Transitioning to Medical School: An Innovative Pre-matriculation Program.

Medical schools use pre-matriculation programs consisting of knowledge-based curricula to prepare at-risk students. There is limited evidence showing the direct benefit of these programs with long-term success. We propose a pre-matriculation program focused on professional development and wellness to facilitate student acclimation and, in turn, academic success.

Audiological characteristics of children with congenital unilateral hearing loss: insights into Age of reliable behavioural audiogram acquisition and change of hearing loss.

Objectives: The aims of this study were to report the audiological characteristics of children with congenital unilateral hearing loss (UHL), examine the age at which the first reliable behavioural audiograms can be obtained, and investigate hearing changes from diagnosis at birth to the first reliable behavioural audiogram. Method: This study included a sample of 91 children who were diagnosed with UHL via newborn hearing screening and had reliable behavioural audiograms before 7 years of age. Information about diagnosis, audiological characteristics and etiology were extracted from clinical reports. Regression analysis was used to explore the potential reasons influencing the age at which first reliable behavioural audiograms were obtained. Correlation and ANOVA analyses were conducted to examine changes in hearing at octave frequencies between 0.5 and 4 kHz. The proportions of hearing loss change, as well as the clinical characteristics of children with and without progressive hearing loss, were described according to two adopted definitions: Definition 1: criterion (1): a decrease in 10 dB or greater at two or more adjacent frequencies between 0.5 and 4 kHz, or criterion (2): a decrease in 15 dB or greater at one octave frequency in the same frequency range. Definition 2: a change of ≥20 dB in the average of pure-tone thresholds at 0.5, 1, and 2 kHz. Results: The study revealed that 48 children (52.7% of the sample of 91 children) had their first reliable behavioural audiogram by 3 years of age. The mean age at the first reliable behavioural audiogram was 3.0 years (SD 1.4; IQR: 1.8, 4.1). We found a significant association between children's behaviour and the presence or absence of ongoing middle ear issues in relation to the delay in obtaining a reliable behavioural audiogram. When comparing the hearing thresholds at diagnosis with the first reliable behavioural audiogram across different frequencies, it was observed that the majority of children experienced deterioration rather than improvement in the initial impaired ear at each frequency. Notably, there were more instances of hearing changes (either deterioration or improvement), in the 500 Hz and 1,000 Hz frequency ranges compared to the 2,000 Hz and 4,000 Hz ranges. Seventy-eight percent (n = 71) of children had hearing deterioration between the diagnosis and the first behavioural audiogram at one or more frequencies between 0.5 and 4 kHz, with a high proportion of them (52 out of the 71, 73.2%) developing severe to profound hearing loss. When using the averaged three frequency thresholds (i.e., definition 2), only 26.4% of children (n = 24) in the sample were identified as having hearing deterioration. Applying definition 2 therefore underestimates the proportion of children that experienced hearing changes. The study also reported diverse characteristics of children with or without hearing deterioration. Conclusion: The finding that 78% of children diagnosed with UHL at birth had a decrease in hearing loss between the hearing levels at first diagnosis and their first behavioural audiogram highlights the importance of monitoring hearing threshold levels after diagnosis, so that appropriate intervention can be implemented in a timely manner. For clinical management, deterioration of 15 dB at one or more frequencies that does not recover warrants action.

Effect of Frailty on Hospital Outcomes Among Pediatric Cancer Patients in the United States: Results From the National Inpatient Sample.

BACKGROUND: Studies on frailty among pediatric patients with cancer are scarce. In this study, we sought to understand the effects of frailty on hospital outcomes in pediatric patients with cancer. METHODS: This retrospective study used data collected and stored in the Nationwide Inpatient Sample (NIS) between 2005 and 2014. These were hospitalized patients and hence represented the sickest group of patients. Frailty was measured using the frailty definition diagnostic indicator by Johns Hopkins Adjusted Clinical Groups. RESULTS: Of 187,835 pediatric cancer hospitalizations included in this analysis, 11,497 (6.1%) were frail. The average hospitalization costs were $86,910 among frail and $40,358 for nonfrail patients. In propensity score matching analysis, the odds of in-hospital mortality (odds ratio, 2.08; 95% CI, 1.71-2.52) and length of stay (odds ratio, 3.76; 95% CI, 3.46-4.09) were significantly greater for frail patients. The findings of our study suggest that frailty is a crucial clinical factor to be considered when treating pediatric cancer patients in a hospital setting. CONCLUSIONS: These findings highlight the need for further research on frailty-based risk stratification and individualized interventions that could improve outcomes in frail pediatric cancer patients. The adaptation and validation of a frailty-defining diagnostic tool in the pediatric population is a high priority in the field.

Acoustic change complex for assessing speech discrimination in normal-hearing and hearing-impaired infants.

OBJECTIVE: This study examined (1) the utility of a clinical system to record acoustic change complex (ACC, an event-related potential recorded by electroencephalography) for assessing speech discrimination in infants, and (2) the relationship between ACC and functional performance in real life. METHODS: Participants included 115 infants (43 normal-hearing, 72 hearing-impaired), aged 3-12 months. ACCs were recorded using [szs], [uiu], and a spectral rippled noise high-pass filtered at 2 kHz as stimuli. Assessments were conducted at age 3-6 months and at 7-12 months. Functional performance was evaluated using a parent-report questionnaire, and correlations with ACC were examined. RESULTS: The rates of onset and ACC responses of normal-hearing infants were not significantly different from those of aided infants with mild or moderate hearing loss but were significantly higher than those with severe loss. On average, response rates measured at 3-6 months were not significantly different from those at 7-12 months. Higher rates of ACC responses were significantly associated with better functional performance. CONCLUSIONS: ACCs demonstrated auditory capacity for discrimination in infants by 3-6 months. This capacity was positively related to real-life functional performance. SIGNIFICANCE: ACCs can be used to evaluate the effectiveness of amplification and monitor development in aided hearing-impaired infants.

Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease.

INTRODUCTION: Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions. METHODS: In three stages, a total of 34 leukocyte antigens were examined by flow cytometry immunophenotyping. Data were analyzed by logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: We identified leukocyte markers differentially expressed in the patients with AD. Pathway analysis revealed a complex network involving upregulation of complement inhibition and downregulation of cargo receptor activity and Aß clearance. A proposed panel including four leukocyte markers - CD11c, CD59, CD91, and CD163 - predicts patients' PET Aß status with an area under the curve (AUC) of 0.93 (0.88 to 0.97). CD163 was the top performer in preclinical models. These findings have been validated in two independent cohorts. CONCLUSION: Our finding of changes on peripheral leukocyte surface antigens in AD implicates the deficit in innate immunity. Leukocyte-based biomarkers prove to be both sensitive and practical for AD screening and diagnosis.

Predicting 9-Year Language Ability from Preschool Speech Recognition in Noise in Children Using Cochlear Implants.

The presence of congenital permanent childhood hearing loss has a negative impact on children's development and lives. The current literature documents weaknesses in speech perception in noise and language development in many children with hearing loss. However, there is a lack of clear evidence for a longitudinal relationship between early speech perception abilities and later language skills. This study addressed the evidence gap by drawing on data collected as part of the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study. Cross-lagged regression analyses were used to examine the influence of speech perception in noise at age 5 years on language ability at age 9 years and vice versa (i.e. the influence of language ability at age 5 years on speech perception in noise at age 9 years). Data from 56 children using cochlear implants were analysed. We found that preschool speech perception in noise was a significant predictor of language ability at school age, after controlling for the effect of early language. The findings lend support to early intervention that targets the improvement of language skills, but also highlight the need for intervention and technology to enhance young children's auditory capabilities for perceiving speech in noise in early childhood so that outcomes of children with hearing loss in school can be maximized.

The Chinese version of the Parents' Evaluation of Aural/Oral Performance of Children (PEACH) rating scale for infants and children with normal hearing.

OBJECTIVE: This study aimed to establish Chinese norms for the Chinese version of the Parent's Evaluation of Aural/Oral of Children (PEACH) rating scale. DESIGN AND STUDY SAMPLE: The PEACH scores were collected from 198 parents whose children have normal hearing. The test-retest reliability of the PEACH scale was evaluated in a subgroup of 34 parents. Another 27 parents also filled out a Putonghua Communicative Development Inventory which was used to explore the relationship between the PEACH ratings and language scores. RESULTS: The normative curve was established using a logit regression function. The total scores increase rapidly with increasing age. A plateau starts from 22 months with the PEACH score reaching 90% and achieves the maximum score of 95% by 47 months of age. The test-retest analyses showed high reliability for all subscales, with all the correlation coefficients values exceeding 0.9 (p < 0.01). The 90% and 95% confidence intervals were provided to facilitate evaluation of differences between scores obtained under different conditions. A significant correlation was found between the PEACH total score and language performance (p < 0.05). CONCLUSIONS: Normative data from the Chinese population was provided to enable performance of an individual child to be related to their normally hearing peers.

Barriers to dementia diagnosis and care in China.

In China, the ageing population and the prevalence of dementia are projected to escalate significantly by 2050 resulting in a substantial increase in health and economic burden on caregivers, healthcare facilities, healthcare providers and communities. There is no published national dementia policy or strategy in China. This case report describes significant barriers contributing to diagnostic problems and inadequate care of dementia through the case of an older female in rural China, whose condition deteriorated due to neuropsychiatric and functional symptoms of undiagnosed dementia. Intersectoral collaboration between care organisations facilitated delivery of a non-pharmacological intervention programme which was associated with improvements in the patient's functional and neuropsychiatric symptoms. The case demonstrates that recruitment and training of a wider range of health and care professionals and caregivers in a systematic approach to non-pharmacological interventions could help overcome barriers to the specialised care needs of people with dementia where resources are lacking.

Characterization of a Dopamine Transporter and Its Splice Variant Reveals Novel Features of Dopaminergic Regulation in the Honey Bee.

Dopamine is an important neuromodulator involved in reward-processing, movement control, motivational responses, and other aspects of behavior in most animals. In honey bees (Apis mellifera), the dopaminergic system has been implicated in an elaborate pheromonal communication network between individuals and in the differentiation of females into reproductive (queen) and sterile (worker) castes. Here we have identified and characterized a honey bee dopamine transporter (AmDAT) and a splice variant lacking exon 3 (AmDATΔex3). Both transcripts are present in the adult brain and antennae as well as at lower levels within larvae and ovaries. When expressed separately in the Xenopus oocyte system, AmDAT localizes to the oocyte surface whereas the splice variant is retained at an internal membrane. Oocytes expressing AmDAT exhibit a 12-fold increase in the uptake of [3H]dopamine relative to non-injected oocytes, whereas the AmDATΔex3-expressing oocytes show no change in [3H]dopamine transport. Electrophysiological measurements of AmDAT activity revealed it to be a high-affinity, low-capacity transporter of dopamine. The transporter also recognizes noradrenaline as a major substrate and tyramine as a minor substrate, but does not transport octopamine, L-Dopa, or serotonin. Dopamine transport via AmDAT is inhibited by cocaine in a reversible manner, but is unaffected by octopamine. Co-expression of AmDAT and AmDATΔex3 in oocytes results in a substantial reduction in AmDAT-mediated transport, which was also detected as a significant decrease in the level of AmDAT protein. This down-regulatory effect is not attributable to competition with AmDATΔex3 for ER ribosomes, nor to a general inhibition of the oocyte's translational machinery. In vivo, the expression of both transcripts shows a high level of inter-individual variability. Gene-focused, ultra-deep amplicon sequencing detected methylation of the amdat locus at ten 5'-C-phosphate-G-3' dinucleotides (CpGs), but only in 5-10% of all reads in whole brains or antennae. These observations, together with the localization of the amdat transcript to a few clusters of dopaminergic neurons, imply that amdat methylation is positively linked to its transcription. Our findings suggest that multiple cellular mechanisms, including gene splicing and epigenomic communication systems, may be adopted to increase the potential of a conserved gene to contribute to lineage-specific behavioral outcomes.

Spoken language and everyday functioning in 5-year-old children using hearing aids or cochlear implants.

OBJECTIVE: This study investigated the factors influencing 5-year language, speech and everyday functioning of children with congenital hearing loss. DESIGN: Standardised tests including PLS-4, PPVT-4 and DEAP were directly administered to children. Parent reports on language (CDI) and everyday functioning (PEACH) were collected. Regression analyses were conducted to examine the influence of a range of demographic variables on outcomes. STUDY SAMPLE: Participants were 339 children enrolled in the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study. RESULTS: Children's average receptive and expressive language scores were approximately 1 SD below the mean of typically developing children, and scores on speech production and everyday functioning were more than 1 SD below. Regression models accounted for 70-23% of variance in scores across different tests. Earlier CI switch-on and higher non-verbal ability were associated with better outcomes in most domains. Earlier HA fitting and use of oral communication were associated with better outcomes on directly administered language assessments. Severity of hearing loss and maternal education influenced outcomes of children with HAs. The presence of additional disabilities affected outcomes of children with CIs. CONCLUSIONS: The findings provide strong evidence for the benefits of early HA fitting and early CI for improving children's outcomes.

Hearing aid fitting and developmental outcomes of children fit according to either the NAL or DSL prescription: fit-to-target, audibility, speech and language abilities.

OBJECTIVE: This study examined the influence of prescription on hearing aid (HA) fitting characteristics and 5-year developmental outcomes of children. DESIGN: A randomised controlled trial implemented as part of a population-based study on Longitudinal Outcomes of Children with Hearing Impairment (LOCHI). STUDY SAMPLE: Two-hundred and thirty-two children that were fit according to either the National Acoustic Laboratories (NAL) or Desired Sensation Level (DSL) prescription. RESULTS: Deviation from targets and root-mean-square error in HA fitting revealed no significant difference between fitting prescriptions. Aided audibility quantified by using the Speech Intelligibility Index (SII) model showed that DSL provided higher audibility than NAL at low and medium input levels but not at high input level. After allowing for hearing loss desensitisation, differences in audibility between prescription groups were significant only at low input level. The randomised trial of prescription that was implemented for 163 children revealed no significant between-group differences in speech production, perception, and language; but parent-rated functional performance was higher for the DSL than for the NAL group. CONCLUSIONS: Proximity to prescriptive targets was similar between fitting prescriptions. The randomised trial revealed differences in aided audibility at low input level between prescription groups, but no significant differences in speech and language abilities.

Factors influencing speech perception in noise for 5-year-old children using hearing aids or cochlear implants.

OBJECTIVE: We investigated the factors influencing speech perception in babble for 5-year-old children with hearing loss who were using hearing aids (HAs) or cochlear implants (CIs). DESIGN: Speech reception thresholds (SRTs) for 50% correct identification were measured in two conditions - speech collocated with babble, and speech with spatially separated babble. The difference in SRTs between the two conditions give a measure of binaural unmasking, commonly known as spatial release from masking (SRM). Multiple linear regression analyses were conducted to examine the influence of a range of demographic factors on outcomes. STUDY SAMPLE: Participants were 252 children enrolled in the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study. RESULTS: Children using HAs or CIs required a better signal-to-noise ratio to achieve the same level of performance as their normal-hearing peers but demonstrated SRM of a similar magnitude. For children using HAs, speech perception was significantly influenced by cognitive and language abilities. For children using CIs, age at CI activation and language ability were significant predictors of speech perception outcomes. CONCLUSIONS: Speech perception in children with hearing loss can be enhanced by improving their language abilities. Early age at cochlear implantation was also associated with better outcomes.

Cortical Auditory Evoked Potentials Reveal Changes in Audibility with Nonlinear Frequency Compression in Hearing Aids for Children: Clinical Implications.

Hearing loss in children is detected soon after birth via newborn hearing screening. Procedures for early hearing assessment and hearing aid fitting are well established, but methods for evaluating the effectiveness of amplification for young children are limited. One promising approach to validating hearing aid fittings is to measure cortical auditory evoked potentials (CAEPs). This article provides first a brief overview of reports on the use of CAEPs for evaluation of hearing aids. Second, a study that measured CAEPs to evaluate nonlinear frequency compression (NLFC) in hearing aids for 27 children (between 6.1 and 16.8 years old) who have mild to severe hearing loss is reported. There was no significant difference in aided sensation level or the detection of CAEPs for /g/ between NLFC on and off conditions. The activation of NLFC was associated with a significant increase in aided sensation levels for /t/ and /s/. It also was associated with an increase in detection of CAEPs for /t/ and /s/. The findings support the use of CAEPs for checking audibility provided by hearing aids. Based on the current data, a clinical protocol for using CAEPs to validate audibility with amplification is presented.

Aided cortical response, speech intelligibility, consonant perception and functional performance of young children using conventional amplification or nonlinear frequency compression.

OBJECTIVE: The aim of this study was to compare conventional processing with nonlinear frequency compression (NLFC) in hearing aids for young children with bilateral hearing loss. METHODS: Sixty-four children aged between 2 and 7 years with bilateral hearing aids were recruited. Evaluations of cortical responses, speech intelligibility rating, consonant perception and functional performance were completed with the children wearing their personal hearing aids with conventional processing. The children were then refitted with new hearing aids with NLFC processing. Following a six-week familiarization period, they were evaluated again while using their hearing aids with NLFC activated. RESULTS: The mean speech intelligibility rating and the number of cortical responses present for /s/were significantly higher when children were using NLFC processing than conventional processing in their hearing aids (p<0.05). Parents judged the children's functional real life performance with the NLFC hearing aids to be similar or better than that with the children's own hearing aids in both quiet and noisy situations. The mean percent consonant score was higher with NLFC processing compared to conventional processing, but the difference did not reach the 5% significance level (p=0.056). An overall figure of merit (FOM) was calculated by averaging the standardized difference scores between processing schemes for all measures. Regression analysis revealed that, on average, greater advantage for NLFC processing was associated with poorer hearing at 4 kHz. CONCLUSIONS: Compared to conventional processing, the use of NLFC was, on average, effective in increasing audibility of /s/as measured by cortical evaluations, and higher ratings on speech intelligibility and functional performance in real life by parents. On average, greater benefits from NLFC processing was associated with poorer hearing at 4 kHz.

Language and speech perception of young children with bimodal fitting or bilateral cochlear implants.

OBJECTIVES: This paper compares language development and speech perception of children with bimodal fitting (a cochlear implant in one ear and a hearing aid in the opposite ear) or bilateral cochlear implantation. METHODS: Participants were children enrolled in the Longitudinal Outcomes of Children with Hearing Impairment study. Language development was assessed at 3 years of age using standardized tests. Speech perception was evaluated at 5 years of age. Speech was presented from a frontal loudspeaker, and babble noise was presented either from the front or from both sides. RESULTS: On average, there was no significant difference in language outcomes between 44 children with bimodal fitting and 49 children with bilateral cochlear implants; after controlling for a range of demographic variables. Earlier age at cochlear implant activation was associated with better outcomes. Speech perception in noise was not significantly different between children with bimodal fitting and those with bilateral cochlear implants. Compared to normal-hearing children, children with cochlear implants required a better signal-to-noise ratio to perform at the same level, but demonstrated spatial release from masking of a similar magnitude. CONCLUSIONS: This population-based study found that language scores for children with bilateral implants were higher than those with bimodal fitting or those with unilateral implants, but neither reached significance level.

A comparison of NAL and DSL prescriptive methods for paediatric hearing-aid fitting: predicted speech intelligibility and loudness.

OBJECTIVE: To examine the impact of prescription on predicted speech intelligibility and loudness for children. DESIGN: A between-group comparison of speech intelligibility index (SII) and loudness, based on hearing aids fitted according to NAL-NL1, DSL v4.1, or DSL m[i/o] prescriptions. A within-group comparison of gains prescribed by DSL m[i/o] and NAL-NL2 for children in terms of SII and loudness. STUDY SAMPLE: Participants were 200 children, who were randomly assigned to first hearing-aid fitting with either NAL-NL1, DSL v4.1, or DSL m[i/o]. Audiometric data and hearing-aid data at 3 years of age were used. RESULTS: On average, SII calculated on the basis of hearing-aid gains were higher for DSL than for NAL-NL1 at low input level, equivalent at medium input level, and higher for NAL-NL1 than DSL at high input level. Greater loudness was associated with DSL than with NAL-NL1, across a range of input levels. Comparing NAL-NL2 and DSL m[i/o] target gains revealed higher SII for the latter at low input level. SII was higher for NAL-NL2 than for DSL m[i/o] at medium- and high-input levels despite greater loudness for gains prescribed by DSL m[i/o] than by NAL-NL2. CONCLUSION: The choice of prescription has minimal effects on speech intelligibility predictions but marked effects on loudness predictions.

A randomized controlled trial of nonlinear frequency compression versus conventional processing in hearing aids: speech and language of children at three years of age.

OBJECTIVE: To determine the effect of nonlinear frequency compression (NLFC) on children's development of speech and language at three years of age. DESIGN: A randomized controlled trial was conducted as part of the population-based longitudinal study on outcomes of children with hearing impairment (LOCHI). Participants were randomly assigned to fitting with NLFC (Phonak Naida V SP or UP) or with conventional processing in hearing aids, prescribed by using either the NAL or the DSL formula. Standardized tests of speech production, receptive and expressive language were administered, and parent ratings were collected. All assessments were double-blinded. STUDY SAMPLE: Participants were 44 of the 450 children in the LOCHI cohort. RESULTS: Compared to children using conventional processing, receptive and expressive language was higher but receptive vocabulary and consonant articulation scores were lower for children who use NLFC. There was increased substitution of affricates by fricatives for children using NLFC, compared to children using conventional amplification. After allowing for the effect of multiple demographic variables, the difference in global language scores between groups was not significant (effect: 0.8 [95% confidence interval: - 6.7, 8.3]). CONCLUSIONS: There is insufficient evidence to indicate a difference in language ability between children using NLFC and those using conventional amplification.

Impact of the presence of auditory neuropathy spectrum disorder (ANSD) on outcomes of children at three years of age.

OBJECTIVE: To determine the influence of the presence of auditory neuropathy spectrum disorder (ANSD) on speech, language, and psycho-social development of children at three years of age. DESIGN: A population-based, longitudinal study was performed on outcomes of children with hearing impairment (LOCHI) in Australia. The demographic characteristics of the children were described, and their developmental outcomes were evaluated at three years of age. Performance of children with ANSD was compared with that of children without ANSD in the LOCHI study. STUDY SAMPLE: There were 47 children with ANSD in the study sample. RESULTS: Sixty-four percent of children with ANSD have hearing sensitivity loss ranging from mild to severe degree, and the remaining have profound hearing loss. At three years, 27 children used hearing aids, 19 used cochlear implants, and one child did not use any hearing device. Thirty percent of children have disabilities in addition to hearing loss. On average, there were no significant differences in performance level between children with and without ANSD. Also, the variability of scores was not significantly different between the two groups. CONCLUSIONS: There was no significant difference in performance levels or variability between children with and without ANSD, both for children who use hearing aids, and children who use cochlear implants.