Naresuan University Journal
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Sentence repetition: what does the task measure?
No full textBackground Sentence repetition is gaining increasing attention as a source of information about children's sentence-level abilities in clinical assessment, and as a clinical marker of specific language impairment. However, it is widely debated what the task is testing and therefore how informative it is. Aims (1) To evaluate the effects of different types of long-term linguistic knowledge on immediate recall, (2) to assess age sensitivity of repetition tasks designed to evaluate these effects, and (3) to establish if the effects are similar across typologically different languages. The study also considers the implications of the findings for the use of sentence repetition as a research and clinical assessment tool. Methods & Procedures Participants were 50 English-speaking and 50 Czech-speaking typically developing 4–5-year-olds. Children's ability to recall sequences of items was compared in seven linguistic conditions ranging from fully well-formed sentences to sequences of non-words. In each condition, children repeated blocks of successively longer stimuli to establish their span. Outcomes & Results Results showed significant but differential effects of all linguistic factors in both languages. While syntactic violations and presence of non-words dramatically reduced children's span, semantic implausibility and the removal of sentence prosody played a significant but much smaller role. Familiarity of function words was more important than familiarity of content words. The effects of different linguistic factors on spans were the same for both languages and did not change between 4 and 5 years, although average spans increased over this age range. Conclusions & Implications Children's ability to repeat sentences is more dependent on their familiarity with morphosyntax and lexical phonology than semantics or prosody, with function words of particular importance. Findings have implications for the use of recall in clinical assessment and as a research tool
Pesticide residue transfer in thai farmer families: using structural equation modeling to determine exposure pathways.
No full textUse of pesticides in agriculture may lead to downstreamexposure of farmers’ families to pesticide residues inadvertently taken home.Identification of the independent contribution of different exposure pathwaysfrom the farmer to their children can provide clear targets to reduce exposureof farmers’ children. Individual contributions of different pesticide transferexposure pathways were investigated using structural equation modelingmethods, and the benefits of these methods compared to standard multipleregression are described. A total of 72 Thai families, consisting of a farmer, aspouse, and a child, participated in this study. Family members completed aquestionnaire and self-collected three spot morning urine samples in thespraying season. Urine samples were analyzed for diethyl phosphate, diethylthiophosphate, diethyl dithiophosphate, dimethyl phosphate, dimethylthiophosphate, and dimethyl dithiophosphate. A path model was developedbased on an a priori hypothesized framework to examine the individual contributions of different exposure pathways that maydirectly or indirectly affect transfer of pesticide residues from farmers to their children. Transfer from the farmer to the childoccurs indirectly, primarily through transfer to the spouse in the first instance, but also through contamination of the homeenvironment. Clear targets for interventions are directly the reduction of farmers’ take-home exposures and indirectly frequentcleaning of the home to avoid buildup of pesticide residues
The yeast La related protein Slf1p is a key activator of translation during the oxidative stress response.
No full textThe mechanisms by which RNA-binding proteins control the translation of subsets of mRNAs are not yet clear. Slf1p and Sro9p are atypical-La motif containing proteins which are members of a superfamily of RNA-binding proteins conserved in eukaryotes. RIP-Seq analysis of these two yeast proteins identified overlapping and distinct sets of mRNA targets, including highly translated mRNAs such as those encoding ribosomal proteins. In paralell, transcriptome analysis of slf1Δ and sro9Δ mutant strains indicated altered gene expression in similar functional classes of mRNAs following loss of each factor. The loss of SLF1 had a greater impact on the transcriptome, and in particular, revealed changes in genes involved in the oxidative stress response. slf1Δ cells are more sensitive to oxidants and RIP-Seq analysis of oxidatively stressed cells enriched Slf1p targets encoding antioxidants and other proteins required for oxidant tolerance. To quantify these effects at the protein level, we used label-free mass spectrometry to compare the proteomes of wild-type and slf1Δ strains following oxidative stress. This analysis identified several proteins which are normally induced in response to hydrogen peroxide, but where this increase is attenuated in the slf1Δ mutant. Importantly, a significant number of the mRNAs encoding these targets were also identified as Slf1p-mRNA targets. We show that Slf1p remains associated with the few translating ribosomes following hydrogen peroxide stress and that Slf1p co-immunoprecipitates ribosomes and members of the eIF4E/eIF4G/Pab1p 'closed loop' complex suggesting that Slf1p interacts with actively translated mRNAs following stress. Finally, mutational analysis of SLF1 revealed a novel ribosome interacting domain in Slf1p, independent of its RNA binding La-motif. Together, our results indicate that Slf1p mediates a translational response to oxidative stress via mRNA-specific translational control
Genetic control of gene expression at novel and established chronic obstructive pulmonary disease loci.
No full textGenetic risk loci have been identified for a wide range of diseases through genome-wide association studies (GWAS), but the relevant functional mechanisms have been identified for only a small proportion of these GWAS-identified loci. By integrating results from the largest current GWAS of chronic obstructive disease (COPD) with expression quantitative trait locus (eQTL) analysis in whole blood and sputum from 121 subjects with COPD from the ECLIPSE Study, this analysis identifies loci that are simultaneously associated with COPD and the expression of nearby genes (COPD eQTLs). After integrative analysis, 19 COPD eQTLs were identified, including all four previously identified genome-wide significant loci near HHIP, FAM13A, and the 15q25 and 19q13 loci. For each COPD eQTL, fine mapping and colocalization analysis to identify causal shared eQTL and GWAS variants identified a subset of sites with moderate-to-strong evidence of harboring at least one shared variant responsible for both the eQTL and GWAS signals. Transcription factor binding site (TFBS) analysis confirms that multiple COPD eQTL lead SNPs disrupt TFBS, and enhancer enrichment analysis for loci with the strongest colocalization signals showed enrichment for blood-related cell types (CD3 and CD4+ T cells, lymphoblastoid cell lines). In summary, integrative eQTL and GWAS analysis confirms that genetic control of gene expression plays a key role in the genetic architecture of COPD and identifies specific blood-related cell types as likely participants in the functional pathway from GWAS-associated variant to disease phenotype
The potential for using a Universal Medication Schedule (UMS) to improve adherence in patients taking multiple medications in the UK: a qualitative evaluation
No full textBACKGROUND: Poor adherence to prescribed medication has major consequences. Managing multiple long-term conditions often involves polypharmacy, potentially increasing complexity and the possibility of poor adherence. As a result of the globally recognised problems in supporting adherence to medication, some researchers have proposed the use of reminder charts. The main aim of the research was to explore the need for and perceptions around the 'Universal Medication Schedule' (UMS). Looking at ways in which pharmacists and General Practitioners (GPs) could use the UMS in NHS settings. METHODS: Semi-structured interviews were carried out with 10 GPs, 10 community pharmacists and 15 patients. Patients were aged 65 years and over, had multiple long-term conditions and were prescribed at least 5 medications. Interviews were recorded and transcribed and thematic analysis was conducted, using a framework approach to manage the data. RESULTS: Attitudes towards the UMS were mixed with stakeholders seeing benefits and limitations to the chart. Practitioners proposed a number of existing services where they thought the UMS could easily be integrated but there was evidence of role conflict with GPs feeling it may be best placed with pharmacists and vice versa. The potential for the UMS to be used as a tool to aid communication between the different services involved in a patient's care was a key theme. CONCLUSIONS: The UMS chart provides consolidated medicines information that might help to improve patients' knowledge and health literacy, which may or may not improve adherence but could help patients in making informed decisions about their treatment. One of the key benefits of using the UMS in practice is that it could be introduced across services. In this way it may aid in medicines reconciliation between healthcare settings to ensure continuity of message, improve patient experience and create more joined up working between services. Further research is needed to test implementation in different services and to assess outcomes on patient understanding and adherence
Search for long-lived heavy charged particles using a ring imaging Cherenkov technique at LHCb
No full textA Comparison of Fire Service IRS and MODIS-Detected Vegetation Fires in Scotland
No full textIncident Recording System (IRS) data for Scotland over four financial years, 2009/10–2012/13, show that 80% of ‘IRS-based wildfires’ (vegetation fires meeting 2013 Scottish Wildfire Operational Guidance IRS-based criteria) occurred in spring. Similarly, 92% of vegetation fire hotspots detected by MODIS thermal sensors on Terra and Aqua satellites also occurred in spring (data from NASA’s FIRMS Web Fire Mapper). Both occurred mainly in the Highlands and Islands. Attempts to match these datasets revealed that MODIS detected only 1 in 10 (53) of IRS-based wildfires because of cloud cover, timing of satellite overpasses, fire size and intensity. Approximately 47% (206) of MODIS vegetation hotspots had near-matches to IRS-based wildfires. The mismatch occurs partly because MODIS detects active fire fronts, with >1 detection for large or long-lasting fires, whereas IRS records the ignition or fire service rendezvous point, sometimes several kilometres away. Matching would be easier if IRS recorded fire perimeters, especially since cloud means that very few MODIS Burned Area perimeters are available. The remaining 53% of MODIS hotspots may not be real fires (although those on non-vegetated land cover were excluded), or were real, unreported fires. Both datasets therefore have different benefits and limitations as tools for monitoring wildfires in Scotland
Risk of vertebral and non-vertebral fractures in patients with sarcoidosis: a population-based cohort.
No full textIn this retrospective cohort study using the Clinical Practice Research Datalink (CPRD), patients with sarcoidosis have an increased risk of clinical vertebral fractures and when on recent treatment with oral glucocorticoids, also an increased risk of any fractures and osteoporotic fractures.INTRODUCTION: Sarcoidosis is a chronic inflammatory disease, in which fragility fractures have been reported despite normal BMD. The aim of this study was to assess whether patients with sarcoidosis have an increased risk of clinical fractures compared to the general population. METHODS: A retrospective cohort study was conducted using the CPRD. All patients with a CPRD code for sarcoidosis between January 1987 and September 2012 were included. Cox proportional hazards models were used to derive adjusted relative risks (RRs) of fractures in all sarcoidosis patients compared to matched controls, and within the sarcoidosis group according to use and dose of systemic glucocorticoids. RESULTS: Five thousand seven hundred twenty-two sarcoidosis patients (mean age 48.0 years, 51 % females, mean follow-up 6.7 years) were identified. Compared to 28,704 matched controls, the risk of any fracture was not different in patients with sarcoidosis. However, the risk of clinical vertebral fractures was significantly increased (adj RR 1.77; 95 % CI 1.06-2.96) and the risk of non-vertebral fractures was decreased although marginally significant (adj RR 0.87; 95 % CI 0.77-0.99). Compared to sarcoidosis patients not taking glucocorticoids, recent use of systemic glucocorticoids was associated with an increased risk of any fracture (adj RR 1.50; 95 % CI 1.20-1.89) and of an osteoporotic fracture (adj RR 1.47; 95 % CI 1.07-2.02). CONCLUSIONS: Patients with sarcoidosis have an increased risk of clinical vertebral fractures, and when using glucocorticoid therapy, an increased risk of any fractures and osteoporotic fractures. In contrast, the risk of non-vertebral fractures maybe decreased. Further investigation is needed to understand the underlying mechanisms of these contrasting effects on fracture risk
The expression of certainty and its perlocutionary effect
No full textIf one takes the view that utterance meaning is the product of interactional processes, then intended perlocutionary effects should be receiving more attention: indeed, their occurrence (or non-occurrence, for that matter) has a direct influence on the circumstances which determine the range of possible language choices for both speaker and hearer. Building on this assumption, this article is concerned with the process whereby the communication of certainty can lead to the intended perlocutionary effect. Using Damasio’s convergence-divergence zone framework, which presupposes an adaptive perspective, I argue that such effects are more likely to come about if certainty is communicated without evidential markers, than when such marking is employed. The presumed effectiveness of this mode of communication would be due to the automatic nature of the mechanism involved, which mechanism relies on an interpretive process that may be seen as a simulation of recall
IL-17 and neutrophils: unexpected players in the type 2 immune response.
No full textThe study of immunity to helminth infection has been central to understanding the function of type 2 cytokines and their targets. Although type 2 cytokines are considered anti-inflammatory and promote tissue repair, they also contribute to allergy and fibrosis. Here, we utilise data from helminth infection models, to illustrate that IL-17 and neutrophils, typically associated with pro-inflammatory responses, are intimately linked with type 2 immunity. Neutrophils work with IL-4Rα-activated macrophages to control incoming larvae but this comes at a cost of enhanced tissue damage. Chitinase like proteins (CLPs) bridge these diverse outcomes, inducing both protective IL-17 and reparative Th2 responses. Dysregulation of CLPs, IL-17 and neutrophils likely contribute to disease severity and pathology associated with type 2 immunity