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Damien F Goldberg,1 Claudio Orlich,2 Brian E Flowers,3 Inder P Singh,4 Sydney Tyson,5 Leonard K Seibold,6 Mohammed K ElMallah,7 Elysia M Ison,8 Med Harbin,8 Heather Reynolds,8 Malik Y Kahook9 1Wolstan & Goldberg Eye Associates, Torrance, CA, USA; 2Clinica 20/20, San Jose, Costa Rica; 3Ophthalmology Associates, Fort Worth, TX, USA; 4The Eye Centers of Racine & Kenosha, Racine, WI, USA; 5Eye Associates & SurgiCenter of Vineland, Vineland, NJ, USA; 6Department of Ophthalmology, University of Colorado Eye Center, Aurora, Colorado, USA; 7Ocala Eye, Ocala, FL, USA; 8New World Medical, Rancho Cucamonga, CA, USA; 9Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USACorrespondence: Malik Y Kahook, Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA, Tel +1 720 848 2501, Email Malik.Kahook@cuanschutz.eduPurpose: To report interim results of the VENICE study, a multi-center, randomized, controlled trial (RCT) comparing STREAMLINE Surgical System (STREAMLINE) canaloplasty with iStent inject W (iStent W) implantation in patients with mild-to-moderate primary open-angle glaucoma (POAG) undergoing phacoemulsification.Patients and Methods: Safety and efficacy analyses involving the first 72 randomized eyes are included in this report. Following pre- (Screening) and post-medication washout (Eligibility) visits, one eye per subject was randomized 1:1 to STREAMLINE or iStent W after undergoing uncomplicated phacoemulsification. Subjects were evaluated postoperatively at Day 1, Week 1, Month 1, 3, and 6. Intraocular pressure (IOP) measurements, number of IOP-lowering medications, and adverse events (AEs) were assessed at each follow-up visit.Results: Seventy-two eyes were randomized; 35 underwent STREAMLINE canaloplasty and 37 were implanted with the iStent W. Seventy eyes completed their 6-month follow-up. Both the mean morning post-washout Baseline IOP between STREAMLINE 24.86± 3.05 mmHg and iStent W 25.16± 3.41 mmHg and the mean IOP at 6 months between STREAMLINE eyes 16.52± 3.63 mmHg and iStent W eyes 16.08± 3.19 mmHg were not statistically significantly different (p=0.691 and 0.596, respectively). At 6 months, more eyes were on zero glaucoma medications in the STREAMLINE group (81.8%) compared to the iStent W group (78.4%). In medication-free eyes, the mean IOP was reduced from 24.80± 2.79 mmHg to 16.00± 3.40 mmHg and 24.60± 3.18 mmHg to 15.80± 2.21 mmHg in the STREAMLINE and iStent W groups, respectively (p=0.752). Both groups showed reduction in IOP-lowering medications at every visit, compared to pre-washout (Screening), with STREAMLINE resulting in numerically fewer medications 0.20± 0.48 compared to iStent W 0.40± 0.79 at 6 months (P=0.384). AEs were mild and self-limited.Conclusion: To our knowledge, the VENICE trial is the first RCT involving canaloplasty. These interim findings demonstrated comparable IOP and medication reduction between STREAMLINE canaloplasty and iStent W implantation, when combined with phacoemulsification.Keywords: primary open-angle glaucoma, POAG, STREAMLINE, iStent inject W, canaloplasty, microinvasive glaucoma surgery, MIGS

Drug absorption via chylomicrons holds significant implications for both pharmacokinetics and pharmacodynamics. However, a mechanistic understanding of predicting in vivo intestinal lymphatic uptake remains largely unexplored. This study aimed to delve into the intestinal lymphatic uptake of drugs, investigating both enhancement and inhibition using various excipients through our previously established in vitro model. It also examined the applicability of the model by assessing the lymphatic uptake enhancement of a lymphotropic formulation with linoleoyl polyoxyl-6 glycerides using the same model. The model successfully differentiated among olive, sesame, and peanut oils in terms of lymphatic uptake. However, it did not distinguish between oils containing long-chain fatty acids and coconut oil. Coconut oil, known for its abundance of medium-chain fatty acids, outperformed other oils. This heightened uptake was attributed to the superior emulsification of this oil in artificial chylomicron media due to its high content of medium-chain fatty acids. Additionally, the enhanced uptake of the tested formulation with linoleoyl polyoxyl-6 glycerides underscored the practical applicability of this model in formulation optimization. Moreover, data suggested that increasing the zeta potential of Intralipid® using sodium lauryl sulfate (SLS) and decreasing it using (+/−) chloroquine led to enhanced and reduced uptake in the in vitro model, respectively. These findings indicate the potential influence of the zeta potential on intestinal lymphatic uptake in this model, though further research is needed to explore the possible translation of this mechanism in vivo.

Whether Latinx families use youth mental health services (MHS) depends on complex influences of barriers and facilitators within and outside of the home. This research sought to shed light on caregiver strain as part of the equation focused on parental identification and responses to youth mental health needs. We examined multiple dimensions of caregiver strain as potential mediators between youth mental health symptom severity and psychological counseling utilization. The present sample consisted of 598 Latinx caregivers to youths ages 6-18 who provided information on youth internalizing and externalizing problems, caregiver strain, and youth psychological counseling service utilization within the last year. Our findings suggest that youth symptom severity (internalizing and externalizing problems) was generally positively associated with dimensions of caregiver strain. Youth symptom severity through objective and subjective internalized strain pathways were associated with greater odds of youth MHS utilization. In contrast, youth symptom severity through subjective externalized strain reduced the odds that Latinx caregivers would report utilizing youth MHS. These models only partially mediated the relationship between youth problems and service use. Findings suggest that Latinx caregivers may navigate conflicting sources of strain related to their child's mental health problem severity in ways that may differentially impact the odds that they access youth MHS. Along with addressing structural and systemic barriers to care, utilization of psychological counseling services may also be improved through interventions that help Latinx caregivers view youth services as avenues for addressing caregiver strain and providing psychoeducation that frames externalized strain within a mental health lens.

Background and purpose: Lysosomal-targeted drug delivery can open a new strategy for drug therapy. However, there is currently no universally accepted simulated or artificial lysosomal fluid utilized in the pharmaceutical industry or recognized by the United States Pharmacopeia (USP). Experimental procedure: We prepared a simulated lysosomal fluid (SLYF) and compared its composition to a commercial artificial counterpart. The developed fluid was used to test the dissolution of a commercial product (Robitussin®) of a lysosomotropic drug (dextromethorphan) and to investigate in-vitro lysosomal trapping of two model drugs (dextromethorphan and (+/-) chloroquine). Findings/Results: The laboratory-prepared fluid or SLYF contained the essential components for the lysosomal function in concentrations reflective of the physiological values, unlike the commercial product. Robitussin® passed the acceptance criteria for the dissolution of dextromethorphan in 0.1 N HCl medium (97.7% in less than 45 min) but not in the SLYF or the phosphate buffer media (72.6% and 32.2% within 45 min, respectively). Racemic chloroquine showed higher lysosomal trapping (51.9%) in the in-vitro model than dextromethorphan (28.3%) in a behavior supporting in-vivo findings and based on the molecular descriptors and the lysosomal sequestration potential of both. Conclusion and implication: A standardized lysosomal fluid was reported and developed for in-vitro investigations of lysosomotropic drugs and formulations.

Janelle Yorke,1,2 Naimat Khan,1,3 Adam Garrow,1 Sarah Tyson,1 Dave Singh,1,3 Jorgen Vestbo,1,4 Paul W Jones5 1Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; 2Christie Patient Centred Research, The Christie NHS Foundation Trust, Whittington, Manchester, UK; 3Medicines Evaluation Unit, Wythenshawe, Manchester, UK; 4Department of Respiratory Medicine, Wythenshawe Hospital, Manchester, UK; 5St George’s Hospital, University of London, London, UKCorrespondence: Janelle Yorke, Tel +44920 264411, Email janelle.yorke@nhs.netPurpose: The modified-Medical Research Council (mMRC) breathlessness scale consists of five grades that contain of a description of different activities. It has wide utility in the assessment of disability due to breathlessness but was originally developed before the advent of modern psychometric methodology and, for example contains more than one activity per grade. We conducted an evaluation of the mMRC structure.Patients and Methods: Cognitive debriefing was conducted with COPD patients to elicit their understanding of each mMRC activity. In a cross-sectional study, patients completed the mMRC scale (grades 0– 4) and an MRC-Expanded (MRC-Ex) version consisting of 10-items, each containing one mMRC activity. Each activity was then given a 4-point response scale (0 “not at all” to 4 “all of the time”) and all 10 items were given to 203 patients to complete Rasch analysis and assess the pattern of MRC item severity and its hierarchical structure.Results: Cognitive debriefing with 36 patients suggested ambiguity with the term “strenuous exercise” and perceived severity differences between mMRC activities. 203 patients completed the mMRC-Ex. Strenuous exercise was located third on the ascending severity scale. Rasch identified the mildest term was “walking up a slight hill” (logit − 2.76) and “too breathless to leave the house” was the most severe (logit 3.42).Conclusion: This analysis showed that items that were combined into a single mMRC grade may be widely separated in terms of perceived severity when assessed individually. This suggests that mMRC grades as a measure of individual disability related to breathlessness contain significant ambiguity due to the combination of activities of different degrees of perceived severity into a single grade.Keywords: psychometrics, Rasch analysis, patient reported outcomes, qualitative, scale development

Abstract Neuroscience research presents contradictory evidence in support of both the protective and destructive effects of cannabinoids in depression. Therefore, this systematic review and meta-analysis summarizes the existing preclinical literature on the effects of cannabinoid administration in the chronic unpredictable stress model of depression in order to evaluate the effects of cannabinoids and identify gaps in the literature. After protocol registration (PROSPERO #CRD42020219986), we systematically searched Scopus, Embase, Psychology & Behavioral Sciences Collection, APA PsychINFO, PubMed, CINAHL Complete, and ProQuest Dissertations & Theses Global from the earliest record of the databases, February 1964, to November 2020 for articles that met inclusion criteria (e.g., rodent subjects and administration of a cannabinoid. A total of 26 articles were included representing a sample size estimate of 1132 rodents with the majority of articles administering daily intraperitoneal injections during chronic unpredictable stress. These articles were evaluated using a modified SYRCLE’s risk-of-bias tool. For each continuous behavioral measure, the standardized mean difference was calculated between cannabinoid and vehicle groups in rodents subjected to chronic unpredictable stress. The effects of cannabinoids on depressive-like behavior was evaluated using a multilevel mixed-effects model with effect size weights nested within control groups. Cannabinoid administration moderately improved the pooled negative effects of chronic unpredictable stress on anhedonia, learned helplessness, novelty suppressed feeding, time in the anxiogenic context, and entries into the anxiogenic context. Although the interpretations are limited, these findings suggest that with further investigation, cannabinoids may be a viable long-term treatment for stress-related psychopathologies such as depression.

Abstract Introduction Children with developmental language disorder (DLD) exhibit cognitive deficits that interfere with their ability to learn language. Little is known about the functional neuroanatomical differences between children developing typically (TD) and children with DLD. Methods Using functional near‐infrared spectroscopy, we recorded oxygenated hemoglobin (O2hb) concentration values associated with neural activity in children with and without DLD during an auditory N‐back task that included 0‐back, 1‐back, and 2‐back conditions. Analyses focused on the left dorsolateral prefrontal cortex (DLPFC) and left inferior parietal lobule (IPL). Multilevel models were constructed with accuracy, response time, and O2hb as outcome measures, with 0‐back outcomes as fixed effects to control for sustained attention. Results Children with DLD were significantly less accurate than their TD peers at both the 1‐back and 2‐back tasks, and they demonstrated slower response times during 2‐back. In addition, children in the TD group demonstrated significantly greater sensitivity to increased task difficulty, showing increased O2hb to the IPL during 1‐back and to the DLPFC during the 2‐back, whereas the DLD group did not. A secondary analysis revealed that higher O2hb in the DLPFC predicted better task accuracy across groups. Conclusion When task difficulty increased, children with DLD failed to recruit the DLPFC for monitoring information and the IPL for processing information. Reduced memory capacity and reduced engagement likely contribute to the language learning difficulties of children with DLD.

Disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) is a ubiquitously expressed membrane-bound enzyme that mediates shedding of a wide variety of important regulators in inflammation including cytokines and adhesion molecules. Hepatic expression of numerous cytokines and adhesion molecules are increased in cholestatic liver diseases including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), however, the pathophysiological role of ADAM17 in regulating these conditions remains unknown. Therefore, we evaluated the role of ADAM17 in a mouse model of cholestatic liver injury due to bile duct ligation (BDL). We found that BDL enhanced hepatic ADAM17 protein expression, paralleled by increased ADAM17 bioactivity. Moreover, inhibition of ADAM17 bioactivity with the specific inhibitor DPC 333 significantly improved both biochemical and histological evidence of liver damage in BDL mice. Patients with cholestatic liver disease commonly experience adverse behavioral symptoms, termed sickness behaviors. Similarly, BDL in mice induces reproducible sickness behavior development, driven by the upregulated expression of cytokines and adhesion molecules that are in turn regulated by ADAM17 activity. Indeed, inhibition of ADAM17 activity significantly ameliorated BDL-associated sickness behavior development. In translational studies, we evaluated changes in ADAM17 protein expression in liver biopsies obtained from patients with PBC and PSC, compared to normal control livers. PSC and PBC patients demonstrated increased hepatic ADAM17 expression in hepatocytes, cholangiocytes and in association with liver-infiltrating immune cells compared to normal controls. In summary, cholestatic liver injury in mice and humans is associated with increased hepatic ADAM17 expression. Furthermore, inhibition of ADAM17 activity improves both cholestatic liver injury and associated sickness behavior development, suggesting that ADAM17 inhibition may represent a novel therapeutic approach for treating patients with PBC/PSC.

Adolescents with a history of child maltreatment experience increased risk for psychopathology that sets them on a trajectory towards a range of difficulties in adulthood. Various factors influence caregivers' decisions to seek mental health services (MHS) that could improve developmental outcomes. The present study applied a machine learning algorithm, elastic net, to a sample of 878 adolescent-caregiver dyads from the Longitudinal Studies of Child Abuse and Neglect. Analyses simultaneously examined a large number of factors to determine their ability to discriminate between caregivers who perceived a need for MHS and those who did not, as well as caregivers who utilized MHS and those who did not. Results highlight family demographics, chronic parental stressors, youth psychopathology, and exposure to recent adversities as good classifiers of caregiver perceived need for (77.6%; sensitivity = .77; specificity = .78) and utilization of (71%; sensitivity = .71; specificity = .71) adolescent MHS. Elastic net identified adolescent clinical externalizing and internalizing problems, and parental stress related to child(ren)'s behavior as high value classifiers of both outcomes. Youth living with non-kin caregivers were also significantly more likely to utilize MHS. Findings highlight the importance of assessing clinical need, stress related to child(ren)'s behavior, and caregiver kinship in understanding the likelihood that at-risk families will seek adolescent MHS.

