Children with persisting speech difficulties: exploring speech production and intelligibility across different contexts

Background and purpose Children with persisting speech difficulties (PSD) may present with severe and ongoing impairments in segmental and prosodic output which can result in poor intelligibility. The purpose of this study was to examine the speech processing skills and intelligibility of four children with PSD, carrying out detailed phonetic and phonological analysis, and investigation of their speech output and intelligibility in single words (SW) and multi-word utterances (MWU). Method Participants were aged 6;5 to 7;3 at the start of the study. Their speech processing was examined through: • Psycholinguistic assessment of input and output processing skills (Joy Stackhouse & Wells, 1997) • Perceptual transcription and analysis of the production of SW, imitated sentences and conversational speech (CS) at two points in time (T1 and T2). Speech output data were considered in the context of phonological process analysis (PPA) and then through further analysis of segmental and prosodic aspects of MWU. Intelligibility was measured through 66 unfamiliar adult listeners orthographically transcribing edited samples from each child of 10 SW, 5 imitated sentences and 5 samples of CS from T1 and T2. Results Psycholinguistic tasks revealed that the children had pervasive and complex speech processing difficulties. PPA based on traditional SW sampling failed to capture important aspects of children's speech; analysis of MWU revealed phonetic and prosodic features essential to describing and understanding children's development of "real talk"(Howard, 2007, p. 20). Intelligibility outcomes revealed listeners' recognition was better for MWU in three of the children; intelligibility was better for all children at T2. Implications Children with PSD benefit from thorough investigation of Input and output speech processing skills; assessment of MWU is essential in capturing segmental and prosodic aspects of speech output to explain poor intelligibility and plan Intervention

Endomembrane targeting of human OAS1 p46 augments antiviral activity

Many host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from cellular innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense RNA generated by viruses that use these compartments for replication. Here, we reveal that an isoform of oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 p46 confers enhanced access to viral replication sites and results in increased antiviral activity against a subset of RNA viruses including flaviviruses, picornaviruses, and SARS-CoV-2. Finally, our human genetic analysis shows that the OAS1 splice-site SNP responsible for production of the OAS1 p46 isoform correlates with protection from severe COVID-19. This study highlights the importance of endomembrane targeting for the antiviral specificity of OAS1 and suggests that early control of SARS-CoV-2 replication through OAS1 p46 is an important determinant of COVID-19 severity

CATALISE: A multinational and multidisciplinary Delphi consensus study. Identifying language impairments in children

Delayed or impaired language development is a common developmental concern, yet thereis little agreement about the criteria used to identify and classify language impairments inchildren. Children's language difficulties are at the interface between education, medicineand the allied professions, who may all adopt different approaches to conceptualising them.Our goal in this study was to use an online Delphi technique to see whether it was possibleto achieve consensus among professionals on appropriate criteria for identifying childrenwho might benefit from specialist services. We recruited a panel of 59 experts representingten disciplines (including education, psychology, speech-language therapy/pathology, paediatricsand child psychiatry) from English-speaking countries (Australia, Canada, Ireland,New Zealand, United Kingdom and USA). The starting point for round 1 was a set of 46statements based on articles and commentaries in a special issue of a journal focusing onthis topic. Panel members rated each statement for both relevance and validity on a sevenpointscale, and added free text comments. These responses were synthesised by the firsttwo authors, who then removed, combined or modified items with a view to improving consensus.The resulting set of statements was returned to the panel for a second evaluation(round 2). Consensus (percentage reporting 'agree' or 'strongly agree') was at least 80 percentfor 24 of 27 round 2 statements, though many respondents qualified their responsewith written comments. These were again synthesised by the first two authors. The resultingconsensus statement is reported here, with additional summary of relevant evidence, and aconcluding commentary on residual disagreements and gaps in the evidence base.</p

Tutorial:Speech assessment for multilingual children who do not speak the same language(s) as the speech-language pathologist

Purpose: The aim of this tutorial is to support speech language pathologists (SLPs) undertaking assessments of multilingual children with suspected speech sound disorders, particularly children who speak languages that are not shared with their SLP. Method: The tutorial was written by the International Expert Panel on Multilingual Children’s Speech, which comprises 46 researchers (SLPs, linguists, phoneticians, and speech scientists) who have worked in 43 countries and used 27 languages in professional practice. Seventeen panel members met for a 1-day workshop to identify key points for inclusion in the tutorial, 26 panel members contributed to writing this tutorial, and 34 members contributed to revising this tutorial online (some members contributed tomore than 1 task). Results: This tutorial draws on international research evidence and professional expertise to provide a comprehensive overview of working with multilingual children with suspected speech sound disorders. This overview addresses referral, case history, assessment, analysis, diagnosis, and goal setting and the SLP’s cultural competence and preparation for working with interpreters and multicultural support workers and dealing with organizational and government barriers to and facilitators of culturally competent practice. Conclusion: The issues raised in this tutorial are applied in a hypothetical case study of an English-speaking SLP’s assessment of a multilingual Cantonese-and English-speaking 4-year-old boy. Resources are listed throughout the tutorial.Australian Research Council: FT0990588United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Deafness & Other Communication Disorders (NIDCD

Phase 2 of CATALISE: a multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology.

