Comparison of Motor-Enhanced and Visual-Enhanced Interventions for Grammar in Young Children With Developmental Language Disorder

Up to 7.6% of children demonstrate a developmental language disorder (DLD), which can persist through adulthood, causing difficulty with academic achievement, social relationships, and financial stability. Grammar development, as a hallmark of DLD, is an important area of need for these children. Existing grammar interventions do not clearly distinguish the sensory input techniques that meet these children’s neurobiological instructional needs. This adapted alternating treatment design study implemented intervention using systematic paired visual and verbal and systematic paired motor, i.e. standardized gestures, and verbal sensory input techniques. A moderate-strong functional relation between intervention techniques using motor supports on grammatical outcomes in natural language practice (Tau-U = 0.68) and a potential functional relation between motor supports on grammatical outcomes in decontextualized tasks (Tau U = 0.45) were found. Both paired visual and verbal and paired motor and verbal interventions were found to have a potential functional relation with natural language use among children with DLD ages 4;7 – 6;9 years (n = 4). Patterns of response were reviewed in participants with comorbid delays in speech sound development, executive function development, and high activity levels. Children with severe grammar delays and ADHD/executive function challenges may derive more benefit from paired verbal and motor support. Children with milder overall language delays may respond better initially to combined verbal and visual supports. Both intervention modalities were socially valid and provided effectively by novice clinicians. Interventionists should consider conscious and consistent use of different sensory techniques within grammar intervention for children with DLD

Enriching Pre-Clinical Education with Near-Peer Learning Experiences

The purpose of this mixed methods study was to examine the outcomes of two instructional methodologies (traditional and peer-assisted learning; PAL) used in a clinical methods course for undergraduate speech-language pathology (SLP) students. The sample included 53 undergraduate SLP students (near-peer learners) as well as 27 graduate SLP students and 7 clinical fellows (near-peer tutors). Traditional instruction was used during the first half of the course and PAL was added during the second half. The undergraduate SLP students’ weekly written reflections and grades (mid-term and final) were collected for analysis. Students demonstrated a preference for peer- and near-peer learning experiences and commented positively on learning via stories throughout the course. They exhibited more positive attitudes during PAL instruction. Further, students reported less clinical confidence and more confusion as the course progressed and they learned more about the demands and expectations for clinical practice. Implications and recommendations for SLP students’ clinical training are discussed

Predicting Language Performance from Narrative Language Samples

Purpose: Analysis of narrative language samples is a recommended clinical practice in the assessment of children’s language skills, but we know little about how results from such analyses relate to overall oral language ability across the early school years. We examined the relations between language sample metrics from a short narrative retell, collected in kindergarten, and an oral language factor in grades kindergarten through 3. Our specific questions were to determine the extent to which metrics from narrative language sample analysis are concurrently related to language in kindergarten and predict language through Grade 3. Method: Participants were a sample of 284 children who were administered a narrative retell task in kindergarten and a battery of vocabulary and grammar measures in kindergarten through Grade 3. Language samples were analyzed for number of different words, mean length of utterance, and a relatively new metric, percent grammatical utterances (PGUs). Structural equation models were used to estimate the concurrent and longitudinal relationships. Results: The narrative language sample metrics were consistently correlated with the individual vocabulary and grammar measures as well as the language factor in each grade, and also consistently and uniquely predicted the language factor in each grade. Standardized path estimates in the structural equation models ranged from 0.20 to 0.39. Conclusions: This study found narrative language sample metrics to be predictive, concurrently and longitudinally, of a latent factor of language from kindergarten through Grade 3. These results further validate the importance of collecting and analyzing narrative language samples, to include PGU along with more traditional metrics, and point to directions for future research

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Enriching Pre-Clinical Education With Near-Peer Learning Experiences

The purpose of this mixed methods study was to examine the outcomes of two instructional methodologies (traditional and peer-assisted learning; PAL) used in a clinical methods course for undergraduate speech-language pathology (SLP) students. The sample included 53 undergraduate SLP students (near-peer learners) as well as 27 graduate SLP students and 7 clinical fellows (near-peer tutors). Traditional instruction was used during the first half of the course and PAL was added during the second half. The undergraduate SLP students’ weekly written reflections and grades (mid-term and final) were collected for analysis. Students demonstrated a preference for peer- and near-peer learning experiences and commented positively on learning via stories throughout the course. They exhibited more positive attitudes during PAL instruction. Further, students reported less clinical confidence and more confusion as the course progressed and they learned more about the demands and expectations for clinical practice. Implications and recommendations for SLP students’ clinical training are discussed

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease