Boys Town National Research Hospital

Asthma among adolescents (aged 12-<18 years) is a common condition with high disease burden. Many are undertreated, at risk of adverse outcomes and exhibit poor adherence to maintenance medication. As-needed albuterol-budesonide 180/160 µg reduced the risk of severe exacerbations by 27% compared with as-needed albuterol 180 µg in patients aged ≥12 years, with moderate-to-severe asthma receiving inhaled corticosteroid (ICS) maintenance therapy in the MANDALA trial. A small number of adolescents were included in MANDALA, but data were inconclusive. The randomised, double-blind, multicentre, phase IIIb ACADIA trial is evaluating as-needed albuterol-budesonide versus as-needed albuterol in adolescents with asthma. A planned 440 adolescents (aged 12-<18 years) with asthma using as-needed albuterol with low- to high-dose ICS-containing maintenance medications (with or without other controllers) and who had ≥1 severe exacerbation in the previous 12 months are randomised to as-needed albuterol-budesonide 180/160 µg or as-needed albuterol 180 µg for 52 weeks while continuing their own maintenance therapy. The primary endpoint is the annualised rate of severe asthma exacerbations. Secondary endpoints are the time to first severe asthma exacerbation and annualised total systemic corticosteroid exposure for asthma per participant. To minimise the number of adolescents exposed to study medications, the treatment effect will be estimated by partially extrapolating results from the patient population in the MANDALA trial using a Bayesian dynamic borrowing approach. Ethical approval was obtained from the investigators' institutional review boards. Enrolment began in May 2024. Results will be presented at respiratory congresses and published in peer-reviewed journals. NCT06307665.

Gradable adjectives (long, happy) differ from absolute adjectives (spotted) in that they are dependent on context and speaker/listener perspective for their interpretation. Such context sensitivity may present challenges for individuals with autism spectrum disorder (ASD); however, this has never been investigated for these linguistic elements. In the current study, we asked adolescents with ASD or typical development (TD), who were part of a larger longitudinal study in which autistic characteristics, nonverbal cognition (NVIQ), and standardized language were also assessed, to sort pictures whose properties were either gradable or absolute. Adolescents sorted pictures on two occasions. In the second sorting, we manipulated the context by adding images representing one end of the scale to induce a shift in interpretation. Contrary to prediction, both groups demonstrated sensitivity to the context-specific properties by shifting their cutoffs of what counted as 'long' or 'happy' when the array was changed. Whereas NVIQ correlated positively with physical property shifts for the TD group, language measures correlated negatively with emotion property shifts for the ASD group. Autistic characteristics were not related to shift patterns in either group. Adolescents with autism are clearly able to take context into account when interpreting gradable adjectives; however, those with better language seem more focused on maintaining their cutoffs more than shifting them.

High rates of hearing loss are observed for individuals with Down syndrome, and regular hearing assessment is recommended for children and adults. Unknown variability of threshold estimates for repeated auditory assessments for individuals with diverse intellectual abilities, such as individuals with Down syndrome, confounds the ability to determine true threshold changes between assessments. This study evaluated variability of pure-tone thresholds measured within and across test sessions for individuals with Down syndrome. Participants included 27 individuals with Down syndrome, ages 5.1-46.5 years (average = 22.7, SD = 11.8). A group of 11 neurotypical individuals, ages 15.9-48.6 years (average = 24.5, SD = 10.3) was included in intrasession variability assessment. Pure-tone thresholds in quiet were measured at 1, 4, 8, and 11.2 kHz during a single session or during repeated audiograms separated by 2.7-11.2 months (average = 5.8, SD = 2.4) and 3.0-3.9 years (average = 3.4, SD = 0.4). Intrasession variability was ≤ 10 dB for 94.3%-100% of thresholds for participants with Down syndrome, with similar variability observed for neurotypical participants. Threshold differences were ≤ 10 dB for 63.2%-85% of responses from audiograms separated by an average of 5.8 months and 37.5%-62.5% of responses separated by an average of 3.4 years. Intrasession variability for participants with Down syndrome aligns with current clinical standards accepting variability of ≤ 10 dB between repeated threshold estimates. Differences in repeated audiometric thresholds greater than 10 dB likely reflect true changes in hearing sensitivity. https://doi.org/10.23641/asha.30052885.

This study aimed to characterize maturation of the binaural intelligibility level difference (BILD) for school-age children in the context of speech-in-speech recognition. Children (5–17 years) and adults completed an adaptive, open-set sentence recognition task in a two-talker masker in two binaural conditions: (1) target and masker speech in-phase across the two ears, and (2) target speech presented 180° out-of-phase across the two ears and masker speech presented in-phase. Estimates of the BILD, computed as the difference score between the two binaural conditions, were mature by ten years of age, consistent with previous data on the BILD for speech-in-noise recognition.

ABSTRACT Reading is influenced by genes and environments throughout life. Using a U.S. twin sample (N = 1086; 564 Male: 522 Female; Age M = 7.46 years, SD = 1.57, with 90% self-reported as White, 8% Black, 1% Asian, 1% Alaskan, Native American, or Native Pacific Islander, and 11% self-reported as Hispanic), we used a Gene-by-Environment model with age as a moderator to examine how the balance of genetic and environmental influences on reading differed by age. Reading was measured with the DIBELS Next Composite from the beginning of academic year 2018/19. We observed small increasing genetic influences and larger decreasing shared environmental influences on reading from ages 5 to 7 that began to plateau around age 8. Non-shared environmental influences on reading were low and relatively stable from ages 6 through 12 following an uptick between ages 5 and 6. Our results are consistent with the bioecological framework, the emerging gene-environment-time model, and theories of reading development.

Identifying new genes responsible for non-syndromic hearing loss remains a critical goal, as many individuals with hereditary deafness still lack a molecular diagnosis despite comprehensive genetic testing. The tectorial membrane (TM) is a specialized, collagen-rich, acellular matrix of the inner ear, essential for stimulating mechanosensitive hair cell bundles during sound transduction, and its structural integrity is critical for frequency tuning and auditory sensitivity. Although mutations in genes encoding a number of non-collagenous proteins found in the TM (TECTA, CEACAM16, OTOG, OTOGL) have been identified as deafness genes, definitive evidence implicating β-tectorin (TECTB) in human hearing loss has been lacking.Here, we present multiple lines of genetic and experimental evidence linking a missense variant in TECTB (c.674G>A, p.Cys225Tyr) to autosomal dominant, non-syndromic hearing loss in a multigenerational family. The variant alters one of eight highly conserved cysteines present within the zona pellucida (ZP) domain of TECTB and is predicted to disrupt protein folding and matrix assembly. Using a Tectb-C225Y knock-in mouse model, we show that homozygous animals exhibit severe hearing loss and profound disruption of TM morphology, while heterozygote animals display decreased matrix content within the TM and increased susceptibility to noise-induced hearing loss—despite normal auditory thresholds.These findings identify TECTB as a novel human deafness gene, further elucidate its structural role in maintaining TM integrity, and highlight its contribution to resilience against environmental and age-related auditory decline.