Naimat Khan,1 Jørgen Vestbo,2 Adam Garrow,3 Pradeep Karur,4 Umme Kolsum,5 Sarah Tyson,6 Dave Singh,7 Janelle Yorke8 1The Medicines Evaluation Unit, Wythenshawe Hospital, Manchester, UK; 2University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 3Division of Population Health, University of Manchester, Manchester, UK; 4Medicines Evaluation Unit, Manchester, UK; 5University of Manchester, Manchester, UK; 6University of Manchester, School of Health Sciences, Manchester Academic Health Sciences Centre, Manchester, UK; 7University of Manchester, The Medicines Evaluation Unit, Manchester, UK; 8University of Manchester, School of Health Sciences, Manchester, UK Background: In COPD disturbed sleep is related to exacerbation frequency, poor quality of life, and early mortality. We developed the Manchester Respiratory-related Sleep Symptoms scale (MaRSS) to assess sleep-time symptoms in COPD. Methods: Focus groups including COPD and age-matched controls were used to develop an item-list, which was then administered to COPD patients and age-matched controls in a cross-sectional study. Hierarchical and Rasch analysis informed item selection and scale unidimensionality. Construct validity was examined using Pearson’s correlation with the Sleep Problems Index, St George’s Respiratory Questionnaire (SGRQ), and FACIT-Fatigue scale. MaRSS change scores from baseline (stable) to exacerbation were assessed in a separate substudy of COPD patients. Results: Thirty-six COPD patients and nine age-matched controls produced an initial 26-item list. The cross-sectional study involved 203 COPD patients (male: 63%, mean age 64.7 years) and 50 age-matched controls (male: 56%, mean age 65.8 years). Eighteen items were removed to develop an eight-item unidimensional scale covering breathlessness, chest tightness, cough, sputum production, lack of sleep, and medication use. MaRSS scores significantly correlated with sleep problems, SGRQ Total, and FACIT-Fatigue (r=0.58–0.62) and demonstrated a good fit to the Rasch model (chi-squared=29.2; P=0.04). In the substudy, MaRSS scores demonstrated a moderate effect size from baseline to exacerbation visit in 27 patients with 32 exacerbation episodes (Cohen’s d=0.6). Conclusion: The MaRSS is a reliable, valid, and clinically responsive measure of respiratory-related symptoms that disturb sleep. It is simple to use and score, making it suitable for research and clinical practice. Keywords: COPD, sleep, dyspnea, cough, sputum, outcome measure

Purpose: According to the interpersonal synergy model of spoken dialogue, interlocutors modify their communicative behaviors to meet the contextual demands of a given conversation. Although a growing body of research supports this postulation for linguistic behaviors (e.g., semantics, syntax), little is understood about how this model applies to speech behaviors (e.g., speech rate, pitch). The purpose of this study is to test the hypothesis that interlocutors adjust their speech behaviors across different conversational tasks with different conversational goals. Method: In this study, 28 participants each engaged in two different types of conversations (i.e., relational and informational) with two partners (i.e., Partner 1 and Partner 2), yielding a total of 112 conversations. We compared six acoustic measures of participant speech behavior across conversational task and partner. Results: Linear mixed-effects models demonstrated significant differences between speech feature measures in informational and relational conversations. Furthermore, these findings were generally robust across conversations with different partners. Conclusions: Results suggest that contextual demands influence speech behaviors. These findings provide empirical support for the interpersonal synergy model and highlight important considerations for assessing speech behaviors in individuals with communication disorders.

Lexical alignment, a communication phenomenon where conversational partners adapt their word choices to become more similar, plays an important role in the development of language and social communication skills. While this has been studied extensively in the conversations of preschool-aged children and their parents in Western, Educated, Industrialized, Rich, and Democratic (WEIRD) communities, research in other pediatric populations is sparse. This study makes significant expansions on the existing literature by focusing on alignment in naturalistic conversations of school-aged children from a non-WEIRD population across multiple conversational tasks and with different types of adult partners. Typically developing children aged 5 to 8 years (n = 45) engaged in four semi-structured conversations that differed by task (problem-solving vs. play-based) and by partner (parent vs. university student), resulting in a corpus of 180 conversations. Lexical alignment scores were calculated and compared to sham conversations, representing alignment occurring at the level of chance. Both children and adults coordinated their conversational utterances by re-using or aligning each other's word choices. This alignment behavior persisted across conversational tasks and partners, although the degree of alignment was moderated by the conversational context. These findings suggest that lexical alignment is a robust phenomenon in conversations between school-age children and adults. Furthermore, this study extends lexical alignment findings to a non-WEIRD culture, suggesting that alignment may be a coordination strategy employed by adults and children across diverse linguistic and cultural backgrounds.

Adam P Garrow,1,2 Janelle Yorke,2 Naimat Khan,1 Jørgen Vestbo,3 Dave Singh,1 Sarah Tyson1 1University of Manchester Medicines Evaluation Unit, University Hospital of South Manchester Foundation Trust, 2School of Nursing, Midwifery and Social Work, University of Manchester, 3The University of Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, Manchester, UK Background: Sleep problems are common in patients with chronic obstructive pulmonary disease (COPD), but the validity of patient-reported outcome measures (PROMs) that measure sleep dysfunction has not been evaluated. We have reviewed the literature to identify disease-specific and non-disease-specific sleep PROMs that have been validated for use in COPD patients. The review also examined the psychometric properties of identified sleep outcome measures and extracted point and variability estimates of sleep instruments used in COPD studies. Methods: The online EMBASE, MEDLINE, PsycINFO, and SCOPUS databases for all years to May 2014 were used to source articles for the review. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Criteria from the Medical Outcomes Trust Scientific Advisory Committee guidelines were used to evaluate the psychometric properties of all sleep PROMs identified. Results: One COPD-specific and six non-COPD-specific sleep outcome measures were identified and 44 papers met the review selection criteria. We only identified one instrument, the COPD and Asthma Sleep Impact Scale, which was developed specifically for use in COPD populations. Ninety percent of the identified studies used one of two non-disease-specific sleep scales, ie, the Pittsburgh Sleep Quality Index and/or the Epworth Sleep Scale, although neither has been tested for reliability or validity in people with COPD. Conclusion: The results highlight a need for existing non-disease-specific instruments to be validated in COPD populations and also a need for new disease-specific measures to assess the impact of sleep problems in COPD. Keywords: sleep, symptom assessment, chronic obstructive pulmonary disease, systematic review

Purpose: Although recruitment of cognitive-linguistic resources to support dysarthric speech perception and adaptation is presumed by theoretical accounts of effortful listening and supported by cross-disciplinary empirical findings, prospective relationships have received limited attention in the disordered speech literature. This study aimed to examine the predictive relationships between cognitive-linguistic parameters and intelligibility outcomes associated with familiarization with dysarthric speech in young adult listeners. Method: A cohort of 156 listener participants between the ages of 18 and 50 years completed a three-phase perceptual training protocol (pretest, training, and posttest) with one of three speakers with dysarthria. Additionally, listeners completed the National Institutes of Health Toolbox Cognition Battery to obtain measures of the following cognitive-linguistic constructs: working memory, inhibitory control of attention, cognitive flexibility, processing speed, and vocabulary knowledge. Results: Elastic net regression models revealed that select cognitive-linguistic measures and their two-way interactions predicted both initial intelligibility and intelligibility improvement of dysarthric speech. While some consistency across models was shown, unique constellations of select cognitive factors and their interactions predicted initial intelligibility and intelligibility improvement of the three different speakers with dysarthria. Conclusions: Current findings extend empirical support for theoretical models of speech perception in adverse listening conditions to dysarthric speech signals. Although predictive relationships were complex, vocabulary knowledge, working memory, and cognitive flexibility often emerged as important variables across the models.

Purpose: The ability to understand speech under adverse listening conditions is highly variable across listeners. Despite this, studies have found that listeners with normal hearing display consistency in their ability to perceive speech across different types of degraded speech, suggesting that, for at least these listeners, global skills may be involved in navigating the ambiguity in speech signals. However, there are substantial differences in the perceptual challenges faced by listeners with normal and impaired hearing. This study examines whether listeners with sensorineural hearing loss demonstrate the same type of consistency as normal-hearing listeners when processing neurotypical (i.e., control) speech that has been degraded by external noise and speech that is neurologically degraded such as dysarthria. Method: Listeners with normal hearing (n = 31) and listeners with sensorineural hearing loss (n = 36) completed an intelligibility task with neurotypical speech in noise and with dysarthric speech in quiet. Results: Findings were consistent with previous work demonstrating a relationship between the ability to perceive neurotypical speech in noise and dysarthric speech for listeners with normal hearing, albeit at a higher intelligibility level than previously observed. This relationship was also observed for listeners with hearing loss, although listeners with more severe hearing losses performed better with dysarthric speech than with neurotypical speech in noise. Conclusions: This study demonstrated a high level of consistency in intelligibility performance for listeners across two different types of degraded speech, even when those listeners were further challenged by the presence of sensorineural hearing loss. Clinical implications for both listeners with hearing loss and their communication partners with dysarthria are discussed.

Purpose: As evidenced by perceptual learning studies involving adult listeners and speakers with dysarthria, adaptation to dysarthric speech is driven by signal predictability (speaker property) and a flexible speech perception system (listener property). Here, we extend adaptation investigations to adolescent populations and examine whether adult and adolescent listeners can learn to better understand an adolescent speaker with dysarthria. Method: Classified by developmental stage, adult (n = 42) and adolescent (n = 40) listeners completed a three-phase perceptual learning protocol (pretest, familiarization, and posttest). During pretest and posttest, all listeners transcribed speech produced by a 13-year-old adolescent with spastic dysarthria associated with cerebral palsy. During familiarization, half of the adult and adolescent listeners engaged in structured familiarization (audio and lexical feedback) with the speech of the adolescent speaker with dysarthria; and the other half, with the speech of a neurotypical adolescent speaker (control). Results: Intelligibility scores increased from pretest to posttest for all listeners. However, listeners who received dysarthria familiarization achieved greater intelligibility improvements than those who received control familiarization. Furthermore, there was a significant effect of developmental stage, where the adults achieved greater intelligibility improvements relative to the adolescents. Conclusions: This study provides the first tranche of evidence that adolescent dysarthric speech is learnable--a finding that holds even for adolescent listeners whose speech perception systems are not yet fully developed. Given the formative role that social interactions play during adolescence, these findings of improved intelligibility afford important clinical implications.

Mental health literacy (MHL) training is essential in college environments. These programs are commonly delivered in-person via workshops or for-credit courses. Campuses now seek high-quality online options. We compare the effectiveness of a for-credit MHL course against a comparison course, focusing on whether online asynchronous delivery was as effective as in-person synchronous delivery. This quasi-experimental pretest/posttest treatment/comparison study included 1049 participants across five semesters (pre-COVID-19) who were 18 years or older and self-selected enrollment in a Mental Health Awareness and Advocacy (MHAA) course (treatment; n = 474) or a general lifespan development course (comparison; n = 575). Using linear mixed effect modeling, changes in MHL were compared across groups and across online/in-person modalities. Students in the treatment group significantly increased their MHL knowledge ([beta][subscript Identifying] = 0.49, p < 0.001; [beta][subscript Locating] = 0.32, p < 0.001; [beta][subscript Responding] = 0.46, p < 0.001) and self-efficacy ([beta] = 0.27, p < 0.001), and treatment effects did not differ across modalities. With increased concern regarding mental health issues of isolated college students during the COVID-19 pandemic, this study supports the efficacy of delivering MHL courses online.

Background: Knowledge regarding barriers faced by Latina/o/x caregivers in accessing youth mental health services (MHS) have largely depended on resource intensive interview-based assessments. Objective: We evaluated a questionnaire for Latina/o/x caregivers of youths that presents a briefer and more feasible alternative. Method: We conducted a psychometric evaluation of the Barriers to Treatment Questionnaire -- Latina/o/x Caregivers (BTQ-LC) with a sample of 598 Latina/o/x caregivers from across the United States. Descriptive statistics and confirmatory factor analyses were used to identify common barriers to services, confirm the factor structure of the scale, and establish construct validity. Results: Descriptive statistics suggest that not knowing where and how to access services, and normalization of youth psychopathology were the most frequently reported barriers among caregivers of youth with clinically elevated problems on the CBCL. Confirmatory factor analysis suggests that the BTQ-LC was best represented by a three-factor structure: (1) structural, (2) perceptions regarding mental health problems, and (3) services. Our finding suggest that the BTQ-LC could also be used as a single factor as fit indices ranged from acceptable to poor. BTQ-LC scales were all negatively correlated with the utilization of common youth MHS (i.e., psychological counseling, medical doctors, school professionals). Conclusions: The BTQ-LC represents an important step towards improving our understanding and assessment of barriers to services contributing to mental health disparities among Latina/o/x youths.

Purpose: Acoustic-prosodic entrainment, defined as the tendency for individuals to modify their speech behaviors to more closely align with the behaviors of their conversation partner, plays an important role in successful interaction. From a mechanistic perspective, acoustic-prosodic entrainment is, by its very nature, a rhythmic activity. Accordingly, it is highly plausible that an individual's rhythm perception abilities play a role in their ability to successfully entrain. Here, we examine the impact of rhythm perception in speaking rate entrainment and subsequent conversational quality. Method: A round-robin paradigm was used to collect 90 dialogues from neurotypical adults. Additional assessments determined participants' rhythm perception abilities, social competence, and partner familiarity (i.e., whether the conversation partners knew each other prior to the interaction. Mediation analysis was used to examine the relationships between rhythm perception scores, speaking rate entrainment (using a measure of static local synchrony), and a measure of conversational success (i.e., conversational quality) based on third-party listener observations. Findings were compared to the same analysis with three additional predictive factors: participant gender, partner familiarity, and social competence. Results: Results revealed a relationship between rhythm perception and speaking rate entrainment. In unfamiliar conversation partners, there was a relationship between speaking rate entrainment and conversational quality. The relationships between entrainment and each of the three additional factors (i.e., gender, partner familiarity, and social competence) were nonsignificant. Conclusions: In unfamiliar conversation partners, better rhythm perception abilities were indicative of increased conversational quality mediated by higher levels of speaking rate entrainment. These results support theoretical postulations specifying rhythm perception abilities as a component of acoustic-prosodic entrainment, which, in turn, facilitates conversational success. Knowledge of this relationship contributes to the development of a causal framework for considering a mechanism by which rhythm perception deficits in clinical populations may impact conversational success.

Abstract Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management.

Purpose: We proposed and tested a causal instantiation of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) framework, linking acoustics, intelligibility, and communicative participation in the context of dysarthria. Method: Speech samples and communicative participation scores were collected from individuals with dysarthria (n = 32). Speech was analyzed for two acoustic metrics (i.e., articulatory precision and speech rate), and an objective measure of intelligibility was generated from listener transcripts. Mediation analysis was used to evaluate pathways of effect between acoustics, intelligibility, and communicative participation. Results: We observed a strong relationship between articulatory precision and intelligibility and a moderate relationship between intelligibility and communicative participation. Collectively, data supported a significant relationship between articulatory precision and communicative participation, which was almost entirely mediated through intelligibility. These relationships were not significant when speech rate was specified as the acoustic variable of interest. Conclusion: The statistical corroboration of our causal instantiation of the ICF framework with articulatory acoustics affords important support toward the development of a comprehensive causal framework to understand and, ultimately, address restricted communicative participation in dysarthria.

Purpose: For individuals with Parkinson's disease (PD), conversational interactions can be challenging. Efforts to improve the success of these interactions have largely fallen on the individual with PD. Successful communication, however, involves contributions from both the individual with PD and their communication partner. The current study examines whether healthy communication partners naturally engage in different acoustic-prosodic behavior (speech compensations) when conversing with an individual with PD and, further, whether such behavior aids communication success. Method: Measures of articulatory precision, speaking rate, and pitch variability were extracted from the speech of healthy speakers engaged in goal-directed dialogue with other healthy speakers (healthy-healthy dyads) and with individuals with PD (healthy-PD dyads). Speech compensations, operationally defined as significant differences in healthy speakers' acoustic-prosodic behavior in healthy-healthy dyads versus healthy-PD dyads, were calculated for the three speech behaviors. Finally, the relationships between speech behaviors and an objective measure of communicative efficiency were examined. Results: Healthy speakers engaged in speech characterized by greater articulatory precision and slower speaking rate when conversing with individuals with PD relative to conversations with other healthy individuals. However, these adaptive speech compensations were not predictive of communicative efficiency. Conclusions: Evidence that healthy speakers naturally engage in speech compensations when conversing with individuals with PD is novel, yet consistent with findings from studies with other populations in which conversation can be challenging. In the case of PD, these compensatory behaviors did not support communication outcomes. While preliminary in nature, the results raise important questions regarding the speech behavior of healthy communication partners and provide directions for future work.

