201 research outputs found

    The Benefit of Cross-Modal Reorganization on Speech Perception in Pediatric Cochlear Implant Recipients Revealed Using Functional Near-Infrared Spectroscopy

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    Cochlear implants (CIs) are the most successful treatment for severe-to-profound deafness in children. However, speech outcomes with a CI often lag behind those of normally-hearing children. Some authors have attributed these deficits to the takeover of the auditory temporal cortex by vision following deafness, which has prompted some clinicians to discourage the rehabilitation of pediatric CI recipients using visual speech. We studied this cross-modal activity in the temporal cortex, along with responses to auditory speech and non-speech stimuli, in experienced CI users and normally-hearing controls of school-age, using functional near-infrared spectroscopy. Strikingly, CI users displayed significantly greater cortical responses to visual speech, compared with controls. Importantly, in the same regions, the processing of auditory speech, compared with non-speech stimuli, did not significantly differ between the groups. This suggests that visual and auditory speech are processed synergistically in the temporal cortex of children with CIs, and they should be encouraged, rather than discouraged, to use visual speech

    Use of Functional Near-Infrared Spectroscopy to Predict and Measure Cochlear Implant Outcomes: A Scoping Review

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    Outcomes following cochlear implantation vary widely for both adults and children, and behavioral tests are currently relied upon to assess this. However, these behavioral tests rely on subjective judgements that can be unreliable, particularly for infants and young children. The addition of an objective test of outcome following cochlear implantation is therefore desirable. The aim of this scoping review was to comprehensively catalogue the evidence for the potential of functional near infrared spectroscopy (fNIRS) to be used as a tool to objectively predict and measure cochlear implant outcomes. A scoping review of the literature was conducted following the PRISMA extension for scoping review framework. Searches were conducted in the MEDLINE, EMBASE, PubMed, CINAHL, SCOPUS, and Web of Science electronic databases, with a hand search conducted in Google Scholar. Key terms relating to near infrared spectroscopy and cochlear implants were used to identify relevant publications. Eight records met the criteria for inclusion. Seven records reported on adult populations, with five records only including post-lingually deaf individuals and two including both pre- and post-lingually deaf individuals. Studies were either longitudinal or cross-sectional, and all studies compared fNIRS measurements with receptive speech outcomes. This review identified and collated key work in this field. The homogeneity of the populations studied so far identifies key gaps for future research, including the use of fNIRS in infants. By mapping the literature on this important topic, this review contributes knowledge towards the improvement of outcomes following cochlear implantation

    Evaluating time-reversed speech and signal-correlated noise as auditory baselines for isolating speech-specific processing using fNIRS

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    Evidence using well-established imaging techniques, such as functional magnetic resonance imaging and electrocorticography, suggest that speech-specific cortical responses can be functionally localised by contrasting speech responses with an auditory baseline stimulus, such as time-reversed (TR) speech or signal-correlated noise (SCN). Furthermore, these studies suggest that SCN is a more effective baseline than TR speech. Functional near-infrared spectroscopy (fNIRS) is a relatively novel, optically-based imaging technique with features that make it ideal for investigating speech and language function in paediatric populations. However, it is not known which baseline is best at isolating speech activation when imaging using fNIRS. We presented normal speech, TR speech and SCN in an event-related format to 25 normally-hearing children aged 6–12 years. Brain activity was measured across frontal and temporal brain areas in both cerebral hemispheres whilst children passively listened to the auditory stimuli. In all three conditions, significant activation was observed bilaterally in channels targeting superior temporal regions when stimuli were contrasted against silence. Unlike previous findings in infants, we found no significant activation in the region of interest over superior temporal cortex in school-age children when normal speech was contrasted against either TR speech or SCN. Although no statistically significant lateralisation effects were observed in the region of interest, a left-sided channel targeting posterior temporal regions showed significant activity in response to normal speech only, and was investigated further. Significantly greater activation was observed in this left posterior channel compared to the corresponding channel on the right side under the normal speech vs SCN contrast only. Our findings suggest that neither TR speech nor SCN are suitable auditory baselines for functionally isolating speech-specific processing in an experimental set up involving fNIRS with 6–12 year old children

    Listening efficiency in adult cochlear-implant users compared with normally-hearing controls at ecologically relevant signal-to-noise ratios

