The Developing Role of the Special Education Needs Coordinater: an Evaluation Study on the Effects of an RTLB Project, which Provided a Wrap around Special Education Needs Coordinator Service to All of the Schools within Its Region

The purpose of this mixed methods study was to investigate the systems level intervention which was initiated by an RTLB (Resource Teachers’ of Learning and Behaviour) cluster, through EPF (enhancing programming funding) and with local Principals’ Association support in order to improve the SENCo (special education needs coordinator) service (outcomes for students) within the region. This intervention based on an inclusive paradigm involved creating dedicated SENCo positions within each of 19 schools involved and assisting in setting up special need’s committees, gaining release time for SENCos, negotiating and arranging professional development, developing a reporting system for SENCos, developing interagency collaboration and fostering a community of practise among the SENCos. This study found that the RTLB cluster, working collaboratively with the local principals, successfully initiated the EPF application in order to aid in the creation of the SENCo positions within all of the schools in the region, along with leading the project of professional development and supporting SENCos in schools in order to provide a better service for special education students within the region. New Zealand’s education system historically either ignored students with special education needs or placed them into special settings. Special education and the Tomorrow Schools policy provided the next step toward inclusive practices. However, the tools to implement shifts in paradigm are found through; professional development, communities of practice, collaborative-consultative approaches, teacher/school change and the management and facilitation of the transfer of learning. The research clearly indicates that further investigation is needed to understand the role of the SENCo within New Zealand schools. Is there a place for SENCos in our post Special Education 2000 schools? Do; release time, PD, professional support and role development affect the SENCo role and does a SENCo service impact on the service provided to students with special educational needs? There is much scope for future research within this area. It would be interesting to follow what happens with this group of SENCos in the long term. A longitudinal study of this kind would be able to answer questions about the long term implications and outcomes that may arise. Do the systems put in place lead to more inclusive classroom practices within the region and better outcomes of the students? Is this fledgling community of practice maintained and do the SENCos take up the mantle of change agents within their schools? It would also be worthwhile to look at the other two clusters who have initiated their own versions of this project. Undertaking case studies for schools which create SENCo positions would shed further light on what works and what doesn’t at the school level and the outcomes for students with special educational needs

“There’s only so much an individual can do”: An ecological systems perspective on mental health and wellbeing in the early stages of doctoral research

Calls to address concerning evidence surrounding mental health and wellbeing in doctoral researchers have grown internationally in recent years. Adopting an ecological systems approach, this article explores doctoral researchers’ perspectives on what influences mental health and wellbeing in early-stage doctoral research. Forty-seven doctoral researchers took part in focus groups exploring mental health and wellbeing in the first year of doctoral study. The framework generated through our thematic and connecting analyses emphasises the interdependency of the various layers of the environment surrounding early-stage doctoral researchers. In line with our theoretical perspective, we describe the influence of: individual factor; the microsystem; the mesosystem; the exosystem; and the macrosystem. Participants highlighted the impact of the broader working culture in academia on their mental health and wellbeing, which permeated other, more proximal layers within their environment. This article contributes knowledge that can aid the development of interventions seeking to support mental health and wellbeing in doctoral researchers. Furthermore, our findings suggest that without the adoption of a whole-systems approach, efforts to improve mental health and wellbeing in these researchers could be difficult

Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female mice--a model of human Filamin A (FLNA) diseases

