356 research outputs found

    Neural measures of social attention across the first years of life: characterizing typical development and markers of autism risk

    Get PDF
    We would like to thank the Infant Sibling Project staff, past and present, for their hard work in collecting these data. We are very grateful for the assistance of Brandon Keehn, Alexandra Libby and Ella Kipervasser with data processing, and we thank Vanessa Vogel-Farley for her constant guidance. Finally, we want to acknowledge the very dedicated families who committed years of their lives to the Infant Sibling Project and who made this work possible. Funding was provided by NIH (R21DC08637) to H.T-F., NIDCD (1R01DC010290-01) to C.A.N. and H. T-F., the Simons Foundation (137186) to C.A.N. and the Autism Speaks Pilot Grants Program to H.T-F. (R21DC08637 - NIH; 1R01DC010290-01 - NIDCD; 137186 - Simons Foundation; Autism Speaks Pilot Grants Program)Published versio

    The impact of the ‘hub and spoke’ model of care for lung cancer and equitable access to surgery

    Get PDF
    Objectives: To determine the influence of where a patient is first seen (either surgical or non-surgical centre) and patient features on having surgery for non-small cell lung cancer (NSCLC). Design: Cross-sectional study from individual patients, between 1January 2008 and 31March 2012. Setting: Linked National Lung Cancer Audit and Hospital Episode Statistics datasets. Participants: 95 818 English patients with a diagnosis of NSCLC, of whom 12 759 (13%) underwent surgical resection. Main outcome measure: Odds of having surgery based on the empirical catchment population of the 30 thoracic surgical centres in England and whether the patient is first seen in a surgical centre or a non-surgical centre. Results: Patients were more likely to be operated on if they were first seen at a surgical centre (OR 1.37; 95% CI 1.29 to 1.45). This was most marked for surgical centres with the largest catchment populations. In these surgical centres with large catchment populations, the resection rate for local patients was 18% and for patients first seen in a non-surgical centre within catchment was 12%. Conclusions: Surgical centres that serve the largest catchment populations have high resection rates for patients first seen in their own centre but, in contrast, low resection rates for patients first seen at the surrounding centres they serve. Our findings demonstrate the importance of going further than relating resection rates to hospital volume or surgeon number, and show that there is a pressing need to design lung cancer services which enable all patients, including those first seen at non-surgical centres, to have equal access to lung cancer surgery

    Epilepsy mortality in Wales during COVID-19

    Get PDF
    Purpose: The COVID-19 pandemic has increased mortality worldwide and those with chronic conditions may have been disproportionally affected. However, it is unknown whether the pandemic has changed mortality rates for people with epilepsy. We aimed to compare mortality rates in people with epilepsy in Wales during the pandemic with pre-pandemic rates. Methods: We performed a retrospective study using individual-level linked population-scale anonymised electronic health records. We identified deaths in people with epilepsy (DPWE), i.e. those with a diagnosis of epilepsy, and deaths associated with epilepsy (DAE), where epilepsy was recorded as a cause of death on death certificates. We compared death rates in 2020 with average rates in 2015–2019 using Poisson models to calculate death rate ratios. Results: There were 188 DAE and 628 DPWE in Wales in 2020 (death rates: 7.7/100,000/year and 25.7/100,000/year). The average rates for DAE and DPWE from 2015 to 2019 were 5.8/100,000/year and 23.8/100,000/year, respectively. Death rate ratios (2020 compared to 2015–2019) for DAE were 1.34 (95%CI 1.14–1.57, p<0.001) and for DPWE were 1.08 (0.99–1.17, p = 0.09). The death rate ratios for non-COVID deaths (deaths without COVID mentioned on death certificates) for DAE were 1.17 (0.99–1.39, p = 0.06) and for DPWE were 0.96 (0.87–1.05, p = 0.37). Conclusions: The significant increase in DAE in Wales during 2020 could be explained by the direct effect of COVID-19 infection. Non-COVID-19 deaths have not increased significantly but further work is needed to assess the longer-term impact

