A profile of expressive inflectional morphology in early school-age children with developmental language disorder

Previous research has established that children with developmental language disorder (DLD) have difficulties producing inflectional morphology, in particular, finiteness marking. However, other categories of inflectional morphology, such as possessive ‘s nominal inflection remain relatively unexplored. Analyses of the characteristics for marking inflection, such as allomorphic categories, may increase our understanding of patterns within disordered grammar to inform the design of interventions and target selection. Data from n = 30 early school-aged children (M = 75 months, SD = 3.38, range = 69–81 months) with DLD were analysed to develop a profile of inflectional morphology skills. Morphological categories included expressive regular past tense, third person singular, and possessive ‘s. Skills were profiled using an elicitation task. The relationships between expressive morphosyntax, and phonological short-term memory and working memory were also explored. Children demonstrated low accuracy in performance across all inflectional categories, including possessive ‘s. There were no significant differences between productions of different morphemes, but syllabic allomorphs ([əd]; [əz]) were produced with significantly lower accuracy than segmental allomorphs ([d], [t]; [z], [s]) across all morphological categories. All correlations between expressive morphosyntax and measures of memory were non-significant. Children with DLD show broad deficits in the ability to mark for inflection, including possessive ‘s; this has implications for theories explaining DLD. Findings may contribute to the design of urgently needed interventions for this clinical population

Evaluating two different dose frequencies and cumulative intervention intensities to improve past tense production for early school-aged children with developmental language disorder

Aims: This study compared two dose frequency conditions of an explicit intervention with 50 trials per session designed to improve past tense marking in early school-aged children with developmental language disorder (DLD). The influence of allomorphs on intervention effects was also examined. Methods: Data from previously conducted intervention studies were combined and analysed. Participants included nine children (mean age = 6;5 years) who received 20–30-min intervention sessions provided twice per week for 10 weeks (1000 trials; 400–600 min) and 20 children (mean age = 6;6) who received 20–30-min intervention sessions provided once per week for 10 weeks (500 trials; 200–300 min). Repeated measures included criterion-referenced probes for production of untrained past tense verbs collected throughout baseline, intervention, and maintenance phases. The rate of progress in each phase was analysed using logistic regression. The proportion of participants who produced past tense allomorphs correctly at pre-intervention, post-intervention, and maintenance testing points was analysed. Results: Logistic regression showed a stable baseline, highly significant progress during the intervention phase, and a marginally significant shallow decline during the maintenance phase. Those in the twice per week group showed a greater rate of progress during the intervention phase leading to significantly higher scores in the maintenance period when compared with the once per week group. The allomorphic category of past tense verbs did not appear to influence outcomes. Conclusions: Participants receiving intervention twice per week appeared to demonstrate a greater rate of progress with intervention than those receiving it once per week, although once per week was also effective. However, these results should be interpreted with caution. Limitations to study design indicate that a larger randomised controlled trial is required. All past tense allomorphs improve to a similar degree when treated with this intervention. What this paper adds: What is already known on the subject Understanding the parameters of dosage and intensity are important for clinical practice. Research evaluating the efficacy and/or effectiveness of interventions delivered in different dose/intensity conditions is scarce. There appears to be different interpretations of what constitutes dosage and intensity in published research. What this paper adds to existing knowledge This study retrospectively compared dosage and intensity conditions of intervention provided twice per week to intervention provided once per week. Both dose frequencies could be delivered in clinical settings. Results from this study were analysed by grouping data from multiple testing points, rather than comparing pre-post results. This approach demonstrated the variability of individual performance that would otherwise be lost with conventional methods of analysis. This study demonstrated that all past tense allomorphs improve to a similar degree when treated with this intervention. What are the potential or actual clinical implications of this work? Parameters of dosage and intensity are still not clearly defined well enough for translation to clinical practice. In consideration of current research, this intervention may be more effective if delivered twice per week. If clinicians are treating past tense, all allomorphs should be considered as priorities for intervention targets

A preliminary evaluation of a manualised intervention to improve early literacy skills in children with developmental language disorder

