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

Adaptive Mesh Refinement for Characteristic Grids

I consider techniques for Berger-Oliger adaptive mesh refinement (AMR) when numerically solving partial differential equations with wave-like solutions, using characteristic (double-null) grids. Such AMR algorithms are naturally recursive, and the best-known past Berger-Oliger characteristic AMR algorithm, that of Pretorius & Lehner (J. Comp. Phys. 198 (2004), 10), recurses on individual "diamond" characteristic grid cells. This leads to the use of fine-grained memory management, with individual grid cells kept in 2-dimensional linked lists at each refinement level. This complicates the implementation and adds overhead in both space and time. Here I describe a Berger-Oliger characteristic AMR algorithm which instead recurses on null \emph{slices}. This algorithm is very similar to the usual Cauchy Berger-Oliger algorithm, and uses relatively coarse-grained memory management, allowing entire null slices to be stored in contiguous arrays in memory. The algorithm is very efficient in both space and time. I describe discretizations yielding both 2nd and 4th order global accuracy. My code implementing the algorithm described here is included in the electronic supplementary materials accompanying this paper, and is freely available to other researchers under the terms of the GNU general public license.Comment: 37 pages, 15 figures (40 eps figure files, 8 of them color; all are viewable ok in black-and-white), 1 mpeg movie, uses Springer-Verlag svjour3 document class, includes C++ source code. Changes from v1: revised in response to referee comments: many references added, new figure added to better explain the algorithm, other small changes, C++ code updated to latest versio

The influence of media violence on youth

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83429/1/2003.Anderson_etal.InfluenceofMediaViolenceonYouth.PsychologicalScienceinthePublicInterest.pd

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe