Phenome risk classification enables phenotypic imputation and gene discovery in developmental stuttering.

Developmental stuttering is a speech disorder characterized by disruption in the forward movement of speech. This disruption includes part-word and single-syllable repetitions, prolongations, and involuntary tension that blocks syllables and words, and the disorder has a life-time prevalence of 6-12%. Within Vanderbilt's electronic health record (EHR)-linked biorepository (BioVU), only 142 individuals out of 92,762 participants (0.15%) are identified with diagnostic ICD9/10 codes, suggesting a large portion of people who stutter do not have a record of diagnosis within the EHR. To identify individuals affected by stuttering within our EHR, we built a PheCode-driven Gini impurity-based classification and regression tree model, PheML, by using comorbidities enriched in individuals affected by stuttering as predicting features and imputing stuttering status as the outcome variable. Applying PheML in BioVU identified 9,239 genotyped affected individuals (a clinical prevalence of ∼10%) for downstream genetic analysis. Ancestry-stratified GWAS of PheML-imputed affected individuals and matched control individuals identified rs12613255, a variant near CYRIA on chromosome 2 (B = 0.323; p value = 1.31 × 10-8) in European-ancestry analysis and rs7837758 (B = 0.518; p value = 5.07 × 10-8), an intronic variant found within the ZMAT4 gene on chromosome 8, in African-ancestry analysis. Polygenic-risk prediction and concordance analysis in an independent clinically ascertained sample of developmental stuttering cases validate our GWAS findings in PheML-imputed affected and control individuals and demonstrate the clinical relevance of our population-based analysis for stuttering risk.

Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing.

BACKGROUND: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB). METHODS AND MATERIALS: We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans. RESULTS: Thirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy. CONCLUSIONS: Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. PLAIN LANGUAGE SUMMARY: In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.

Left hippocampal dosimetry correlates with visual and verbal memory outcomes in survivors of pediatric brain tumors.

BACKGROUND: Radiotherapy (RT) in the pediatric brain tumor population causes late neurocognitive effects. In the current study, the authors investigated associations between clinical and dosimetric risk factors and memory outcomes in a cohort of patients treated with proton radiotherapy (PRT). METHODS: A total of 70 patients (median age at PRT, 12.1 years [range, 5.0-22.5 years]) who were treated with PRT were identified with baseline and follow-up evaluations of visual and verbal memory (Children's Memory Scale and the third edition of the Wechsler Memory Scale). Whole-brain as well as bilateral hippocampal and temporal lobe contours were delineated for the calculation of dosimetric indices. Multivariate analyses were performed to assess associations of score changes over time with clinical factors and dosimetric indices. RESULTS: The median neurocognitive follow-up was 3.0 years (range, 1.1-11.4 years). For the entire cohort, delayed and immediate verbal memory scaled scores demonstrated small declines. The mean decline for delayed verbal memory scores was 0.6 (P = .01), and that for immediate verbal memory scores was 0.5 (P = .06). Immediate and delayed visual memory scores were not found to change significantly (+0.1 and -0.3, respectively; P>.30). A higher left hippocampal V20GyE (percentage of the volume of a particular anatomical region receiving at least a 20 gray equivalent) was correlated with a score decline in all 4 measures. Female sex was found to be predictive of lower delayed verbal memory follow-up scores (P = .035). CONCLUSIONS: Only delayed verbal memory scores were found to have declined statistically significantly at follow-up after PRT, reflecting some weakness in verbal memory retrieval. Given a correlation of left hippocampal dosimetry and memory outcomes after PRT, left hippocampal-sparing PRT plans may assist patients with pediatric brain tumors in preserving memory-retrieval abilities. Cancer 2018;124:2238-45. © 2018 American Cancer Society.

Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study.

