Diversity-oriented synthesis yields novel multistage antimalarial inhibitors.

Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets.

Phonological Priming as a Lens for Phonological Organization in Children With Cochlear Implants.

OBJECTIVES: To evaluate the subconscious knowledge of between-word phonological similarities in children with cochlear implants as compared with children with typical hearing. DESIGN: Participants included 30 children with cochlear implants between the ages of five and seven who used primarily spoken English to communicate, 30 children matched for chronological age, and 30 children matched for vocabulary size. Participants completed an animacy judgment task in either a (a) neutral condition, (b) a phonological prime condition where the consonant and vowel onset of the pictured word was presented prior to the visual target's appearance, (c) an inhibition prime condition where a consonant and vowel onset not matching the pictured word was presented prior to the target's appearance. Reaction times were recorded. RESULTS: Children with cochlear implants reacted differently and more slowly than children with typical hearing in both groups to the primes: children with typical hearing experienced a phonological facilitation effect in the phonological prime condition, whereas children with cochlear implants did not. Children with cochlear implants also had reaction times that, overall, were slower than children matched for chronological age but similar to children matched for vocabulary size. CONCLUSIONS: The different experience of children with cochlear implants with phonological facilitation and inhibition effects may indicate children with cochlear implants have phonological organization strategies that are different from those of children with typical hearing.

Impact of Meeting Early Hearing Detection and Intervention Benchmarks on Spoken Language.

This study compared preschool spoken language outcomes for children with hearing loss who met Early Hearing Detection and Intervention (EHDI) guidelines to those who did not, as well as to compare outcomes for those who met current EHDI guidelines to those who met earlier benchmarks. Finally, the predictive role of meeting each component of the guidelines was evaluated relative to language outcomes. Children who met the EHDI guidelines had higher language scores than those who did not; however, there was no difference between children who met the current guidelines and those who met the earlier benchmarks. Entering early intervention by six months of age was the only unique predictor of spoken language outcomes. The findings suggest that EHDI programs should target increasing the number of children with hearing loss who meet the current 1-3-6 benchmarks with a particular focus on enrollment in early intervention by six months.

Suicide among veterans with amyotrophic lateral sclerosis.

BACKGROUND: The purpose of this study was to estimate the risk of death by suicide for those with amyotrophic lateral sclerosis (ALS) seeking care within the Veterans Health Administration (VHA). METHODS: This was a retrospective, cohort study. Extended Cox regression models were used to compare the hazard of suicide between the ALS and the unexposed groups. RESULTS: The hazard of suicide was 3.98 times higher for those with ALS than for those without (95% confidence interval [CI] , 2.64-6.00; P < .0001). After adjusting for covariates, those with ALS remained at increased risk (hazard ratio, 3.48; 95% CI, 2.31-5.24; P < .001). CONCLUSIONS: Among those seeking care in the VHA, individuals with ALS are at increased risk for dying by suicide. Additional suicide prevention efforts, including strategies for reducing access to lethal means, are warranted.

Location Effects on Spoken Language and Literacy for Children who are DHH.

The purpose of this study was to consider how living in an area that qualifies for a rural health grant interacts with a child's hearing status to affect early language and literacy development. Four-year-old children with hearing aids (n = 45), cochlear implants (n = 47), and with typical hearing (n = 66) completed measures of spoken language knowledge and of emergent literacy skills as part of a larger longitudinal investigation. A significant interaction effect between location (rural or urban/suburban) and amplification group was detected for letter knowledge: children with hearing aids exhibit a performance that is particularly affected by rural location. Overall, children with cochlear implants performed lower across all measures than children with typical hearing, and children with hearing aids performed lower than children with typical hearing on measures of phonological awareness, vocabulary, omnibus language knowledge and articulation.

Examining the Contributions of Disability to Suicidality in the Context of Depression Symptoms and Other Sociodemographic Factors.

We examined the contribution of disability status to suicidality when accounting for depression and sociodemographic risk factors in 438 American adults, 82 (18.7%) of whom identified as having disabilities. Participants with disabilities had significantly higher depression scores and were more likely to be unemployed and unpartnered, all of which were also associated with increased suicidality. However, disability remained a significant predictor of suicidality even when depression and sociodemographic risk factors were accounted for in a linear regression. Other significant predictors of suicidality in this regression were female gender, depression symptoms, and family and friend suicide history; identifying as a member of a religion was a significant protective factor against suicidality. Our findings suggest that the contribution of disability to suicidality goes beyond that which can be explained by increased depression symptoms and sociodemographic vulnerability.

"It's Awful When We Get It Wrong": An Exploratory Qualitative Study of Vocational Rehabilitation Counselors' Perspectives on Suicide.