<p>Abstract</p> <p>Background</p> <p>Some abnormalities of mouse corneal epithelial maintenance can be identified by the atypical mosaic patterns they produce in X-chromosome inactivation mosaics and chimeras. Human <it>FLNA</it>/+ females, heterozygous for X-linked, filamin A gene (<it>FLNA</it>) mutations, display a range of disorders and X-inactivation mosaicism is sometimes quantitatively unbalanced. <it>Flna</it>^{<it>Dilp2/+ </it>}mice, heterozygous for an X-linked filamin A (<it>Flna</it>) nonsense mutation have variable eye, skeletal and other abnormalities, but X-inactivation mosaicism has not been investigated. The aim of this study was to determine whether X-inactivation mosaicism in the corneal epithelia of <it>Flna</it>^{<it>Dilp2/+ </it>}mice was affected in any way that might predict abnormal corneal epithelial maintenance.</p> <p>Results</p> <p>X-chromosome inactivation mosaicism was studied in the corneal epithelium and a control tissue (liver) of <it>Flna</it>^{<it>Dilp2/+ </it>}and wild-type (WT) female X-inactivation mosaics, hemizygous for the X-linked, <it>LacZ </it>reporter H253 transgene, using β-galactosidase histochemical staining. The corneal epithelia of <it>Flna</it>^{<it>Dilp2/+ </it>}and WT X-inactivation mosaics showed similar radial, striped patterns, implying epithelial cell movement was not disrupted in <it>Flna</it>^{<it>Dilp2/+ </it>}corneas. Corrected stripe numbers declined with age overall (but not significantly for either genotype individually), consistent with previous reports suggesting an age-related reduction in stem cell function. Corrected stripe numbers were not reduced in <it>Flna</it>^{<it>Dilp2/+ </it>}compared with WT X-inactivation mosaics and mosaicism was not significantly more unbalanced in the corneal epithelia or livers of <it>Flna</it>^{<it>Dilp2/+ </it>}than wild-type <it>Flna^+/+</it>X-inactivation mosaics.</p> <p>Conclusions</p> <p>Mosaic analysis identified no major effect of the mouse <it>Flna^Dilp2</it>mutation on corneal epithelial maintenance or the balance of X-inactivation mosaicism in the corneal epithelium or liver.</p

Effect of atrioventricular optimization on circulating N-terminal pro brain natriuretic peptide following cardiac resynchronization therapy.

AIMS: Following CRT, atrioventricular (AV) optimization is not routinely practised. To evaluate its clinical utility, we examined the effect of AV delay optimization on the prognostic biomarker NT-proBNP. METHODS AND RESULTS: We prospectively studied 72 patients (mean age 73 ± 12.5 years, 70.8% male, 55.6% ischaemic) undergoing iterative AV optimization. Patients were divided into those whose nominal setting appeared ideal and not changed (Group 1, n = 22) and those whose AV delay was optimized (Group 2, n = 50). All patients underwent NT-proBNP assessment prior to CRT, and pre- and a median 5 days post-optimization. Compared with Group 1, NT-proBNP fell significantly in Group 2 patients (median 474 pg/mL) following optimization (P = 0.00001). A significant change in filling pattern (defined as a change in AV delay >50 ms) was required in 30% of patients, and it was this subgroup that derived the greater reduction in NT-proBNP levels [-1407 pg/mL, interquartile range (IQR) -3042 to -346 pg/mL] compared with those requiring <50 ms AV delay change (-125 pg/mL, IQR -1038 to 6 pg/mL), P = 0.0011. The benefit of AV optimization was principally observed in reverse remodelling non-responders (median -2167 pg/mL, IQR -3042 to -305 pg/mL) and in patients with a pseudonormal or restrictive filling pattern (median -1407 pg/mL, IQR -2809 to -342 pg/mL), compared with those with more benign diastolic filling (median - 264 pg/mL, IQR -1038 to -21 pg/mL), P = 0.033. CONCLUSIONS: In one-third of patients, major filling pattern changes are achieved with AV optimization, associated with subsequent rapid falls in NT-proBNP. The greater the AV delay change, the larger the NT-proBNP fall, and non-responders and those with restrictive or pseudonormal filling despite CRT are most likely to benefit

Informing efficient randomised controlled trials: Exploration of challenges in developing progression criteria for internal pilot studies

Objectives: Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or 'progression' criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. Design: A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. Results: There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decisionmaking process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Conclusions: Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials

Development and validation of a diagnostic aid for convulsive epilepsy in sub-Saharan Africa: a retrospective case-control study

Background: Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa. Methods: In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region. Findings: We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91–0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92–0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93–0·96, sensitivity 88·2%, specificity 95·3%). Interpretation: On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy

Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells

Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines compose a class of compounds that target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo[1,2-a]pyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo[1,2-a]pyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo[1,2-a]pyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical–genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure–activity relationships