BACKGROUND: Compared with traditional photon radiotherapy, proton radiotherapy irradiates less normal tissue and might improve health outcomes associated with photon radiotherapy by reducing toxic effects to normal tissue. We did a trial to assess late complications, acute side-effects, and survival associated with proton radiotherapy in children with medulloblastoma. METHODS: In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients aged 3-21 years who had medulloblastoma. Patients had craniospinal irradiation of 18-36 Gy radiobiological equivalents (GyRBE) delivered at 1·8 GyRBE per fraction followed by a boost dose. The primary outcome was cumulative incidence of ototoxicity at 3 years, graded with the Pediatric Oncology Group ototoxicity scale (0-4), in the intention-to-treat population. Secondary outcomes were neuroendocrine toxic effects and neurocognitive toxic effects, assessed by intention-to-treat. This study is registered at ClinicalTrials.gov, number NCT00105560. FINDINGS: We enrolled 59 patients from May 20, 2003, to Dec 10, 2009: 39 with standard-risk disease, six with intermediate-risk disease, and 14 with high-risk disease. 59 patients received chemotherapy. Median follow-up of survivors was 7·0 years (IQR 5·2-8·6). All patients received the intended doses of proton radiotherapy. The median craniospinal irradiation dose was 23·4 GyRBE (IQR 23·4-27·0) and median boost dose was 54·0 GyRBE (IQR 54·0-54·0). Four (9%) of 45 evaluable patients had grade 3-4 ototoxicity according to Pediatric Oncology Group ototoxicity scale in both ears at follow-up, and three (7%) of 45 patients developed grade 3-4 ototoxicity in one ear, although one later reverted to grade 2. The cumulative incidence of grade 3-4 hearing loss at 3 years was 12% (95% CI 4-25). At 5 years, it was 16% (95% CI 6-29). Pediatric Oncology Group hearing ototoxicity score at a follow-up of 5·0 years (IQR 2·9-6·4) was the same as at baseline or improved by 1 point in 34 (35%) of 98 ears, worsened by 1 point in 21 (21%), worsened by 2 points in 35 (36%), worsened by 3 points in six (6%), and worsened by 4 points in two (2%). Full Scale Intelligence Quotient decreased by 1·5 points (95% CI 0·9-2·1) per year after median follow-up up of 5·2 years (IQR 2·6-6·4), driven by decrements in processing speed and verbal comprehension index. Perceptual reasoning index and working memory did not change significantly. Cumulative incidence of any neuroendocrine deficit at 5 years was 55% (95% CI 41-67), with growth hormone deficit being most common. We recorded no cardiac, pulmonary, or gastrointestinal late toxic effects. 3-year progression-free survival was 83% (95% CI 71-90) for all patients. In post-hoc analyses, 5-year progression-free survival was 80% (95% CI 67-88) and 5-year overall survival was 83% (95% CI 70-90). INTERPRETATION: Proton radiotherapy resulted in acceptable toxicity and had similar survival outcomes to those noted with conventional radiotherapy, suggesting that the use of the treatment may be an alternative to photon-based treatments. FUNDING: US National Cancer Institute and Massachusetts General Hospital.

The function of repeating: The relation between word class and repetition type in developmental stuttering.

BACKGROUND: It is already known that preschool-age children who stutter (CWS) tend to stutter on function words at the beginning of sentences. It is also known that phonological errors potentially resulting in part-word repetitions tend to occur on content words. However, the precise relation between word class and repetition type in preschool-age stuttering is unknown. AIMS: To investigate repetitions associated with monosyllabic words in preschool-age CWS. Specifically, it was hypothesized that repetition type should vary according to word class in preschool-age CWS and children who do not stutter (CWNS). METHODS & PROCEDURES: Thirteen preschool-age CWS and 15 preschool-age CWNS produced age-appropriate narratives, which were transcribed and coded for part-word repetitions (PWR) and whole-word repetitions (WWR) occurring on monosyllabic words. Each repetition type was also coded for word class (i.e., function versus content). OUTCOMES & RESULTS: Results indicated that although CWS and CWNS were significantly more likely to produce PWR on content words, this tendency did not differ between the two talker groups. Further, CWS and CWNS did not differ in their tendencies to produce PWR versus WWR overall, but the tendency to produce repetitions on function words was significantly greater for CWS versus CWNS. CONCLUSIONS & IMPLICATIONS: Findings are taken to suggest that repetitions of monosyllabic words in young children are not easily explained from the perspective of phonological errors, but may instead be considered from an incremental planning of speech perspective.

Diversity of Research Participant Gender, Race, and Ethnicity in Communication Sciences and Disorders: A Systematic Review and Quantitative Synthesis of American Speech-Language-Hearing Association Publications in 2020.

