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OBJECTIVES: Audiometric testing typically does not include frequencies above 8 kHz. However, recent research suggests that extended high-frequency (EHF) sensitivity could affect hearing in natural communication environments. Clinical assessment of hearing often employs pure tones and frequency-modulated (FM) tones interchangeably regardless of frequency. The present study was designed to evaluate how the stimulus chosen to measure EHF thresholds affects estimates of hearing sensitivity. DESIGN: The first experiment used standard audiometric procedures to measure 8- and 16-kHz thresholds for 5- to 28-year olds with normal hearing in the standard audiometric range (250 to 8000 Hz). Stimuli were steady tones, pulsed tones, and FM tones. The second experiment tested 18- to 28-year olds with normal hearing in the standard audiometric range using psychophysical procedures to evaluate how changes in sensitivity as a function of frequency affect detection of stimuli that differ with respect to bandwidth, including bands of noise. Thresholds were measured using steady tones, pulsed tones, FM tones, narrow bands of noise, and one-third-octave bands of noise at a range of center frequencies in one ear. RESULTS: In experiment 1, thresholds improved with increasing age at 8 kHz and worsened with increasing age at 16 kHz. Thresholds for individual participants were relatively similar for steady, pulsed, and FM tones at 8 kHz. At 16 kHz, mean thresholds were approximately 5 dB lower for FM tones than for steady or pulsed tones. This stimulus effect did not differ as a function of age. Experiment 2 replicated this greater stimulus effect at 16 kHz than at 8 kHz and showed that the slope of the audibility curve accounted for these effects. CONCLUSIONS: Contrary to prior expectations, there was no evidence that the choice of stimulus type affected school-age children more than adults. For individual participants, audiometric thresholds at 16 kHz were as much as 20 dB lower for FM tones than for steady tones. Threshold differences across stimuli at 16 kHz were predicted by differences in audibility across frequency, which can vary markedly between listeners. These results highlight the importance of considering spectral width of the stimulus used to evaluate EHF thresholds.
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Audiometria , Audição , Adulto , Criança , Humanos , Adolescente , Limiar Auditivo , Audiometria/métodos , Ruído , Testes AuditivosRESUMO
PURPOSE: Common clinical application of auditory brainstem response (ABR) testing is limited to 0.25-4 kHz. Prior research has demonstrated associations between ABR and behavioral thresholds for tone burst stimuli > 4 kHz in adults, but there are no comparable data for children. The ability to predict behavioral thresholds > 4 kHz clinically based on the ABR would provide valuable audiologic information for individuals who are unable to provide behavioral thresholds. This study included children with hearing loss and children with normal hearing to determine the association between ABR and behavioral thresholds at 6 and 8 kHz. METHOD: ABR and behavioral thresholds were obtained for children ages 4.7-16.7 years (M = 10.5, SD = 3.4) with sensorineural hearing loss (n = 24) or normal hearing sensitivity (n = 16) and for adults ages 18.4-54.4 years (M = 32.7, SD = 10.4) with sensorineural hearing loss (n = 13) or normal hearing sensitivity (n = 11). Thresholds obtained for 6 and 8 kHz using ABR and conventional audiometry were compared. RESULTS: Differences between ABR and behavioral thresholds averaged 5-6 dB for both children and adults for both test frequencies, with differences of ≤ 20 dB in all instances. Linear mixed modeling for data from participants with hearing loss suggested that ABR threshold is a good predictor of behavioral threshold at 6 and 8 kHz for both children and adults. Test specificity was 100%; no participants with behavioral thresholds ≤ 20 dB HL had ABR thresholds > 25 dB nHL. CONCLUSIONS: Initial evidence suggests that ABR testing at 6 and 8 kHz is reliable for estimating behavioral threshold in listeners with hearing loss and accurately identifies normal hearing sensitivity. The results of this study contribute to efforts to improve outcomes for vulnerable populations by reducing barriers to clinical implementation of ABR testing at > 4 kHz.
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Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Adulto , Criança , Humanos , Audiometria/métodos , Audiometria de Tons Puros/métodos , Limiar Auditivo/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva Neurossensorial/diagnóstico , Pré-Escolar , Adolescente , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Individuals with Down syndrome are known to have high rates of hearing loss, but it is unclear how this impacts their ability to communicate and function in real-world environments. METHODS: Sixteen English-speaking and Spanish-speaking mothers of individuals with Down syndrome ages 6-40 years participated in individual, semi-structured interviews using a videoconferencing platform. Session transcripts were analysed using applied thematic analysis. RESULTS: Mothers described listening environments, the impact of hearing on daily life, barriers to successful listening, and strategies to overcome communication barriers for their children with Down syndrome. CONCLUSIONS: Hearing was largely discussed in terms of challenges and detriments, suggesting that hearing experiences are predominately considered to negatively impact the functional abilities of individuals with Down syndrome. Background noise and hearing loss were sources of communication difficulties. Parent-reported barriers and strategies can inform ecologically valid research priorities aimed at improving outcomes for individuals with Down syndrome.
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Síndrome de Down , Perda Auditiva , Deficiência Intelectual , Criança , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Mães , AudiçãoRESUMO
OBJECTIVE: The purpose of this study was to 1) characterise word recognition in a speech masker for preschoolers tested using closed-set, forced-choice procedures and 2) better understand the stimulus and listener factors affecting performance. DESIGN: Speech recognition thresholds (SRTs) in a two-talker masker were evaluated using a picture-pointing response with two sets of disyllabic target words. ChEgSS words were previously developed for children ≥5 years of age, and simple words were developed for preschoolers. Familiarisation ensured accurate identification of target words before testing. STUDY SAMPLE: Participants were 3- and 4-year olds (n = 21) and young adults (n = 10) with normal hearing. RESULTS: Preschoolers and adults had significantly lower SRTs for the simple words than the ChEgSS words, and lower SRTs for early-acquired than later-acquired ChEgSS words. For both word sets, SRTs were approximately 11-dB higher for preschoolers than adults, and child age was associated with SRTs. Preschoolers' receptive vocabulary size predicted performance for ChEgSS words but not simple words. CONCLUSIONS: Preschoolers were more susceptible to speech-in-speech masking than adults, with a similar child-adult difference for the ChEgSS and simple words. Effects of receptive vocabulary in preschoolers' recognition of ChEgSS words indicate that vocabulary size is an important consideration, even when using closed-set methods.
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Mascaramento Perceptivo , Percepção da Fala , Adulto Jovem , Humanos , Mascaramento Perceptivo/fisiologia , Fala , Percepção da Fala/fisiologia , Reconhecimento Psicológico , VocabulárioRESUMO
PURPOSE: Normative auditory brainstem response (ABR) data for infants and young children are available for 0.25-4 kHz, limiting clinical assessment to this range. As such, the high-frequency hearing sensitivity of infants and young children remains unknown until behavioral testing can be completed, often not until late preschool or early school ages. The purpose of this study was to obtain normative ABR data at 6 and 8 kHz in young infants. METHOD: Participants were 173 full-term infants seen clinically for ABR testing at 0.4-6.7 months chronological age (M = 1.4 months, SD = 1.0), 97% of whom were ≤ 12 weeks chronological age. Stimuli included 6 and 8 kHz tone bursts presented at a rate of 27.7/s or 30.7/s using Blackman window gating with six cycles (6 kHz) or eight cycles (8 kHz) rise/fall time and no plateau. Presentation levels included 20, 40, and 60 dB nHL. The ABR threshold was estimated in 5- to 10-dB steps. RESULTS: As previously observed with lower frequency stimuli, ABR waveforms obtained in response to 6 and 8 kHz tone bursts decreased in latency with increasing intensity and increasing age. Latency was shorter for 8-kHz tone bursts than 6-kHz tone bursts. Data tables are presented for clinical reference for infants ≤ 4 weeks, 4.1-8 weeks, and 8.1-12 weeks chronological age including median ABR latency for Waves I, III, and V and the upper and lower boundaries of the 90% prediction interval. Interpeak Latencies I-III, III-V, and I-V are also reported. CONCLUSION: The results from this study demonstrate that ABR assessment at 6 and 8 kHz is feasible for young infants within a standard clinical appointment and provide reference data for clinical interpretation of ABR waveforms for frequencies above 4 kHz.
