1,346 research outputs found

    PHP24 USE OF POLICY MODELING TO PROMOTE INFORMED DECISION MAKING: DEVELOPMENT AND APPLICATION OF THE CANADIAN STROKE POLICY MODEL

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    Is philosophy of education a historical mistake? Connecting philosophy and education differently

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    In this article, I suggest that the question whether the proper place for philosophy of education is in the domain of philosophy or the domain of education cannot be resolved as long as we think of the connection between philosophy and education in terms of the idea of 'philosophy of education'. To substantiate this point, I look into the history of the idea of 'philosophy of education', both as a general idea and with regard to the way in which it became institutionalised in universities in the English-speaking world. I contrast this with the way in which the academic study of education developed in German-speaking countries in order to highlight that 'philosophy of education' is not the only way in which philosophy and education can be connected. Being aware that the connection between philosophy and education can be made differently not only provides a way out of the discussion about the proper identity and location of philosophy of education, but also hints at forms of philosophically informed scholarship that are more firmly based with the academic field of education rather than that they remain a halfway house in between philosophy and education

    First-line support for assistance in breathing in children: statistical and health economic analysis plan for the FIRST-ABC trial

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    BACKGROUND: The FIRST-ABC trial comprises of two pragmatic, multicentre, parallel groups, non-inferiority randomised clinical trials designed to evaluate the clinical non-inferiority of first-line use of high flow nasal cannula (HFNC) to continuous positive airway pressure (CPAP) in critically ill children who require non-invasive respiratory support (NRS). OBJECTIVES: To describe the pre-specified statistical and health economic analysis for the FIRST-ABC trial before completion of patient recruitment and data collection. METHODS: The statistical analysis plan was designed by the chief investigators and statisticians. We define the primary and secondary outcomes, summarise methods for data collection and safety monitoring, and present a detailed description of the planned statistical and health economic analysis. RESULTS: The primary clinical outcome is time to liberation from respiratory support. The primary effect estimate will be the adjusted hazard ratio, reported with a 95% confidence interval. As a sensitivity analysis, the primary analysis will be repeated using time to start weaning of NRS. Subgroup analyses will be performed to test for interactions between the effect of allocated treatment group and pre-specified baseline covariates. The health economic analysis will follow the intention-to-treat principle and report the mean (95% confidence interval) incremental costs, quality-adjusted life years (QALYs) and cost-effectiveness up to 6 months. All analyses will be performed separately for each of the two trials, and any results will not be combined. CONCLUSION: The FIRST-ABC trial will assess the non-inferiority of HFNC compared to CPAP in two parallel trials with shared infrastructure (step-up RCT and step-down RCT). We have developed a pre-specified statistical and health economics analysis plan for the FIRST-ABC study before trial completion to minimise analytical bias. TRIAL REGISTRATION: ISRCTN ISRCTN60048867 . Registered on 19 June 2019

    Climate impacts of energy technologies depend on emissions timing

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    Energy technologies emit greenhouse gases with differing radiative efficiencies and atmospheric lifetimes. Standard practice for evaluating technologies, which uses the global warming potential (GWP) to compare the integrated radiative forcing of emitted gases over a fixed time horizon, does not acknowledge the importance of a changing background climate relative to climate change mitigation targets. Here we demonstrate that the GWP misvalues the impact of CH[subscript 4]-emitting technologies as mid-century approaches, and we propose a new class of metrics to evaluate technologies based on their time of use. The instantaneous climate impact (ICI) compares gases in an expected radiative forcing stabilization year, and the cumulative climate impact (CCI) compares their time-integrated radiative forcing up to a stabilization year. Using these dynamic metrics, we quantify the climate impacts of technologies and show that high-CH[subscript 4]-emitting energy sources become less advantageous over time. The impact of natural gas for transportation, with CH[subscript 4] leakage, exceeds that of gasoline within 1–2 decades for a commonly cited 3 W m[superscript −2] stabilization target. The impact of algae biodiesel overtakes that of corn ethanol within 2–3 decades, where algae co-products are used to produce biogas and corn co-products are used for animal feed. The proposed metrics capture the changing importance of CH[subscript 4] emissions as a climate threshold is approached, thereby addressing a major shortcoming of the GWP for technology evaluation.New England University Transportation Center (DOT Grant DTRT07-G-0001

