Auditory feedback control mechanisms do not contribute to cortical hyperactivity within the voice production network in adductor spasmodic dysphonia

Adductor spasmodic dysphonia (ADSD), the most common form of spasmodic dysphonia, is a debilitating voice disorder characterized by hyperactivity and muscle spasms in the vocal folds during speech. Prior neuroimaging studies have noted excessive brain activity during speech in ADSD participants compared to controls. Speech involves an auditory feedback control mechanism that generates motor commands aimed at eliminating disparities between desired and actual auditory signals. Thus, excessive neural activity in ADSD during speech may reflect, at least in part, increased engagement of the auditory feedback control mechanism as it attempts to correct vocal production errors detected through audition. To test this possibility, functional magnetic resonance imaging was used to identify differences between ADSD participants and age-matched controls in (i) brain activity when producing speech under different auditory feedback conditions, and (ii) resting state functional connectivity within the cortical network responsible for vocalization. The ADSD group had significantly higher activity than the control group during speech (compared to a silent baseline task) in three left-hemisphere cortical regions: ventral Rolandic (sensorimotor) cortex, anterior planum temporale, and posterior superior temporal gyrus/planum temporale. This was true for speech while auditory feedback was masked with noise as well as for speech with normal auditory feedback, indicating that the excess activity was not the result of auditory feedback control mechanisms attempting to correct for perceived voicing errors in ADSD. Furthermore, the ADSD group had significantly higher resting state functional connectivity between sensorimotor and auditory cortical regions within the left hemisphere as well as between the left and right hemispheres, consistent with the view that excessive motor activity frequently co-occurs with increased auditory cortical activity in individuals with ADSD.First author draf

Vocal motor control in school-age children with and without vocal fold nodules

The purpose of this dissertation was to examine voice and vocal motor control in school-age children (5 – 12 years of age) with vocal fold nodules (CwVN) and children with typical voices (CwTV). This work is divided into three chapters, the first two examining CwTV and CwVN and the third providing a comprehensive examination of vocal motor control in adults and children without voice disorder. Study one analyzed relative fundamental frequency (RFF), an acoustic measure of fo change during vowels before and after a voiceless consonant. Average RFF values for offset cycle 10 and onset cycle 1 did not differ between CwVN and CwTV; however, variability of offset cycle 10 was decreased in CwVN. Across both groups, male children had lower offset cycle 10 RFF values as compared to female children. Additionally, onset cycle 1 values were decreased in younger children as compared to older children. Study two examined auditory discrimination to changes in vocal fo in CwVN and CwTV. There were no differences in pitch discrimination abilities between CwVN and CwTV. Younger CwTV had significantly poorer discrimination than older CwTV and adults. However, some CwTV across all ages examined were able to achieve adult-like discrimination abilities, suggesting that these abilities are mitigated by more than solely age in children. Study three evaluated the relationships among vocal pitch discrimination, feedback control, and sensorimotor adaptation in vocally healthy children and adults. Prior to analysis, children were subdivided into two groups based on their auditory discrimination abilities, defined as either being adult-like or immature. Children with immature auditory pitch discrimination had significantly larger vocal responses to unexpected pitch-shifts and significantly smaller responses to sustained pitch-shifts over time.2020-06-18T00:00:00

Vascular Endothelial Growth Factor-A Gene Electrotransfer Promotes Angiogenesis in a Porcine Model of Cardiac Ischemia

This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility. Arteriograms suggest growth of new arteries as early as 2 weeks after treatment in electrotransfer animals. There is a significant reduction of infarct area and left ventricular contractility is improved in GET-treated group compared with controls. There was no significant difference in mortality of animals treated with GET of plasmid encoding VEGF-A from the control groups. Gene delivery of plasmid encoding VEGF-A to ischemic myocardium in a porcine model can be accomplished safely with potential for myocardial repair and regeneration

Prioritising between direct observation of therapy and case-finding interventions for tuberculosis: use of population impact measures