Despite the high prevalence of suicide among people with disabilities, little research has explored suicide in the context of the vocational rehabilitation (VR) system. We analyzed the responses of 27 VR counselors who responded to an open-ended qualitative prompt regarding their experiences with suicide training and competency. Key themes included a desire for more training on suicide and the experience of seeking and receiving suicide training and experience outside of VR. Responses also underscored the heavy emotional impact of working with suicidal clients, especially when one feels unprepared to do so. These results suggest that it is important to provide VR counselors with resources and training for addressing suicide in their client populations.

"I Honestly Would Not Have Known What to Do": An Exploratory Study of Perspectives on Client Suicide Among Vocational Rehabilitation Support Staff.

Despite the high prevalence of suicide both overall and among people with disabilities in particular, little research has explored suicide in the context of the vocational rehabilitation (VR) system or in counseling support staff in general. We analyzed the responses of 14 VR support staff who responded to an open-ended qualitative prompt regarding their experiences with suicide training and competency. Key themes included a perceived lack of and desire for more training regarding suicide, seeking and receiving suicide training outside of VR, and a perceived lack of resources for working with suicidal clients. Responses also underscored the heavy emotional impact of working with these clients, especially when one feels unprepared to do so. These results suggest that it is important to provide VR support staff with resources and training for addressing suicide in their client populations.

Novel ERCC2 mutation in two siblings with trichothiodystrophy.

Trichothiodystrophy describes a group of recessively inherited multisystem neuroectodermal disorders that takes its name from the characteristic feature of brittle, sulfur-deficient hair. We describe two siblings with trichothiodystrophy due to a novel genotype. The maternal mutation (p.Arg722Trp) is a previously described pathogenic mutation in ERCC2 that has been shown to result in a severe phenotype, while the paternal mutation (c.1480-1G > C) has not been previously reported. Our cases confirm the severe phenotype associated with the p.Arg722Trp mutation and expand the known genetic mutations associated with trichothiodystrophy by demonstrating a novel pathogenic mutation in ERCC2.

Comparing Word Characteristic Effects on Vocabulary of Children with Cochlear Implants.

Many studies have evaluated overall vocabulary knowledge of children who use cochlear implants, but there has been minimal focus on how word form characteristics affect this knowledge. This study evaluates the effects of neighborhood density and phonotactic probability on the expressive vocabulary of 81 children between five and seven years old (n = 27 cochlear implant users, n = 27 children matched for chronological age, and n = 27 children matched for vocabulary size). Children were asked to name pictures associated with words that have common and rare phonotactic probability and high and sparse neighborhood density. Results indicate that children with cochlear implants, similar to both groups of children with typical hearing, tend to know words with common probability/high density or with rare probability/ sparse density. Patterns of word knowledge for children with cochlear implants mirrored younger children matched for vocabulary size rather than age-matched children with typical hearing.

Utility of routine electrocardiographic screening before initiation of propranolol for infantile hemangiomas.

Screening electrocardiography (ECG) before initiation of propranolol for treatment of infantile hemangiomas (IH) is controversial. A retrospective chart review was conducted to assess the utility of pretreatment ECG in infants with IH starting propranolol. Although nearly half of the ECGs were abnormal, no contraindications to treatment were identified from screening ECG, and no association was found between any of the reported side effects and abnormal ECG. These results support previously published data, and in a larger cohort, providing further confirmation that pretreatment ECG is not necessary in most infants with IH.

Syntax and reading comprehension: a meta-analysis of different spoken-syntax assessments.

BACKGROUND: Syntax is a language skill purported to support children's reading comprehension. However, researchers who have examined whether children with average and below-average reading comprehension score significantly different on spoken-syntax assessments report inconsistent results. AIMS: To determine if differences in how syntax is measured affect whether children with average and below-average reading comprehension score significantly different on spoken-syntax assessments. METHODS & PROCEDURES: Studies that included a group comparison design, children with average and below-average reading comprehension, and a spoken-syntax assessment were selected for review. Fourteen articles from a total of 1281 reviewed met the inclusionary criteria. The 14 articles were coded for the age of the children, score on the reading comprehension assessment, type of spoken-syntax assessment, type of syntax construct measured and score on the spoken-syntax assessment. A random-effects model was used to analyze the difference between the effect sizes of the types of spoken-syntax assessments and the difference between the effect sizes of the syntax construct measured. OUTCOMES & RESULTS: There was a significant difference between children with average and below-average reading comprehension on spoken-syntax assessments. Those with average and below-average reading comprehension scored significantly different on spoken-syntax assessments when norm-referenced and researcher-created assessments were compared. However, when the type of construct was compared, children with average and below-average reading comprehension scored significantly different on assessments that measured knowledge of spoken syntax, but not on assessments that measured awareness of spoken syntax. CONCLUSIONS & IMPLICATIONS: The results of this meta-analysis confirmed that the type of spoken-syntax assessment, whether norm-referenced or researcher-created, did not explain why some researchers reported that there were no significant differences between children with average and below-average reading comprehension, but the syntax construct, awareness or knowledge, did. Thus, when selecting how to measure syntax among school-age children, researchers and practitioners should evaluate whether they are measuring children's awareness of spoken syntax or knowledge of spoken syntax. Other differences, such as participant diagnosis and the format of items on the spoken-syntax assessments, also were discussed as possible explanations for why researchers found that children with average and below-average reading comprehension did not score significantly differently on spoken-syntax assessments.

