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Streptococcus pneumoniae is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 3-4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined. Using a genome-wide association approach, we identified a large number of potential affectors of Ply activity, including a gene acquired horizontally on the antibiotic resistance-conferring Integrative and Conjugative Element (ICE) ICE Sp 23FST81. This gene encodes a novel modular protein, ZomB, which has an N-terminal UvrD-like helicase domain followed by two Cas4-like domains with potent ATP-dependent nuclease activity. We found the regulatory effect of ZomB to be specific for the ply operon, potentially mediated by its high affinity for the BOX repeats encoded therein. Using a murine model of pneumococcal colonization, we further demonstrate that a ZomB mutant strain colonizes both the upper respiratory tract and lungs at higher levels when compared to the wild-type strain. While the antibiotic resistance-conferring aspects of ICE Sp 23FST81 are often credited with contributing to the success of the S. pneumoniae lineages that acquire it, its ability to control the expression of a major virulence factor implicated in bacterial transmission is also likely to have played an important role.

Humans have evolved the unique capacity to efficiently communicate using the spoken word. Hearing plays a key role as a receiver in this process and dysfunction leads to difficulties in listening and communication. It is widely accepted that effective communication is not adequately captured with current behavioral speech tests that principally focus on passive sound detection and speech recognition with idealized stimuli. To address the question of what it will take to obtain more ecologically valid outcomes from behavioral speech tests, recent approaches, and test paradigms devised to address some of the acknowledged shortcomings of current speech tests were reviewed. Additionally, some recent work which has focused on understanding brain function in social and dynamic interaction scenarios, so-called second person neuroscience, was reviewed. These reviews revealed that, while recent efforts in bridging the gap between behavioral speech tests and everyday communication situations represent important steps in the right direction, they are unlikely to provide a complete account of everyday communication situations. Further, brain imaging studies, together with our growing understanding of "mirror" neurons and the development of theories around embodied cognition, have demonstrated that the brain networks recruited during emotionally engaged interaction between interlocutors are far more complex when compared to that of a passive listener. Speech and nonspeech (e.g., gaze direction, body posture, etc.) interactions between the interlocutors give rise to the perception of effective interaction (sense of "agency") and activate neural networks important in decision-making and subsequent communication interaction. Successful conversational interaction represents the negotiation of a dynamic context and the emergence of a state of shared understanding between participants. In conclusion, to achieve highly ecologically valid outcomes related to communication, future testing will most likely require an interactive or conversational paradigm to elicit the brain states that are present in everyday social interactions.

Ecological validity is a relatively new concept in hearing science. It has been cited as relevant with increasing frequency in publications over the past 20 years, but without any formal conceptual basis or clear motive. The sixth Eriksholm Workshop was convened to develop a deeper understanding of the concept for the purpose of applying it in hearing research in a consistent and productive manner. Inspired by relevant debate within the field of psychology, and taking into account the World Health Organization's International Classification of Functioning, Disability, and Health framework, the attendees at the workshop reached a consensus on the following definition: "In hearing science, ecological validity refers to the degree to which research findings reflect real-life hearing-related function, activity, or participation." Four broad purposes for striving for greater ecological validity in hearing research were determined: A (Understanding) better understanding the role of hearing in everyday life; B (Development) supporting the development of improved procedures and interventions; C (Assessment) facilitating improved methods for assessing and predicting ability to accomplish real-world tasks; and D (Integration and Individualization) enabling more integrated and individualized care. Discussions considered the effects of variables and phenomena commonly present in hearing-related research on the level of ecological validity of outcomes, supported by examples from a few selected outcome domains and for different types of studies. Illustrated with examples, potential strategies were offered for promoting a high level of ecological validity in a study and for how to evaluate the level of ecological validity of a study. Areas in particular that could benefit from more research to advance ecological validity in hearing science include: (1) understanding the processes of hearing and communication in everyday listening situations, and specifically the factors that make listening difficult in everyday situations; (2) developing new test paradigms that include more than one person (e.g., to encompass the interactive nature of everyday communication) and that are integrative of other factors that interact with hearing in real-life function; (3) integrating new and emerging technologies (e.g., virtual reality) with established test methods; and (4) identifying the key variables and phenomena affecting the level of ecological validity to develop verifiable ways to increase ecological validity and derive a set of benchmarks to strive for.

The outer-ear's location-dependent pattern of spectral filtering generates cues used to determine a sound source's elevation as well as front-back location. The authors aim to identify these features using a reverse correlation analysis (RCA), combining free-field localization behaviour with the associated head-related transfer functions' (HRTFs) magnitude spectrum from a sample of 73 participants. Localization responses were collected before and immediately after introducing a pair of outer-ear inserts which modified the listener's HRTFs to varying extent. The RCA identified several different features responsible for eliciting localization responses. The efficacy of these was examined using two models of monaural localization. In general, the predicted performance was closely aligned with the free-field localization error for the bare-ear condition; however, both models tended to grossly over-estimate the localization error based on HRTFs modified by the outer-ear inserts. The RCA's feature selection notably had the effect of better aligning the predicted performance of both models to the actual localization performance. This suggests that the RCA revealed sufficient detail for both models to correctly predict localization performance and also limited the influence of filtered-out elements in the distorted HRTFs that contributed to the degraded accuracy of both models.

This study examined the effect of a change in target voice on word recall during a multi-talker conversation. Two experiments were conducted using matrix sentences to assess the cost of a single endogenous switch in non-spatial attention. Performance in a yes-no recognition task was significantly worse when a target voice changed compared to when it remained the same after a turn-taking gap. We observed a decrease in target hit rate and sensitivity, and an increase in masker confusion errors following a change in voice. These results highlight the cognitive demands of not only engaging attention on a new talker, but also of disengaging attention from a previous target voice. This shows that exposure to a voice can have a biasing effect on attention that persists well after a turn-taking gap. A second experiment showed that there was no change in switching performance using different talker combinations. This demonstrates that switching costs were consistent and did not depend on the degree of acoustic differences in target voice characteristics.

In order to perceive meaningful speech, the auditory system must recognize different phonemes amidst a noisy and variable acoustic signal. To better understand the processing mechanisms underlying this ability, evoked cortical responses to different spoken consonants were measured with electroencephalography (EEG). Using multivariate pattern analysis (MVPA), binary classifiers attempted to discriminate between the EEG activity evoked by two given consonants at each peri-stimulus time sample, providing a dynamic measure of their cortical dissimilarity. To examine the relationship between representations at the auditory periphery and cortex, MVPA was also applied to modelled auditory-nerve (AN) responses of consonants, and time-evolving AN-based and EEG-based dissimilarities were compared with one another. Cortical dissimilarities between consonants were commensurate with their articulatory distinctions, particularly their manner of articulation, and to a lesser extent, their voicing. Furthermore, cortical distinctions between consonants in two periods of activity, centered at 130 and 400 ms after onset, aligned with their peripheral dissimilarities in distinct onset and post-onset periods, respectively. In relating speech representations across articulatory, peripheral, and cortical domains, the understanding of crucial transformations in the auditory pathway underlying the ability to perceive speech is advanced.

This review considers the nature of the sound generated by wind turbines focusing on the low-frequency sound (LF) and infrasound (IS) to understand the usefulness of the sound measures where people work and sleep. A second focus concerns the evidence for mechanisms of physiological transduction of LF/IS or the evidence for somatic effects of LF/IS. While the current evidence does not conclusively demonstrate transduction, it does present a strong prima facia case. There are substantial outstanding questions relating to the measurement and propagation of LF and IS and its encoding by the central nervous system relevant to possible perceptual and physiological effects. A range of possible research areas are identified.

The capacity of healthy adult listeners to accommodate to altered spectral cues to the source locations of broadband sounds has now been well documented. In recent years we have demonstrated that the degree and speed of accommodation are improved by using an integrated sensory-motor training protocol under anechoic conditions. Here we demonstrate that the learning which underpins the localization performance gains during the accommodation process using anechoic broadband training stimuli generalize to environmentally relevant scenarios. As previously, alterations to monaural spectral cues were produced by fitting participants with custom-made outer ear molds, worn during waking hours. Following acute degradations in localization performance, participants then underwent daily sensory-motor training to improve localization accuracy using broadband noise stimuli over ten days. Participants not only demonstrated post-training improvements in localization accuracy for broadband noises presented in the same set of positions used during training, but also for stimuli presented in untrained locations, for monosyllabic speech sounds, and for stimuli presented in reverberant conditions. These findings shed further light on the neuroplastic capacity of healthy listeners, and represent the next step in the development of training programs for users of assistive listening devices which degrade localization acuity by distorting or bypassing monaural cues.

Eppin is a serine protease inhibitor expressed in male reproductive tissues.The aim of this study was to investigate the localisation and regulation of eppin expression in myeloid and epithelial cell lines, and explore its potential role as a multifunctional host defence protein.Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with acute respiratory distress syndrome and cystic fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with Toll-like receptor agonists, cytokines and hormone receptor agonists. However, upregulated expression and secretion of eppin was observed following treatment of monocytes with epidermal growth factor. Incubation of recombinant eppin with monocytic cells resulted in significant inhibition of lipopolysaccharide-induced chemokine production. Furthermore, eppin inhibited lipopolysaccharide-induced NF-κB activation by a mechanism which involved accumulation of phosphorylated IκBα. In an in vivo model of lung inflammation induced by lipopolysaccharide, eppin administration resulted in decreased recruitment of neutrophils to the lung with a concomitant reduction in the levels of the neutrophil chemokine macrophage inflammatory protein-2.Overall, these results suggest a role for eppin outside of the reproductive tract and that eppin may have a role in the innate immune response in the lung., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

Objective: To develop, in Australian English, the first mixed-gender, multi-talker matrix sentence test., Design: Speech material consisted of a 50-word base matrix whose elements can be combined to form sentences of identical syntax but unpredictable content. Ten voices (five female and five male) were recorded for editing and preliminary level equalization. Elements were presented as single-talker sentences-in-noise during two perceptual tests: an optimization phase that provided the basis for further level correction, and an evaluation phase that perceptually validated those changes., Study Sample: Ten listeners participated in the optimization phase; these and an additional 32 naïve listeners completed the evaluation test. All were fluent in English and all but one had lived in Australia for >2 years., Results: Optimization reduced the standard deviation (SD) and speech reception threshold (SRT) range across all speech material (grand mean SRT = -10.6 dB signal-to-noise ratio, median = -10.8, SD =1.4, range =13.7, slope =19.3%/dB), yielding data consistent with cross-validated matrix tests in other languages. Intelligibility differences between experienced and naïve listeners were minimal., Conclusions: The Australian matrix corpus provides a robust set of test materials suitable for both clinical assessment and research into the dynamics of active listening in multi-talker environments.

Here we report the methods and output of a workshop examining possible futures of speech and hearing science out to 2030. Using a design thinking approach, a range of human-centered problems in communication were identified that could provide the motivation for a wide range of research. Nine main research programs were distilled and are summarized: (a) measuring brain and other physiological parameters, (b) auditory and multimodal displays of information, (c) auditory scene analysis, (d) enabling and understanding shared auditory virtual spaces, (e) holistic approaches to health management and hearing impairment, (f) universal access to evolving and individualized technologies, (g) biological intervention for hearing dysfunction, (h) understanding the psychosocial interactions with technology and other humans as mediated by technology, and (i) the impact of changing models of security and privacy. The design thinking approach attempted to link the judged level of importance of different research areas to the "end in mind" through empathy for the real-life problems embodied in the personas created during the workshop.

A natural auditory scene often contains sound moving at varying velocities. Using a velocity contrast paradigm, we compared sensitivity to velocity changes between continuous and discontinuous trajectories. Subjects compared the velocities of two stimulus intervals that moved along a single trajectory, with and without a 1 second inter stimulus interval (ISI). We found thresholds were threefold larger for velocity increases in the instantaneous velocity change condition, as compared to instantaneous velocity decreases or thresholds for the delayed velocity transition condition. This result cannot be explained by the current static "snapshot" model of auditory motion perception and suggest a continuous process where the percept of velocity is influenced by previous history of stimulation.

The location of a sound is derived computationally from acoustical cues rather than being inherent in the topography of the input signal, as in vision. Since Lord Rayleigh, the descriptions of that representation have swung between "labeled line" and "opponent process" models. Employing a simple variant of a two-point separation judgment using concurrent speech sounds, we found that spatial discrimination thresholds changed nonmonotonically as a function of the overall separation. Rather than increasing with separation, spatial discrimination thresholds first declined as two-point separation increased before reaching a turning point and increasing thereafter with further separation. This "dipper" function, with a minimum at 6 ° of separation, was seen for regions around the midline as well as for more lateral regions (30 and 45 °). The discrimination thresholds for the binaural localization cues were linear over the same range, so these cannot explain the shape of these functions. These data and a simple computational model indicate that the perception of auditory space involves a local code or multichannel mapping emerging subsequent to the binaural cue coding.

The growing availability of efficient and relatively inexpensive virtual auditory display technology has provided new research platforms to explore the perception of auditory motion. At the same time, deployment of these technologies in command and control as well as in entertainment roles is generating an increasing need to better understand the complex processes underlying auditory motion perception. This is a particularly challenging processing feat because it involves the rapid deconvolution of the relative change in the locations of sound sources produced by rotational and translations of the head in space (self-motion) to enable the perception of actual source motion. The fact that we perceive our auditory world to be stable despite almost continual movement of the head demonstrates the efficiency and effectiveness of this process. This review examines the acoustical basis of auditory motion perception and a wide range of psychophysical, electrophysiological, and cortical imaging studies that have probed the limits and possible mechanisms underlying this perception., (© The Author(s) 2016.)

The ability to actively follow a moving auditory target with our heads remains unexplored even though it is a common behavioral response. Previous studies of auditory motion perception have focused on the condition where the subjects are passive. The current study examined head tracking behavior to a moving auditory target along a horizontal 100° arc in the frontal hemisphere, with velocities ranging from 20 to 110°/s. By integrating high fidelity virtual auditory space with a high-speed visual presentation we compared tracking responses of auditory targets against visual-only and audio-visual "bisensory" stimuli. Three metrics were measured-onset, RMS, and gain error. The results showed that tracking accuracy (RMS error) varied linearly with target velocity, with a significantly higher rate in audition. Also, when the target moved faster than 80°/s, onset and RMS error were significantly worst in audition the other modalities while responses in the visual and bisensory conditions were statistically identical for all metrics measured. Lastly, audio-visual facilitation was not observed when tracking bisensory targets.

A recent study has demonstrated how the focus of auditory attention can rapidly shift to follow spectrally dynamic speech-like sounds in the presence of a similar interferer. This requires multidimensional variation in sound features and a minimum spacing in spectral feature space., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Following a multi-talker conversation relies on the ability to rapidly and efficiently shift the focus of spatial attention from one talker to another. The current study investigated the listening costs associated with shifts in spatial attention during conversational turn-taking in 16 normally-hearing listeners using a novel sentence recall task. Three pairs of syntactically fixed but semantically unpredictable matrix sentences, recorded from a single male talker, were presented concurrently through an array of three loudspeakers (directly ahead and +/-30° azimuth). Subjects attended to one spatial location, cued by a tone, and followed the target conversation from one sentence to the next using the call-sign at the beginning of each sentence. Subjects were required to report the last three words of each sentence (speech recall task) or answer multiple choice questions related to the target material (speech comprehension task). The reading span test, attention network test, and trail making test were also administered to assess working memory, attentional control, and executive function. There was a 10.7 ± 1.3% decrease in word recall, a pronounced primacy effect, and a rise in masker confusion errors and word omissions when the target switched location between sentences. Switching costs were independent of the location, direction, and angular size of the spatial shift but did appear to be load dependent and only significant for complex questions requiring multiple cognitive operations. Reading span scores were positively correlated with total words recalled, and negatively correlated with switching costs and word omissions. Task switching speed (Trail-B time) was also significantly correlated with recall accuracy. Overall, this study highlights (i) the listening costs associated with shifts in spatial attention and (ii) the important role of working memory in maintaining goal relevant information and extracting meaning from dynamic multi-talker conversations.