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Potenciais Evocados Auditivos do Tronco Encefálico , Audição , Lactente , Criança , Humanos , Pré-Escolar , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Audiometria de Tons Puros/métodos , Limiar Auditivo/fisiologia , Audição/fisiologia , Estimulação Acústica/métodosRESUMO
PURPOSE: Down syndrome occurs in one of 700 births, and high rates of hearing loss are reported in this population. This puts children with Down syndrome at risk for communication, learning, and social development difficulties, compounding known language and cognitive vulnerabilities in this population. The purpose of this study was to comprehensively characterize audiological profiles in children with Down syndrome, including the use of extended high-frequency sensitivity and speech intelligibility index assessment. METHOD: Participants were 18 children with Down syndrome between 5 and 17 years of age. Audiological profiles were characterized using behavioral audiometry, tympanometry, and wideband acoustic immittance (WAI). Audibility was characterized using the speech intelligibility index. RESULTS: Of the participants successfully completing behavioral audiometry, hearing loss of a moderate or greater degree was observed in one or both ears for 46% of the participants at conventional audiometric test frequencies and 85% of the participants at frequencies above 8 kHz. Seven children met criteria for amplification based on the speech intelligibility index, but only two wore hearing aids. Abnormal middle ear function was found in approximately 50% of the participants for whom WAI or tympanometry were successfully measured. CONCLUSIONS: Consistent with prior research, high rates of hearing loss and middle ear dysfunction were observed. The high prevalence of hearing loss above 8 kHz suggests the importance of including extended high-frequency assessment in audiologic characterization of children with Down syndrome. Few children meeting audibility-based guidelines for amplification wore hearing aids, putting them at additional risk for speech/language and educational difficulties. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21200422.
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Síndrome de Down , Auxiliares de Audição , Perda Auditiva , Criança , Humanos , Síndrome de Down/complicações , Inteligibilidade da Fala , Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , AudiometriaRESUMO
Having a large receptive vocabulary benefits speech-in-noise recognition for young children, though this is not always the case for older children or adults. These observations could indicate that effects of receptive vocabulary size on speech-in-noise recognition differ depending on familiarity of the target words, with effects observed only for more recently acquired and less frequent words. Two experiments were conducted to evaluate effects of vocabulary size on open-set speech-in-noise recognition for adults with normal hearing. Targets were words acquired at 4, 9, 12 and 15 years of age, and they were presented at signal-to-noise ratios (SNRs) of -5 and -7 dB. Percent correct scores tended to fall with increasing age of acquisition (AoA), with the caveat that performance at -7 dB SNR was better for words acquired at 9 years of age than earlier- or later-acquired words. Similar results were obtained whether the AoA of the target words was blocked or mixed across trials. Differences in word duration appear to account for nonmonotonic effects of AoA. For all conditions, a positive correlation was observed between recognition and vocabulary size irrespective of target word AoA, indicating that effects of vocabulary size are not limited to recently acquired words. This dataset does not support differential assessment of AoA, lexical frequency, and other stimulus features known to affect lexical access.
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Percepção da Fala , Vocabulário , Adolescente , Criança , Pré-Escolar , Audição , Humanos , Ruído , Fala , Adulto JovemRESUMO
This work evaluated the feasibility and reliability of remotely assessing masked speech recognition and the binaural intelligibility level difference (BILD) in children. Participants were 28 children (6-17 years) and 11 adults (22-45 years) with self-reported normal hearing. A three-alternative forced-choice word recognition task was completed using participants' personal hardware (headphones and computer) and custom software that uploaded results to a central database. Results demonstrate that assessment of masked speech recognition and the BILD is feasible and generally reliable in a remote setting. Variability of results across individuals would likely have been reduced by distributing or specifying appropriate headphones.
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Purpose Talkers often modify their speech when communicating with individuals who struggle to understand speech, such as listeners with hearing loss. This study evaluated the benefit of clear speech in school-age children and adults with normal hearing for speech-in-noise and speech-in-speech recognition. Method Masked sentence recognition thresholds were estimated for school-age children and adults using an adaptive procedure. In Experiment 1, the target and masker were summed and presented over a loudspeaker located directly in front of the listener. The masker was either speech-shaped noise or two-talker speech, and target sentences were produced using a clear or conversational speaking style. In Experiment 2, stimuli were presented over headphones. The two-talker speech masker was diotic (M0). Clear and conversational target sentences were presented either in-phase (T0) or out-of-phase (Tπ) between the two ears. The M0Tπ condition introduces a segregation cue that was expected to improve performance. Results For speech presented over a single loudspeaker (Experiment 1), the clear-speech benefit was independent of age for the noise masker, but it increased with age for the two-talker masker. Similar age effects for the two-talker speech masker were seen under headphones with diotic presentation (M0T0), but comparable clear-speech benefit as a function of age was observed with a binaural cue to facilitate segregation (M0Tπ). Conclusions Consistent with prior research, children showed a robust clear-speech benefit for speech-in-noise recognition. Immaturity in the ability to segregate target from masker speech may limit young children's ability to benefit from clear-speech modifications for speech-in-speech recognition under some conditions. When provided with a cue that facilitates segregation, children as young as 4-7 years of age derived a clear-speech benefit in a two-talker masker that was similar to the benefit experienced by adults.
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Percepção da Fala , Adulto , Criança , Pré-Escolar , Humanos , Ruído , Mascaramento Perceptivo , Instituições Acadêmicas , FalaRESUMO
The growing prevalence and popularity of interval training necessitate additional guidelines in regard to maximal levels of time and intensity. PURPOSE: To correlate salivary hormones and time in varying heart-rate (HR) zones. The hypothesis was that chronic exercise durations >9% of total exercise time in the >90% maximum HR zone would lead to decreased variation in salivary cortisol concentration after exercise in a 2-bout high-intensity protocol compared with less or more time in this zone. METHODS: A total of 35 healthy adults who regularly exercised for an average of 8 hours per week recorded their HR during every training session for 3 weeks. Later, they completed an experimental day composed of two 30-minute high-intensity interval sessions separated by 4 hours of nonactive recovery. The authors collected saliva samples before, immediately following, and 30 minutes after each exercise session to assess changes in cortisol concentrations. RESULTS: There was a correlation between weekly time training at an intensity >90% maximum HR and the variables associated with overtraining. Salivary cortisol concentration fluctuated less in the participants who exercised in this extreme zone for >40 minutes per week (P < .001). CONCLUSION: Based on the current study data, for individuals who regularly exercise, 4% to 9% total training time above 90% maximum HR is the ideal duration to maximize fitness and minimize symptoms related to overreaching.
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Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Treinamento Intervalado de Alta Intensidade/métodos , Hidrocortisona/metabolismo , Saliva/metabolismo , Adulto , Afeto/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Aptidão Cardiorrespiratória/psicologia , Metabolismo Energético , Exercício Físico/psicologia , Feminino , Treinamento Intervalado de Alta Intensidade/psicologia , Humanos , Masculino , Sono/fisiologia , Fatores de TempoRESUMO
Purpose Low-frequency detection thresholds in quiet vary across transducers. This experiment tested the hypothesis that transducer effects are larger in young children than adults, due to higher levels of self-generated noise in children. Method Listeners were normal-hearing 4.6- to 11.7-year-olds and adults. Warble-tone detection was measured at 125, 250, 500, and 1000 Hz with a sound-field speaker, insert earphones, and supra-aural headphones. Probe microphone recordings measured self-generated noise levels. Results Thresholds were similar across ages for speaker measurements. Transducer effects were larger for children than adults, with mean child-adult threshold differences at 125 Hz of 3.4 dB (insert earphones) and 6.6 dB (supra-aural headphones). Age effects on threshold were broadly consistent with noise levels measured in the ear canal. Conclusions Self-generated noise appears to elevate children's low-frequency thresholds measured with occluding transducers. These effects could be particularly relevant to the diagnosis of minimal and mild hearing loss in children.
