Direct administration of 2-hydroxypropyl-beta-cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements

<p>Cochlear response measurements from two different animals made before (red) and after (blue) treatment with HPβCD (Panel A) and TTX (Panel B) to 80 dB SPL 4 kHz tone bursts. Cochlear response waveform maintained CAP-like morphology after HPβCD treatment, consistent with reduced mechanical drive to neural excitation (Panel B, blue). In contrast, response waveform is EPSP-like following TTX treatment. Unlike TTX, results from HPβCD do not support the hypothesis that the auditory nerve is a site of action for 13 mM HPβCD.</p

Improved outer boundary conditions for Einstein's field equations

In a recent article, we constructed a hierarchy B_L of outer boundary conditions for Einstein's field equations with the property that, for a spherical outer boundary, it is perfectly absorbing for linearized gravitational radiation up to a given angular momentum number L. In this article, we generalize B_2 so that it can be applied to fairly general foliations of spacetime by space-like hypersurfaces and general outer boundary shapes and further, we improve B_2 in two steps: (i) we give a local boundary condition C_2 which is perfectly absorbing including first order contributions in 2M/R of curvature corrections for quadrupolar waves (where M is the mass of the spacetime and R is a typical radius of the outer boundary) and which significantly reduces spurious reflections due to backscatter, and (ii) we give a non-local boundary condition D_2 which is exact when first order corrections in 2M/R for both curvature and backscatter are considered, for quadrupolar radiation.Comment: accepted Class. Quant. Grav. numerical relativity special issue; 17 pages and 1 figur

Effects of cochlear implantation on binaural hearing in adults with unilateral hearing loss

A FDA clinical trial was carried out to evaluate the potential benefit of cochlear implant (CI) use for adults with unilateral moderate-to-profound sensorineural hearing loss. Subjects were 20 adults with moderate-to-profound unilateral sensorineural hearing loss and normal or near-normal hearing on the other side. A MED-EL standard electrode was implanted in the impaired ear. Outcome measures included: (a) sound localization on the horizontal plane (11 positions, −90° to 90°), (b) word recognition in quiet with the CI alone, and (c) masked sentence recognition with the target at 0° and the masker at −90°, 0°, or 90°. This battery was completed preoperatively and at 1, 3, 6, 9, and 12 months after CI activation. Normative data were also collected for 20 age-matched control subjects with normal or near-normal hearing bilaterally. The CI improved localization accuracy and reduced side bias. Word recognition with the CI alone was similar to performance of traditional CI recipients. The CI improved masked sentence recognition when the masker was presented from the front or from the side of normal or near-normal hearing. The binaural benefits observed with the CI increased between the 1- and 3-month intervals but appeared stable thereafter. In contrast to previous reports on localization and speech perception in patients with unilateral sensorineural hearing loss, CI benefits were consistently observed across individual subjects, and performance was at asymptote by the 3-month test interval. Cochlear implant settings, consistent CI use, and short duration of deafness could play a role in this result

Schwarzschild Tests of the Wahlquist-Estabrook-Buchman-Bardeen Tetrad Formulation for Numerical Relativity

A first order symmetric hyperbolic tetrad formulation of the Einstein equations developed by Estabrook and Wahlquist and put into a form suitable for numerical relativity by Buchman and Bardeen (the WEBB formulation) is adapted to explicit spherical symmetry and tested for accuracy and stability in the evolution of spherically symmetric black holes (the Schwarzschild geometry). The lapse and shift which specify the evolution of the coordinates relative to the tetrad congruence are reset at frequent time intervals to keep the constant-time hypersurfaces nearly orthogonal to the tetrad congruence and the spatial coordinate satisfying a kind of minimal rate of strain condition. By arranging through initial conditions that the constant-time hypersurfaces are asymptotically hyperbolic, we simplify the boundary value problem and improve stability of the evolution. Results are obtained for both tetrad gauges (``Nester'' and ``Lorentz'') of the WEBB formalism using finite difference numerical methods. We are able to obtain stable unconstrained evolution with the Nester gauge for certain initial conditions, but not with the Lorentz gauge.Comment: (accepted by Phys. Rev. D) minor changes; typos correcte

Electrostatic Patch Effect in Cylindrical Geometry. I. Potential and Energy between Slightly Non-Coaxial Cylinders

We study the effect of any uneven voltage distribution on two close cylindrical conductors with parallel axes that are slightly shifted in the radial and by any length in the axial direction. The investigation is especially motivated by certain precision measurements, such as the Satellite Test of the Equivalence Principle (STEP). By energy conservation, the force can be found as the energy gradient in the vector of the shift, which requires determining potential distribution and energy in the gap. The boundary value problem for the potential is solved, and energy is thus found to the second order in the small transverse shift, and to lowest order in the gap to cylinder radius ratio. The energy consists of three parts: the usual capacitor part due to the uniform potential difference, the one coming from the interaction between the voltage patches and the uniform voltage difference, and the energy of patch interaction, entirely independent of the uniform voltage. Patch effect forces and torques in the cylindrical configuration are derived and analyzed in the next two parts of this work.Comment: 26 pages, 1 Figure. Submitted to Classical and Quantum Gravit

