The development of lexical processing: Real-time phonological competition and semantic activation in school age children.

Prior research suggests that the development of speech perception and word recognition stabilises in early childhood. However, recent work suggests that development of these processes continues throughout adolescence. This study aimed to investigate whether these developmental changes are based solely within the lexical system or are due to domain general changes, and to extend this investigation to lexical-semantic processing. We used two Visual World Paradigm tasks: one to examine phonological and semantic processing, one to capture non-linguistic domain-general skills. We tested 43 seven- to nine-year-olds, 42 ten- to thirteen-year-olds, and 30 sixteen- to seventeen-year-olds. Older children were quicker to fixate the target word and exhibited earlier onset and offset of fixations to both semantic and phonological competitors. Visual/cognitive skills explained significant, but not all, variance in the development of these effects. Developmental changes in semantic activation were largely attributable to changes in upstream phonological processing. These results suggest that the concurrent development of linguistic processes and broader visual/cognitive skills lead to developmental changes in real-time phonological competition, while semantic activation is more stable across these ages.

Predictors of Listening-Related Fatigue in Adolescents With Hearing Loss.

PURPOSE: Self-reported listening-related fatigue in adolescents with hearing loss (HL) was investigated. Specifically, the extent to which listening-related fatigue is associated with school accommodations, audiologic characteristics, and listening breaks was examined. METHOD: Participants were 144 adolescents with HL ages 12-19 years. Data were collected online via Qualtrics. The Vanderbilt Fatigue Scale-Child was used to measure listening-related fatigue. Participants also reported on their use of listening breaks and school accommodations, including an Individualized Education Program (IEP) or 504 plan, remote microphone systems, closed captioning, preferential seating, sign language interpreters, live transcriptions, and notetakers. RESULTS: After controlling for age, HL laterality, and self-perceived listening difficulty, adolescents with an IEP or a 504 plan reported lower listening-related fatigue compared to adolescents without an IEP or a 504 plan. Adolescents who more frequently used remote microphone systems or notetakers reported higher listening-related fatigue compared to adolescents who used these accommodations less frequently, whereas increased use of a sign language interpreter was associated with decreased listening-related fatigue. Among adolescents with unilateral HL, higher age was associated with lower listening-related fatigue; no effect of age was found among adolescents with bilateral HL. Listening-related fatigue did not differ based on hearing device configuration. CONCLUSIONS: Adolescents with HL should be considered at risk for listening-related fatigue regardless of the type of hearing devices used or the degree of HL. The individualized support provided by an IEP or 504 plan may help alleviate listening-related fatigue, especially by empowering adolescents with HL to be self-advocates in terms of their listening needs and accommodations in school. Additional research is needed to better understand the role of specific school accommodations and listening breaks in addressing listening-related fatigue.

Evaluation of serial monitoring of donor-specific antibodies in pediatric and adult intestinal/multivisceral transplant recipients.

BACKGROUND: The study purpose was to add to limited literature assessing anti-HLA donor-specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring. METHODS: This single-center retrospective review included intestinal/MV recipients transplanted 1/1/15-9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post-transplant. The primary outcome was biopsy-proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed. RESULTS: Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post-transplant DSA. Fifteen patients in the DSA(+) group had T-cell-mediated BPAR versus five in the DSA(-) group (63% vs 45%, p = .47). Days to BPAR were 25 [IQR 19-165] (DSA(+) group) versus 232 [IQR 25.5-632.5] (DSA(-) group) (p = .066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow-up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA- DQ (35%). Time to first DSA and to clearance did not differ between class I and II. CONCLUSION: Findings confirm previous data that suggest post-transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients.

Utilization of donor-derived Cell-Free DNA in pediatric kidney transplant recipients: A single center study.