Children with Developmental Language Disorder (DLD) commonly present with oral language weaknesses which disrupt the development of literacy and impede related academic progress. While there is evidence to support the delivery of manualised Tier 2 interventions with this population, little is known about the effects of Tier 1 interventions. A retrospective cohort comparison was used to evaluate whether there was an observable effect of a manualised Tier 1 intervention compared to ‘business-as-usual’ on early literacy skills for children with DLD. Participants were 140 children attending a specialised education program with equivalent oral language skills and alphabetic knowledge at baseline. After 18 months formal literacy intervention, both groups were assessed on measures of early literacy skills. The differences between group means on all measures favoured the manualised intervention group, and they performed significantly better on a measure of nonword reading fluency. The findings indicate that a manualised Tier 1 intervention may be advantageous for children with DLD in developing proficiency in phonological recoding. This research contributes to the sparse evidence-base supporting the implementation of Tier 1 interventions for at risk populations, and findings warrant future research using experimental designs with tighter controls

Combining implicit and explicit intervention approaches to target grammar in young children with Developmental Language Disorder

Children with Developmental Language Disorder are likely to experience difficulties with morphosyntax, especially regular past tense marking. Few studies have evaluated the effectiveness of intervention to improve morphosyntax in young school-aged children with DLD. This study investigated the efficacy of combined explicit and implicit intervention techniques delivered by a speech pathologist to improve receptive and expressive grammar, including the use of past tense morphosyntax, using a multiple baseline single case experimental design. Participants were aged six to seven years and received two 1:1 45 minute sessions per week for five weeks (total 7.5 hours) using Shape Coding intervention techniques combined with implicit approaches. Two of the three participants made statistically significant gains on standardized tests of general receptive and expressive grammar. Two of the three children made statistically significant improvement on measures of expressive morphosyntax, with one participant continuing to improve five weeks post treatment. Findings suggest that this approach was efficacious. These findings warrant further investigation using larger group comparison research studies

Vascular Dysfunction Induced in Offspring by Maternal Dietary Fat Involves Altered Arterial Polyunsaturated Fatty Acid Biosynthesis

Nutrition during development affects risk of future cardiovascular disease. Relatively little is known about whether the amount and type of fat in the maternal diet affect vascular function in the offspring. To investigate this, pregnant and lactating rats were fed either 7%(w/w) or 21%(w/w) fat enriched in either18:2n-6, trans fatty acids, saturated fatty acids, or fish oil. Their offspring were fed 4%(w/w) soybean oil from weaning until day 77. Type and amount of maternal dietary fat altered acetylcholine (ACh)-mediated vaso-relaxation in offspring aortae and mesenteric arteries, contingent on sex. Amount, but not type, of maternal dietary fat altered phenylephrine (Pe)-induced vasoconstriction in these arteries. Maternal 21% fat diet decreased 20:4n-6 concentration in offspring aortae. We investigated the role of Δ6 and Δ5 desaturases, showing that their inhibition in aortae and mesenteric arteries reduced vasoconstriction, but not vaso-relaxation, and the synthesis of specific pro-constriction eicosanoids. Removal of the aortic endothelium did not alter the effect of inhibition of Δ6 and Δ5 desaturases on Pe-mediated vasoconstriction. Thus arterial smooth muscle 20:4n-6 biosynthesis de novo appears to be important for Pe-mediated vasoconstriction. Next we studied genes encoding these desaturases, finding that maternal 21% fat reduced Fads2 mRNA expression and increased Fads1 in offspring aortae, indicating dysregulation of 20:4n-6 biosynthesis. Methylation at CpG −394 bp 5′ to the Fads2 transcription start site predicted its expression. This locus was hypermethylated in offspring of dams fed 21% fat. Pe treatment of aortae for 10 minutes increased Fads2, but not Fads1, mRNA expression (76%; P<0.05). This suggests that Fads2 may be an immediate early gene in the response of aortae to Pe. Thus both amount and type of maternal dietary fat induce altered regulation of vascular tone in offspring though differential effects on vaso-relaxation, and persistent changes in vasoconstriction via epigenetic processes controlling arterial polyunsaturated fatty acid biosynthesis

The Confidence Database

Understanding how people rate their confidence is critical for the characterization of a wide range of perceptual, memory, motor and cognitive processes. To enable the continued exploration of these processes, we created a large database of confidence studies spanning a broad set of paradigms, participant populations and fields of study. The data from each study are structured in a common, easy-to-use format that can be easily imported and analysed using multiple software packages. Each dataset is accompanied by an explanation regarding the nature of the collected data. At the time of publication, the Confidence Database (which is available at https://osf.io/s46pr/) contained 145 datasets with data from more than 8,700 participants and almost 4 million trials. The database will remain open for new submissions indefinitely and is expected to continue to grow. Here we show the usefulness of this large collection of datasets in four different analyses that provide precise estimations of several foundational confidence-related effects

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders