Making Sense of Listening: The IMAP Test Battery

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the abilities to extract and use the information encoded in the auditory signal. We refer to these as listening skills (or auditory processing AP). Deficits in these skills are associated with delayed language and literacy development, though the nature of the relevant deficits and their causal connection with these delays is hotly debated

Is auditory discrimination mature by middle childhood? A study using time-frequency analysis of mismatch responses from 7 years to adulthood

Behavioural and electrophysiological studies give differing impressions of when auditory discrimination is mature. Ability to discriminate frequency and speech contrasts reaches adult levels only around 12 years of age, yet an electrophysiological index of auditory discrimination, the mismatch negativity (MMN), is reported to be as large in children as in adults. Auditory ERPs were measured in 30 children (7 to 12 years), 23 teenagers (13 to 16 years) and 32 adults (35 to 56 years) in an oddball paradigm with tone or syllable stimuli. For each stimulus type, a standard stimulus (1000 Hz tone or syllable [ba]) occurred on 70% of trials, and one of two deviants (1030 or 1200 Hz tone, or syllables [da] or [bi]) equiprobably on the remaining trials. For the traditional MMN interval of 100–250 ms post-onset, size of mismatch responses increased with age, whereas the opposite trend was seen for an interval from 300 to 550 ms post-onset, corresponding to the late discriminative negativity (LDN). Time-frequency analysis of single trials revealed that the MMN resulted from phase-synchronization of oscillations in the theta (4–7 Hz) range, with greater synchronization in adults than children. Furthermore, the amount of synchronization was significantly correlated with frequency discrimination threshold. These results show that neurophysiological processes underlying auditory discrimination continue to develop through childhood and adolescence. Previous reports of adult-like MMN amplitudes in children may be artefactual results of using peak measurements when comparing groups that differ in variance

Mismatch Response to Polysyllabic Nonwords: A Neurophysiological Signature of Language Learning Capacity

Background: The ability to repeat polysyllabic nonwords such as ‘‘blonterstaping’’ has frequently been shown to correlate with language learning ability but it is not clear why such a correlation should exist. Three alternative explanations have been offered, stated in terms of differences in: (a) perceptual ability; (b) efficiency of phonological loop functioning; (c) preexisting vocabulary knowledge and/or articulatory skills. In the present study, we used event-related potentials to assess the contributions from these three factors to explaining individual variation in nonword repetition ability. Methodology/Principal Findings: 59 adults who were subdivided according to whether they were good or poor nonwordrepeaters participated. Electrophysiologically measured mismatch responses were recorded to changes in consonants as participants passively listened to a repeating four syllable CV-string. The consonant change could occur in one of four positions along the CV-string and we predicted that: (a) if nonword repetition depended purely on auditory discrimination ability, then reduced mismatch responses to all four consonant changes would be observed in the poor nonword-repeaters, (b) if it depended on encoding or decay of information in a capacity-limited phonological store, then a position specific decrease in mismatch response would be observed, (c) if neither cognitive capacity was involved, then the two groups of participants would provide equivalent mismatch responses. Consistent with our second hypothesis, a position specific difference located on the third syllable was observed in the late discriminative negativity (LDN) window (230–630 ms postsyllable onset). Conclusions/Significance: Our data thus confirm that people who are poorer at nonword repetition are less efficient in early processing of polysyllabic speech materials, but this impairment is not attributable to deficits in low level auditory discrimination. We conclude by discussing the significance of the observed relationship between LDN amplitude and nonword repetition ability and describe how this relatively little understood ERP component provides a biological window onto processes required for successful language learning

Population genetic analysis of the Plasmodium falciparum 6-cys protein Pf38 in Papua New Guinea reveals domain-specific balancing selection