High donor-derived cell-free DNA (dd-cfDNA) levels indicate transplant allograft injury and can identify graft rejection in kidney transplant recipients. Here, we evaluated the use of dd-cfDNA in pediatric kidney transplant rejection monitoring and treatment. METHODS: Forty-two pediatric kidney transplant patients were enrolled between February 2020 and August 2021. Dd-cfDNA was tested before and after biopsy/rejection treatment. There was a total of 61 allograft biopsies (44 for-cause, 17 surveillance). RESULTS: Graft rejection was found in 35/61 biopsies. Rejection was more common in basiliximab induction compared to rATG (77.1% vs. 22.9%, p = .0121). Median dd-cfDNA was higher in those with rejection (1.2% [0.34-3.12] vs. 0.24% [0.08-0.78], p < .0001). Dd-cfDNA was highest in biopsies with AMR and mixed AMR/TCMR. In addition, dd-cfDNA in basiliximab induction was higher compared to rATG (0.92% [0.27-1.8] vs. 0.26% [0.08-2], p = .0437). Median change in dd-cfDNA after rejection treatment was -0.57% (-1.67 to 0.05). Median time to dd-cfDNA <1% post-rejection treatment was 8.5 days (3.0-19.5). Dd-cfDNA in AMR was higher compared to TCMR or mixed rejection, and levels remained higher in AMR after treatment. In surveillance biopsies, 4/17 had rejection. Median dd-cfDNA was not different in those with versus without rejection (0.48% vs. 0.28%, p = .2342). Those without rejection all had dd-cfDNA <1%. In those with rejection, only one patient had dd-cfDNA >1%, and all had TCMR. CONCLUSIONS: Our findings support dd-cfDNA as a useful indicator of graft rejection and response to treatment. Additional studies are needed to determine the role of dd-cfDNA in graft health surveillance.

Safety and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Solid Organ Transplant Recipients.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may be effective in reducing body weight and hemoglobin A1c (HbA1c) post-kidney transplantation. Limited literature exists on use of these agents outside of kidney transplant. The purpose of this program evaluation was to evaluate the safety and efficacy of SGLT2i in kidney, liver, and lung transplant recipients. Methods: This was a retrospective program evaluation of adult kidney, liver, and lung transplant recipients between August 31, 2016 and July 31, 2021. Patients initiated on SGLT2i for diabetes for a minimum of 90 days with at least 1 follow-up appointment were screened for inclusion. Outcomes were compared between SGLT2i initiation to nadir values 3-12-months post-initiation. Outcomes included change in hemoglobin A1c, fasting blood glucose, actual body weight, and body mass index. Safety outcomes included adverse effects, cardiovascular events, death-censored graft loss, and all-cause mortality. Results: Forty-nine patients met inclusion criteria, (26 liver, 18 kidney, 4 lung, and 1 simultaneous liver-kidney recipient). The median time from transplant to SGLT2i initiation was 1216 days (IQR 524-2256). Glycemic and weight loss outcomes showed a statistically significant benefit from SGLT2i use. Total safety outcome incidence was minimal at 12 months. No patient experienced myocardial infarctions, graft loss, or mortality at 3-12 months. One incidence of urinary tract infection and stroke occurred each. The most common adverse effects included hypotension and hypoglycemia. Conclusion: This program evaluation demonstrated that SGLT2i can be used safely in solid organ transplant recipients. These agents can provide an additional non-insulin agent for post-transplant diabetes mellitus management in solid organ transplant.

Delayed Lexical Access and Cascading Effects on Spreading Semantic Activation During Spoken Word Recognition in Children With Hearing Aids and Cochlear Implants: Evidence From Eye-Tracking.

OBJECTIVE: The objective of this study was to characterize the dynamics of real-time lexical access, including lexical competition among phonologically similar words, and spreading semantic activation in school-age children with hearing aids (HAs) and children with cochlear implants (CIs). We hypothesized that developing spoken language via degraded auditory input would lead children with HAs or CIs to adapt their approach to spoken word recognition, especially by slowing down lexical access. DESIGN: Participants were children ages 9- to 12-years old with normal hearing (NH), HAs, or CIs. Participants completed a Visual World Paradigm task in which they heard a spoken word and selected the matching picture from four options. Competitor items were either phonologically similar, semantically similar, or unrelated to the target word. As the target word unfolded, children's fixations to the target word, cohort competitor, rhyme competitor, semantically related item, and unrelated item were recorded as indices of ongoing lexical access and spreading semantic activation. RESULTS: Children with HAs and children with CIs showed slower fixations to the target, reduced fixations to the cohort competitor, and increased fixations to the rhyme competitor, relative to children with NH. This wait-and-see profile was more pronounced in the children with CIs than the children with HAs. Children with HAs and children with CIs also showed delayed fixations to the semantically related item, although this delay was attributable to their delay in activating words in general, not to a distinct semantic source. CONCLUSIONS: Children with HAs and children with CIs showed qualitatively similar patterns of real-time spoken word recognition. Findings suggest that developing spoken language via degraded auditory input causes long-term cognitive adaptations to how listeners recognize spoken words, regardless of the type of hearing device used. Delayed lexical access directly led to delays in spreading semantic activation in children with HAs and CIs. This delay in semantic processing may impact these children's ability to understand connected speech in everyday life.