Background: Lack of agreement about criteria and terminology for children’s language problems affects access to services as well as hindering research and practice. We report the second phase of a study using an online Delphi method to address these issues. In the first phase, we focused on criteria for language disorder. Here we consider terminology.Methods: The Delphi method is an iterative process in which an initial set of statements is rated by a panel of experts, who then have the opportunity to view anonymised ratings from other panel members. On this basis they can either revise their views or make a case for their position. The statements are then revised based on panel feedback, and again rated by and commented on by the panel. In this study, feedback from a second round was used to prepare a final set of statements in narrative form. The panel included 57 individuals representing a range of professions and nationalities. Results: We achieved at least 78% agreement for 19 of 21 statements within two rounds of ratings. These were collapsed into 12 statements for the final consensus reported here. The term ‘Language Disorder’ is recommended to refer to a profile of difficulties that causes functional impairment in everyday life and is associated with poor prognosis. The term, ‘Developmental Language Disorder’ (DLD) was endorsed for use when the language disorder was not associated with a known biomedical aetiology. It was also agreed that (a) presence of risk factors (neurobiological or environmental) does not preclude a diagnosis of DLD, (b) DLD can co-occur with other neurodevelopmental disorders (e.g. ADHD) and (c) DLD does not require a mismatch between verbal and nonverbal ability. Conclusions: This Delphi exercise highlights reasons for disagreements about terminology for language disorders and proposes standard definitions and nomenclature. </p

Early Prognostic Indicators of Subsequent Hospitalization in Patients with Mild COVID-19

Comprehensive data on early prognostic indicators in patients with mild COVID-19 remains sparse. In this single center case series, we characterized the initial clinical presentation in 180 patients with mild COVID-19 and defined the earliest predictors of subsequent deterioration and need for hospitalization. Three broad patient phenotypes and four symptom clusters were characterized, differentiated by varying risk for adverse outcomes. Among 14 symptoms assessed, subjective shortness of breath (SOB) most strongly associated with adverse outcomes (odds ratio (OR) 21.3, 95% confidence interval (CI): 2.7–166.4; p &lt; 0.0001). In combination, SOB and number of comorbidities were highly predictive of subsequent hospitalization (area under the curve (AUC) 92%). Additionally, initial lymphopenia (OR 21.0, 95% CI: 2.1–210.1; p = 0.002) and male sex (OR 3.5, 95% CI: 0.9–13.0; p = 0.05) were associated with increased risk of poor outcomes. Patients with known comorbidities, especially multiple, and those presenting with subjective SOB or lymphopenia should receive close monitoring and consideration for preemptive treatment, even when presenting with mild symptoms

Shifts in isoform usage underlie transcriptional differences in regulatory T cells in type 1 diabetes

Abstract Genome-wide association studies have identified numerous loci with allelic associations to Type 1 Diabetes (T1D) risk. Most disease-associated variants are enriched in regulatory sequences active in lymphoid cell types, suggesting that lymphocyte gene expression is altered in T1D. Here we assay gene expression between T1D cases and healthy controls in two autoimmunity-relevant lymphocyte cell types, memory CD4+/CD25+ regulatory T cells (Treg) and memory CD4+/CD25- T cells, using a splicing event-based approach to characterize tissue-specific transcriptomes. Limited differences in isoform usage between T1D cases and controls are observed in memory CD4+/CD25- T-cells. In Tregs, 402 genes demonstrate differences in isoform usage between cases and controls, particularly RNA recognition and splicing factor genes. Many of these genes are regulated by the variable inclusion of exons that can trigger nonsense mediated decay. Our results suggest that dysregulation of gene expression, through shifts in alternative splicing in Tregs, contributes to T1D pathophysiology

International aspirations for speech-language pathologists' practice with multilingual children with speech sound disorders : development of a position paper

A major challenge for the speech-language pathology profession in many cultures is to address the mismatch between the ‘‘linguistic homogeneity of the speech-language pathology profession and the linguistic diversity of its clientele’’ (Caesar & Kohler, 2007, p. 198). This paper outlines the development of the Multilingual Children with Speech Sound Disorders: Position Paper created to guide speech-language pathologists’ (SLPs’) facilitation of multilingual children’s speech. An international expert panel was assembled comprising 57 researchers (SLPs, linguists, phoneticians, and speech scientists) with knowledge about multilingual children’s speech, or children with speech sound disorders. Combined, they had worked in 33 countries and used 26 languages in professional practice. Fourteen panel members met for a one-day workshop to identify key points for inclusion in the position paper. Subsequently, 42 additional panel members participated online to contribute to drafts of the position paper. A thematic analysis was undertaken of the major areas of discussion using two data sources: (a) face-to-face workshop transcript (133 pages) and (b) online discussion artifacts (104 pages). Finally, a moderator with international expertise in working with children with speech sound disorders facilitated the incorporation of the panel’s recommendations. The following themes were identified: definitions, scope, framework, evidence, challenges, practices, and consideration of a multilingual audience. The resulting position paper contains guidelines for providing services to multilingual children with speech sound disorders (http://www.csu.edu.au/ research/multilingual-speech/position-paper). The paper is structured using the International Classification of Functioning, Disability and Health: Children and Youth Version (World Health Organization, 2007) and incorporates recommendations for (a) children and families, (b) SLPs’ assessment and intervention, (c) SLPs’ professional practice, and (d) SLPs’ collaboration with other professionals. Learning outcomes: Readers will 1. recognize that multilingual children with speech sound disorders have both similar and different needs to monolingual children when working with speech-language pathologists. 2. Describe the challenges for speech-language pathologists who work with multilingual children. 3. Recall the importance of cultural competence for speech-language pathologists. 4. Identify methods for international collaboration and consultation. 5. Recognize the importance of engaging with families and people within their local communities for supporting multilingual children in context