Word-learning performance of children with and without cochlear implants given synchronous and asynchronous cues.

This study sought to evaluate the effects of synchronous and asynchronous auditory-visual cues on the word-learning performance of children with cochlear implants and children with normal hearing matched for chronological age. Children with cochlear implants (n = 9) who had worn the implant for less than one year and children matched for chronological age (n = 9) participated in rapid word-learning trials. Children with cochlear implants did not learn words in either the synchronous or asynchronous condition (U = 49.5, p = .99; d = 0.05). Children with normal hearing learned more words in the synchronous rather than asynchronous condition (U = 78.5, p = .04; d = 0.95). These findings represent a first step toward determining how task-level factors influence the lexical outcomes of children with cochlear implants.

Vocabulary Knowledge of Children With Cochlear Implants: A Meta-Analysis.

This article employs meta-analysis procedures to evaluate whether children with cochlear implants demonstrate lower spoken-language vocabulary knowledge than peers with normal hearing. Of the 754 articles screened and 52 articles coded, 12 articles met predetermined inclusion criteria (with an additional 5 included for one analysis). Effect sizes were calculated for relevant studies and forest plots were used to compare differences between groups of children with normal hearing and children with cochlear implants. Weighted effect size averages for expressive vocabulary measures (g = -11.99; p < .001) and for receptive vocabulary measures (g = -20.33; p < .001) indicated that children with cochlear implants demonstrate lower vocabulary knowledge than children with normal hearing. Additional analyses confirmed the value of comparing vocabulary knowledge of children with hearing loss to a tightly matched (e.g., socioeconomic status-matched) sample. Age of implantation, duration of implantation, and chronological age at testing were not significantly related to magnitude of weighted effect size. Findings from this analysis represent a first step toward resolving discrepancies in the vocabulary knowledge literature.

Synchrony of maternal auditory and visual cues about unknown words to children with and without cochlear implants.

OBJECTIVES: The purpose of this study was to compare types of maternal auditory-visual input about word referents available to children with cochlear implants, children with normal hearing matched for age, and children with normal hearing matched for vocabulary size. Although other works have considered the acoustic qualities of maternal input provided to children with cochlear implants, this study is the first to consider auditory-visual maternal input provided to children with cochlear implants. DESIGN: Participants included 30 mother-child dyads from three groups: children who wore cochlear implants (n = 10 dyads), children matched for chronological age (n = 10 dyads), and children matched for expressive vocabulary size (n = 10 dyads). All participants came from English-speaking families, with the families of children with hearing loss committed to developing listening and spoken language skills (not sign language). All mothers had normal hearing. Mother-child interactions were video recorded during mealtimes in the home. Each dyad participated in two mealtime observations. Maternal utterances were transcribed and coded for (a) nouns produced, (b) child-directed utterances, (c) nouns unknown to children per maternal report, and (d) auditory and visual cues provided about referents for unknown nouns. Auditory and visual cues were coded as either converging, diverging, or auditory-only. RESULTS: Mothers of children with cochlear implants provided percentages of converging and diverging cues that were similar to the percentages of mothers of children matched for chronological age. Mothers of children matched for vocabulary size, on the other hand, provided a higher percentage of converging auditory-visual cues and lower percentage of diverging cues than did mothers of children with cochlear implants. Groups did not differ in provision of auditory-only cues. CONCLUSIONS: The present study represents the first step toward identification of environmental input characteristics that may affect lexical learning outcomes of children with cochlear implants. Given that children with cochlear implants demonstrate slower rates of lexical growth than children with normal hearing, the findings from this study provide an important direction for further investigation of how environmental factors affect lexical outcomes for this population. If mothers can provide auditory and visual cues to increase the salience of a relevant object in word-learning contexts, they may be able to facilitate the language growth of their children.

Effects of a word-learning training on children with cochlear implants.