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>merozoite surface protein Pf38 is targeted by antibodies of malaria immune adults and has been shown to be under balancing (immune) selection in a Gambian parasite population, indicating potential as a malaria vaccine candidate. This study explores the population genetics of <it>Pf</it>38 in Papua New Guinea, to determine the extent and geographic distribution of diversity and to measure selective pressure along the length of the gene.</p> <p>Methods</p> <p>Using samples collected during community-based cross-sectional surveys in the Mugil and Wosera regions, the <it>Pf38 </it>genes of 59 <it>P. falciparum </it>isolates were amplified and sequenced. These sequences, along with previously sequenced Gambian and laboratory isolates, were then subjected to an array of population genetic analyses, examining polymorphisms, haplotype diversity and balancing selection. In addition to whole-gene analysis, the two 6-cys domains were considered separately, to investigate domain specific polymorphism and selection.</p> <p>Results</p> <p>Nineteen polymorphic sites were identified in the <it>Pf </it>38 gene. Of these, 13 were found in the Gambia, 10 in Mugil and 8 in Wosera. Notably, the majority of common polymorphisms were confined to domain I. Although only moderate levels of nucleotide diversity were observed, the haplotype diversity was high in all populations, suggesting extensive recombination. Analyses of the full-length sequence provided only modest evidence for balancing selection. However, there was a strong contrast between domain I, which showed strong evidence for positive balancing selection, and domain II which was neutral. Analyses of the geographic distribution of Pf38 haplotypes showed that four haplotypes accounted for the majority of sequences found world-wide, but there were many more haplotypes unique to the African than the PNG populations.</p> <p>Conclusion</p> <p>This study confirmed previous findings that <it>Pf38 </it>is a polymorphic gene under balancing selection. However, analysing polymorphism and selection across the length of the gene painted a considerably different picture. Domain I is highly polymorphic and the target of significant balancing selection. In contrast, domain II is relatively conserved and does not show evidence of immune selective pressure. The findings have implications for future population genetic studies on vaccine candidates, showing that the biological context must also be considered as a framework for analysis.</p

A scoping review to catalogue tinnitus problems in children

© 2019 The Authors Background: The reported prevalence of tinnitus in children is similar to that in adults. However, unlike adults, there is relatively little understanding of the tinnitus-related problems children experience. Knowledge of the problems experienced by adults has led to the development of numerous clinical questionnaires used by health professionals in assessment and treatment practices; to date no child-specific questionnaire measure of tinnitus has been developed. To support development of a questionnaire measure of tinnitus in children, the aim of this scoping review was to catalogue the peer-reviewed and grey scientific literature according to 1) the methods used to identify problems experienced by children with tinnitus, 2) tinnitus-related problems observed in or reported by children, and 3) research recommendations suggested by investigators with regards to tinnitus in children. Methods: A scoping review was conducted following an established methodological framework. Records were included where a tinnitus-related problem was reported in a child 18 years or younger, and tinnitus was reported as the primary complaint. Tinnitus problems were extracted and categorised into problem themes. Results: Thirty-five records met the inclusion criteria for this review. Methods used to identify tinnitus-related problems in children, and the number and range of problems reported, varied across the records. Symptom impact was summarised according to six problem themes; Physical health, Cognitive health, Hearing and listening, Emotional health, Quality of life, and Feeling different/isolated. Identified research recommendations highlighted a demand for more standardised approaches. Conclusions: The findings evidence the detrimental impact tinnitus can have on a child's quality of life and emotional wellbeing. The current British Society of Audiology Tinnitus in Children Practice Guidance recommends management practices to address the most broadly reported problems identified in this review; sleep difficulties, emotional difficulties, and concentration and hearing problems at school. Given the finding of this review, we suggest problems relating to the impact of tinnitus on quality of life and feelings of isolation are also important problem domains to consider when managing a child who has tinnitus. Current variability in the approach to identifying children's tinnitus problems underlines the importance of developing a standardised and dedicated measure of tinnitus in children

An evaluation of paediatric tinnitus services in UK National Health Service audiology departments

© 2020 The Author(s). Background: Whilst evidence indicates many children experience troublesome tinnitus, specialist services for children are far less established than those available for adults. To date, there is limited understanding of how paediatric tinnitus is managed in the UK, and to what extent current practice reflects what is recommended. This service evaluation aimed to 1) profile how tinnitus in children is managed in UK clinical practice, and assess to what extent care provided by services reflects advice included in the British Society of Audiology (BSA) Tinnitus in Children Practice Guidance, 2) collate clinician opinions on how services may be optimised, and 3) identify common problems experienced by children who present with bothersome tinnitus in clinic. Methods: As part of a larger survey, eight questions regarding services for paediatric tinnitus were distributed to UK NHS audiology services via email and social media. Representatives from eighty-seven services responded between July and September 2017. Results: Fifty-three percent of respondents reported that their department provided a paediatric tinnitus service. Among these services, there was widespread use of most BSA recommended assessments and treatments. Less widely used practices were the assessment of mental health (42%), and the use of psychological treatment approaches; cognitive behavioural therapy (CBT) (28%), mindfulness (28%), and narrative therapy (14%). There was varied use of measurement tools to assess tinnitus in children, and a minority of respondents reported using adult tinnitus questionnaires with children. Frequently reported tinnitus-related problems presented by children were sleep difficulties, concentration difficulties at school, situation-specific concentration difficulties, and emotional distress. Conclusions: Approaches used to manage children with troublesome tinnitus in UK NHS services are largely consistent and reflective of the current practice guidance. However, findings from this study indicate specialist staff training, access to child-specific tools, and the treatment and referral of children with tinnitus-related psychological problems represent key areas in need of optimisation

Reducing Vulnerability to Climate Change in the Arctic: The Case of Nunavut, Canada

Research conducted with the communities of Arctic Bay and Igloolik in Nunavut identified key areas where policy can help Inuit reduce their vulnerability to climate change, focusing on the renewable resource harvesting sector. The policy responses are based on an understanding of policy development and decision making and on an understanding of the processes that shape vulnerability, which in Nunavut comprise the erosion of traditional Inuit knowledge and land-based skills, the weakening of social networks, and a reduction in harvesting flexibility. Policies relating to cultural preservation, wildlife comanagement, and harvester support can serve as entry points for influencing these processes. Our recommendations fall within the mandates of the Government of Nunavut and the institutions created under the Nunavut Land Claims Agreement, and they have been identified as policy priorities by communities and Inuit organizations.Grâce à des recherches effectuées auprès des collectivités de la baie de l’Arctique et d’Igloolik au Nunavut, on a réussi à déterminer comment la politique peut rendre les Inuits moins vulnérables au changement climatique en se concentrant sur le secteur de l’exploitation des ressources renouvelables. La compréhension de l’élaboration des politiques, de la prise de décisions et des processus qui engendrent la vulnérabilité permet d’aboutir à des réponses en vue de l’établissement de politiques. Au Nunavut, cette vulnérabilité se traduit par l’érosion des connaissances traditionnelles inuites et des habiletés d’utilisation de la terre, l’affaiblissement des réseaux sociaux et l’atténuation de la souplesse caractérisant l’exploitation. Les politiques en matière de conservation culturelle, de cogestion de la faune et de soutien à l’exploitation servent de point d’entrée pour influencer ces processus. Nos recommandations cadrent avec les mandats du gouvernement du Nunavut et des établissements créés en vertu de l’Entente de revendication territoriale du Nunavut. Les collectivités et organismes inuits les considèrent comme des priorités en matière de politique

Disparate Independent Genetic Events Disrupt the Secondary Metabolism Gene \u3cem\u3eperA\u3c/em\u3e in Certain Symbiotic \u3cem\u3eEpichloë\u3c/em\u3e Species