Purpose: Perceptual training paradigms, which leverage the mechanism of perceptual learning, show that naïve listeners, those with no prior experience with dysarthria, benefit from explicit familiarization with a talker with dysarthria. It is theorized that familiarization affords listeners an opportunity to acquire distributional knowledge of the degraded speech signal. Here, we extend investigations to clinically experienced listeners, speech-language pathologists (SLPs), and advance models of listener recognition and adaptation to dysarthric speech. Method: Forty-seven SLPs completed a standard three-phase perceptual training protocol (pretest, familiarization, and posttest) with a novel talker with dysarthria. Intelligibility scores were compared with historical data from naïve listeners. Potential relationships between intelligibility scores and characteristics of clinical experience were examined. Results: Intelligibility scores of SLPs improved by an average of 19% from pretest to posttest. This intelligibility improvement was lower than naïve listeners, although the difference was small. Moreover, clinical characteristics related to level of dysarthria experience (e.g., percent of caseload composed of dysarthria) predicted pretest/initial intelligibility. No predictive relationships between clinical characteristics and intelligibility improvement were revealed. Conclusions: As a group, SLPs benefitted from perceptual training, suggesting that, despite prior experience, the opportunity to acquire knowledge of talker-specific cue distributions is crucial for optimal adaptation. However, SLPs with greater dysarthria experience were better at initially understanding the talker with dysarthria. This suggests that, through regular interaction with individuals with dysarthria, clinicians acquire knowledge of the cue distributions of dysarthric speech more generally and can generalize this group-specific knowledge to aid in understanding other talkers with dysarthria. Consistent with theoretical models of perceptual learning, both talker- and group-specific knowledge informed recognition and adaptation to dysarthric speech.

Purpose: Perceptual training is a listener-targeted means for improving intelligibility of dysarthric speech. Recent work has shown that training with one talker generalizes to a novel talker of the same sex and that the magnitude of benefit is maximized when the talkers are perceptually similar. The current study expands previous findings by investigating whether perceptual training effects generalize between talkers of different sex. Method: Forty new listeners were recruited for this study and completed a pretest, familiarization, and posttest perceptual training paradigm. Historical data collected using the same three-phase protocol were included in the data analysis. All listeners were exposed to the same talker with dysarthria during the pretest and posttest phases. For the familiarization phase, listeners were exposed to one of four talkers with dysarthria, differing in sex and level of perceptual similarity to the test talker or a control talker. During the testing phases, listener transcribed phrases produced by the test talker with dysarthria. Listener transcriptions were then used to calculate a percent words correct intelligibility score. Results: Multiple linear regression analysis revealed that intelligibility at posttest was not predicted by sex of the training talker. Consistent with earlier work, the magnitude of intelligibility gain was greater when the familiarization and test talkers were perceptually similar. Additional analyses revealed greater between-listeners variability in the dissimilar conditions as compared to the similar conditions. Conclusions: Learning as a result of perceptual training with one talker with dysarthria generalized to another talker regardless of sex. In addition, listeners trained with perceptually similar talkers had greater and more consistent intelligibility improvement. Together, these results add to previous evidence demonstrating that learning generalizes to novel talkers with dysarthria and that perceptual training is suitable for many listeners.

Purpose: Coordination of communicative behavior supports shared understanding in conversation. The current study brings together analysis of two speech coordination strategies, entrainment and compensation of articulation, in a preliminary investigation into whether strategy organization is shaped by a challenging communicative context--conversing with a person who has a communication disorder. Method: As an initial clinical test case, an automated measure of articulatory precision was analyzed in a corpus of spoken dialogue, where a confederate conversed with participants with traumatic brain injury (n = 28) and participants with no brain injury (n = 48). Results: Overall, the confederate engaged in significant entrainment and high compensation (hyperarticulation) in conversations with participants with traumatic brain injury relative to significant entrainment and low compensation (hypoarticulation) in conversations with participants with no brain injury. Furthermore, the confederate's articulatory precision changed over the course of the conversations. Conclusions: Findings suggest that the organization of conversational coordination is sensitive to context, supporting synergistic models of spoken dialogue. While corpus limitations are acknowledged, these initial results point to differences in the way in which speech strategies are realized in challenging communicative contexts, highlighting a viable and important target for investigation with clinical populations. A framework for investigating speech coordination strategies in tandem and ideas for advancing this line of inquiry serve as key contributions of this work.

Purpose: This study was conducted in a large Midwestern metropolitan area to examine the language environments at home and in center-based childcare for young children who are living in poverty. We compared child language use and exposure in the home and childcare settings using extended observations with automated Language Environment Analysis to gain a deeper understanding of the environmental factors that may affect change in language outcomes for young children. Method: Thirty-eight children, along with parents (n = 38) and childcare providers (n = 14) across five childcare centers, participated in this study. Each child completed a standardized language assessment and two daylong recordings with Language Environment Analysis to determine the number of adult words, conversational turns, and child vocalizations that occurred in each setting. Data were analyzed at 5-min intervals across each recording. Results: Comparisons between home recordings in this sample and a comparison group showed reliably higher rates of adult words and conversational turns in the home setting. Linear mixed-effects regression models showed significant differences in the child language environments, with the home setting providing higher levels of language input and use. These effects were still meaningful after accounting for the time of day, participant demographic characteristics, and child language ability. Conclusions: Practical implications for supporting child language development across settings are discussed, and suggestions for further research are provided.