Preschool children with hearing loss who use cochlear implants demonstrate vocabulary delays when compared to their peers without hearing loss. These delays may be a result of deficient word-learning abilities; children with cochlear implants perform more poorly on rapid word-learning tasks than children with normal hearing. This study explored the malleability of rapid word learning of preschoolers with cochlear implants by evaluating the effects of a word-learning training on rapid word learning. A single-subject, multiple probe design across participants measured the impact of the training on children's rapid word-learning performance. Participants included 5 preschool children with cochlear implants who had an expressive lexicon of less than 150 words. An investigator guided children to identify, repeat, and learn about unknown sets of words in 2-weekly sessions across 10 weeks. The probe measure, a rapid word-learning task with a different set of words than those taught during training, was collected in the baseline, training, and maintenance conditions. All participants improved their receptive rapid word-learning performance in the training condition. The functional relation indicates that the receptive rapid word-learning performance of children with cochlear implants is malleable.

Knowledge and Perspectives of Developmental Language Disorders: The Pilot Development of a Survey of Professionals Working in Law Enforcement.

PURPOSE: The purpose of this study was to pilot test a survey of professionals within the justice system about their knowledge and perceptions of developmental language disorders (DLDs) and to gather initial data supporting their knowledge and perceptions. METHOD: One hundred thirty-six adults in Texas with law enforcement jobs, primarily police officers, participated in this study. Participants completed a survey consisting of 78 questions about their background, experiences with DLD, and beliefs about communication. Additionally, 42 adults who did not work in law enforcement completed the survey twice to establish the initial measures of survey reliability. RESULTS: This survey demonstrated sufficient test-retest reliability with adults not in law enforcement, and results indicated the emergence of two subscales within the survey. Law enforcement professionals appeared to have limited knowledge of DLD, and many linked language-related behaviors with credibility. A majority did agree with giving accommodations to individuals who struggle with language and reported interest in receiving training to recognize and accommodate DLD. CONCLUSIONS: This pilot study demonstrates a need for collaboration between speech-language pathologists and law enforcement professionals and provides data for a survey that could be used across professional groups in the justice system to measure knowledge and perspectives of DLDs. This work represents an initial step in an iterative process of survey development for law enforcement professionals. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25033718.

Determining an Effective Language Sample Elicitation Strategy for Early Language Learners Who Speak Using Augmentative and Alternative Communication.

PURPOSE: This study evaluates three different language sample elicitation strategies to determine a valid elicitation strategy for early language learners who speak using augmentative and alternative communication (AAC). METHOD: Ten children who speak using AAC participated in this study. Language samples were elicited from each participant using three strategies: the Communication and Symbolic Behavior Scales (CSBS), a generic play-based elicitation strategy, and automatic data logging. Samples were transcribed and coded. Additionally, each participant's school speech-language pathologist completed a Communication Matrix. Data from coded language samples were correlated with Communication Matrix results to determine the elicitation strategy that yielded the most valid language sample in comparison to Communication Matrix results. RESULTS: Both the CSBS and the play-based strategy yielded clinically relevant information. Because the log lacked communicative context, resulting data from the log was limited. An analysis of variance revealed significant differences in the amount of information elicited from each elicitation strategy. The CSBS repeatedly elicited the most data, followed by the play-based strategy and then the log. Generic play-based strategy results yielded the most correlations with Communication Matrix data. CONCLUSIONS: This preliminary data suggest that the play-based elicitation strategy elicited the most valid language sample when compared to the Communication Matrix from early language learners who speak using AAC. Additionally, results suggest that the CSBS may be an effective tool to measure the limits of this population's expressive language abilities.

Examining the roles of disability-related body esteem and perceived burdensomeness in suicidal ideation among adults with vision- and mobility-related disabilities.

PURPOSE/OBJECTIVE: People with disabilities (PWD) generally exhibit an increased risk of suicidal ideation (SI) and behaviors. Underlying cognitive states, namely perceived burdensomeness, have been identified as a contributor to the increased risk of suicidal thoughts and behaviors in PWD. However, the role of body esteem in the development of SI in this population remains unexamined, despite its salience in other populations. In this study, we examined whether the interaction of perceived burdensomeness and body esteem contributed to the perceived likelihood of future SI among PWD, and whether this relationship was further moderated by disability type. METHOD: Participants included 119 adults with self-reported vision- and mobility-related disabilities who participated in a larger study focused on disability and suicide involving interviews and self-report measures. We examined the interaction between perceived burdensomeness and disability-related body esteem on self-reported likelihood of future SI and whether this interaction was further moderated by disability type (i.e., vision- or mobility-related disability). RESULTS: Greater perceived burdensomeness was associated with a greater perceived likelihood of future SI only for participants with vision impairments and at low levels of body esteem. CONCLUSIONS/IMPLICATIONS: The combination of experiences of perceived burdensomeness and low body esteem may be particularly relevant to SI among people with vision-related versus mobility-related disabilities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).