Peramine is an insect-feeding deterrent produced by Epichloë species in symbiotic association with C3 grasses. The perA gene responsible for peramine synthesis encodes a two-module nonribosomal peptide synthetase. Alleles of perA are found in most Epichloë species; however, peramine is not produced by many perA-containing Epichloë isolates. The genetic basis of these peramine-negative chemotypes is often unknown. Using PCR and DNA sequencing, we analyzed the perA genes from 72 Epichloë isolates and identified causative mutations of perA null alleles. We found nonfunctional perA-ΔR* alleles, which contain a transposon-associated deletion of the perA region encoding the C-terminal reductase domain, are widespread within the Epichloë genus and represent a prevalent mutation found in nonhybrid species. Disparate phylogenies of adjacent A2 and T2 domains indicated that the deletion of the reductase domain (R*) likely occurred once and early in the evolution of the genus, and subsequently there have been several recombinations between those domains. A number of novel point, deletion, and insertion mutations responsible for abolishing peramine production in full-length perA alleles were also identified. The regions encoding the first and second adenylation domains (A1 and A2, respectively) were common sites for such mutations. Using this information, a method was developed to predict peramine chemotypes by combining PCR product size polymorphism analysis with sequencing of the perA adenylation domains

Arene ruthenium dithiolato-carborane complexes for boron neutron capture theory (BNCT)

YesWe report the effect of low-energy thermal neutron irradiation on the antiproliferative activities of a highly hydrophobic organometallic arene ruthenium dithiolatoecarborane complex [Ru(p-cymene) (1,2- dicarba-closo-dodecarborane-1,2-dithiolato)] (1), and of its formulation in Pluronic® triblock copolymer P123 coreeshell micelles (RuMs). Complex 1 was highly active, with and without neutron irradiation, towards human ovarian cancer cells (A2780; IC50 0.14 mM and 0.17 mM, respectively) and cisplatinresistant human ovarian cancer cells (A2780cisR; IC50 0.05 and 0.13 mM, respectively). Complex 1 was particularly sensitive to neutron irradiation in A2780cisR cells (2.6 more potent after irradiation compared to non-irradiation). Although less potent, the encapsulated complex 1 as RuMs nanoparticles resulted in higher cellular accumulation (2.5 ), and was sensitive to neutron irradiation in A2780 cells (1.4 more potent upon irradiation compared to non-irradiation).We thank the Leverhulme Trust (Early Career Fellowship No. ECF-2013-414 to NPEB), the University of Warwick (Grant No. RD14102 to NPEB), the University of Birmingham/EPSRC Follow-on- Fund (Grant No UOBFOF026 to BP), the ERC (Grant No. 247450 to PJS), EPSRC (EP/F034210/1 to PJS)

Precious metal carborane polymer nanoparticles: characterisation of micellar formulations and anticancer activity

YesWe report the encapsulation of highly hydrophobic 16-electron organometallic ruthenium and osmium carborane complexes [Ru/Os(p-cymene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolate)] (1 and 2) in Pluronic® triblock copolymer P123 core–shell micelles. The spherical nanoparticles RuMs and OsMs, dispersed in water, were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), and synchrotron small-angle X-ray scattering (SAXS; diameter ca. 15 and 19 nm, respectively). Complexes 1 and 2 were highly active towards A2780 human ovarian cancer cells (IC50 0.17 and 2.50 μM, respectively) and the encapsulated complexes, as RuMs and OsMs nanoparticles, were less potent (IC50 6.69 μM and 117.5 μM, respectively), but more selective towards cancer cells compared to normal cells.We thank the Leverhulme Trust (Early Career Fellowship no. ECF-2013-414 to NPEB), the University of Warwick (Grant no. RDF 2013-14 to NPEB), the Swiss National Science Foundation (Grant no. PA00P2_145308 to NPEB and PBNEP2_142949 to APB), the ERC (Grant no. 247450 to PJS), EPSRC (EP/G004897/ 1 to APB, and EP/F034210/1 to PJS), Institute of Advanced Study (IAS) – University of Warwick (Fellowship to JJSB), and Science City (AWM/ERDF) for support. We thank the Wellcome Trust (055663/Z/98/Z) for funding to the Electron Microscopy Facility, School of Life Sciences, University of Warwick