Effect of Hepatitis C Viremia on Posttransplant Diabetes Mellitus in Liver Transplant Recipients.

INTRODUCTION: Posttransplant diabetes mellitus (PTDM) can increase morbidity and mortality in liver transplant recipients. Although hepatitis C seropositivity is a known risk factor for PTDM, the impact of viremia versus no viremia at time of transplant is unknown. PROJECT AIMS: This program evaluation sought to compare PTDM in hepatitis C seropositive patients with and without viremia at the time of liver transplant. DESIGN: This single-center retrospective review included adult hepatitis C seropositive liver transplant recipients transplanted between January 1, 2010 to September 5, 2017 without pretransplant diabetes. Primary outcome was PTDM within 1 year. Secondary outcomes included evaluating 1-year posttransplant death-censored graft loss, mortality, and metabolic outcomes. RESULTS: Fifty-seven liver transplant recipients with hepatitis C were included, of which 53% (n = 30) were viremic at transplant. Baseline characteristics were similar between groups. Significantly more patients with pretransplant viremia developed PTDM by 1-year posttransplant compared to the patients without viremia (43% vs 11%, P = 0.01). There were no differences between groups outside of more patients with viremia requiring antihypertensives by 1-year posttransplant compared to patients without viremia (57% vs 22%, P = 0.01). CONCLUSION: Liver transplant patients with hepatitis C viremia at transplant were more likely to develop PTDM at 1 year compared to those without pretransplant viremia. This is an added consideration when deciding the timing of direct-acting antiviral (DAA) utilization in the context of liver transplant for hepatitis C seropositive patients.

The profile of real-time competition in spoken and written word recognition: More similar than different.

Word recognition occurs across two sensory modalities: auditory (spoken words) and visual (written words). While each faces different challenges, they are often described in similar terms as a competition process by which multiple lexical candidates are activated and compete for recognition. While there is a general consensus regarding the types of words that compete during spoken word recognition, there is less consensus for written word recognition. The present study develops a novel version of the Visual World Paradigm (VWP) to examine written word recognition and uses this to assess the nature of the competitor set during word recognition in both modalities using the same experimental design. For both spoken and written words, we found evidence for activation of onset competitors (cohorts, e.g., cat, cap) and words that contain the same phonemes or letters in reverse order (anadromes, e.g., cat, tack). We found no evidence of activation for rhymes (e.g., cat, hat). The results across modalities were quite similar, with the exception that for spoken words, cohorts were more active than anadromes, whereas for written words activation was similar. These results suggest a common characterisation of lexical similarity across spoken and written words: temporal or spatial order is coarsely coded, and onsets may receive more weight in both systems. However, for spoken words, temporary ambiguity during the moment of processing gives cohorts an additional boost during real-time recognition.

Effects of Grade and School Services on Children's Responsibility for Hearing Aid Care.

Purpose We investigated trends in hearing aid maintenance and assumption of responsibility for hearing aids in school-age children who are hard of hearing. Specifically, we examined the extent to which families own necessary hearing aid maintenance equipment, whether and by whom hearing aid maintenance tasks are being completed, and the effects of grade and receipt of an Individualized Education Program (IEP) or 504 plan on a child's assumption of responsibility for hearing aid care. Method Participants included 167 children who are hard of hearing in 1st to 4th grade. Caregivers reported whether the families owned various types of hearing aid maintenance equipment (listening tube, battery tester, and dri-aid kit) and who normally completes various hearing aid maintenance tasks. Information about children's audiological characteristics was also collected. Results Thirty-two percent of families reported not owning at least 1 piece of hearing aid maintenance equipment. Using a battery tester and performing a listening check were the maintenance tasks completed the least frequently, with 49% and 28% of caregivers reporting that these tasks are not completed regularly, respectively. Children's responsibility for hearing aid maintenance increased with grade. After controlling for maternal education and degree of hearing loss, children with an IEP or 504 plan took more responsibility for hearing aid maintenance tasks than children without these services. Conclusion Important hearing aid maintenance tasks, such as listening checks, are not completed regularly for many children, even when families own the necessary equipment. Ensuring that children who are hard of hearing have an IEP or 504 plan throughout elementary school may support self-advocacy and encourage children to take responsibility for their hearing aids, which may lead to more consistent hearing aid functioning.

Time-Gated Word Recognition in Children: Effects of Auditory Access, Age, and Semantic Context.