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Ruído , Transdutores , Adulto , Audiometria de Tons Puros , Limiar Auditivo , Criança , Pré-Escolar , Humanos , Instituições AcadêmicasRESUMO
Purpose It can be challenging to collect reliable behavioral responses to sound from individuals with significant motor or developmental impairments, the most common types of comorbid disability found in children with hearing loss (e.g., Gallaudet Research Institute, 2011). The purpose of this study was to test the feasibility of using a 2-interval, forced-choice, observer-based method for individuals considered to be difficult-to-test using behavioral audiometric assessments. Method Participants were 5 children with motor and developmental impairments, ages 5-15 years (M = 11.6, SD = 4.6). The functional abilities of all participants were greater than 2 SDs below the mean, as measured by the Vineland-II Parent Caregiver Rating Form. Participants listened to either a male talker saying the word "playground" or a 1000-Hz warble tone, presented via an insert earphone or a sound field speaker. An observer, blind to signal presentation, selected 1 of 2 temporal intervals, determining which contained the signal based only on participant behavior. Criterion was reached when the observer correctly identified the interval containing the signal for 8 of the last 10 trials. Results An 80%-correct criterion was met for all participants, suggesting feasibility for use in children with motor or developmental impairment. Two participants were tested using an adaptive tracking procedure; a reliable threshold estimate was obtained for both children. This method offers promise for children who have difficulty performing behavioral audiometric assessments currently in use clinically.
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Perda Auditiva/diagnóstico , Testes Auditivos/métodos , Percepção da Fala , Adolescente , Transtorno Autístico/complicações , Paralisia Cerebral/complicações , Criança , Pré-Escolar , Condicionamento Psicológico , Deficiências do Desenvolvimento/complicações , Estudos de Viabilidade , Feminino , Perda Auditiva/complicações , Humanos , MasculinoRESUMO
IMPORTANCE: Advanced liver fibrosis is a precursor to cirrhosis, a leading cause of mortality. People with severe psoriasis are at risk for liver disease, but our understanding of advanced fibrosis in individuals with psoriasis is limited. OBJECTIVES: To describe the prevalence of and evaluate the clinical factors associated with advanced liver fibrosis in people with severe psoriasis. DESIGN, SETTING, AND PARTICIPANTS: The Co-morbidities in Severe Psoriasis study, a prospective observational cohort study in a large center serving London and Southeast England, was conducted from October 18, 2012, to April 2, 2015; 400 adults with severe psoriasis (Psoriasis Area Severity Index score, ≥10) were recruited from outpatient clinics. Statistical analysis was conducted from October 2, 2016, to March 3, 2017. MAIN OUTCOMES AND MEASURES: The primary outcome was a diagnosis of advanced liver fibrosis determined by transient elastography, a noninvasive criterion standard test. Clinical factors evaluated included psoriasis-specific and metabolic indices, alcohol use, and methotrexate exposure. RESULTS: Of 400 patients recruited (108 women and 289 men; mean [SD] age, 49.5 [13] years), 333 had a successful transient elastography scan and were included in final analysis. Forty-seven patients (14.1%; 95% CI, 10.4%-17.9%) had advanced liver fibrosis as diagnosed by transient elastography. The clinical factors that produced the best-fit model for advanced fibrosis were central obesity (waist circumference), insulin resistance, aspartate aminotransferase level, platelet count, psoriasis disease severity, and reduced alcohol use (R2 = 0.54). CONCLUSIONS AND RELEVANCE: Findings from this study suggest that advanced fibrosis is common in severe psoriasis. Abdominal obesity (by waist circumference) and insulin resistance were associated with the presence of advanced fibrosis. Longitudinal work to characterize the hepatic sequelae of central obesity, insulin resistance, and inflammation as well as the influence of systemic drugs (methotrexate and biologics) will inform future personalized therapeutic decision-making. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02174367.
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Purpose: This experiment sought to determine whether children's increased susceptibility to nonsimultaneous masking, particularly backward masking, is evident for speech stimuli. Method: Five- to 9-year-olds and adults with normal hearing heard nonsense consonant-vowel-consonant targets. In Experiments 1 and 2, those targets were presented between two 250-ms segments of 70-dB-SPL speech-shaped noise, at either -30 dB signal-to-noise ratio (Experiment 1) or at the listener's word recognition threshold (Experiment 2). In Experiment 3, the target was presented in steady speech-shaped noise at listener threshold. For all experiments, percent correct was estimated for initial and final consonants. Results: In the nonsimultaneous noise conditions, child-adult differences were larger for the final consonant than the initial consonant whether listeners were tested at -30 dB signal-to-noise ratio (Experiment 1) or at their individual word recognition threshold (Experiment 2). Children were not particularly susceptible to backward masking relative to adults when tested in a steady masker (Experiment 3). Conclusions: Child-adult differences were greater for backward than forward masking for speech in a nonsimultaneous noise masker, as observed in previous psychophysical studies using tonal stimuli. Children's greater susceptibility to nonsimultaneous masking, and backward masking in particular, could play a role in their limited ability to benefit from masker envelope modulation when recognizing masked speech.
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Estimulação Acústica/psicologia , Limiar Auditivo , Mascaramento Perceptivo , Percepção da Fala , Estimulação Acústica/métodos , Adulto , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Humanos , Masculino , Ruído , Semântica , Razão Sinal-Ruído , Adulto JovemRESUMO
The persistence of common, heritable psychiatric disorders that reduce reproductive fitness is an evolutionary paradox. Here, we investigate the selection pressures on sequence variants that predispose to schizophrenia, autism, bipolar disorder, major depression and attention deficit hyperactivity disorder (ADHD) using genomic data from 150,656 Icelanders, excluding those diagnosed with these psychiatric diseases. Polygenic risk of autism and ADHD is associated with number of children. Higher polygenic risk of autism is associated with fewer children and older age at first child whereas higher polygenic risk of ADHD is associated with having more children. We find no evidence for a selective advantage of a high polygenic risk of schizophrenia or bipolar disorder. Rare copy-number variants conferring moderate to high risk of psychiatric illness are associated with having fewer children and are under stronger negative selection pressure than common sequence variants.
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Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno Autístico/genética , Transtorno Bipolar/genética , Aptidão Genética , Esquizofrenia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Predisposição Genética para Doença , Genética Populacional , Genótipo , Humanos , Islândia , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Children perform more poorly than adults on a wide range of masked speech perception paradigms, but this effect is particularly pronounced when the masker itself is also composed of speech. The present study evaluated two factors that might contribute to this effect: the ability to perceptually isolate the target from masker speech, and the ability to recognize target speech based on sparse cues (glimpsing). Speech reception thresholds (SRTs) were estimated for closed-set, disyllabic word recognition in children (5-16 years) and adults in a one- or two-talker masker. Speech maskers were 60 dB sound pressure level (SPL), and they were either presented alone or in combination with a 50-dB-SPL speech-shaped noise masker. There was an age effect overall, but performance was adult-like at a younger age for the one-talker than the two-talker masker. Noise tended to elevate SRTs, particularly for older children and adults, and when summed with the one-talker masker. Removing time-frequency epochs associated with a poor target-to-masker ratio markedly improved SRTs, with larger effects for younger listeners; the age effect was not eliminated, however. Results were interpreted as indicating that development of speech-in-speech recognition is likely impacted by development of both perceptual masking and the ability recognize speech based on sparse cues.
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Comportamento do Adolescente , Comportamento Infantil , Sinais (Psicologia) , Ruído/efeitos adversos , Mascaramento Perceptivo , Reconhecimento Psicológico , Percepção da Fala , Estimulação Acústica , Adolescente , Adulto , Fatores Etários , Limiar Auditivo , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Psicoacústica , Teste do Limiar de Recepção da Fala , Adulto JovemRESUMO
Burgeoning availability of genome-wide association study (GWAS) results and national biobank data has led to growing interest in performing multi-trait genetic analyses. Numerous multi-trait GWAS methods that exploit either summary statistics or individual-level data have been developed, but their relative performance is unclear. Here we develop a simulation framework to model the complex networks underlying multivariate genetic epidemiology, enabling the vast model space of genetic effects on multiple correlated traits to be explored systematically. We perform a comprehensive comparison of the leading multi-trait GWAS methods, finding: (1) method performance is highly sensitive to the specific combination of genetic effects and phenotypic correlations, (2) most of the current multivariate methods have remarkably similar statistical power, and (3) multivariate methods may offer a substantial increase in the discovery of genetic variants over the standard univariate approach. We believe our findings offer the clearest picture to date of the relative performance of multi-trait GWAS methods and act as a guide for method selection. We provide a web application and open-source software program implementing our simulation framework, for: (i) further benchmarking of multivariate GWAS methods, (ii) power calculations for multivariate genetic studies, and (iii) generating data for testing any multivariate method in genetic epidemiology.
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Bioestatística/métodos , Biologia Computacional/métodos , Estudo de Associação Genômica Ampla/métodos , Simulação por Computador , SoftwareRESUMO
Purpose: The age at which gap detection becomes adultlike differs, depending on the stimulus characteristics. The present study evaluated whether the developmental trajectory differs as a function of stimulus frequency region or duration of the onset and offset ramps bounding the gap. Method: Thresholds were obtained for wideband noise (500-4500 Hz) with 4- or 40-ms raised-cosine ramps and for a 25-Hz-wide low-fluctuation narrowband noise centered on either 500 or 5000 Hz with 40-ms ramps. Stimuli were played continuously at 70 dB SPL, and the task was to indicate which of 3 intervals contained a gap. Listeners were 5.2- to 15.1-year-old children (n = 40) and adults (n = 10) with normal hearing. Results: Regardless of listener age, gap detection thresholds for the wideband noise tended to be lower when gaps were shaped using 4-ms rather than 40-ms ramps. Thresholds also tended to be lower for the low-fluctuation narrowband noise centered on 5000 Hz than 500 Hz. Performance reached adult levels after 11 years of age for all 4 stimuli. Maturation was not uniform across individuals, however; a subset of young children performed like adults, including some 5-year-olds. Conclusion: For these stimuli, the developmental trajectory was similar regardless of narrowband noise center frequency or wideband noise onset and offset ramp duration.
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Percepção Auditiva , Detecção de Sinal Psicológico , Adolescente , Adulto , Criança , Desenvolvimento Infantil , Pré-Escolar , Humanos , Adulto JovemRESUMO
The purpose of this study was to determine the effects of age on the spectro-temporal integration of speech. The hypothesis was that the integration of speech fragments distributed over frequency, time, and ear of presentation is reduced in older listeners-even for those with good audiometric hearing. Younger, middle-aged, and older listeners (10 per group) with good audiometric hearing participated. They were each tested under seven conditions that encompassed combinations of spectral, temporal, and binaural integration. Sentences were filtered into two bands centered at 500 Hz and 2500 Hz, with criterion bandwidth tailored for each participant. In some conditions, the speech bands were individually square wave interrupted at a rate of 10 Hz. Configurations of uninterrupted, synchronously interrupted, and asynchronously interrupted frequency bands were constructed that constituted speech fragments distributed across frequency, time, and ear of presentation. The over-arching finding was that, for most configurations, performance was not differentially affected by listener age. Although speech intelligibility varied across condition, there was no evidence of performance deficits in older listeners in any condition. This study indicates that age, per se, does not necessarily undermine the ability to integrate fragments of speech dispersed across frequency and time.