An axisymmetric evolution code for the Einstein equations on hyperboloidal slices

We present the first stable dynamical numerical evolutions of the Einstein equations in terms of a conformally rescaled metric on hyperboloidal hypersurfaces extending to future null infinity. Axisymmetry is imposed in order to reduce the computational cost. The formulation is based on an earlier axisymmetric evolution scheme, adapted to time slices of constant mean curvature. Ideas from a previous study by Moncrief and the author are applied in order to regularize the formally singular evolution equations at future null infinity. Long-term stable and convergent evolutions of Schwarzschild spacetime are obtained, including a gravitational perturbation. The Bondi news function is evaluated at future null infinity.Comment: 21 pages, 4 figures. Minor additions, updated to agree with journal versio

Testing outer boundary treatments for the Einstein equations

Various methods of treating outer boundaries in numerical relativity are compared using a simple test problem: a Schwarzschild black hole with an outgoing gravitational wave perturbation. Numerical solutions computed using different boundary treatments are compared to a `reference' numerical solution obtained by placing the outer boundary at a very large radius. For each boundary treatment, the full solutions including constraint violations and extracted gravitational waves are compared to those of the reference solution, thereby assessing the reflections caused by the artificial boundary. These tests use a first-order generalized harmonic formulation of the Einstein equations. Constraint-preserving boundary conditions for this system are reviewed, and an improved boundary condition on the gauge degrees of freedom is presented. Alternate boundary conditions evaluated here include freezing the incoming characteristic fields, Sommerfeld boundary conditions, and the constraint-preserving boundary conditions of Kreiss and Winicour. Rather different approaches to boundary treatments, such as sponge layers and spatial compactification, are also tested. Overall the best treatment found here combines boundary conditions that preserve the constraints, freeze the Newman-Penrose scalar Psi_0, and control gauge reflections.Comment: Modified to agree with version accepted for publication in Class. Quantum Gra

Intraoperative electrocochleographic characteristics of auditory neuropathy spectrum disorder in cochlear implant subjects

Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163). Magnitudes of the responses to tones of different frequencies were summed to measure the “total response” (ECochG-TR), a metric often dominated by hair cell activity, and auditory nerve activity was estimated visually from the compound action potential (CAP) and auditory nerve neurophonic (ANN) as a ranked “Nerve Score”. Subjects identified as ANSD (45 ears in children, 3 in adults) had higher values of ECochG-TR than adult and pediatric subjects also receiving CIs not identified as ANSD. However, nerve scores of the ANSD group were similar to the other cohorts, although dominated by the ANN to low frequencies more than in the non-ANSD groups. To high frequencies, the common morphology of ANSD cases was a large CM and summating potential, and small or absent CAP. Common morphologies in other groups were either only a CM, or a combination of CM and CAP. These results indicate that responses to high frequencies, derived primarily from hair cells, are the main source of the CM used to evaluate ANSD in the clinical setting. However, the clinical tests do not capture the wide range of neural activity seen to low frequency sounds

Electrically Evoked Auditory Event-Related Responses in Patients with Auditory Brainstem Implants: Morphological Characteristics, Test–Retest Reliability, Effects of Stimulation Level, and Association with Auditory Detection

This study aimed to 1) characterize morphological characteristics of the electrically-evoked cortical auditory event-related potentials (eERP) and explore the potential association between onset eERP morphology and auditory vs non-auditory stimulation; 2) assess test-retest reliability of onset eERPs; 3) investigate effects of stimulation level on onset eERPs; and 4) explore the feasibility of using the onset eERP to estimate the lowest stimulation level that can be detected for individual stimulating electrodes in patients with auditory brainstem implants (ABIs)

Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects

Cochlear synaptopathy is the loss of synapses between the inner hair cells and the auditory nerve despite survival of sensory hair cells. The findings of extensive cochlear synaptopathy in animals after moderate noise exposures challenged the long-held view that hair cells are the cochlear elements most sensitive to insults that lead to hearing loss. However, cochlear synaptopathy has been difficult to identify in humans. We applied novel algorithms to determine hair cell and neural contributions to electrocochleographic (ECochG) recordings from the round window of animal and human subjects. Gerbils with normal hearing provided training and test sets for a deep learning algorithm to detect the presence of neural responses to low frequency sounds, and an analytic model was used to quantify the proportion of neural and hair cell contributions to the ECochG response. The capacity to detect cochlear synaptopathy was validated in normal hearing and noise-exposed animals by using neurotoxins to reduce or eliminate the neural contributions. When the analytical methods were applied to human surgical subjects with access to the round window, the neural contribution resembled the partial cochlear synaptopathy present after neurotoxin application in animals. This result demonstrates the presence of viable hair cells not connected to auditory nerve fibers in human subjects with substantial hearing loss and indicates that efforts to regenerate nerve fibers may find a ready cochlear substrate for innervation and resumption of function