NA. PV-cardiomyocytes differ from LA-cells and respond heterogeneously to NA

Mental health assessments in refugees and asylum seekers

Background Mental health problems resulting from persecution and forced migration are very common among refugees and asylum seekers and evolve into a major public health challenge in hosting societies. Language barriers often prevent timely access to appropriate health care, leading to chronic trajectories and abortive social integration. Tools for multilingual screening and assessment could be of great benefit for this particularly vulnerable population as well as for policy makers. This study aimed at testing the reliability, feasibility and usability of the Multi-Adaptive Psychological Screening Software (MAPSS), a newly developed Audio Computer-Assisted Self- Interview Software (ACASI) for touchscreen devices, for screening purposes in a clinical setting. Methods In a randomized cross-over design including both MAPSS and paper-pencil clinician-administered interviews, 30 treatment-seeking refugees completed clinical measures and a feasibility questionnaire to rate the user interface of MAPSS. Five professionals performed given tasks in MAPSS and completed usability questionnaires for the administration interface. Results Results showed no differences between the two assessment modalities with regard to symptom scores. The findings suggest good feasibility and usability of MAPSS in traumatized refugees. The administration via MAPSS was significantly shorter than the paper-pencil interview. Conclusion MAPSS may be a cost-effective, flexible and valid alternative to interpreter-based psychometric screening and assessment

Solitons and admissible families of rational curves in twistor spaces

It is well known that twistor constructions can be used to analyse and to obtain solutions to a wide class of integrable systems. In this article we express the standard twistor constructions in terms of the concept of an admissible family of rational curves in certain twistor spaces. Examples of of such families can be obtained as subfamilies of a simple family of rational curves using standard operations of algebraic geometry. By examination of several examples, we give evidence that this construction is the basis of the construction of many of the most important solitonic and algebraic solutions to various integrable differential equations of mathematical physics. This is presented as evidence for a principal that, in some sense, all soliton-like solutions should be constructable in this way.Comment: 15 pages, Abstract and introduction rewritten to clarify the objectives of the paper. This is the final version which will appear in Nonlinearit

The Sydney-AAO Multi-object Integral field spectrograph (SAMI)

We demonstrate a novel technology that combines the power of the multi-object spectrograph with the spatial multiplex advantage of an integral field spectrograph (IFS). The Sydney-AAO Multi-object IFS (SAMI) is a prototype wide-field system at the Anglo-Australian Telescope (AAT) that allows 13 imaging fibre bundles ("hexabundles") to be deployed over a 1-degree diameter field of view. Each hexabundle comprises 61 lightly-fused multimode fibres with reduced cladding and yields a 75 percent filling factor. Each fibre core diameter subtends 1.6 arcseconds on the sky and each hexabundle has a field of view of 15 arcseconds diameter. The fibres are fed to the flexible AAOmega double-beam spectrograph, which can be used at a range of spectral resolutions (R=lambda/delta(lambda) ~ 1700-13000) over the optical spectrum (3700-9500A). We present the first spectroscopic results obtained with SAMI for a sample of galaxies at z~0.05. We discuss the prospects of implementing hexabundles at a much higher multiplex over wider fields of view in order to carry out spatially--resolved spectroscopic surveys of 10^4 to 10^5 galaxies.Comment: 24 pages, 16 figures. Accepted by MNRA

GNOSIS: the first instrument to use fibre Bragg gratings for OH suppression

GNOSIS is a prototype astrophotonic instrument that utilizes OH suppression fibres consisting of fibre Bragg gratings and photonic lanterns to suppress the 103 brightest atmospheric emission doublets between 1.47-1.7 microns. GNOSIS was commissioned at the 3.9-meter Anglo-Australian Telescope with the IRIS2 spectrograph to demonstrate the potential of OH suppression fibres, but may be potentially used with any telescope and spectrograph combination. Unlike previous atmospheric suppression techniques GNOSIS suppresses the lines before dispersion and in a manner that depends purely on wavelength. We present the instrument design and report the results of laboratory and on-sky tests from commissioning. While these tests demonstrated high throughput and excellent suppression of the skylines by the OH suppression fibres, surprisingly GNOSIS produced no significant reduction in the interline background and the sensitivity of GNOSIS and IRIS2 is about the same as IRIS2. It is unclear whether the lack of reduction in the interline background is due to physical sources or systematic errors as the observations are detector noise-dominated. OH suppression fibres could potentially impact ground-based astronomy at the level of adaptive optics or greater. However, until a clear reduction in the interline background and the corresponding increasing in sensitivity is demonstrated optimized OH suppression fibres paired with a fibre-fed spectrograph will at least provide a real benefits at low resolving powers.Comment: 15 pages, 13 figures, accepted to A

Inhibition of a TREK-like K⁺ channel current by noradrenaline requires both β₁- and β₂-adrenoceptors in rat atrial myocytes

AIMS: Noradrenaline plays an important role in the modulation of atrial electrophysiology. However, the identity of the modulated channels, their mechanisms of modulation, and their role in the action potential remain unclear. This study aimed to investigate the noradrenergic modulation of an atrial steady-state outward current (I(Kss)). METHODS AND RESULTS: Rat atrial myocyte whole-cell currents were recorded at 36°C. Noradrenaline potently inhibited I(Kss) (IC(50) = 0.90 nM, 42.1 ± 4.3% at 1 µM, n = 7) and potentiated the L-type Ca(2+) current (I(CaL), EC(50) = 136 nM, 205 ± 40% at 1 µM, n = 6). Noradrenaline-sensitive I(Kss) was weakly voltage-dependent, time-independent, and potentiated by the arachidonic acid analogue, 5,8,11,14-eicosatetraynoic acid (EYTA; 10 µM), or by osmotically induced membrane stretch. Noise analysis revealed a unitary conductance of 8.4 ± 0.42 pS (n = 8). The biophysical/pharmacological properties of I(Kss) indicate a TREK-like K(+) channel. The effect of noradrenaline on I(Kss) was abolished by combined β(1)-/β(2)-adrenoceptor antagonism (1 µM propranolol or 10 µM β(1)-selective atenolol and 100 nM β(2)-selective ICI-118,551 in combination), but not by β(1)- or β(2)-antagonist alone. The action of noradrenaline could be mimicked by β(2)-agonists (zinterol and fenoterol) in the presence of β(1)-antagonist. The action of noradrenaline on I(Kss), but not on I(CaL), was abolished by pertussis toxin (PTX) treatment. The action of noradrenaline on I(CaL) was mediated by β(1)-adrenoceptors via a PTX-insensitive pathway. Noradrenaline prolonged APD(30) by 52 ± 19% (n = 5; P < 0.05), and this effect was abolished by combined β(1)-/β(2)-antagonism, but not by atenolol alone. CONCLUSION: Noradrenaline inhibits a rat atrial TREK-like K(+) channel current via a PTX-sensitive mechanism involving co-operativity of β(1)-/β(2)-adrenoceptors that contributes to atrial APD prolongation

Organization theory and military metaphor: time for a reappraisal?

A ‘conventional’ use of military metaphor would use it to convey attributes such as hierarchical organization, vertical communication and limited autonomy. This is often used in contrast to a looser form of organization based on the metaphor of the network. However, this article argues that military practice is more complex, with examples of considerable autonomy within the constraints of central direction. It is suggested that not only might this be a more useful metaphor for many contemporary organizations, but also that simplistic uses of military metaphor divert our attention away from the functions that management hierarchies play. The discussion is embedded within a critical realist account of metaphor, arguing for both its value and the need for its further development