Purpose: One manifestation of systemic inequities in communication sciences and disorders (CSD) is the chronic underreporting and underrepresentation of sex, gender, race, and ethnicity in research. The present study characterized recent demographic reporting practices and representation of participants across CSD research. Methods: We systematically reviewed and extracted key reporting and participant data from empirical studies conducted in the United States (US) with human participants published in the year 2020 in journals by the American Speech-Language-Hearing Association (ASHA; k = 407 articles comprising a total n = 80,058 research participants, search completed November 2021). Sex, gender, race, and ethnicity were operationalized per National Institutes of Health guidelines (National Institutes of Health, 2015a, 2015b). Results: Sex or gender was reported in 85.5% of included studies; race was reported in 33.7%; and ethnicity was reported in 13.8%. Sex and gender were clearly differentiated in 3.4% of relevant studies. Where reported, median proportions for race and ethnicity were significantly different from the US population, with underrepresentation noted for all non-White racial groups and Hispanic participants. Moreover, 64.7% of studies that reported sex or gender and 67.2% of studies that reported race or ethnicity did not consider these respective variables in analyses or discussion. Conclusion: At present, research published in ASHA journals frequently fails to report key demographic data summarizing the characteristics of participants. Moreover, apparent gaps in representation of minoritized racial and ethnic groups threaten the external validity of CSD research and broader health care equity endeavors in the US. Although our study is limited to a single year and publisher, our results point to several steps for readers that may bring greater accountability, consistency, and diversity to the discipline.

A reconsideration of Gallicolumba (Aves: Columbidae) relationships using fresh source material reveals pseudogenes, chimeras, and a novel phylogenetic hypothesis.

Phylogenetic analyses of nuclear and mitochondrial DNA sequences were used to test a recent phylogenetic hypothesis for the avian genus Gallicolumba that relied heavily on preserved museum study skins for DNA samples. Our comparisons show that several published gene sequences represent pseudogenes or chimeras of multiple taxa, and these sequences had an adverse influence on phylogeny estimation. A new phylogenetic hypothesis strongly supports the monophyly of Philippine bleeding-hearts, the monophyly of Gallicolumba sensu stricto, and places Leucosarcia as part of an Australasian radiation rather than sister to Alopecoenas. These findings clarify Gallicolumba biogeography and also highlight the need for greater caution in the use of suboptimal source material in molecular systematic studies.

Behavioral and cognitive-affective features of stuttering in preschool-age children: Regression and exploratory cluster analyses.

PURPOSE: The purpose of this study was to investigate associations among behavioral and cognitive-affective features of stuttering in preschool-age children who stutter, and the extent to which participants may or may not cluster together based on multiple indices of stuttering. METHODS: Participants were 296 preschool-age children who stutter (mean age 47.9 months). Correlation and regression analyses, as well as k-means cluster analyses were conducted between and among several indices of stuttering: frequency of stuttering- and non-stuttering-like disfluencies (SLDs and NSLDs), ratios of repetitions and prolongations/blocks out of total number of SLDs, associated nonspeech behaviors, duration of stuttering events, KiddyCAT scores (Vanryckeghem & Brutten, 2007), and a TOCS parent-rated scale (Gillam et al., 2009). RESULTS: For preschool-age children who stutter, most indices of overt stuttering behaviors were intercorrelated (e.g., more SLDs were associated with higher ratio of repetitions). Self-reported KiddyCAT scores (Vanryckeghem & Brutten, 2007) were largely not significantly associated with stuttering. Cluster analyses yielded two participant groupings: a larger group with less prominent stuttering features and a smaller group with more prominent features. CONCLUSIONS: This study contributes to an increasingly comprehensive and nuanced understanding of the heterogeneous features of stuttering and their development in preschool-age children. Findings show strong intercorrelations between measures of stuttering behaviors, but more tenuous relationships between behaviors and cognitive-affective reactions to stuttering. Exploration of clusters of characteristics within this population revealed potential opportunities for future research.

A study of respiratory sinus arrhythmia and stuttering persistence.

INTRODUCTION: The present study investigated potential differences in respiratory sinus arrhythmia between preschool-age children with persisting stuttering, children who recovered from stuttering, and children who do not stutter. METHODS: Participants were 10 children with persisting stuttering (persisting group), 20 children who recovered from stuttering (recovered group), and 36 children who do not stutter (non-stuttering group). Participants viewed a neutral video clip to establish a pre-arousal baseline and then viewed two emotionally-arousing video clips (positive and negative, counterbalanced). Age-appropriate speaking tasks followed each of the video clips (post-baseline, post-positive, and post-negative). Respiratory sinus arrhythmia (RSA), an index of parasympathetic nervous system activity, was measured during the video clips and subsequent speaking tasks. RESULTS: First, the persisting group, recovered group, and non-stuttering group did not significantly differ in baseline RSA. Second, during the emotionally-arousing video clips, there was a significant group x condition interaction, with the recovered group exhibiting significantly lower RSA in the positive than negative condition, and the non-stuttering group exhibiting significantly higher RSA in the positive than negative condition. Third, in the narrative tasks, there was a significant group x condition interaction, with a greater difference in RSA between the post-baseline speaking task and the post-positive and post-negative speaking tasks for the persisting compared to the non-stuttering group. Lastly, a follow-up analysis indicated that the recovered and nonstuttering groups, compared to the persisting group, exhibited significantly greater RSA during the baseline (neutral) condition compared to the post-neutral narrative task. CONCLUSIONS: Findings provide a physiological perspective of emotion within children who stutter and persist and children who stutter and recover. Future investigations with larger sample sizes and diverse methodologies are necessary to provide novel insights on the specific emotion-related processes that are potentially involved with persistence of stuttering in young children.

A Preliminary Study of Speech Rhythm Differences as Markers of Stuttering Persistence in Preschool-Age Children.

PURPOSE: The purpose of this study was twofold: (a) to determine whether there are speech rhythm differences between preschool-age children who stutter that were eventually diagnosed as persisting (CWS-Per) or recovered (CWS-Rec) and children who do not stutter (CWNS), using empirical spectral analysis and empirical mode decomposition of the speech amplitude envelope, and (b) to determine whether speech rhythm characteristics close to onset are predictive of later persistence. METHOD: Fifty children (3-4 years of age) participated in the study. Approximately 2-2.5 years after the experimental testing took place, children were assigned to the following groups: CWS-Per (nine boys, one girl), CWS-Rec (18 boys, two girls), and CWNS (18 boys, two girls). All children produced a narrative based on a text-free storybook. From the audio recordings of these narratives, fluent utterances were selected for each child from which seven envelope-based measures were extracted. Group-based differences on each measure as well as predictive analyses were conducted to identify measures that discriminate CWS-Per versus CWS-Rec. RESULTS: CWS-Per were found to have a relatively higher degree of power in suprasyllabic oscillations and greater variability in the timing of syllabic rhythms especially for longer utterances. A logistic regression model using two speech rhythm measures was able to discriminate the eventual outcome of recovery versus persistence, with 80% sensitivity and 75% specificity. CONCLUSION: Findings suggest that envelope-based speech rhythm measures are a promising approach to assess speech rhythm differences in developmental stuttering, and its potential for identification of children at risk of developing persistent stuttering should be investigated further.

Predicting Persistent Developmental Stuttering Using a Cumulative Risk Approach.

PURPOSE: The purpose of this study was to explore how well a cumulative risk approach, based on empirically supported predictive factors, predicts whether a young child who stutters is likely to develop persistent developmental stuttering. In a cumulative risk approach, the number of predictive factors indicating a child is at risk to develop persistent stuttering is evaluated, and a greater number of indicators of risk are hypothesized to confer greater risk of persistent stuttering. METHOD: We combined extant data on 3- to 5-year-old children who stutter from two longitudinal studies to identify cutoff values for continuous predictive factors (e.g., speech and language skills, age at onset, time since onset, stuttering frequency) and, in combination with binary predictors (e.g., sex, family history of stuttering), used all-subsets regression and receiver operating characteristic curves to compare the predictive validity of different combinations of 10 risk factors. The optimal combination of predictive factors and the odds of a child developing persistent stuttering based on an increasing number of factors were calculated. RESULTS: Based on 67 children who stutter (i.e., 44 persisting and 23 recovered) with relatively strong speech-language skills, the predictive factor model that yielded the best predictive validity was based on time since onset (≥ 19 months), speech sound skills (≤ 115 standard score), expressive language skills (≤ 106 standard score), and stuttering severity (≥ 17 Stuttering Severity Instrument total score). When the presence of at least two predictive factors was used to confer elevated risk to develop persistent stuttering, the model yielded 93% sensitivity and 65% specificity. As a child presented with a greater number of these four risk factors, the odds for persistent stuttering increased. CONCLUSIONS: Findings support the use of a cumulative risk approach and the predictive utility of assessing multiple domains when evaluating a child's risk of developing persistent stuttering. Clinical implications and future directions are discussed.