    Age‐related telomere attrition in the human putamen

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    Data Availability Statement: The raw data that support the findings of this study are available from the corresponding authors upon reasonable request. Demographic and clinical details of human control spleen-brain tissue donors used in this study are available from Table S1. Gene expression data used in this study are available from GTEx portal and from (Trabzuni et al., 2011).Supporting Information is available online at https://onlinelibrary.wiley.com/doi/10.1111/acel.13861#support-information-section .Copyright © 2023 The Authors. . Age is a major risk factor for neurodegenerative diseases. Shortening of leucocyte telomeres with advancing age, arguably a measure of “biological” age, is a known phenomenon and epidemiologically correlated with age-related disease. The main mechanism of telomere shortening is cell division, rendering telomere length in post-mitotic cells presumably stable. Longitudinal measurement of human brain telomere length is not feasible, and cross-sectional cortical brain samples so far indicated no attrition with age. Hence, age-related changes in telomere length in the brain and the association between telomere length and neurodegenerative diseases remain unknown. Here, we demonstrate that mean telomere length in the putamen, a part of the basal ganglia, physiologically shortens with age, like leukocyte telomeres. This was achieved by using matched brain and leukocyte-rich spleen samples from 98 post-mortem healthy human donors. Using spleen telomeres as a reference, we further found that mean telomere length was brain region-specific, as telomeres in the putamen were significantly shorter than in the cerebellum. Expression analyses of genes involved in telomere length regulation and oxidative phosphorylation revealed that both region- and age-dependent expression pattern corresponded with region-dependent telomere length dynamics. Collectively, our results indicate that mean telomere length in the human putamen physiologically shortens with advancing age and that both local and temporal gene expression dynamics correlate with this, pointing at a potential mechanism for the selective, age-related vulnerability of the nigro-striatal network.Cancer Research UK. Grant Number: C36439/A12097; Horizon 2020 Framework Programme. Grant Number: 634821

    The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

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    Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

    Sedation AND Weaning In Children (SANDWICH): protocol for a cluster randomised stepped wedge trial.

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    Introduction: Weaning from ventilation is a complex process involving several stages that include recognition of patient readiness to begin the weaning process; steps to reduce ventilation while optimising sedation in order not to induce distress; and removing the endotracheal tube. Delay at any stage can prolong the duration of mechanical ventilation. We developed a multi-component intervention targeted at helping clinicians to safely expedite this process and minimise the harms associated with unnecessary mechanical ventilation. Methods and analysis: This is a 20-month cluster-randomised stepped wedge clinical and cost-effectiveness trial with an internal pilot and a process evaluation. It is being conducted in 18 paediatric intensive care units in the UK to evaluate a protocol-based intervention for reducing the duration of invasive mechanical ventilation. Following an initial eight-week baseline data collection period in all sites, one site will be randomly chosen to transition to the intervention every four weeks and will start an eight-week training period after which it will continue the intervention for the remaining duration of the study. We aim to recruit approximately 10,000 patients. The primary analysis will compare data from before the training (control) with that from after the training (intervention) in each site. Full details of the analyses will be in the statistical analysis plan. Ethics and dissemination: This Protocol was reviewed and approved by NRES Committee East Midlands - Nottingham 1 Research Ethics Committee (reference: 17/EM/0301). All sites started patient recruitment on 5 February 2018 before randomisation in April 2018. Results will be disseminated in 2020. The results will be presented at national and international conferences and published in peer reviewed medical journals

    Towards democratizing and automating online conferences: lessons from the neuromatch conferences

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    Legacy conferences are costly and time consuming, and exclude scientists lacking various resources or abilities. During the 2020 pandemic, we created an online conference platform, Neuromatch Conferences (NMC), aimed at developing technological and cultural changes to make conferences more democratic, scalable, and accessible. We discuss the lessons we learned

    Background risk of breast cancer and the association between physical activity and mammographic density

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    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0
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