The Efficacy of an Explicit Intervention Approach to Improve Past Tense Marking for Early School-Age Children With Developmental Language Disorder

Purpose The aim of the study was to evaluate the efficacy of a theoretically motivated explicit intervention approach to improve regular past tense marking for early school-age children with developmental language disorder (DLD). Method Twenty-one children with DLD (ages 5;9–6;9 [years;months]) were included in a crossover randomized controlled trial (intervention, n = 10; waiting control, n = 11). Intervention included once-weekly sessions over 10 weeks using the SHAPE CODING system, in combination with a systematic cueing hierarchy to teach past tense marking. Once the first group completed intervention, the waiting control group crossed over to the intervention condition. The primary outcome was criterion-referenced measures of past tense marking with standardized measures of expressive and receptive grammar as the secondary outcome. Ancillary analyses on extension and behavioral control measures of morphosyntax were also conducted. Results There was a significant Time × Group interaction (p < .001) with a significant difference in pre–post intervention improvement in favor of the intervention group (p < .001, d = 3.03). Further analysis once both groups had received the intervention revealed no improvement for either group on past tense production during the 5-week pre-intervention period, significant improvement pre–post intervention (p < .001, d = 1.22), with gains maintained for 5 weeks postintervention. No significant differences were found on pre- to postintervention standardized measures of grammar, or on extension or control measures. Conclusions The efficacy of the theoretically motivated explicit grammar intervention was demonstrated. Results contribute to the evidence base supporting this intervention to improve past tense production in early school-age children with DLD, suggesting it is a viable option for clinicians to select when treating morphosyntactic difficulties for this population

Explicit Grammar Intervention in Young School-Aged Children With Developmental Language Disorder: An Efficacy Study Using Single-Case Experimental Design

PURPOSE: This study evaluated the efficacy of an explicit, combined metalinguistic training and grammar facilitation intervention aimed at improving regular past tense marking for nine children aged 5;10–6;8 (years;months) with developmental language disorder. METHOD: This study used an ABA across-participant multiple-baseline single-case experimental design. Participants were seen one-on-one twice a week for 20- to 30-min sessions for 10 weeks and received explicit grammar intervention combining metalinguistic training using the SHAPE CODING system with grammar facilitation techniques (a systematic cueing hierarchy). In each session, 50 trials to produce the target form were completed, resulting in a total of 1,000 trials over 20 individual therapy sessions. Repeated measures of morphosyntax were collected using probes, including trained past tense verbs, untrained past tense verbs, third-person singular verbs as an extension probe, and possessive 's as a control probe. Probing contexts included expressive morphosyntax and grammaticality judgment. Outcome measures also included pre–poststandard measures of expressive and receptive grammar. RESULTS: Analyses of repeated measures demonstrated significant improvement in past tense production on trained verbs (eight of nine children) and untrained verbs (seven of nine children), indicating efficacy of the treatment. These gains were maintained for 5 weeks. The majority of children made significant improvement on standardized measures of expressive grammar (eight of nine children). Only five of nine children improved on grammaticality judgment or receptive measures. CONCLUSIONS: Results continue to support the efficacy of explicit grammar interventions to improve past tense marking in early school-aged children. Future research should aim to evaluate the efficacy of similar interventions with group comparison studies and determine whether explicit grammar interventions can improve other aspects of grammatical difficulty for early school-aged children with developmental language disorder

Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented. However, here we demonstrate that DCs can directly induce fibrosis. In the mouse model of allergic eye disease (AED), classical CD11b(+) DCs in the ocular mucosa showed increased activity of aldehyde dehydrogenase (ALDH), the enzyme required for retinoic acid synthesis. In vitro, CD11b(+) DC-derived ALDH was associated with 9-cis-retinoic acid ligation to retinoid x receptor (RXR), which induced conjunctival fibroblast activation. In vivo, stimulating RXR led to rapid onset of ocular mucosal fibrosis, whereas inhibiting ALDH activity in DCs or selectively depleting DCs markedly reduced fibrosis. Collectively, these data reveal a profibrotic ALDH-dependent pathway by DCs and uncover a role for DC retinoid metabolism

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Mind the gap: sentencing, rehabilitation and civic purgatory

This article discusses the relationships and tensions between the sentencing, statutory supervision and legal rehabilitation of lawbreakers under UK legislation. It does so with reference to both the Rehabilitation of Offenders Act 1974, which allows some criminal records to become ‘spent’ after a set period of time, and the Offender Rehabilitation Act 2014, which was designed to significantly expand statutory supervision arrangements. The article also demonstrates how, post-supervision, many former lawbreakers are cast into a state of ‘civic purgatory’, before suggesting that a more fully integrated approach to rehabilitation is required