Use of inhaled corticosteroids and the risk of hospitalisation for pneumonia in children with asthma: a nationwide cohort study.

BACKGROUND: The potential association between the use of inhaled corticosteroids (ICS) and the risk of pneumonia among adults is disputed and paediatric-specific evidence is scarce. AIM: To assess the potential association between ICS, use and the risk of hospitalisation for pneumonia among children (age 2-17 years) with asthma. METHODS: This was a cohort study based on nationwide data from routine clinical practice in Sweden (January 2007 to November 2021). From 425 965 children with confirmed asthma, episodes of new ICS use and no use were identified using records of dispensed drugs. We adjusted for potential confounders with propensity score overlap weighting and the risk of a hospitalisation with pneumonia as primary diagnosis was estimated. Multiple subgroup and sensitivity analyses were also performed. RESULTS: We identified 249 351 ICS (mean follow-up of 0.9 years) and 214 840 no-use (mean follow-up of 0.7 years) episodes. During follow-up, 369 and 181 events of hospitalisation for pneumonia were observed in the ICS and no-use episodes, respectively. The weighted incidence rates of hospitalisation for pneumonia was 14.5 per 10 000 patient-years for ICS use episodes and 14.6 for no-use episodes. The weighted HR for hospitalisation for pneumonia associated with ICS use was 1.06 (95% CI 0.88 to 1.28) and the absolute rate difference was -0.06 (95% CI -2.83 to 2.72) events per 10 000 patient-years, compared with no use. CONCLUSIONS: In this nationwide cohort study, we found no evidence of an association between ICS use and the risk of hospitalisation for pneumonia among children with asthma, as compared with no use.

Second-language word recognition in noise: Interdependent neuromodulatory effects of semantic context and crosslinguistic interactions driven by word form similarity.

Spoken language comprehension is a fundamental component of our cognitive skills. We are quite proficient at deciphering words from the auditory input despite the fact that the speech we hear is often masked by noise such as background babble originating from talkers other than the one we are attending to. To perceive spoken language as intended, we rely on prior linguistic knowledge and context. Prior knowledge includes all sounds and words that are familiar to a listener and depends on linguistic experience. For bilinguals, the phonetic and lexical repertoire encompasses two languages, and the degree of overlap between word forms across languages affects the degree to which they influence one another during auditory word recognition. To support spoken word recognition, listeners often rely on semantic information (i.e., the words we hear are usually related in a meaningful way). Although the number of multilinguals across the globe is increasing, little is known about how crosslinguistic effects (i.e., word overlap) interact with semantic context and affect the flexible neural systems that support accurate word recognition. The current multi-echo functional magnetic resonance imaging (fMRI) study addresses this question by examining how prime-target word pair semantic relationships interact with the target word's form similarity (cognate status) to the translation equivalent in the dominant language (L1) during accurate word recognition of a non-dominant (L2) language. We tested 26 early-proficient Spanish-Basque (L1-L2) bilinguals. When L2 targets matching L1 translation-equivalent phonological word forms were preceded by unrelated semantic contexts that drive lexical competition, a flexible language control (fronto-parietal-subcortical) network was upregulated, whereas when they were preceded by related semantic contexts that reduce lexical competition, it was downregulated. We conclude that an interplay between semantic and crosslinguistic effects regulates flexible control mechanisms of speech processing to facilitate L2 word recognition, in noise.

Phonemic contrasts under construction? Evidence from Basque.

Attunement theories of speech perception development suggest that native-language exposure is one of the main factors shaping infants' phonemic discrimination capacity within the second half of their first year. Here, we focus on the role of acoustic-perceptual salience and language-specific experience by assessing the discrimination of acoustically subtle Basque sibilant contrasts. We used the infant-controlled version of the habituation procedure to assess discrimination in 6- to 7-month and 11- to 12-month-old infants who varied in their amount of exposure to Basque and Spanish. We observed no significant variation in the infants' discrimination behavior as a function of their linguistic experience. Infants in both age-groups exhibited poor discrimination, consistent with Basque adults finding these contrasts more difficult than some others. Our findings are in agreement with previous research showing that perceptual discrimination of subtle speech sound contrasts may follow a different developmental trajectory, where increased native-language exposure seems to be a requisite.

Prediction of Agreement and Phonetic Overlap Shape Sublexical Identification.

The mapping between the physical speech signal and our internal representations is rarely straightforward. When faced with uncertainty, higher-order information is used to parse the signal and because of this, the lexicon and some aspects of sentential context have been shown to modulate the identification of ambiguous phonetic segments. Here, using a phoneme identification task (i.e., participants judged whether they heard [o] or [a] at the end of an adjective in a noun-adjective sequence), we asked whether grammatical gender cues influence phonetic identification and if this influence is shaped by the phonetic properties of the agreeing elements. In three experiments, we show that phrase-level gender agreement in Spanish affects the identification of ambiguous adjective-final vowels. Moreover, this effect is strongest when the phonetic characteristics of the element triggering agreement and the phonetic form of the agreeing element are identical. Our data are consistent with models wherein listeners generate specific predictions based on the interplay of underlying morphosyntactic knowledge and surface phonetic cues.

Lexical representations are malleable for about one second: Evidence for the non-automaticity of perceptual recalibration.

In listening to speech, people have been shown to apply several types of adjustment to their phonemic categories that take into account variations in the prevailing linguistic environment. These adjustments include selective adaptation, lexically driven recalibration, and audiovisually determined recalibration. Prior studies have used dual task procedures to test whether these adjustments are automatic or if they require attention, and all of these tests have supported automaticity. The current study instead uses a method of targeted distraction to demonstrate that lexical recalibration does in fact require attention. Building on this finding, the targeted distraction method is used to measure the period of time during which the lexical percept remains malleable. The results support a processing window of approximately one second, consistent with the results of a small number of prior studies that bear on this question. The results also demonstrate that recalibration is closely linked to the completion of lexical access.

How lexical is the lexicon? Evidence for integrated auditory memory representations.

Previous research has shown that lexical representations must include not only linguistic information (what word was said), but also indexical information (how it was said, and by whom). The present work demonstrates that even this expansion is not sufficient. Seemingly irrelevant information, such as an unattended background sound, is retained in memory and can facilitate subsequent speech perception. We presented participants with spoken words paired with environmental sounds (e.g., a phone ringing), and had them make an "animate/inanimate" decision for each word. Later performance identifying filtered versions of the words was impaired to a similar degree if the voice changed or if the environmental sound changed. Moreover, when quite dissimilar words were used at exposure and test, we observed the same result when we reversed the roles of the words and the environmental sounds. The experiments also demonstrated limits to these effects, with no benefit from repetition. Theoretically, our results support two alternative possibilities: (1) Lexical representations are memory representations, and are not walled off from those for other sounds. Indexical effects reflect simply one type of co-occurrence that is incorporated into such representations. (2) The existing literature on indexical effects does not actually bear on lexical representations - voice changes, like environmental sounds heard with a word, produce implicit memory effects that are not tied to the lexicon. We discuss the evidence and implications of these two theoretical alternatives.

The relationship of speech perception and speech production: It's complicated.

A widely held belief is that speech perception and speech production are tightly linked, with each modality available to help with learning in the other modality. This positive relationship is often summarized as perception and production being "two sides of the same coin." There are, indeed, many situations that have shown this mutually supportive relationship. However, there is a growing body of research showing very different results, with the modalities operating independently, or even in opposition to each other. We review the now-sizeable literature demonstrating the negative effect that speech production can have on perceptual learning of speech, at multiple levels (particularly at the lexical and sublexical levels). By comparing the situations that show this pattern with ones in which more positive interactions occur, we provide an initial account of why the different outcomes are found, identifying factors that lead to either positive or negative effects of production on perception. The review clarifies the complex relationship that exists between the two modalities: They are indeed linked, but their relationship is more complicated than is suggested by the notion that they are two sides of the same coin.

When Jack isn't Jacques: Simultaneous opposite language-specific speech perceptual learning in French-English bilinguals.

Humans are remarkably good at understanding spoken language, despite the huge variability of the signal as a function of the talker, the situation, and the environment. This success relies on having access to stable representations based on years of speech input, coupled with the ability to adapt to short-term deviations from these norms, e.g. accented speech or speech altered by ambient noise. In the last two decades, there has been a robust research effort focused on a possible mechanism for adjusting to accented speech. In these studies, listeners typically hear 15 - 20 words in which a speech sound has been altered, creating a short-term deviation from its longer-term representation. After exposure to these items, listeners demonstrate "lexically driven phonetic recalibration"-they alter their categorization of speech sounds, expanding a speech category to take into account the recently heard deviations from their long-term representations. In the current study, we investigate such adjustments by bilingual listeners. French-English bilinguals were first exposed to nonstandard pronunciations of a sound (/s/ or /f/) in one language and tested for recalibration in both languages. Then, the exposure continued with both the original type of mispronunciation in the same language, plus mispronunciations in the other language, in the opposite direction. In a final test, we found simultaneous recalibration in opposite directions for the two languages-listeners shifted their French perception in one direction and their English in the other: Bilinguals can maintain separate adjustments, for the same sounds, when a talker's speech differs across two languages.

Phylogenetic and pathotypic characterization of newcastle disease viruses circulating in west Africa and efficacy of a current vaccine.

Newcastle disease (ND) is a deadly avian disease worldwide. In Africa, ND is enzootic and causes large economic losses, but little is known about the Newcastle disease virus (NDV) strains circulating in African countries. In this study, 27 NDV isolates collected from apparently healthy chickens in live-bird markets of the West African countries Benin and Togo in 2009 were characterized. All isolates had polybasic fusion (F)-protein cleavage sites and were shown to be highly virulent in standard pathogenicity assays. Infection of 2-week-old chickens with two of the isolates resulted in 100% mortality within 4 days. Phylogenetic analysis of the 27 isolates based on a partial F-protein gene sequence identified three clusters: one containing all the isolates from Togo and one from Benin (cluster 2), one containing most isolates from Benin (cluster 3), and an outlier isolate from Benin (cluster 1). All the three clusters are related to genotype VII strains of NDV. In addition, the cluster of viruses from Togo contained a recently identified 6-nucleotide insert between the hemagglutinin-neuraminidase (HN) and large polymerase (L) genes in a complete genome of an NDV isolate from this geographical region. Multiple strains that include this novel element suggest local emergence of a new genome length class. These results reveal genetic diversity within and among local NDV populations in Africa. Sequence analysis showed that the F and HN proteins of six West African isolates share 83.2 to 86.6% and 86.5 to 87.9% identities, respectively, with vaccine strain LaSota, indicative of considerable diversity. A vaccine efficacy study showed that the LaSota vaccine protected birds from morbidity and mortality but did not prevent shedding of West African challenge viruses.

Complete genome sequences of Newcastle disease virus strains circulating in chicken populations of Indonesia.

Eight highly virulent Newcastle disease virus (NDV) strains were isolated from vaccinated commercial chickens in Indonesia during outbreaks in 2009 and 2010. The complete genome sequences of two NDV strains and the sequences of the surface protein genes (F and HN) of six other strains were determined. Phylogenetic analysis classified them into two new subgroups of genotype VII in the class II cluster that were genetically distinct from vaccine strains. This is the first report of complete genome sequences of NDV strains isolated from chickens in Indonesia.

Complete genome sequence of a novel Newcastle disease virus strain isolated from a chicken in West Africa.

The complete genome sequence of an African Newcastle disease virus (NDV) strain isolated from a chicken in Togo in 2009 was determined. The genome is 15,198 nucleotides (nt) in length and is classified in genotype VII in the class II cluster. Compared to common vaccine strains, the African strain contains a previously described 6-nt insert in the downstream untranslated region of the N gene and a novel 6-nt insert in the HN-L intergenic region. Genome length differences are a marker of the natural history of NDV. This is the first description of a class II NDV strain with a genome of 15,198 nt and a 6-nt insert in the HN-L intergenic region. Sequence divergence relative to vaccine strains was substantial, likely contributes to outbreaks, and illustrates the continued evolution of new NDV strains in West Africa.

Bad maps may not always get you lost: Lexically driven perceptual recalibration for substituted phonemes.

The speech perception system adjusts its phoneme categories based on the current speech input and lexical context. This is known as lexically driven perceptual recalibration, and it is often assumed to underlie accommodation to non-native accented speech. However, recalibration studies have focused on maximally ambiguous sounds (e.g., a sound ambiguous between "sh" and "s" in a word like "superpower"), a scenario that does not represent the full range of variation present in accented speech. Indeed, non-native speakers sometimes completely substitute a phoneme for another, rather than produce an ambiguous segment (e.g., saying "shuperpower"). This has been called a "bad map" in the literature. In this study, we scale up the lexically driven recalibration paradigm to such cases. Because previous research suggests that the position of the critically accented phoneme modulates the success of recalibration, we include such a manipulation in our study. And to ensure that participants treat all critical items as words (an important point for successful recalibration), we use a new exposure task that incentivizes them to do so. Our findings suggest that while recalibration is most robust after exposure to ambiguous sounds, it also occurs after exposure to bad maps. But interestingly, positional effects may be reversed: recalibration was more likely for ambiguous sounds late in words, but more likely for bad maps occurring early in words. Finally, a comparison of an online versus in-lab version of these conditions shows that experimental setting may have a non-trivial effect on the results of recalibration studies.

Risk factors for severe respiratory syncytial virus infection during the first year of life: development and validation of a clinical prediction model.

BACKGROUND: Novel immunisation methods against respiratory syncytial virus (RSV) are emerging, but knowledge of risk factors for severe RSV disease is insufficient for optimal targeting of interventions against them. Our aims were to identify predictors for RSV hospital admission from registry-based data and to develop and validate a clinical prediction model to guide RSV immunoprophylaxis for infants younger than 1 year. METHODS: In this model development and validation study, we studied all infants born in Finland between June 1, 1997, and May 31, 2020, and in Sweden between June 1, 2006, and May 31, 2020, along with the data for their parents and siblings. Infants were excluded if they died or were admitted to hospital for RSV within the first 7 days of life. The outcome was hospital admission due to RSV bronchiolitis during the first year of life. The Finnish study population was divided into a development dataset (born between June 1, 1997, and May 31, 2017) and a temporal hold-out validation dataset (born between June 1, 2017, and May 31, 2020). The development dataset was used for predictor discovery and selection in which we screened 1511 candidate predictors from the infants', parents', and siblings' data, and developed a logistic regression model with the 16 most important predictors. This model was then validated using the Finnish hold-out validation dataset and the Swedish dataset. FINDINGS: In total, there were 1 124 561 infants in the Finnish development dataset, 130 352 infants in the Finnish hold-out validation dataset, and 1 459 472 infants in the Swedish dataset. In addition to known predictors such as severe congenital heart defects (adjusted odds ratio 2·89, 95% CI 2·28-3·65), we confirmed some less established predictors for RSV hospital admission, most notably oesophageal malformations (3·11, 1·86-5·19) and lower complexity congenital heart defects (1·43, 1·25-1·63). The prediction model's C-statistic was 0·766 (95% CI 0·742-0·789) in Finnish data and 0·737 (0·710-0·762) in Swedish validation data. The infants in the highest decile of predicted RSV hospital admission probability had 4·5 times higher observed risk compared with others. Calibration varied according to epidemic intensity. The model's performance was similar to a machine learning (XGboost) model using all 1511 candidate predictors (C-statistic in Finland 0·771, 95% CI 0·754-0·788). The prediction model showed clinical utility in decision curve analysis and in hypothetical number needed to treat calculations for immunisation, and its C-statistic was similar across different strata of parental income. INTERPRETATION: The identified predictors and the prediction model can be used in guiding RSV immunoprophylaxis in infants, or as a basis for further immunoprophylaxis targeting tools. FUNDING: Sigrid Jusélius Foundation, European Research Council, Pediatric Research Foundation, and Academy of Finland.

Roles of the fusion and hemagglutinin-neuraminidase proteins in replication, tropism, and pathogenicity of avian paramyxoviruses.

Virulent and moderately virulent strains of Newcastle disease virus (NDV), representing avian paramyxovirus serotype 1 (APMV-1), cause respiratory and neurological disease in chickens and other species of birds. In contrast, APMV-2 is avirulent in chickens. We investigated the role of the fusion (F) and hemagglutinin-neuraminidase (HN) envelope glycoproteins in these contrasting phenotypes by designing chimeric viruses in which the F and HN glycoproteins or their ectodomains were exchanged individually or together between the moderately virulent, neurotropic NDV strain Beaudette C (BC) and the avirulent APMV-2 strain Yucaipa. When we attempted to exchange the complete F and HN glycoproteins individually and together between the two viruses, the only construct that could be recovered was recombinant APMV-2 strain Yucaipa (rAPMV-2), containing the NDV F glycoprotein in place of its own. This substitution of NDV F into APMV-2 was sufficient to confer the neurotropic, neuroinvasive, and neurovirulent phenotypes, in spite of all being at reduced levels compared to what was seen for NDV-BC. When the ectodomains of F and HN were exchanged individually and together, two constructs could be recovered: NDV, containing both the F and HN ectodomains of APMV-2; and APMV-2, containing both ectodomains of NDV. This supported the idea that homologous cytoplasmic tails and matched F and HN ectodomains are important for virus replication. Analysis of these viruses for replication in vitro, syncytium formation, mean embryo death time, intracerebral pathogenicity index, and replication and tropism in 1-day-old chicks and 2-week-old chickens showed that the two contrasting phenotypes of NDV and APMV-2 could largely be transferred between the two backbones by transfer of homotypic F and HN ectodomains. Further analysis provided evidence that the homologous stalk domain of NDV HN is essential for virus replication, while the globular head domain of NDV HN could be replaced with that of APMV-2 with only a minimal attenuating effect. These results demonstrate that the F and HN ectodomains together determine the cell fusion, tropism, and virulence phenotypes of NDV and APMV-2 and that the regions of HN that are critical to replication and the species-specific phenotypes include the cytoplasmic tail and stalk domain but not the globular head domain.

Speech perception.

Speech perception has been studied for over a half century. During this time, one subfield has examined perception of phonetic information independent of its contribution to word recognition. Theories in this subfield include ones that are based on auditory properties of speech, the motor commands involved in speech production, and a Direct Realist approach that emphasizes the structure of the information reaching the perceiver. A second subfield has been less concerned with the acoustic-phonetic properties of speech and more concerned with how words are segmented and recognized. In this subfield, there has been a focus on the nature of communication among different levels of analysis (e.g., phonetic and lexical). In recent years, there has been a growing appreciation of the need to understand how the perceptual system dynamically changes in order to allow listeners to successfully process the variable input and new words that they constantly encounter.

Reconciling the contradictory effects of production on word learning: Production may help at first, but it hurts later.

Does saying a novel word help to recognize it later? Previous research on the effect of production on this aspect of word learning is inconclusive, as both facilitatory and detrimental effects of production are reported. In a set of three experiments, we sought to reconcile the seemingly contrasting findings by disentangling the production from other effects. In Experiment 1, participants learned eight new words and their visual referents. On each trial, participants heard a novel word twice: either (a) by hearing the same speaker produce it twice (Perception-Only condition) or (b) by first hearing the speaker once and then producing it themselves (Production condition). At test, participants saw two pictures while hearing a novel word and were asked to choose its correct referent. Experiment 2 was identical to Experiment 1, except that in the Perception-Only condition each word was spoken by 2 different speakers (equalizing talker variability between conditions). Experiment 3 was identical to Experiment 2, but at test words were spoken by a novel speaker to assess generalizability of the effect. Accuracy, reaction time, and eye-movements to the target image were collected. Production had a facilitatory effect during early stages of learning (after short training), but its effect became detrimental after additional training. The results help to reconcile conflicting findings regarding the role of production on word learning. This work is relevant to a wide range of research on human learning in showing that the same factor may play a different role at different stages of learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Just give it time: Differential effects of disruption and delay on perceptual learning.

Speech perception and production are critical skills when acquiring a new language. However, the nature of the relationship between these two processes is unclear, particularly for non-native speech sound contrasts. Although it has been assumed that perception and production are supportive, recent evidence has demonstrated that, under some circumstances, production can disrupt perceptual learning. Specifically, producing the to-be-learned contrast on each trial can disrupt perceptual learning of that contrast. Here, we treat speech perception and speech production as separate tasks. From this perspective, perceptual learning studies that include a production component on each trial create a task switch. We report two experiments that test how task switching can disrupt perceptual learning. One experiment demonstrates that the disruption caused by switching to production is sensitive to time delays: Increasing the delay between perception and production on a trial can reduce and even eliminate disruption of perceptual learning. The second experiment shows that if a task other than producing the to-be-learned contrast is imposed, the task-switching component of disruption is not influenced by a delay. These experiments provide a new understanding of the relationship between speech perception and speech production, and clarify conditions under which the two cooperate or compete.

Intermodality differences in statistical learning: phylogenetic and ontogenetic influences.

In Basque-Spanish bilinguals, statistical learning (SL) in the visual modality was more efficient on nonlinguistic than linguistic input; in the auditory modality, we found the reverse pattern of results. We hypothesize that SL was shaped for processing nonlinguistic environmental stimuli and only later, as the language faculty emerged, recycled for speech processing. This led to further adaptive changes in the neurocognitive mechanisms underlying speech processing, including SL. By contrast, as a recent cultural innovation, written language has not yet led to adaptations. The current study investigated whether such phylogenetic influences on SL can be modulated by ontogenetic influences on a shorter timescale, over the course of individual development. We explored how SL is modulated by the ambient linguistic environment. We found that SL in the auditory modality can be further modulated by exposure to a bilingual environment, in which speakers need to process a wider range of diverse speech cues. This effect was observed only on linguistic, not nonlinguistic, material. We conclude that ontogenetic factors modulate the efficiency of already existing SL ability, honing it for specific types of input, by providing new targets for selection via exposure to different cues in the sensory input.

Lexico-semantic access and audiovisual integration in the aging brain: Insights from mixed-effects regression analyses of event-related potentials.

We investigated how aging modulates lexico-semantic processes in the visual (seeing written items), auditory (hearing spoken items) and audiovisual (seeing written items while hearing congruent spoken items) modalities. Participants were young and older adults who performed a delayed lexical decision task (LDT) presented in blocks of visual, auditory, and audiovisual stimuli. Event-related potentials (ERPs) revealed differences between young and older adults despite older adults' ability to identify words and pseudowords as accurately as young adults. The observed differences included more focalized lexico-semantic access in the N400 time window in older relative to young adults, stronger re-instantiation and/or more widespread activity of the lexicality effect at the time of responding, and stronger multimodal integration for older relative to young adults. Our results offer new insights into how functional neural differences in older adults can result in efficient access to lexico-semantic representations across the lifespan.