Purpose We employed a time-gated word recognition task to investigate how children who are hard of hearing (CHH) and children with normal hearing (CNH) combine cognitive-linguistic abilities and acoustic-phonetic cues to recognize words in sentence-final position. Method The current study included 40 CHH and 30 CNH in 1st or 3rd grade. Participants completed vocabulary and working memory tests and a time-gated word recognition task consisting of 14 high- and 14 low-predictability sentences. A time-to-event model was used to evaluate the effect of the independent variables (age, hearing status, predictability) on word recognition. Mediation models were used to examine the associations between the independent variables (vocabulary size and working memory), aided audibility, and word recognition. Results Gated words were identified significantly earlier for high-predictability than low-predictability sentences. First-grade CHH and CNH showed no significant difference in performance. Third-grade CHH needed more information than CNH to identify final words. Aided audibility was associated with word recognition. This association was fully mediated by vocabulary size but not working memory. Conclusions Both CHH and CNH benefited from the addition of semantic context. Interventions that focus on consistent aided audibility and vocabulary may enhance children's ability to fill in gaps in incoming messages.

Nonverbal Visual Sequential Learning in Children With Cochlear Implants: Preliminary Findings.

The authors tested the hypothesis that children with cochlear implants (CIs) experience domain-general deficits in sequential learning. Twenty children with CIs and 40 children with normal hearing (NH) participated. Participants completed a serial reaction time task that measured implicit sequential learning. During random sequence phases, the CI group had significantly slower reaction times than the NH group. However, there were no significant differences in the rates of sequential learning between groups. Age at implantation was not significantly associated with learning rate in the CI group. Children with CIs demonstrated nonverbal sequential learning that is comparable to children with NH. Contrary to previous research, early auditory deprivation may not be associated with deficits in domain-general sequential learning, but may affect sequential processing. Further investigation is needed to understand the mechanisms underlying the overall delayed reaction times of children with CIs.

Cognitive Abilities Contribute to Spectro-Temporal Discrimination in Children Who Are Hard of Hearing.

OBJECTIVES: Spectral ripple discrimination tasks have received considerable interest as potential clinical tools for use with adults and children with hearing loss. Previous results have indicated that performance on ripple tasks is affected by differences in aided audibility [quantified using the Speech Intelligibility Index, or Speech Intelligibility Index (SII)] in children who wear hearing aids and that ripple thresholds tend to improve over time in children with and without hearing loss. Although ripple task performance is thought to depend less on language skills than common speech perception tasks, the extent to which spectral ripple discrimination might depend on other general cognitive abilities such as nonverbal intelligence and working memory is unclear. This is an important consideration for children because age-related changes in ripple test results could be due to developing cognitive ability and could obscure the effect of any changes in unaided or aided hearing over time. The purpose of this study was to establish the relationship between spectral ripple discrimination in a group of children who use hearing aids and general cognitive abilities such as nonverbal intelligence, visual and auditory working memory, and executive function. It was hypothesized that, after controlling for listener age, general cognitive ability would be associated with spectral ripple thresholds and performance on both auditory and visual cognitive tasks would be associated with spectral ripple thresholds. DESIGN: Children who were full-time users of hearing aids for at least 1 year (n = 24, ages 6 to 13 years) participated in this study. Children completed a spectro-temporal modulated ripple discrimination task in the sound field using their personal hearing aids. Threshold was determined from the average of two repetitions of the task. Participants completed standard measurements of executive function, nonverbal intelligence, and visual and verbal working memory. Real ear verification measures were completed for each child with their personal hearing aids to determine aided SII. RESULTS: Consistent with past findings, spectro-temporal ripple thresholds improved with greater listener age. Surprisingly, aided SII was not significantly correlated with spectro-temporal ripple thresholds potentially because this particular group of listeners had overall better hearing and greater aided SII than participants in previous studies. Partial correlations controlling for listener age revealed that greater nonverbal intelligence and visual working memory were associated with better spectro-temporal ripple discrimination thresholds. Verbal working memory, executive function, and language ability were not significantly correlated with spectro-temporal ripple discrimination thresholds. CONCLUSIONS: These results indicate that greater general cognitive abilities are associated with better spectro-temporal ripple discrimination ability, independent of children's age or aided SII. It is possible that these relationships reflect the cognitive demands of the psychophysical task rather than a direct relationship of cognitive ability to spectro-temporal processing in the auditory system. Further work is needed to determine the relationships of cognitive abilities to ripple discrimination in other populations, such as children with cochlear implants or with a wider range of aided SII.