Validation of the Vanderbilt Responses to Your Child's Speech Rating Scale for Parents of Young Children Who Stutter.

PURPOSE: This study reports the development, refinement, and exploration of the psychometric properties of the Vanderbilt Responses to Your Child's Speech (VRYCS) rating scale, a novel measure designed to assess parents' self-perceived responses to the speech of their children who stutter (CWS). METHOD: Parents of 214 young (ages 2;4[years;months]-5;11) CWS completed the original 40-item version of the VRYCS. Content analyses and an exploratory factor analysis determined the scale's factors and identified specific items corresponding to each. Items that did not load onto the factors were removed and internal consistency was assessed. RESULTS: The final 18-item VRYCS rating scale includes five factors relating to parents' responses to the speech of their CWS including (a) Requesting Change, (b) Speaking for the Child, (c) Supporting Communication, (d) Slowing and Simplifying, and (e) Responding Emotionally. Reliability was demonstrated, responses by parents of CWS were described, and a revised scoring form developed. CONCLUSIONS: The VRYCS is a valid and reliable tool for assessing and exploring parents' perceptions of their own responses to the speech of their CWS for clinical and research purposes. Clinical applications of the VRYCS for assessment and treatment of childhood stuttering are discussed.

Population-based genetic effects for developmental stuttering.

Despite a lifetime prevalence of at least 5%, developmental stuttering, characterized by prolongations, blocks, and repetitions of speech sounds, remains a largely idiopathic speech disorder. Family, twin, and segregation studies overwhelmingly support a strong genetic influence on stuttering risk; however, its complex mode of inheritance combined with thus-far underpowered genetic studies contribute to the challenge of identifying and reproducing genes implicated in developmental stuttering susceptibility. We conducted a trans-ancestry genome-wide association study (GWAS) and meta-analysis of developmental stuttering in two primary datasets: The International Stuttering Project comprising 1,345 clinically ascertained cases from multiple global sites and 6,759 matched population controls from the biobank at Vanderbilt University Medical Center (VUMC), and 785 self-reported stuttering cases and 7,572 controls ascertained from The National Longitudinal Study of Adolescent to Adult Health (Add Health). Meta-analysis of these genome-wide association studies identified a genome-wide significant (GWS) signal for clinically reported developmental stuttering in the general population: a protective variant in the intronic or genic upstream region of SSUH2 (rs113284510, protective allele frequency = 7.49%, Z = -5.576, p = 2.46 × 10-8) that acts as an expression quantitative trait locus (eQTL) in esophagus-muscularis tissue by reducing its gene expression. In addition, we identified 15 loci reaching suggestive significance (p < 5 × 10-6). This foundational population-based genetic study of a common speech disorder reports the findings of a clinically ascertained study of developmental stuttering and highlights the need for further research.

Decade-long disease, secondary malignancy, and brainstem injury outcomes in pediatric and young adult medulloblastoma patients treated with proton radiotherapy.

BACKGROUND: Survivors of pediatric medulloblastoma experience long-term morbidity associated with the toxic effects of postoperative radiotherapy (RT). Proton RT limits radiation dose to normal tissues thereby reducing side effects of treatment while maintaining high cure rates. However, long-term data on disease outcomes and long-term effects of proton RT remain limited. METHODS: One hundred seventy-eight pediatric medulloblastoma patients treated with proton RT between 2002 and 2016 at the Massachusetts General Hospital comprise the cohort of patients who were treated with surgery, radiation therapy, and chemotherapy. We evaluated event-free survival (EFS), overall survival (OS), and local control using the Kaplan-Meier method. The cumulative incidence of brainstem injury and secondary malignancies was assessed. RESULTS: Median follow-up was 9.3 years. One hundred fifty-nine patients (89.3%) underwent a gross total resection (GTR). The 10-year OS for the entire cohort, standard-risk (SR), and intermediate/high-risk (IR/HR) patients was 79.3%, 86.9%, and 68.9%, respectively. The 10-year EFS for the entire cohort, SR, and IR/HR cohorts was 73.8%, 79.5%, and 66.2%. The 10-year EFS and OS for patients with GTR/NTR were 75.3% and 81.0% vs 57.7% and 61.0% for subtotal resection (STR). On univariate analysis, IR/HR status was associated with inferior EFS, while both anaplastic histology and IR/HR status were associated with worse OS. The 10-year cumulative incidence of secondary tumors and brainstem injury was 5.6% and 2.1%, respectively. CONCLUSIONS: In this cohort study of pediatric medulloblastoma, proton RT was effective, and disease outcomes were comparable to historically treated photon cohorts. The incidence of secondary malignancies and brainstem injury was low in this cohort with mature follow-up.

The impact of self-reported levels of anxiety on respiratory sinus arrhythmia levels in adults who stutter.

PURPOSE: This study investigated whether subjective levels of anxiety predict respiratory sinus arrythmia (RSA) levels in adults who stutter (AWS) compared to (ANS) during baseline and social stress situations. METHODS: Participants were eight AWS and 10 ANS who performed a modified version of the Trier Social Stress Test (TSST-M). For this, participants were required to prepare and deliver a 5-minute speech and perform a nonword reading task in front of what was perceived as a group of professionals trained in public speaking. Measures of respiratory sinus arrhythmia (RSA) were calculated for baseline and TSST-M conditions. Participants also completed the State-Trait Anxiety Inventory (STAI), both the trait (STAI-T) and state (STAI-S) portion, which served as subjective anxiety ratings. Univariate analyses of variances (UNIANOVA) were used to assess the effects of the STAI-T and STAI-S anxiety on respiratory sinus arrhythmia (RSA) levels at pre-stress and TSST-M conditions. RSA, an index of parasympathetic nervous system activity, is considered to be a measure of emotional regulation. The strength of the effects of STAI-T and STAI-S on RSA levels was evaluated with the unstandardized coefficients for each group separately. RESULTS: Results showed a significant difference between groups for the effects of STAI-T on RSA values for the pre-stress nonword reading task. No other significant differences were found between groups for the pre-stress or TSST-M conditions. Slope estimates showed that STAI-T was a significant predictor of RSA values for pre-stress speaking conditions for the AWS but not ANS. No significant fixed effects or interaction effects were found for the STAI-S and RSA levels in the AWS or ANS. Nor were there significant effects of STAI-T on RSA levels in the AWS or ANS for TSST-M conditions. Descriptive analysis revealed the effects found in the AWS during pre-stress conditions were attributed to a subgroup of AWS who reported low self-reports of anxiety (i.e. STAI-T) and high levels of emotional regulation (i.e. RSA) across social stress conditions. DISCUSSION: Low self-reported STAI-T scores simultaneous with high RSA levels in some AWS may reflect a self-regulatory strategy adapted in response to chronic, daily stress associated with stuttering.

Identifying developmental stuttering and associated comorbidities in electronic health records and creating a phenome risk classifier.

PURPOSE: This study aimed to identify cases of developmental stuttering and associated comorbidities in de-identified electronic health records (EHRs) at Vanderbilt University Medical Center, and, in turn, build and test a stuttering prediction model. METHODS: A multi-step process including a keyword search of medical notes, a text-mining algorithm, and manual review was employed to identify stuttering cases in the EHR. Confirmed cases were compared to matched controls in a phenotype code (phecode) enrichment analysis to reveal conditions associated with stuttering (i.e., comorbidities). These associated phenotypes were used as proxy variables to phenotypically predict stuttering in subjects within the EHR that were not otherwise identifiable using the multi-step identification process described above. RESULTS: The multi-step process resulted in the manually reviewed identification of 1,143 stuttering cases in the EHR. Highly enriched phecodes included codes related to childhood onset fluency disorder, adult-onset fluency disorder, hearing loss, sleep disorders, atopy, a multitude of codes for infections, neurological deficits, and body weight. These phecodes were used as variables to create a phenome risk classifier (PheRC) prediction model to identify additional high likelihood stuttering cases. The PheRC prediction model resulted in a positive predictive value of 83 %. CONCLUSIONS: This study demonstrates the feasibility of using EHRs in the study of stuttering and found phenotypic associations. The creation of the PheRC has the potential to enable future studies of stuttering using existing EHR data, including investigations into the genetic etiology.

Clinical outcomes in a large pediatric cohort of patients with ependymoma treated with proton radiotherapy.

BACKGROUND: Treatment for pediatric ependymoma includes surgical resection followed by local radiotherapy (RT). Proton RT (PRT) enables superior sparing of critical structures compared with photons, with potential to reduce late effects. We report mature outcomes, patterns of failure, and predictors of outcomes in patients treated with PRT. METHODS: One hundred fifty patients (<22 y) with World Health Organization grades II/III ependymoma were treated with PRT between January 2001 and January 2019 at Massachusetts General Hospital. Demographic, tumor, and treatment-related characteristics were analyzed. Event-free survival (EFS), overall survival (OS), and local control (LC) were assessed. RESULTS: Median follow-up was 6.5 years. EFS, OS, and LC for the intracranial cohort (n = 145) at 7 years were 63.4%, 82.6%, and 76.1%. Fifty-one patients recurred: 26 (51.0%) local failures, 19 (37.3%) distant failures, and 6 (11.8%) synchronous failures. One hundred sixteen patients (77.3%) underwent gross total resection (GTR), 5 (3.3%) underwent near total resection (NTR), and 29 (19.3%) underwent subtotal resection (STR). EFS for the intracranial cohort at 7 years for GTR/NTR and STR was 70.3% and 35.2%. With multivariate analysis, the effect of tumor excision persisted after controlling for tumor location. There was no adverse effect on disease control if surgery to RT interval was within 9 weeks of GTR/NTR. CONCLUSION: PRT is effective and safe in pediatric ependymoma. Similar to previous studies, GTR/NTR was the most important prognostic factor. Intervals up to 9 weeks from surgery to PRT did not compromise disease outcomes. There was no LC benefit between patients treated with >54 Gray relative biological effectiveness (GyRBE) versus ≤54 GyRBE.

Is what I think I think really what I think? Implicit and explicit attitudes toward stuttering among practicing speech-language pathologists.

PURPOSE: Two studies assessed implicit (Study 1) and explicit (Study 2) attitudes toward stuttering and those who stutter among speech-language pathologists (SLPs). METHOD: In Study 1, 15 SLPs completed the Stuttering Implicit Association Test, a measure of implicit attitudes toward stuttered speech. In Study 2, 40 SLPs provided explicit attitudes about individuals who stutter, assessed via self-report ratings of an adult who stutters and one who does not. Participants also completed measures of experience with stuttering. RESULTS: As a group, clinicians displayed negative implicit attitudes toward stuttering. Explicit attitudes toward a person who stutters were positive, albeit less positive than attitudes toward a person who does not stutter. Amount of prior exposure to stuttering among these experienced SLPs was not significantly associated with either implicit or explicit attitudes. CONCLUSIONS: These findings highlight the importance of evaluating both implicit and explicit attitudes toward stuttering. The finding of positive explicit attitudes but negative implicit attitudes among similar samples of SLPs underscores the need to study implicit attitudes toward stuttering. Considering only explicit attitudes could lead to incomplete conclusions about the complex nature of attitudes toward stuttering.

Attention, Speech-Language Dissociations, and Stuttering Chronicity.

The purpose of this study was to investigate the singular and joint contributions of speech-language dissociations and attention (i.e., distractibility and attention span) to stuttering chronicity. Method Participants, aged 3;0-4;11 (years;months) at an initial visit, were classified as persisting (n = 10; 9 boys), recovered (n = 32; 23 boys), and nonstuttering (n = 28; 19 boys) based on multiple speech and language evaluations spread across 2 years. The evaluations included assessments of articulation, receptive and expressive vocabulary, and omnibus receptive and expressive language. These measures were used to identify speech-language dissociations using a correlation-based statistical approach. Attentional characteristics, which included measures of distractibility and attention span, were based on parent report. Analyses investigated between-group differences related to dissociations and attentional characteristics as well as the relation between these indices. Results There were no significant between-group differences for the persisting and recovered groups on measures of speech-language dissociations; however, the recovered group was found to exhibit less optimal attention span than the persisting group. In addition, children with dissociations exhibited less optimal distractibility and attention spans at the final time point than children without dissociations. Conclusions Present results indicate that attention is related to both stuttering chronicity and the presence of speech-language dissociations; however, they do not support the notion that dissociations are associated with stuttering persistence. These results provide novel insights into the complex nature of the association between developmental stuttering, speech-language dissociations, and attention.