    Predicting death from surgery for lung cancer: a comparison of two scoring systems in two European countries

    Get PDF
    Objectives: Current British guidelines advocate the use of risk prediction scores such as Thoracoscore to estimate mortality prior to radical surgery for non-small cell lung cancer (NSCLC). A recent publication used the National Lung Cancer Audit (NLCA) to produce a score to predict 90 day mortality (NLCA score). The aim of this study is to validate the NLCA score, and compare its performance with Thoracoscore. Materials and methods: We performed an internal validation using 2858 surgical patients from NLCA and an external validation using 3191 surgical patients from the Danish Lung Cancer Registry (DLCR). We calculated the proportion that died within 90 days of surgery. The discriminatory power of both scores was assessed by a receiver operating characteristic (ROC) and an area under the curve (AUC) calculation. Results: Ninety day mortality was 5% in both groups. AUC values for internal and external validation of NLCA score and validation of Thoracoscore were 0.68 (95% CI 0.63–0.72), 0.60 (95% CI 0.56–0.65) and 0.60 (95% CI 0.54–0.66) respectively. Post-hoc analysis was performed using NLCA records on 15554 surgical patients to derive summary tables for 30 and 90 day mortality, stratified by procedure type, age and performance status. Conclusions: Neither score performs well enough to be advocated for individual risk stratification prior to lung cancer surgery. It may be that additional physiological parameters are required; however this is a further project. In the interim we propose the use of our summary tables that provide the real-life range of mortality for lobectomy and pneumonectomy

    Synthetic mimetics of the endogenous gastrointestinal nanomineral: Silent constructs that trap macromolecules for intracellular delivery.

    Get PDF
    Amorphous magnesium-substituted calcium phosphate (AMCP) nanoparticles (75-150nm) form constitutively in large numbers in the mammalian gut. Collective evidence indicates that they trap and deliver luminal macromolecules to mucosal antigen presenting cells (APCs) and facilitate gut immune homeostasis. Here, we report on a synthetic mimetic of the endogenous AMCP and show that it has marked capacity to trap macromolecules during formation. Macromolecular capture into AMCP involved incorporation as shown by STEM tomography of the synthetic AMCP particle with 5nm ultra-fine iron (III) oxohydroxide. In vitro, organic cargo-loaded synthetic AMCP was taken up by APCs and tracked to lysosomal compartments. The AMCP itself did not regulate any gene, or modify any gene regulation by its cargo, based upon whole genome transcriptomic analyses. We conclude that synthetic AMCP can efficiently trap macromolecules and deliver them to APCs in a silent fashion, and may thus represent a new platform for antigen delivery

    Evidence-based intervention for preschool children with primary speech and language impairments: Child Talk - an exploratory mixed-methods study

    Get PDF
    BackgroundThe Child Talk study aimed to develop an evidence-based framework to support the decision-making of speech and language therapists (SLTs) as they design and plan interventions appropriate to the needs of individual children with primary speech and language impairments and their families. The need for early identification and effective intervention for these children continues to be a government policy priority because of the link between children’s early speech and language skills and their broader well-being and outcomes in later life. The first phase of Child Talk sought to map and describe current SLT practice for these children; identify and summarise the existing research evidence relating to practice; and investigate the perspectives of parents, early years practitioners, preschool children and ‘underserved’ communities on speech and language therapy. The second phase of Child Talk focused on the development of a toolkit – assessment tools, outcome measures and a data set – to support future service and economic evaluations of the framework.MethodsChild Talk adopted a mixed-methods design. Quantitative methods included surveys and investigated the prevalence and patterns of intervention usage; qualitative data collection methods included focus groups, interviews and reflection to investigate participants’ perspectives and understandings of interventions. Data analysis methods included descriptive and inferential statistics, thematic and content analysis and framework analysis. Participants were recruited nationally through six NHS sites, professional bodies, parent groups and advertising. Participants included SLTs (n = 677), parents (n = 84), preschool children (n = 24), early years practitioners (n = 31) and ‘underserved’ communities (n = 52).Key findingsSpeech and language therapy interventions were characterised in terms of nine themes, viewed as comprehensive and inclusive by practitioners. Relevant assessments, interventions and outcome domains were identified for the nine themes. Areas of tacit knowledge and underspecified processes contributed to variability in the detail of the framework. Systematic reviews identified 58 relevant and robust studies (from 55,271 papers retrieved from the initial literature search). The number of studies relevant to each theme varied from 1 to 33. Observational data on preschool children’s perspectives on speech and language therapy interventions revealed the dynamic nature of their interaction with different activities and people within therapy sessions. Parents’ experiences of speech and language therapy were generally positive although some reported that the rationale for therapy was not always clear. Parental perspectives in underserved communities suggested that, although parents were confident about how to support children’s language development, they were less informed about the nature of language impairments and the function of speech and language therapy. The availability of information regarding resources directed towards speech and language therapy services was poor. In particular, services lacked both a culture of collecting outcome data routinely and measures of professional input and costs associated with their activities.ConclusionA descriptive framework of SLT practice has been developed to support the discussions between therapists and families when making decisions regarding the selection of interventions and outcome measures. Further research is needed to address gaps in the intervention framework and evaluate its effectiveness and cost-effectiveness in improving outcomes for preschool children with primary speech and language impairments.Study registrationThis study is registered as PROSPERO CRD42013006369

    A Working Taxonomy for Describing the Sensory Differences of Autism

    Get PDF
    Background: Individuals on the autism spectrum have been long described to process sensory information differently than neurotypical individuals. While much effort has been leveraged towards characterizing and investigating the neurobiology underlying the sensory differences of autism, there has been a notable lack of consistency in the terms being used to describe the nature of those differences. Main body: We argue that inconsistent and interchangeable terminology-use when describing the sensory differences of autism has become problematic beyond mere pedantry and inconvenience. We begin by highlighting popular terms that are currently being used to describe the sensory differences of autism (e.g. sensitivity , reactivity and responsivity ) and discuss why poor nomenclature may hamper efforts towards understanding the aetiology of sensory differences in autism. We then provide a solution to poor terminology-use by proposing a hierarchical taxonomy for describing and referring to various sensory features. Conclusion: Inconsistent terminology-use when describing the sensory features of autism has stifled discussion and scientific understanding of the sensory differences of autism. The hierarchical taxonomy proposed was developed to help resolve lack of clarity when discussing the sensory differences of autism and to place future research targets at appropriate levels of analysis

    Risk factors for cardiovascular disease in people with idiopathic pulmonary fibrosis: a population-based study

    Get PDF
    OBJECTIVE: People with idiopathic pulmonary fibrosis (IPF) have been shown to be at an increased risk for cardiovascular (CV) disease, but reasons for this are unknown. The aim of this study was to compare the prevalence of common CV risk factors in people with IPF and the general population and establish the incidence of ischemic heart disease (IHD) and stroke after the diagnosis of IPF, controlling for these risk factors. METHODS: We used data from a large, UK primary care database to identify incident cases of IPF and matched general-population control subjects. We compared the prevalence of risk factors for CV disease and prescription of CV medications in people with IPF (before diagnosis) with control subjects from the general population and assessed the incidence of IHD and stroke in people with IPF (after diagnosis) compared with control subjects. RESULTS: We identified 3,211 cases of IPF and 12,307 control subjects. Patients with IPF were more likely to have a record of hypertension (OR, 1.31; 95% CI, 1.19-1.44), and diabetes (OR, 1.20; 95% CI, 1.07-1.34) compared with control subjects; they were also more likely to have been prescribed several CV drugs. The rate of first-time IHD events was more than twice as high in patients than control subjects (rate ratio, 2.32; 95% CI, 1.85-2.93; P &lt; .001), but the incidence of stroke was only marginally higher (P = .09). Rate ratios for IHD and stroke were not altered substantially after adjusting for CV risk factors. CONCLUSIONS: Several CV risk factors were more prevalent in people with IPF; however, this did not account for the increased rate of IHD in this group of patients
    • …
    corecore