Supporting early oral language skills for English language learners in inner city preschool provision

BACKGROUND: A significant number of children now enter formal education in England with reduced levels of proficiency in oral language. Children who come from disadvantaged backgrounds and who are English language learners (ELL) are at risk of limited oral language skills in English which impacts on later educational achievement. AIMS: This paper reports the development of a theoretically motivated oral language intervention, Talking Time, designed to meet the needs of preschool children with poor language skills in typical preschool provision. SAMPLE: One hundred and forty-two 4-year-old children attending three inner city preschools in a disadvantaged area of London, England. METHOD: This is a quasi-experimental intervention study comparing children exposed to Talking Time with children exposed to a contrast intervention and children receiving the statutory early years curriculum. Measures were taken of both targeted and non-targeted language and cognitive skills. RESULTS: Data were analysed for the ELL. The intervention had a significant effect on vocabulary, oral comprehension, and sentence repetition but not narrative skills. As predicted, there were no effects on the skills which were not targeted. CONCLUSIONS: Regular evidence-based oral language interactions can make significant improvements in children's oral language. There is a need to examine the efficacy of more intensive interventions to raise language skills to allow learners to access the curriculum

Deficits in orthographic knowledge in children poor at rapid automatized naming (RAN) tasks?

The degree to which orthographic knowledge accounts for the link between Rapid Automatized Naming (RAN) and reading is contested, with mixed results reported. This longitudinal study compared two groups of 10-11 year old children, a low RAN group (N=69) and matched controls (N=74) on various measures of orthographic knowledge. The low RAN group showed a deficit in orthographic knowledge, both at the level of sub-word letter sequences and of whole words, as well as an unexpected strength in orthographic learning. Our findings underline the persistence of RAN-related reading problems, and raise questions about reading strategies in this group

The relationship between rapid naming and word spelling in English

A study of the concurrent relationships between naming speed, phonological awareness and spelling ability in 146 children in Year 3 and 4 of state funded school in SE England (equivalent to US Grades 2 and 3) is reported. Seventy-two children identified as having normal phonological awareness but reduced rapid automatized naming (RAN) performance (1 standard deviation below the mean) participated in the study. A group of 74 children were further identified. These children were matched on phonological awareness, verbal and non verbal IQ, and visual acuity but all members of this group showed normal rapid automatized naming performance. Rapid automatized naming made a significant unique contribution to spelling performance. Further analyses showed that the participants with low naming performance were significantly poorer spellers overall and had a specific difficulty in spelling irregular words. The findings support the view that rapid automatized naming may be indexing processes that are implicated in the establishment of fully specified orthographic representations

An experimental comparison between rival theories of rapid automatized naming performance and its relationship to reading

Two studies investigated the degree to which the relationship between Rapid Automatized Naming (RAN) performance and reading development is driven by shared phonological processes. Study 1 assessed RAN, phonological awareness and reading performance in 1010 children aged 7-10 years. Results showed that RAN deficits occurred in the absence of phonological awareness deficits. These were accompanied by modest reading delays. In structural equation modeling, solutions where RAN was subsumed within a phonological processing factor did not provide a good fit to the data, suggesting that processes outside phonology may drive RAN performance and its association with reading. Study 2 investigated Kail's (1991) proposal that speed of processing underlies this relationship. Children with single RAN deficits showed slower speed of processing than closely matched controls performing normally on RAN. However, regression analysis revealed that RAN made a unique contribution to reading even after accounting for processing speed. Theoretical implications are discussed

Trichostatin A Blocks Aldosterone-Induced Na+ Transport And Control Of Serum- And Glucocorticoid-Inducible Kinase 1 In Cortical Collecting Duct Cells

Background and Purpose: Aldosterone stimulates epithelial Na+ channel (ENaC)-dependent Na+ retention in the cortical collecting duct (CCD) of the kidney by activating mineralocorticoid receptors that promote expression of serum and glucocorticoid-inducible kinase 1 (SGK1). This response is critical to BP homeostasis. It has previously been suggested that inhibiting lysine deacetylases (KDACs) can post-transcriptionally disrupt this response by promoting acetylation of the mineralocorticoid receptor. The present study critically evaluates this hypothesis. Experimental Approach: Electrometric and molecular methods were used to define the effects of a pan-KDAC inhibitor, trichostatin A, on the responses to a physiologically relevant concentration of aldosterone (3 nM) in murine mCCDcl1 cells. Key Results: Aldosterone augmented ENaC-induced Na+ absorption and increased SGK1 activity and abundance, as expected. In the presence of trichostatin A, these responses were suppressed. Trichostatin A-induced inhibition of KDAC was confirmed by increased acetylation of histone H3, H4, and α-tubulin. Trichostatin A did not block the electrometric response to insulin, a hormone that activates SGK1 independently of increased transcription, indicating that trichostatin A has no direct effect upon the SGK1/ENaC pathway. Conclusions and Implications: Inhibition of lysine de-acetylation suppresses aldosterone-dependent control over the SGK1–ENaC pathway but does not perturb post-transcriptional signalling, providing a physiological basis for the anti-hypertensive action of KDAC inhibition seen in vivo

The effects of a video intervention on posthospitalization pulmonary rehabilitation uptake

Rationale: Pulmonary rehabilitation (PR) after hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life and reduces readmissions. However, posthospitalization PR uptake is low. To date, no trials of interventions to increase uptake have been conducted.Objectives: To study the effect of a codesigned education video as an adjunct to usual care on posthospitalization PR uptake.Methods: The present study was an assessor- and statistician-blinded randomized controlled trial with nested, qualitative interviews of participants in the intervention group. Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including PR information leaflet) or usual care plus the codesigned education video delivered via a handheld tablet device at discharge. Randomization used minimization to balance age, sex, FEV1 % predicted, frailty, transport availability, and previous PR experience.Measurements and Main Results: The primary outcome was PR uptake within 28 days of hospital discharge. A total of 200 patients were recruited, and 196 were randomized (51% female, median FEV1% predicted, 36 [interquartile range, 27-48]). PR uptake was 41% and 34% in the usual care and intervention groups, respectively (P = 0.37), with no differences in secondary (PR referral and completion) or safety (readmissions and death) endpoints. A total of 6 of the 15 participants interviewed could not recall receiving the video.Conclusions: A codesigned education video delivered at hospital discharge did not improve posthospitalization PR uptake, referral, or completion

Visual processing deficits in children with slow RAN performance

Two groups of 8- to 10-year-olds differing in rapid automatized naming speed but matched for age, verbal and nonverbal ability, phonological awareness, phonological memory, and visual acuity participated in four experiments investigating early visual processing. As low RAN children had significantly slower simple reaction times (SRT) this was entered as a covariate in all subsequent data analyses. Low RAN children were significantly slower to make same/different judgments to simple visual features, non-nameable letter-like forms and letters, with difference in SRT controlled. Speed differences to letter-like forms and letters disappeared once RTs to simple visual features were controlled. We conclude that slow RAN children have difficulty in discriminating simple visual features that cannot be explained in terms of a more general speed of processing deficit, a deficit in making same/different judgments, or to differences in word reading ability

Evidence for semantic involvement in regular and exception word reading in emergent readers of English

We investigated the relationship between semantic knowledge and word reading. A sample of 27 6-year-old children read words both in isolation and in context. Lexical knowledge was assessed using general and item-specific tasks. General semantic knowledge was measured using standardized tasks in which children defined words and made judgments about the relationships between words. Item-specific knowledge of to-be-read words was assessed using auditory lexical decision (lexical phonology) and definitions (semantic) tasks. Regressions and mixed-effects models indicated a close relationship between semantic knowledge (but not lexical phonology) and both regular and exception word reading. Thus, during the early stages of learning to read, semantic knowledge may support word reading irrespective of regularity. Contextual support particularly benefitted reading of exception words. We found evidence that lexical–semantic knowledge and context make separable contributions to word reading

Mapping the Transcriptome Underpinning Acute Corticosteroid Action within the Cortical Collecting Duct

Funding: British Heart Foundation (BHF): Research Excellence Award RE/13/3/30183; Kidney Research UK: Innovation Grant IN_001_201703 Postdoctoral Fellowship PDF_008_20151127; Scottish Funding Council (SFC): St Andrews Restarting Research Funding Scheme; Society for Endocrinology (SFE): Early Career Grant.We report the transcriptomes associated with acute corticosteroid regulation of ENaC activity in polarised mCCDcl1 collecting duct cells. 9 genes were regulated by aldosterone (ALDO), 0 with corticosterone alone and 151 with corticosterone when 11βHSD2 activity was inhibited. We validated 3 novel ALDO-induced genes: Rasd1, Sult1d1 and Gm43305 in primary cells isolated from a novel collecting duct reporter mouse. Background Corticosteroids regulate distal nephron and collecting duct Na+ reabsorption, contributing to fluid-volume and blood pressure homeostasis. The transcriptional landscape underpinning the acute stimulation of the epithelial sodium channel (ENaC) by physiological concentrations of corticosteroids remains unclear. Methods Transcriptomic profiles underlying corticosteroid-stimulated ENaC activity in polarised mCCDcl1 cells were generated by coupling electrophysiological measurements of amiloride-sensitive currents with RNAseq. Generation of a collecting-duct specific reporter mouse line, mT/mG-Aqp2Cre, enabled isolation of primary collecting duct cells by FACS and ENaC activity was measured in cultured primary cells following acute application of corticosteroids. Expression of target genes was assessed by qRT-PCR in cultured cells or freshly isolated cells following acute elevation of steroid hormones in mT/mG-Aqp2Cre mice. Results Physiological relevance of the mCCDcl1 model was confirmed with aldosterone-specific stimulation of SGK1 and ENaC activity. Corticosterone only modulated these responses at supraphysiological concentrations or when 11βHSD2 was inhibited. When 11βHSD2 protection was intact, corticosterone caused no significant change in transcripts. We identified a small number of aldosterone-induced transcripts associated with stimulated ENaC activity in mCCDcl1 cells and a much larger number with corticosterone in the absence of 11βHSD2 activity. Cells isolated from mT/mG-Aqp2Cre mice were validated as collecting duct-specific and assessment of identified aldosterone-induced genes revealed that Sgk1, Zbtbt16, Sult1d1, Rasd1 and Gm43305 are acutely upregulated by corticosteroids both in vitro and in vivo. Conclusions This study reports the transcriptome of mCCDcl1 collecting duct cells and identifies a small number of aldosterone-induced genes associated with acute stimulation of ENaC, including 3 previously undescribed genes.PostprintPeer reviewe

CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer Outcomes: Analysis of a Large Cohort, Systematic Review of Endoscopic Surveillance, and Secondary Cancer Risk Postulation

Hereditary diffuse gastric cancer (HDGC) is a rare signet-ring cell adenocarcinoma (SRCC) linked to CDH1 (E-cadherin) inactivating germline mutations, and increasingly other gene mutations. Female CDH1 mutation carriers have additional risk of lobular breast cancer. Risk management includes prophylactic total gastrectomy (PTG). The utility of endoscopic surveillance is unclear, as early disease lacks macroscopic lesions. The current systematic biopsy protocols have unknown efficacy, and other secondary cancer risks are postulated. We conducted a retrospective study of consecutive asymptomatic HDGC patients undergoing PTG, detailing endoscopic, pathologic, and outcome results. A systematic review compared endoscopic biopsy foci detection via random sampling versus Cambridge Protocol against PTG findings. A population-level secondary-cancer-risk postulation among sporadic gastric SRCC patients was completed using the Surveillance, Epidemiology, and End Results database. Of 97 patients, 67 underwent PTG, with 25% having foci detection on random endoscopic biopsy despite 75% having foci on final pathology. There was no improvement in the endoscopic detection rate by Cambridge Protocol. The postulated hazard ratio among sporadic gastric SRCC patients for a secondary colorectal SRCC was three-fold higher, relative to conventional adenocarcinoma patients. Overall, HDGC patients should not rely on endoscopic surveillance to delay PTG, and may have secondary SRCC risks. A definitive determination of actual risk requires collaborative patient outcome data bankin