Purpose: Robust improvements in intelligibility following familiarization, a listener-targeted perceptual training paradigm, have been revealed for talkers diagnosed with spastic, ataxic, and hypokinetic dysarthria but not for talkers with hyperkinetic dysarthria. While the theoretical explanation for the lack of intelligibility improvement following training with hyperkinetic talkers is that there is insufficient distributional regularity in the speech signals to support perceptual adaptation, it could simply be that the standard training protocol was inadequate to facilitate learning of the unpredictable talker. In a pair of experiments, we addressed this possible alternate explanation by modifying the levels of exposure and feedback provided by the perceptual training protocol to offer listeners a more robust training experience. Method: In Experiment 1, we examined the exposure modifications, testing whether perceptual adaptation to an unpredictable talker with hyperkinetic dysarthria could be achieved with greater or more diverse exposure to dysarthric speech during the training phase. In Experiment 2, we examined feedback modifications, testing whether perceptual adaptation to the unpredictable talker could be achieved with the addition of internally generated somatosensory feedback, via vocal imitation, during the training phase. Results: Neither task modification led to improved intelligibility of the unpredictable talker with hyperkinetic dysarthria. Furthermore, listeners who completed the vocal imitation task demonstrated significantly reduced intelligibility at posttest. Conclusion: Together, the results from Experiments 1 and 2 replicate and extend findings from our previous work, suggesting perceptual adaptation is inhibited for talkers whose speech is largely characterized by unpredictable degradations. Collectively, these results underscore the importance of integrating signal predictability into theoretical models of perceptual learning.

Purpose: Despite the import of conversational entrainment to successful spoken dialogue, the systematic characterization of this behavioral syncing phenomenon represents a critical gap in the field of speech pathology. The goal of this study was to acoustically characterize conversational entrainment in the context of dysarthria using a multidimensional approach previously validated in healthy populations (healthy conversations; Borrie, Barrett, Willi, & Berisha, 2019). Method: A large corpus of goal-oriented conversations between participants with dysarthria and healthy participants (disordered conversations) was elicited using a "spot the difference" task. Expert clinical assessment of entrainment and a measure of conversational success (communicative efficiency) was obtained for each of the audio-recorded conversations. Conversational entrainment of acoustic features representing rhythmic, articulatory, and phonatory dimensions of speech was identified using cross-recurrence quantification analysis with clinically informed model parameters and validated with a sham condition involving conversational participants who did not converse with one another. The relationship between conversational entrainment and communicative efficiency was examined. Results: Acoustic evidence of entrainment was observed in phonatory, but not rhythmic and articulatory, behavior, a finding that differs from healthy conversations in which entrainment was observed in all speech signal dimensions. This result, that disordered conversations showed less acoustic entrainment than healthy conversations, is corroborated by clinical assessment of entrainment in which the disordered conversations were rated, overall, as being less in sync than healthy conversations. Furthermore, acoustic entrainment was predictive of communicative efficiency, corroborated by a relationship between clinical assessment and the same outcome measure. Conclusions: The findings confirm our hypothesis that the pathological speech production parameters of dysarthria disrupt the seemingly ubiquitous phenomenon of conversational entrainment, thus advancing entrainment deficits as an important variable in dysarthria, one that may have causative effects on the success of everyday communication. Results further reveal that while this approach provides a broad overview, methodologies for characterizing conversational entrainment in dysarthria must continue to be developed and refined, with a focus on clinical utility.

Dyad reading involves a lower level reader paired with a higher level reading partner who models proficient oral reading while providing access to challenging texts. Previous research has reported increased reading fluency and comprehension for participants of dyad reading; however, to date no research has investigated how dyad reading may influence student attitudes toward reading. Using mixed effects linear modeling, this quasi-experimental study of third graders investigated the academic and attitudinal outcomes for students who read in dyads for 15 minutes daily for 90 school days. Results indicated that dyad readers experienced mixed outcomes in improving reading proficiency and a pattern of decline in reading attitudes compared to students in the control group. While lower level dyad readers demonstrated significant gains on a measure of comprehension, there were no differences between groups on several other measures of reading. Recommendations target how to maximize the use of dyad reading to support students' reading development without eroding their perceptions of themselves as readers.

Purpose: Listener-targeted perceptual training paradigms, which leverage the mechanism of perceptual learning, show strong promise for improving intelligibility in dysarthria, offsetting the communicative burden from the speaker onto the listener. Theoretical models of perceptual learning underscore the importance of acoustic regularity (i.e., signal predictability) for listener adaptation to degraded speech. The purpose of the current investigation was to evaluate intelligibility outcomes following perceptual training with hyperkinetic dysarthria, a subtype characterized by reduced signal predictability. Method: Forty listeners completed the standard 3-phase perceptual training protocol (pretest, training, and posttest) with 1 of 2 talkers with hyperkinetic dysarthria. Perceptual data were compared to a historical data set for 1 other talker with hyperkinetic dysarthria to examine the effect of perceptual training on intelligibility. Results: When controlling for pretest intelligibility, regression results suggest listeners of the 2 novel talkers with hyperkinetic dysarthria performed comparably to the listeners of the original talker on the posttest following training. Furthermore, differences between pretest and posttest intelligibility failed to reach clinical significance for all 3 talkers and statistical significance for 2 of the 3. Conclusion: The current findings are consistent with theoretical models of perceptual learning and suggest that listener adaptation to degraded speech may be negligible for talkers with dysarthria whose speech is marked by reduced signal predictability.