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  • The Inspired Sinewave Technique: A Comparison Study With Body Plethysmography in Healthy Volunteers.

    3 July 2018

    The inspired sinewave technique is a noninvasive method to measure airway dead space, functional residual capacity, pulmonary blood flow, and lung inhomogeneity simultaneously. The purpose of this paper was to assess the repeatability and accuracy of the current device prototype in measuring functional residual capacity, and also participant comfort when using such a device. To assess within-session repeatability, six sinewave measurements were taken over two-hour period in 17 healthy volunteers. To assess day-to-day repeatability, measurements were taken over 16 days in 3 volunteers. To assess accuracy, sinewave measurements were compared to body plethysmography in 44 healthy volunteers. Finally, 18 volunteers who experienced the inspired sinewave device, body plethysmography and spirometry were asked to rate the comfort of each technique on a scale of 1-10. The repeatability coefficients for dead space, functional residual capacity, and blood flow were 48.7 ml, 0.48L, and 2.4L/min respectively. Bland-Altman analyses showed a mean BIAS(SD) of -0.68(0.42)L for functional residual capacity when compared with body plethysmography. 14 out of 18 volunteers rated the inspired sinewave device as their preferred technique. The repeatability and accuracy of functional residual capacity measurements were found to be as good as other techniques in the literature. The high level of comfort and the non-requirement of patient effort meant that, if further refined, the inspired sinewave technique could be an attractive solution for difficult patient groups such as very young children, elderly, and ventilated patients.

  • The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes.

    13 August 2018

    Congenital myasthenic syndromes (CMS) are genetic disorders characterised by impaired neuromuscular transmission. This review provides an overview on CMS and highlights recent advances in the field, including novel CMS causative genes and improved therapeutic strategies. CMS due to mutations in SLC5A7 and SLC18A3, impairing the synthesis and recycling of acetylcholine, have recently been described. In addition, a novel group of CMS due to mutations in SNAP25B, SYT2, VAMP1, and UNC13A1 encoding molecules implicated in synaptic vesicles exocytosis has been characterised. The increasing number of presynaptic CMS exhibiting CNS manifestations along with neuromuscular weakness demonstrate that the myasthenia can be only a small part of a much more extensive disease phenotype. Moreover, the spectrum of glycosylation abnormalities has been increased with the report that GMPPB mutations can cause CMS, thus bridging myasthenic disorders with dystroglycanopathies. Finally, the discovery of COL13A1 mutations and laminin α5 deficiency has helped to draw attention to the role of extracellular matrix proteins for the formation and maintenance of muscle endplates. The benefit of β2-adrenergic agonists alone or combined with pyridostigmine or 3,4-Dyaminopiridine is increasingly being reported for different subtypes of CMS including AChR-deficiency and glycosylation abnormalities, thus expanding the therapeutic repertoire available.

  • IN-SYNC. VII. Evidence for a Decreasing Spectroscopic Binary Fraction (from 1 to 100 Myr) within the IN-SYNC Sample

    13 August 2018

    © 2017. The American Astronomical Society. All rights reserved. We study the occurrence of spectroscopic binaries in young star-forming regions using the INfrared Spectroscopy of Young Nebulous Clusters (IN-SYNC) survey, carried out in SDSS-III with the APOGEE spectrograph. Multi-epoch observations of thousands of low-mass stars in Orion A, NGC 2264, NGC 1333, IC 348, and the Pleiades have been carried out, yielding H-band spectra with a nominal resolution of R = 22,500 for sources with H < 12 mag. Radial velocity precisions of ∼0.3 were achieved, which we use to identify radial velocity variations indicative of undetected companions. We use Monte Carlo simulations to assess the types of spectroscopic binaries to which we are sensitive, finding sensitivity to binaries with orbital periods ≲ 103.5days, for stars with 2500 K ≤ Teff≤ 6000 K and v sin i <100 km s-1. Using Bayesian inference, we find evidence for a decline in the spectroscopic binary fraction, by a factor of 3-4, from the age of our pre-main-sequence (PMS) sample to the Pleiades age . The significance of this decline is weakened if spot-induced radial-velocity jitter is strong in the sample, and is only marginally significant when comparing any one of the PMS clusters against the Pleiades. However, the same decline in both sense and magnitude is found for each of the five PMS clusters, and the decline reaches a statistical significance of greater than 95% confidence when considering the PMS clusters jointly. Our results suggest that dynamical processes disrupt the widest spectroscopic binaries (Porb≈ 103- 104days) as clusters age, indicating that this occurs early in the stars' evolution, while they still reside within their nascent clusters.

  • In Reply.

    13 August 2018

  • An assessment of central-peripheral ventilatory chemoreflex interaction using acid and bicarbonate infusions in humans.

    3 July 2018

    1. The object of this study was to investigate the effect of central chemoreceptor stimulation on the ventilatory responses to peripheral chemoreceptor stimulation. 2. The level of central chemoreceptor stimulation was varied by performing experiments at two different levels of end-tidal CO2 pressure (PCO2). Variations in peripheral chemoreceptor stimulus were achieved by varying arterial pH (at constant end-tidal PCO2) and by varying end-tidal O2 pressure (PO2). 3. Two protocols were each performed on six human subjects. In one protocol ventilatory measurements were made during eucapnia, when the arterial pH was lowered from 7.4 to 7.3. The variation in pH was achieved by the progressive infusion of acid (0.1 M HCl). In the other protocol ventilatory measurements were made during hypercapnia, when the arterial pH was increased from 7.3 to 7.4. The variation in pH was achieved by the progressive infusion of 1.26% NaHCO3. In each protocol ventilatory responses were measured during euoxia (end-tidal PO2, 100 Torr), hypoxia (end-tidal PO2, 50 Torr) and hyperoxia (end-tidal PO2, 300 Torr), with end-tidal PCO2 held constant. 4. The increase in ventilatory sensitivity to arterial pH induced by hypoxia (50 Torr) was not significantly different between protocols (acid protocol, -104 +/- 31 l min-1 (pH unit)-1 vs. bicarbonate protocol, -60 +/- 44 l min-1 (pH unit)-1; mean +/- S.E.M.; not significant (n.s.)). The ventilatory sensitivity to hypoxia at an arterial pH of 7.35 was not significantly different between protocols (acid protocol, 14.7 +/- 3.3 l min-1 vs. bicarbonate protocol, 15.6 +/- 2.4 l min-1; mean +/- S.E.M.; n.s.). The results provide no evidence to suggest that peripheral chemoreflex ventilatory responses are modulated by central chemoreceptor stimulation.