Evaluating cortical responses to speech in children: A functional near-infrared spectroscopy (fNIRS) study.

Functional neuroimaging of speech processing has both research and clinical potential. This work is facilitating an ever-increasing understanding of the complex neural mechanisms involved in the processing of speech. Neural correlates of speech understanding also have potential clinical value, especially for infants and children, in whom behavioural assessments can be unreliable. Such measures would not only benefit normally hearing children experiencing speech and language delay, but also hearing impaired children with and without hearing devices. In the current study, we examined cortical correlates of speech intelligibility in normally hearing paediatric listeners. Cortical responses were measured using functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging technique that is fully compatible with hearing devices, including cochlear implants. In nineteen normally hearing children (aged 6 – 13 years) we measured activity in temporal and frontal cortex bilaterally whilst participants listened to both clear- and noise-vocoded sentences targeting four levels of speech intelligibility. Cortical activation in superior temporal and inferior frontal cortex was generally stronger in the left hemisphere than in the right. Activation in left superior temporal cortex grew monotonically with increasing speech intelligibility. In the same region, we identified a trend towards greater activation on correctly vs. incorrectly perceived trials, suggesting a possible sensitivity to speech intelligibility per se, beyond sensitivity to changing acoustic properties across stimulation conditions. Outside superior temporal cortex, we identified other regions in which fNIRS responses varied with speech intelligibility. For example, channels overlying posterior middle temporal regions in the right hemisphere exhibited relative deactivation during sentence processing (compared to a silent baseline condition), with the amplitude of that deactivation being greater in more difficult listening conditions. This finding may represent sensitivity to components of the default mode network in lateral temporal regions, and hence effortful listening in normally hearing paediatric listeners. Our results indicate that fNIRS has the potential to provide an objective marker of speech intelligibility in normally hearing children. Should these results be found to apply to individuals experiencing language delay or to those listening through a hearing device, such as a cochlear implant, fNIRS may form the basis of a clinically useful measure of speech understanding

Recommended Personal Protective Equipment for Cochlear Implant and Other Mastoid Surgery During the COVID-19 Era

© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA) Objectives/Hypothesis: The overall aim of this study was to evaluate personal protective equipment (PPE) that may facilitate the safe recommencement of cochlear implantation in the COVID-19 era, with the broader goal of minimizing the period of auditory deprivation in prelingually deaf children and reducing the risk of cochlear ossification in individuals following meningitis. Methods: The study design comprised 1) an objective assessment of mastoid drilling-induced droplet spread conducted during simulated cochlear implant (CI) surgery and its mitigation via the use of a protective drape tent and 2) an evaluation of three PPE configurations by otologists while performing mastoid drilling on ex vivo temporal bones. The various PPE solutions were assessed in terms of their impact on communication, vital physiological parameters, visual acuity and fields, and acceptability to surgeons using a systematic risk-based approach. Results: Droplet spread during simulated CI surgery extended over 2 m, a distance greater than previously reported. A drape tent significantly reduced droplet spread. The ensemble of a half-face mask and safety spoggles (foam lined safety goggles) had consistently superior performance across all aspects of clinical usability. All other PPE options were found to substantially restrict the visual field, making them unsafe for microsurgery. Conclusions: The results of this preclinical study indicate that the most viable solution to enable the safe conduct of CI and other mastoid surgery is a combination of a filtering facepiece (FFP)3 mask or half-face respirator with safety spoggles as PPE. Prescription spoggles are an option for surgeons who need to wear corrective glasses to operate. A drape tent reduces droplet spread. A multicenter clinical trial to evaluate the effectiveness of PPE should be the next step toward safely performing CI surgery during the COVID-19 era. Level of Evidence: 4 Laryngoscope, 2020

Sea ice and pollution-modulated changes in Greenland ice core methanesulfonate and bromine

Reconstruction of past changes in Arctic sea ice extent may be critical for understanding its future evolution. Methanesulfonate (MSA) and bromine concentrations preserved in ice cores have both been proposed as indicators of past sea ice conditions. In this study, two ice cores from central and north-eastern Greenland were analysed at sub-annual resolution for MSA (CH3SO3H) and bromine, covering the time period 1750–2010. We examine correlations between ice core MSA and the HadISST1 ICE sea ice dataset and consult back trajectories to infer the likely source regions. A strong correlation between the low-frequency MSA and bromine records during pre-industrial times indicates that both chemical species are likely linked to processes occurring on or near sea ice in the same source regions. The positive correlation between ice core MSA and bromine persists until the mid-20th century, when the acidity of Greenland ice begins to increase markedly due to increased fossil fuel emissions. After that time, MSA levels decrease as a result of declining sea ice extent but bromine levels increase. We consider several possible explanations and ultimately suggest that increased acidity, specifically nitric acid, of snow on sea ice stimulates the release of reactive Br from sea ice, resulting in increased transport and deposition on the Greenland ice sheet

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

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

Cortical correlates of speech intelligibility measured using functional near-infrared spectroscopy (fNIRS)

Functional neuroimaging has identified that the temporal, frontal and parietal cortex support core aspects of speech processing. An objective measure of speech intelligibility based on cortical activation in these brain regions would be extremely useful to speech communication and hearing device applications. In the current study, we used noise-vocoded speech to examine cortical correlates of speech intelligibility in normally-hearing listeners using functional near-infrared spectroscopy (fNIRS), a non-invasive, neuroimaging technique that is fully-compatible with hearing devices, including cochlear implants. In twenty-three normally-hearing adults we measured (1) activation in superior temporal, inferior frontal and inferior parietal cortex bilaterally and (2) behavioural speech intelligibility. Listeners heard noise-vocoded sentences targeting five equally spaced levels of intelligibility between 0 and 100% correct. Activation in superior temporal regions increased linearly with intelligibility. This relationship appears to have been driven in part by changing acoustic properties across stimulation conditions, rather than solely by intelligibility per se. Superior temporal activation was also predictive of individual differences in intelligibility in a challenging listening condition. Beyond superior temporal cortex, we identified regions in which activation varied non-linearly with intelligibility. For example, in left inferior frontal cortex, activation peaked in response to heavily degraded, yet still somewhat intelligible, speech. Activation in this region was linearly related to response time on a simultaneous behavioural task, suggesting it may contribute to decision making. Our results indicate that fNIRS has the potential to provide an objective measure of speech intelligibility in normally-hearing listeners. Should these results be found to apply similarly in the case of individuals listening through a cochlear implant, fNIRS would demonstrate potential for a clinically useful measure not only of speech intelligibility, but also of listening effort

Impact of mutations in Toll-like receptor pathway genes on esophageal carcinogenesis.

Esophageal adenocarcinoma (EAC) develops in an inflammatory microenvironment with reduced microbial diversity, but mechanisms for these influences remain poorly characterized. We hypothesized that mutations targeting the Toll-like receptor (TLR) pathway could disrupt innate immune signaling and promote a microenvironment that favors tumorigenesis. Through interrogating whole genome sequencing data from 171 EAC patients, we showed that non-synonymous mutations collectively affect the TLR pathway in 25/171 (14.6%, PathScan p = 8.7x10-5) tumors. TLR mutant cases were associated with more proximal tumors and metastatic disease, indicating possible clinical significance of these mutations. Only rare mutations were identified in adjacent Barrett's esophagus samples. We validated our findings in an external EAC dataset with non-synonymous TLR pathway mutations in 33/149 (22.1%, PathScan p = 0.05) tumors, and in other solid tumor types exposed to microbiomes in the COSMIC database (10,318 samples), including uterine endometrioid carcinoma (188/320, 58.8%), cutaneous melanoma (377/988, 38.2%), colorectal adenocarcinoma (402/1519, 26.5%), and stomach adenocarcinoma (151/579, 26.1%). TLR4 was the most frequently mutated gene with eleven mutations in 10/171 (5.8%) of EAC tumors. The TLR4 mutants E439G, S570I, F703C and R787H were confirmed to have impaired reactivity to bacterial lipopolysaccharide with marked reductions in signaling by luciferase reporter assays. Overall, our findings show that TLR pathway genes are recurrently mutated in EAC, and TLR4 mutations have decreased responsiveness to bacterial lipopolysaccharide and may play a role in disease pathogenesis in a subset of patients

The medium-term sustainability of organisational innovations in the national health service

Background: There is a growing recognition of the importance of introducing new ways of working into the UK's National Health Service (NHS) and other health systems, in order to ensure that patient care is provided as effectively and efficiently as possible. Researchers have examined the challenges of introducing new ways of working-'organisational innovations'-into complex organisations such as the NHS, and this has given rise to a much better understanding of how this takes place-and why seemingly good ideas do not always result in changes in practice. However, there has been less research on the medium-and longer-term outcomes for organisational innovations and on the question of how new ways of working, introduced by frontline clinicians and managers, are sustained and become established in day-to-day practice. Clearly, this question of sustainability is crucial if the gains in patient care that derive from organisational innovations are to be maintained, rather than lost to what the NHS Institute has called the 'improvement-evaporation effect'. Methods: The study will involve research in four case-study sites around England, each of which was successful in sustaining its new model of service provision beyond an initial period of pilot funding for new genetics services provided by the Department of Health. Building on findings relating to the introduction and sustainability of these services already gained from an earlier study, the research will use qualitative methods-in-depth interviews, observation of key meetings, and analysis of relevant documents-to understand the longer-term challenges involved in each case and how these were surmounted. The research will provide lessons for those seeking to sustain their own organisational innovations in wide-ranging clinical areas and for those designing the systems and organisations that make up the NHS, to make them more receptive contexts for the sustainment of innovation. Discussion: Through comparison and contrast across four sites, each involving different organisational innovations, different forms of leadership, and different organisational contexts to contend with, the findings of the study will have wide relevance. The research will produce outputs that are useful for managers and clinicians responsible for organisational innovation, policy makers and senior managers, and academics

Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products

Metformin is used globally to treat type II diabetes, has demonstrated anti-ageing and COVID mitigation effects and is a major anthropogenic pollutant to be bioremediated by wastewater treatment plants (WWTPs). Metformin is not adsorbed well by activated carbon and toxic N-chloro derivatives can form in chlorinated water. Most earlier studies on metformin biodegradation have used wastewater consortia and details of the genomes, relevant genes, metabolic products, and potential for horizontal gene transfer are lacking. Here, two metformin-biodegrading bacteria from a WWTP were isolated and their biodegradation characterized. Aminobacter sp. MET metabolized metformin stoichiometrically to guanylurea, an intermediate known to accumulate in some environments including WWTPs. Pseudomonasmendocina MET completely metabolized metformin and utilized all the nitrogen atoms for growth. Pseudomonas mendocina MET also metabolized metformin breakdown products sometimes observed in WWTPs: 1-N-methylbiguanide, biguanide, guanylurea, and guanidine. The genome of each bacterium was obtained. Genes involved in the transport of guanylurea in Aminobacter sp. MET were expressed heterologously and shown to serve as an antiporter to expel the toxic guanidinium compound. A novel guanylurea hydrolase enzyme was identified in Pseudomonas mendocina MET, purified, and characterized. The Aminobacter and Pseudomonas each contained one plasmid of 160 kb and 90 kb, respectively. In total, these studies are significant for the bioremediation of a major pollutant in WWTPs today

A Comparison Between the Teg 6s and Teg 5000 Analyzers to Assess Coagulation in Trauma Patients

BACKGROUND Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients. METHODS Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices. RESULTS A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05, ρ = 0.9), CFF.MA (ß = 0.99, ρ = 0.95), CK.LY30 (ß = 1.01, ρ = 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06, ρ = 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93, ρ = 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30. CONCLUSION The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing. LEVEL OF EVIDENCE Diagnostic test, level II

Advances in land surface modelling

Land surface models have an increasing scope. Initially designed to capture the feedbacks between the land and the atmosphere as part of weather and climate prediction, they are now used as a critical tool in the urgent need to inform policy about land-use and water-use management in a world that is changing physically and economically. This paper outlines the way that models have evolved through this change of purpose and what might the future hold. It highlights the importance of distinguishing between advances in the science within the modelling components, with the advances of how to represent their interaction. This latter aspect of modelling is often overlooked but will increasingly manifest as an issue as the complexity of the system, the time and space scales of the system being modelled increase. These increases are due to technology, data availability and the urgency and range of the problems being studied