Sensitivity to interaural time differences in the medial superior olive of a small mammal, the Mexican free-tailed bat

Neurons in the medial superior olive (MSO) are thought to encode interaural time differences (ITDs), the main binaural cues used for localizing low-frequency sounds in the horizontal plane. The underlying mechanism is supposed to rely on a coincidence of excitatory inputs from the two ears that are phase-locked to either the stimulus frequency or the stimulus envelope. Extracellular recordings from MSO neurons in several mammals conform with this theory. However, there are two aspects that remain puzzling. The first concerns the role of the MSO in small mammals that have relatively poor low-frequency hearing and whose heads generate only very small ITDs. The second puzzling aspect of the scenario concerns the role of the prominent binaural inhibitory inputs to MSO neurons. We examined these two unresolved issues by recording from MSO cells in the Mexican free-tailed bat. Using sinusoidally amplitude-modulated tones, we found that the ITD sensitivities of many MSO cells in the bat were remarkably similar to those reported for larger mammals. Our data also indicate an important role for inhibition in sharpening ITD sensitivity and increasing the dynamic range of ITD functions. A simple model of ITD coding based on the timing of multiple inputs is proposed. Additionally, our data suggest that ITD coding is a by-product of a neuronal circuit that processes the temporal structure of sounds. Because of the free-tailed bat's small head size, ITD coding is most likely not the major function of the MSO in this small mammal and probably other small mammals

Neural delays shape selectivity to interaural intensity differences in the lateral superior olive

Neurons in the lateral superior olive (LSO) respond selectively to interaural intensity differences (IIDs), one of the chief cues used to localize sounds in space. LSO cells are innervated in a characteristic pattern: they receive an excitatory input from the ipsilateral ear and an inhibitory input from the contralateral ear. Consistent with this pattern, LSO cells generally are excited by sounds that are more intense at the ipsilateral ear and inhibited by sounds that are more intense at the contralateral ear. Despite their relatively homogeneous pattern of innervation, IID selectivity varies substantially from cell to cell, such that selectivities are distributed over the range of IIDs that would be encountered in nature. For some time, researchers have speculated that the relative timing of the excitatory and inhibitory inputs to an LSO cell might shape IID selectivity. To test this hypothesis, we recorded from 50 LSO cells in the free-tailed bat while presenting stimuli that varied in interaural intensity and in interaural time of arrival. The results suggest that, for more than half of the cells, the latency of inhibition was several hundred microseconds longer than the latency of excitation. Increasing the intensity to the inhibitory ear shortened the latency of inhibition and brought the timing of the inputs from the two ears into register. Thus, a neural delay of the inhibition helped to define the IID selectivity of these cells, accounting for a significant part of the variation in selectivity among LSO cells

Work distribution for the driven harmonic oscillator with time-dependent strength: Exact solution and slow driving

We study the work distribution of a single particle moving in a harmonic oscillator with time-dependent strength. This simple system has a non-Gaussian work distribution with exponential tails. The time evolution of the corresponding moment generating function is given by two coupled ordinary differential equations that are solved numerically. Based on this result we study the behavior of the work distribution in the limit of slow but finite driving and show that it approaches a Gaussian distribution arbitrarily well

Use of cost-effectiveness analysis to compare the efficiency of study identification methods in systematic reviews