BACKGROUND: Population impact measures (PIMs) have been developed as tools to help policy-makers with locally relevant decisions over health risks and benefits. This involves estimating and prioritising potential benefits of interventions in specific populations. Using tuberculosis (TB) in India as an example, we examined the population impact of two interventions: direct observation of therapy and increasing case-finding. METHODS: PIMs were calculated using published literature and national data for India, and applied to a notional population of 100 000 people. Data included the incidence or prevalence of smear-positive TB and the relative risk reduction from increasing case finding and the use of direct observation of therapy (applied to the baseline risks over the next year), and the incremental proportion of the population eligible for the proposed interventions. RESULTS: In a population of 100 000 people in India, the directly observed component of the Directly Observed Treatment, Short-course (DOTS) programme may prevent 0.188 deaths from TB in the next year compared with 1.79 deaths by increasing TB case finding. The costs of direct observation are (in international dollars) I$5960 and of case finding are I$4839 or I$31702 and I$2703 per life saved respectively. CONCLUSION: Increasing case-finding for TB will save nearly 10 times more lives than will the use of the directly observed component of DOTS in India, at a smaller cost per life saved. The demonstration of the population impact, using simple and explicit numbers, may be of value to policy-makers as they prioritise interventions for their populations

Tidal Venuses: Triggering a Climate Catastrophe via Tidal Heating

Traditionally stellar radiation has been the only heat source considered capable of determining global climate on long timescales. Here we show that terrestrial exoplanets orbiting low-mass stars may be tidally heated at high enough levels to induce a runaway greenhouse for a long enough duration for all the hydrogen to escape. Without hydrogen, the planet no longer has water and cannot support life. We call these planets "Tidal Venuses," and the phenomenon a "tidal greenhouse." Tidal effects also circularize the orbit, which decreases tidal heating. Hence, some planets may form with large eccentricity, with its accompanying large tidal heating, and lose their water, but eventually settle into nearly circular orbits (i.e. with negligible tidal heating) in the habitable zone (HZ). However, these planets are not habitable as past tidal heating desiccated them, and hence should not be ranked highly for detailed follow-up observations aimed at detecting biosignatures. Planets orbiting stars with masses <0.3 solar masses may be in danger of desiccation via tidal heating. We apply these concepts to Gl 667C c, a ~4.5 Earth-mass planet orbiting a 0.3 solar mass star at 0.12 AU. We find that it probably did not lose its water via tidal heating as orbital stability is unlikely for the high eccentricities required for the tidal greenhouse. As the inner edge of the HZ is defined by the onset of a runaway or moist greenhouse powered by radiation, our results represent a fundamental revision to the HZ for non-circular orbits. In the appendices we review a) the moist and runaway greenhouses, b) hydrogen escape, c) stellar mass-radius and mass-luminosity relations, d) terrestrial planet mass-radius relations, and e) linear tidal theories. [abridged]Comment: 59 pages, 11 figures, accepted to Astrobiology. New version includes an appendix on the water loss timescal

Gene Electro Transfer of Plasmid Encoding Vascular Endothelial Growth Factor for Enhanced Expression and Perfusion in the Ischemic Swine Heart

Myocardial ischemia can damage heart muscle and reduce the heart\u27s pumping efficiency. This study used an ischemic swine heart model to investigate the potential for gene electro transfer of a plasmid encoding vascular endothelial growth factor for improving perfusion and, thus, for reducing cardiomyopathy following acute coronary syndrome. Plasmid expression was significantly greater in gene electro transfer treated tissue compared to injection of plasmid encoding vascular endothelial growth factor alone. Higher gene expression was also seen in ischemic versus non-ischemic groups with parameters 20 Volts (

Luminosity Discrepancy in the Equal-Mass, Pre--Main Sequence Eclipsing Binary Par 1802: Non-Coevality or Tidal Heating?

Parenago 1802, a member of the ~1 Myr Orion Nebula Cluster, is a double-lined, detached eclipsing binary in a 4.674 d orbit, with equal-mass components (M_2/M_1 = 0.985 \pm 0.029). Here we present extensive VIcJHKs light curves spanning ~15 yr, as well as a Keck/HIRES optical spectrum. The light curves evince a third light source that is variable with a period of 0.73 d, and is also manifested in the high-resolution spectrum, strongly indicating the presence of a third star in the system, probably a rapidly rotating classical T Tauri star. We incorporate this third light into our radial velocity and light curve modeling of the eclipsing pair, measuring accurate masses (M_1 = 0.391 \pm 0.032, M_2 = 0.385 \pm 0.032 M\odot), radii (R_1 = 1.73 \pm 0.02, R_2 = 1.62 \pm 0.02 R\odot), and temperature ratio (T_1/T_2 = 1.0924 \pm 0.0017). Thus the radii of the eclipsing stars differ by 6.9 \pm 0.8%, the temperatures differ by 9.2 \pm 0.2%, and consequently the luminosities differ by 62 \pm 3%, despite having masses equal to within 3%. This could be indicative of an age difference of ~3x10^5 yr between the two eclipsing stars, perhaps a vestige of the binary formation history. We find that the eclipsing pair is in an orbit that has not yet fully circularized, e = 0.0166 \pm 0.003. In addition, we measure the rotation rate of the eclipsing stars to be 4.629 \pm 0.006 d; they rotate slightly faster than their 4.674 d orbit. The non-zero eccentricity and super-synchronous rotation suggest that the eclipsing pair should be tidally interacting, so we calculate the tidal history of the system according to different tidal evolution theories. We find that tidal heating effects can explain the observed luminosity difference of the eclipsing pair, providing an alternative to the previously suggested age difference.Comment: 49 pages, 16 figures, 11 tables. Accepted for publication to Ap

Circumbinary disc survival during binary-single scattering: towards a dynamical model of the Orion BN/KL complex

The Orion BN/KL complex is the nearest site of ongoing high-mass star formation. Recent proper motion observations provide convincing evidence of a recent (about 500 years ago) dynamical interaction between two massive young stellar objects in the region resulting in high velocities: the BN object and radio Source I. At the same time, Source I is surrounded by a nearly edge-on disc with radius ~50 au. These two observations taken together are puzzling: a dynamical encounter between multiple stars naturally yields the proper motions, but the survival of a disc is challenging to explain. In this paper we take the first steps to numerically explore the preferred dynamical scenario of Goddi et al., in which Source I is a binary that underwent a scattering encounter with BN, in order to determine if a pre-existing disc can survive this encounter in some form. Treating only gravitational forces, we are able to thoroughly and efficiently cover a large range of encounter parameters. We find that disc material can indeed survive a three-body scattering event if 1) the encounter is close, i.e. BN's closest approach to Source I is comparable to Source I's semi-major axis; and 2) the interplay of the three stars is of a short duration. Furthermore, we are able to constrain the initial conditions that can broadly produce the orientation of the present-day system's disc relative to its velocity vector. To first order we can thus confirm the plausibility of the scattering scenario of Goddi et al., and we have significantly constrained the parameters and narrowed the focus of future, more complex and expensive attempts to computationally model the complicated BN/KL region.Comment: MNRAS in pres

Radial velocity eclipse mapping of exoplanets

Planetary rotation rates and obliquities provide information regarding the history of planet formation, but have not yet been measured for evolved extrasolar planets. Here we investigate the theoretical and observational perspective of the Rossiter-McLauglin effect during secondary eclipse (RMse) ingress and egress for transiting exoplanets. Near secondary eclipse, when the planet passes behind the parent star, the star sequentially obscures light from the approaching and receding parts of the rotating planetary surface. The temporal block of light emerging from the approaching (blue-shifted) or receding (red-shifted) parts of the planet causes a temporal distortion in the planet's spectral line profiles resulting in an anomaly in the planet's radial velocity curve. We demonstrate that the shape and the ratio of the ingress-to-egress radial velocity amplitudes depends on the planetary rotational rate, axial tilt and impact factor (i.e. sky-projected planet spin-orbital alignment). In addition, line asymmetries originating from different layers in the atmosphere of the planet could provide information regarding zonal atmospheric winds and constraints on the hot spot shape for giant irradiated exoplanets. The effect is expected to be most-pronounced at near-infrared wavelengths, where the planet-to-star contrasts are large. We create synthetic near-infrared, high-dispersion spectroscopic data and demonstrate how the sky-projected spin axis orientation and equatorial velocity of the planet can be estimated. We conclude that the RMse effect could be a powerful method to measure exoplanet spins.Comment: 7 pages, 3 figures, 1 table, accepted for publication in ApJ on 2015 June 1