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    Introduction: Due to having to work with an impoverished auditory signal, cochlear-implant (CI) users may experience reduced speech intelligibility and/or increased listening effort in real-world listening situations, compared to their normally-hearing (NH) peers. These two challenges to perception may be usefully integrated in a measure of listening efficiency: conceptually, the amount of accuracy achieved for a certain amount of effort expended. Methods: We describe a novel approach to quantifying listening efficiency based on the rate of evidence accumulation toward a correct response in a linear ballistic accumulator (LBA) model of choice decision-making. Estimation of this objective measure within a hierarchical Bayesian framework confers further benefits, including full quantification of uncertainty in parameter estimates. We applied this approach to examine the speech-in-noise performance of a group of 24 CI users (M age: 60.3, range: 20–84 years) and a group of 25 approximately age-matched NH controls (M age: 55.8, range: 20–79 years). In a laboratory experiment, participants listened to reverberant target sentences in cafeteria noise at ecologically relevant signal-to-noise ratios (SNRs) of +20, +10, and +4 dB SNR. Individual differences in cognition and self-reported listening experiences were also characterised by means of cognitive tests and hearing questionnaires. Results: At the group level, the CI group showed much lower listening efficiency than the NH group, even in favourable acoustic conditions. At the individual level, within the CI group (but not the NH group), higher listening efficiency was associated with better cognition (i.e., working-memory and linguistic-closure) and with more positive self-reported listening experiences, both in the laboratory and in daily life. Discussion: We argue that listening efficiency, measured using the approach described here, is: (i) conceptually well-motivated, in that it is theoretically impervious to differences in how individuals approach the speed-accuracy trade-off that is inherent to all perceptual decision making; and (ii) of practical utility, in that it is sensitive to differences in task demand, and to differences between groups, even when speech intelligibility remains at or near ceiling level. Further research is needed to explore the sensitivity and practical utility of this metric across diverse listening situations

    Responsibility and laboratory animal research governance

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    The use of animals in experiments and research remains highly contentious. Laboratory animal research governance provides guidance and regulatory frameworks to oversee the use and welfare of laboratory animals and relies heavily on the replacement, reduction, and refinement (3Rs) principles to demonstrate responsibility. However, the application of the 3Rs is criticized for being too narrow in focus and closing down societal concerns and political questions about the purpose of animal laboratory research. These critiques challenge the legitimacy of responsibility in laboratory animal research governance and call for new approaches. With the advent of the "Responsible Research and Innovation" (RRI) agenda, we investigate whether the notion of responsibility in the controversial area of animal research governance could be enhanced by examining the 3Rs through RRI. Our analysis reveals RRI has the potential to helpfully augment the 3Rs in three key ways: recognizing the need to include a broader range of experts and publics in animal research governance; emphasizing the importance for animal research scientists of taking societal, and not just role, responsibilities into account; and acknowledging the political questions animal research raises

    Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei

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    As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification of several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme

    The Yin and Yang of Yeast Transcription: Elements of a Global Feedback System between Metabolism and Chromatin

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    When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions

    Detection and Characterization of Wolbachia Infections in Natural Populations of Aphids: Is the Hidden Diversity Fully Unraveled?

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    Aphids are a serious threat to agriculture, despite being a rather small group of insects. The about 4,000 species worldwide engage in highly interesting and complex relationships with their microbial fauna. One of the key symbionts in arthropods is Wolbachia, an α-Proteobacterium implicated in many important biological processes and believed to be a potential tool for biological control. Aphids were thought not to harbour Wolbachia; however, current data suggest that its presence in aphids has been missed, probably due to the low titre of the infection and/or to the high divergence of the Wolbachia strains of aphids. The goal of the present study is to map the Wolbachia infection status of natural aphids populations, along with the characterization of the detected Wolbachia strains. Out of 425 samples from Spain, Portugal, Greece, Israel and Iran, 37 were found to be infected. Our results, based mainly on 16S rRNA gene sequencing, indicate the presence of two new Wolbachia supergroups prevailing in aphids, along with some strains belonging either to supergroup B or to supergroup A

    The Dark Energy Survey : more than dark energy – an overview

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    This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from ‘Science Verification’, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be +cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)
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