BACKGROUND: Meta-research studies investigating methods, systems, and processes designed to improve the efficiency of systematic review workflows can contribute to building an evidence base that can help to increase value and reduce waste in research. This study demonstrates the use of an economic evaluation framework to compare the costs and effects of four variant approaches to identifying eligible studies for consideration in systematic reviews. METHODS: A cost-effectiveness analysis was conducted using a basic decision-analytic model, to compare the relative efficiency of 'safety first', 'double screening', 'single screening' and 'single screening with text mining' approaches in the title-abstract screening stage of a 'case study' systematic review about undergraduate medical education in UK general practice settings. Incremental cost-effectiveness ratios (ICERs) were calculated as the 'incremental cost per citation 'saved' from inappropriate exclusion' from the review. Resource use and effect parameters were estimated based on retrospective analysis of 'review process' meta-data curated alongside the 'case study' review, in conjunction with retrospective simulation studies to model the integrated use of text mining. Unit cost parameters were estimated based on the 'case study' review's project budget. A base case analysis was conducted, with deterministic sensitivity analyses to investigate the impact of variations in values of key parameters. RESULTS: Use of 'single screening with text mining' would have resulted in title-abstract screening workload reductions (base case analysis) of >60 % compared with other approaches. Across modelled scenarios, the 'safety first' approach was, consistently, equally effective and less costly than conventional 'double screening'. Compared with 'single screening with text mining', estimated ICERs for the two non-dominated approaches (base case analyses) ranged from £1975 ('single screening' without a 'provisionally included' code) to £4427 ('safety first' with a 'provisionally included' code) per citation 'saved'. Patterns of results were consistent between base case and sensitivity analyses. CONCLUSIONS: Alternatives to the conventional 'double screening' approach, integrating text mining, warrant further consideration as potentially more efficient approaches to identifying eligible studies for systematic reviews. Comparable economic evaluations conducted using other systematic review datasets are needed to determine the generalisability of these findings and to build an evidence base to inform guidance for review authors

Regularization, Renormalization and Range: The Nucleon-Nucleon Interaction from Effective Field Theory

Regularization and renormalization is discussed in the context of low-energy effective field theory treatments of two or more heavy particles (such as nucleons). It is desirable to regulate the contact interactions from the outset by treating them as having a finite range. The low energy physical observables should be insensitive to this range provided that the range is of a similar or greater scale than that of the interaction. Alternative schemes, such as dimensional regularization, lead to paradoxical conclusions such as the impossibility of repulsive interactions for truly low energy effective theories where all of the exchange particles are integrated out. This difficulty arises because a nonrelativistic field theory with repulsive contact interactions is trivial in the sense that the $S$ matrix is unity and the renormalized coupling constant zero. Possible consequences of low energy attraction are also discussed. It is argued that in the case of large or small scattering lengths, the region of validity of effective field theory expansion is much larger if the contact interactions are given a finite range from the beginning.Comment: 7 page

Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood.

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment

Structure and Thermodynamics of the Mixed Alkali Alanates

The thermodynamics and structural properties of the hexahydride alanates (M2M'AlH6) with the elpasolite structure have been investigated. A series of mixed alkali alanates (Na2LiAlH6, K2LiAlH6 and K2NaAlH6) were synthesized and found to reversibly absorb and desorb hydrogen without the need for a catalyst. Pressure-composition isotherms were measured to investigate the thermodynamics of the absorption and desorption reactions with hydrogen. Isotherms for catalyzed (4 mol% TiCl3) and uncatalyzed Na2LiAlH6 exhibited an increase in kinetics, but no change in the bulk thermodynamics with the addition of a dopant. A structural analysis using synchrotron x-ray diffraction showed that these compounds favor the Fm-3m space group with the smaller ion (M') occupying an octahedral site. These results demonstrate that appropriate cation substitutions can be used to stabilize or destabilize the material and may provide an avenue to improving the unfavorable thermodynamics of a number of materials with promising gravimetric hydrogen densities.Comment: 6 pages, 7 figures,3 tables, submitted to PR

Dynamics of Gas-Fluidized Granular Rods

We study a quasi-two-dimensional monolayer of granular rods fluidized by a spatially and temporally homogeneous upflow of air. By tracking the position and orientation of the particles, we characterize the dynamics of the system with sufficient resolution to observe ballistic motion at the shortest time scales. Particle anisotropy gives rise to dynamical anisotropy and superdiffusive dynamics parallel to the rod’s long axis, causing the parallel and perpendicular mean-square displacements to become diffusive on different time scales. The distributions of free times and free paths between collisions deviate from exponential behavior, underscoring the nonthermal character of the particle motion. The dynamics show evidence of rotationaltranslational coupling similar to that of an anisotropic Brownian particle. We model rotational-translational coupling in the single-particle dynamics with a modified Langevin model using nonthermal noise sources. This suggests a phenomenological approach to thinking about collections of self-propelling particles in terms of enhanced memory effects

The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials & methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans