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

Implementing the global plan to stop TB, 2011-2015 - optimizing allocations and the global fund's contribution: A scenario projections study

Background: The Global Plan to Stop TB estimates funding required in low- and middle-income countries to achieve TB control targets set by the Stop TB Partnership within the context of the Millennium Development Goals. We estimate the contribution and impact of Global Fund investments under various scenarios of allocations across interventions and regions. Methodology/Principal Findings: Using Global Plan assumptions on expected cases and mortality, we estimate treatment costs and mortality impact for diagnosis and treatment for drug-sensitive and multidrug-resistant TB (MDR-TB), including antiretroviral treatment (ART) during DOTS for HIV-co-infected patients, for four country groups, overall and for the Global Fund investments. In 2015, China and India account for 24% of funding need, Eastern Europe and Central Asia (EECA) for 33%, sub-Saharan Africa (SSA) for 20%, and other low- and middle-income countries for 24%. Scale-up of MDR-TB treatment, especially in EECA, drives an increasing global TB funding need - an essential investment to contain the mortality burden associated with MDR-TB and future disease costs. Funding needs rise fastest in SSA, reflecting increasing coverage need of improved TB/HIV management, which saves most lives per dollar spent in the short term. The Global Fund is expected to finance 8-12% of Global Plan implementation costs annually. Lives saved through Global Fund TB support within the available funding envelope could increase 37% if allocations shifted from current regional demand patterns to a prioritized scale-up of improved TB/HIV treatment and secondly DOTS, both mainly in Africa - with EECA region, which has disproportionately high per-patient costs, funded from alternative resources. Conclusions/Significance: These findings, alongside country funding gaps, domestic funding and implementation capacity and equity considerations, should inform strategies and policies for international donors, national governments and disease control programs to implement a more optimal investment approach focusing on highest-impact populations and interventions

The r-Process Enriched Low Metallicity Giant HD 115444

New high resolution, very high signal-to-noise spectra of ultra-metal-poor (UMP) giant stars HD 115444 and HD 122563 have been gathered with the High-Resolution Echelle Spectrometer of the McDonald Observatory 2.7m Telescope. With these spectra, line identification and model atmosphere analyses have been conducted, emphasizing the neutron-capture elements. Twenty elements with Z > 30 have been identified in the spectrum of HD 115444. This star is known to have overabundances of the neutron-capture elements, but it has lacked a detailed analysis necessary to compare with nucleosynthesis predictions. The new study features a line-by-line differential abundance comparison of HD 115444 with the bright, well-studied halo giant HD 122563. For HD 115444, the overall metallicity is [Fe/H]~ -3.0. The abundances of the light and iron-peak elements generally show the same pattern as other UMP stars (e.g. overdeficiencies of manganese and chromium, overabundances of cobalt), but the differential analysis indicates several nucleosynthesis signatures that are unique to each star.Comment: To Appear in the Astrophysical Journa

The Rise of the s-Process in the Galaxy

From newly-obtained high-resolution, high signal-to-noise ratio spectra the abundances of the elements La and Eu have been determined over the stellar metallicity range -3<[Fe/H]<+0.3 in 159 giant and dwarf stars. Lanthanum is predominantly made by the s-process in the solar system, while Eu owes most of its solar system abundance to the r-process. The changing ratio of these elements in stars over a wide metallicity range traces the changing contributions of these two processes to the Galactic abundance mix. Large s-process abundances can be the result of mass transfer from very evolved stars, so to identify these cases, we also report carbon abundances in our metal-poor stars. Results indicate that the s-process may be active as early as [Fe/H]=-2.6, alalthough we also find that some stars as metal-rich as [Fe/H]=-1 show no strong indication of s-process enrichment. There is a significant spread in the level of s-process enrichment even at solar metallicity.Comment: 64 pages, 15 figures; ApJ 2004 in pres

The Compound Action Potential in Subjects Receiving a Cochlear Implant

The compound action potential (CAP) is a purely neural component of the cochlea’s response to sound, and may provide information about the existing neural substrate in cochlear implant (CI) subjects that can help account for variance in speech perception outcomes

The Chemical Composition and Age of the Metal-Poor Halo Star BD +17^\circ 3248

We have combined new high-resolution spectra obtained with the Hubble Space Telescope (HST) and ground-based facilities to make a comprehensive new abundance analysis of the metal-poor, halo star BD +17^\circ 3248. We have detected the third r-process peak elements osmium, platinum, and (for the first time in a metal-poor star) gold, elements whose abundances can only be reliably determined using HST. Our observations illustrate a pattern seen in other similar halo stars with the abundances of the heavier neutron-capture elements, including the third r-process peak elements, consistent with a scaled solar system r-process distribution. The abundances of the lighter neutron-capture elements, including germanium and silver, fall below that same scaled solar r-process curve, a result similar to that seen in the ultra-metal-poor star CS 22892--052. A single site with two regimes or sets of conditions, or perhaps two different sites for the lighter and heavier neutron-capture elements, might explain the abundance pattern seen in this star. In addition we have derived a reliable abundance for the radioactive element thorium. We tentatively identify U II at 3859 A in the spectrum of BD +17^\circ 3248, which makes this the second detection of uranium in a very metal-poor halo star. Our combined observations cover the widest range in proton number (from germanium to uranium) thus far of neutron-capture elements in metal-poor Galactic halo stars. Employing the thorium and uranium abundances in comparison with each other and with several stable elements, we determine an average cosmochronological age for BD +17^\circ 3248 of 13.8 +/- 4 Gyr, consistent with that found for other similar metal-poor halo stars.Comment: 58 pages, 4 tables, 11 figures; To appear in ApJ Typo correcte

In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-Synuclein within E. coli cells

α-Synuclein is a small protein strongly implicated in the pathogenesis of Parkinson’s disease and related neurodegenerative disorders. We report here the use of in-cell NMR spectroscopy to observe directly the structure and dynamics of this protein within E. coli cells. To improve the accuracy in the measurement of backbone chemical shifts within crowded in-cell NMR spectra, we have developed a deconvolution method to reduce inhomogeneous line broadening within cellular samples. The resulting chemical shift values were then used to evaluate the distribution of secondary structure populations which, in the absence of stable tertiary contacts, are a most effective way to describe the conformational fluctuations of disordered proteins. The results indicate that, at least within the bacterial cytosol, α-synuclein populates a highly dynamic state that, despite the highly crowded environment, has the same characteristics as the disordered monomeric form observed in aqueous solution

Small-scale societies exhibit fundamental variation in the role of intentions in moral judgment

Intent and mitigating circumstances play a central role in moral and legal assessments in large-scale industrialized societies. Although these features of moral assessment are widely assumed to be universal, to date, they have only been studied in a narrow range of societies. We show that there is substantial cross-cultural variation among eight traditional small-scale societies (ranging from hunter-gatherer to pastoralist to horticulturalist) and two Western societies (one urban, one rural) in the extent to which intent and mitigating circumstances influence moral judgments. Although participants in all societies took such factors into account to some degree, they did so to very different extents, varying in both the types of considerations taken into account and the types of violations to which such considerations were applied. The particular patterns of assessment characteristic of large-scale industrialized societies may thus reflect relatively recently culturally evolved norms rather than inherent features of human moral judgment