Using a Digital Language Processor to Quantify the Auditory Environment and the Effect of Hearing Aids for Adults with Hearing Loss.

BACKGROUND: Auditory environments can influence the communication function of individuals with hearing loss and the effects of hearing aids. Therefore, a tool that can objectively characterize a patient's real-world auditory environments is needed. PURPOSE: To use the Language Environment Analysis (LENA) system to quantify the auditory environments of adults with hearing loss, to examine if the use of hearing aids changes a user's auditory environment, and to determine the association between LENA variables and self-report hearing aid outcome measures. RESEARCH DESIGN: This study used a crossover design. STUDY SAMPLE: Participants included 22 adults with mild-to-moderate hearing loss, age 64-82 yr. INTERVENTION: Participants were fitted with bilateral behind-the-ear hearing aids from a major manufacturer. DATA COLLECTION AND ANALYSIS: The LENA system consists of a digital language processor (DLP) that is worn by an individual and records up to 16 hr of the individual's auditory environment. The recording is then automatically categorized according to time spent in different types of auditory environments (e.g., meaningful speech and TV/electronic sound) by the LENA algorithms. The LENA system also characterizes the user's auditory environment by providing the sound levels of different auditory categories. Participants in the present study wore a LENA DLP in an unaided condition and aided condition, which each lasted six to eight days. Participants wore bilateral hearing aids in the aided condition. Percentage of time spent in each auditory environment, as well as median levels of TV/electronic sounds and speech, were compared between subjects' unaided and aided conditions using paired sample t tests. LENA data were also compared to self-report measures of hearing disability and hearing aid benefit using Pearson correlations. RESULTS: Overall, participants spent the greatest percentage of time in silence (∼40%), relative to other auditory environments. Participants spent ∼12% and 26% of their time in meaningful speech and TV/electronic sound environments, respectively. No significant differences were found between mean percentage of time spent in each auditory environment in the unaided and aided conditions. Median TV/electronic sound levels were on average 2.4 dB lower in the aided condition than in the unaided condition; speech levels were not significantly different between the two conditions. TV/electronic sound and speech levels did not significantly correlate with self-report data. CONCLUSIONS: The LENA system can provide rich data to characterize the everyday auditory environments of older adults with hearing loss. Although TV/electronic sound level was significantly lower in the aided than unaided condition, the use of hearing aids seemed not to substantially change users' auditory environments. Because there is no significant association between objective LENA variables and self-report questionnaire outcomes, these two types of measures may assess different aspects of communication function. The feasibility of using LENA in clinical settings is discussed.

Vocabulary Facilitates Speech Perception in Children With Hearing Aids.

Purpose: We examined the effects of vocabulary, lexical characteristics (age of acquisition and phonotactic probability), and auditory access (aided audibility and daily hearing aid [HA] use) on speech perception skills in children with HAs. Method: Participants included 24 children with HAs and 25 children with normal hearing (NH), ages 5-12 years. Groups were matched on age, expressive and receptive vocabulary, articulation, and nonverbal working memory. Participants repeated monosyllabic words and nonwords in noise. Stimuli varied on age of acquisition, lexical frequency, and phonotactic probability. Performance in each condition was measured by the signal-to-noise ratio at which the child could accurately repeat 50% of the stimuli. Results: Children from both groups with larger vocabularies showed better performance than children with smaller vocabularies on nonwords and late-acquired words but not early-acquired words. Overall, children with HAs showed poorer performance than children with NH. Auditory access was not associated with speech perception for the children with HAs. Conclusions: Children with HAs show deficits in sensitivity to phonological structure but appear to take advantage of vocabulary skills to support speech perception in the same way as children with NH. Further investigation is needed to understand the causes of the gap that exists between the overall speech perception abilities of children with HAs and children with NH.

Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature.

INTRODUCTION: Over the past decade, ketamine has been studied for major depressive disorder and bipolar depression. Ketamine is believed to exert its antidepressant properties through N-methyl-D-aspartate receptor antagonism. METHODS: Study authors completed a literature review of seven randomized controlled trials of ketamine usage in major depressive disorder and bipolar depression. RESULTS: Ketamine demonstrated a statistically significant improvement over placebo or midazolam in major depressive disorder. Ketamine also exhibited a statistically significant improvement over placebo in bipolar depression. DISCUSSION: Ketamine has shown promise in quickly reducing symptoms in patients with treatment resistant depression and bipolar depression. Using ketamine may be helpful for patients that have exhausted other therapeutic options.