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Speech is perceived relative to the speech rate in the context. It is unclear, however, what information listeners use to compute speech rate. The present study examines whether listeners use the number of syllables per unit time (i.e., syllable rate) as a measure of speech rate, as indexed by subsequent vowel perception. We ran two rate-normalization experiments in which participants heard duration-matched word lists that contained either monosyllabic vs. bisyllabic words (Experiment 1), or monosyllabic vs. trisyllabic pseudowords (Experiment 2). The participants’ task was to categorize an /ɑ-aː/ continuum that followed the word lists. The monosyllabic condition was perceived as slower (i.e., fewer /aː/ responses) than the bisyllabic and trisyllabic condition. However, no difference was observed between bisyllabic and trisyllabic contexts. Therefore, while syllable rate is used in perceiving speech rate, other factors, such as fast speech processes, mean F0, and intensity, must also influence rate normalization.

Over the course of a conversation, interlocutors sound more and more like each other in a process called convergence. However, the automaticity and grain size of convergence are not well established. This study therefore examined whether female native Dutch speakers converge to large yet sub-phonemic shifts in the F2 of the vowel /e/. Participants first performed a short reading task to establish baseline F2s for the vowel /e/, then shadowed 120 target words (alongside 360 fillers) which contained one instance of a manipulated vowel /e/ where the F2 had been shifted down to that of the vowel /ø/. Consistent exposure to large (sub-phonemic) downward shifts in F2 did not result in convergence. The results raise issues for theories which view convergence as a product of automatic integration between perception and production.

During listening, brain activity tracks the rhythmic structures of speech signals. Here, we directly dissociated the contribution of neural envelope tracking in the processing of speech acoustic cues from that related to linguistic processing. We examined the neural changes associated with the comprehension of Noise-Vocoded (NV) speech using magnetoencephalography (MEG). Participants listened to NV sentences in a 3-phase training paradigm: (1) pre-training, where NV stimuli were barely comprehended, (2) training with exposure of the original clear version of speech stimulus, and (3) post-training, where the same stimuli gained intelligibility from the training phase. Using this paradigm, we tested if the neural responses of a speech signal was modulated by its intelligibility without any change in its acoustic structure. To test the influence of spectral degradation on neural envelope tracking independently of training, participants listened to two types of NV sentences (4-band and 2-band NV speech), but were only trained to understand 4-band NV speech. Significant changes in neural tracking were observed in the delta range in relation to the acoustic degradation of speech. However, we failed to find a direct effect of intelligibility on the neural tracking of speech envelope in both theta and delta ranges, in both auditory regions-of-interest and whole-brain sensor-space analyses. This suggests that acoustics greatly influence the neural tracking response to speech envelope, and that caution needs to be taken when choosing the control signals for speech-brain tracking analyses, considering that a slight change in acoustic parameters can have strong effects on the neural tracking response.

Additional file 4. Example of the Icelandic word familiarization and grammar training tasks.

Additional file 1. Overview of adaptive set-up of the artificial language learning task.

Additional file 2. List of Icelandic nouns.

Additional file 3. Icelandic grammar rules.

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention., In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.

CONTEXT: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism. OBJECTIVE: This work aimed to study cortisol metabolism during DR-HC and TID-HC. DESIGN: A randomized, 12-week, crossover study was conducted. INTERVENTION AND PARTICIPANTS: DC-HC and same daily dose of TID-HC were administered to patients with primary adrenal insufficiency (n = 50) vs healthy individuals (n = 124) as controls. MAIN OUTCOME MEASURES: Urinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections. RESULTS: Total cortisol metabolites decreased during DR-HC compared to TID-HC (P Funding: Swedish Research CouncilSwedish Research CouncilEuropean Commission [2015-02561]; Swedish federal government under the LUA/ALF agreement [ALFGBG-719531]; Shire International GmbH [SWE_000991]; FRM (Fondation pour la Recherche Medicale)Fondation pour la Recherche Medicale

The GluN2 subtype (2A versus 2B) determines biophysical properties and signaling of forebrain NMDA receptors (NMDARs). During development, GluN2A becomes incorporated into previously GluN2B-dominated NMDARs. This “switch” is proposed to be driven by distinct features of GluN2 cytoplasmic C-terminal domains (CTDs), including a unique CaMKII interaction site in GluN2B that drives removal from the synapse. However, these models remain untested in the context of endogenous NMDARs. We show that, although mutating the endogenous GluN2B CaMKII site has secondary effects on GluN2B CTD phosphorylation, the developmental changes in NMDAR composition occur normally and measures of plasticity and synaptogenesis are unaffected. Moreover, the switch proceeds normally in mice that have the GluN2A CTD replaced by that of GluN2B and commences without an observable decline in GluN2B levels but is impaired by GluN2A haploinsufficiency. Thus, GluN2A expression levels, and not GluN2 subtype-specific CTD-driven events, are the overriding factor in the developmental switch in NMDAR composition.

Speaking is a complex motor skill which requires near instantaneous integration of sensory and motor-related information. Current theory hypothesizes a complex interplay between motor and auditory processes during speech production, involving the online comparison of the speech output with an internally generated forward model. To examine the neural correlates of this intricate interplay between sensory and motor processes, the current study uses altered auditory feedback (AAF) in combination with magnetoencephalography (MEG). Participants vocalized the vowel/e/and heard auditory feedback that was temporarily pitch-shifted by only 25 cents, while neural activity was recorded with MEG. As a control condition, participants also heard the recordings of the same auditory feedback that they heard in the first half of the experiment, now without vocalizing. The participants were not aware of any perturbation of the auditory feedback. We found auditory cortical areas responded more strongly to the pitch shifts during vocalization. In addition, auditory feedback perturbation resulted in spectral power increases in the θ and lower β bands, predominantly in sensorimotor areas. These results are in line with current models of speech production, suggesting auditory cortical areas are involved in an active comparison between a forward model's prediction and the actual sensory input. Subsequently, these areas interact with motor areas to generate a motor response. Furthermore, the results suggest that θ and β power increases support auditory-motor interaction, motor error detection and/or sensory prediction processing.

The healthcare sector stands to benefit most from frugal innovation, the idea that more can be done for less for many more people, globally. As a first step for health systems to leverage new approaches to offset escalating health expenditures and to improve health outcomes, the most relevant frugal innovations have to be found. The Institute of Global Health Innovation was commissioned by the US-based Commonwealth Fund to identify frugal innovations from around the world that could, if transferred to the USA, offer approaches for expanding access to care and dramatically lower costs. Our global scan was motivated by the need to extend the list of frugal innovations in healthcare beyond the impressive but oft-repeated examples such as GE’s MAC 400, a US$800 portable ECG machine, Narayana’s US$1500 cardiac surgery and Aravind’s US$30 cataract surgery. Our search involved (1) scanning innovation databases, (2) refining frameworks to identify frugal innovations and evaluate their reverse potential and (3) developing in-depth case studies. From 520 possible innovations, we shortlisted 16 frugal innovations that we considered as frugal and with potential for reverse diffusion into high-income country health systems. Our global search was narrowed down to three care delivery models for case analysis: The Brazilian Family Health Strategy around community health workers; Singapore-based GeriCare@North use of telemedicine and Brazil’s Saude Crianca community involvement and citizenship programme. We share core features of the three frugal innovations and outline lessons for practitioners, scholars and policymakers seeking to lower healthcare costs while increasing access and quality.

The National Air Quality Forecast Capability (NAQFC) project provides the US with operational and experimental real-time ozone predictions using two different versions of the three-dimensional Community Multi-scale Air Quality (CMAQ) modeling system. Routine evaluation using near-real-time AIRNow ozone measurements through 2011 showed better performance of the operational ozone predictions. In this work, quality-controlled and -assured Air Quality System (AQS) ozone and nitrogen dioxide (NO2) observations are used to evaluate the experimental predictions in 2010. It is found that both ozone and NO2 are overestimated over the contiguous US (CONUS), with annual biases of +5.6 and +5.1 ppbv, respectively. The annual root mean square errors (RMSEs) are 15.4 ppbv for ozone and 13.4 ppbv for NO2. For both species the overpredictions are most pronounced in the summer. The locations of the AQS monitoring sites are also utilized to stratify comparisons by the degree of urbanization. Comparisons for six predefined US regions show the highest annual biases for ozone predictions in Southeast (+10.5 ppbv) and for NO2 in the Lower Middle (+8.1 ppbv) and Pacific Coast (+7.1 ppbv) regions. The spatial distributions of the NO2 biases in August show distinctively high values in the Los Angeles, Houston, and New Orleans areas. In addition to the standard statistics metrics, daily maximum eight-hour ozone categorical statistics are calculated using the current US ambient air quality standard (75 ppbv) and another lower threshold (70 ppbv). Using the 75 ppbv standard, the hit rate and proportion of correct over CONUS for the entire year are 0.64 and 0.96, respectively. Summertime biases show distinctive weekly patterns for ozone and NO2. Diurnal comparisons show that ozone overestimation is most severe in the morning, from 07:00 to 10:00 local time. For NO2, the morning predictions agree with the AQS observations reasonably well, but nighttime concentrations are overpredicted by around 100%.

We investigated music and language processing in a group of early bilinguals who spoke a tone language and a non-tone language (Cantonese and Dutch). We assessed online speech-music processing interactions, that is, interactions that occur when speech and music are processed simultaneously in songs, with a speeded classification task. In this task, participants judged sung pseudowords either musically (based on the direction of the musical interval) or phonologically (based on the identity of the sung vowel). We also assessed longer-term effects of linguistic experience on musical ability, that is, the influence of extensive prior experience with language when processing music. These effects were assessed with a task in which participants had to learn to identify musical intervals and with four pitch-perception tasks. Our hypothesis was that due to their experience in two different languages using lexical versus intonational tone, the early Cantonese-Dutch bilinguals would outperform the Dutch control participants. In online processing, the Cantonese-Dutch bilinguals processed speech and music more holistically than controls. This effect seems to be driven by experience with a tone language, in which integration of segmental and pitch information is fundamental. Regarding longer-term effects of linguistic experience, we found no evidence for a bilingual advantage in either the music-interval learning task or the pitch-perception tasks. Together, these results suggest that being a Cantonese-Dutch bilingual does not have any measurable longer-term effects on pitch and music processing, but does have consequences for how speech and music are processed jointly.

Reading is an audiovisual process that requires the learning of systematic links between graphemes and phonemes. It is thus possible that reading impairments reflect an audiovisual processing deficit. In this study, we compared audiovisual processing in adults with developmental dyslexia and adults without reading difficulties. We focused on differences in cross-modal temporal sensitivity both for speech and for non-speech events. When compared to adults without reading difficulties, adults with developmental dyslexia presented a wider temporal window in which unsynchronized speech events were perceived as synchronized. No differences were found between groups for the non-speech events. These results suggests a deficit in dyslexia in the perception of cross-modal temporal synchrony for speech events.