550 research outputs found

    Modulating Innate Immunity Improves Outcomes in Acute Lung Injury

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    Pulmonary inflammation following traumatic injury disrupts the lung architecture, leading to impaired oxygen exchange and rendering patients susceptible to life threatening bacterial infections. Innate immunity is central to the resolution of infection; however, excessive immune responses cause unresolved inflammation that exacerbate tissue damage. We hypothesize that partially attenuating recruitment of innate immune cells without impairing their function in situ will improve outcomes for patients diagnosed with acute lung injury (ALI) following burns and smoke inhalation by restoring homeostasis. Using mouse models of injury, we characterized the innate immune response in the lung following burns and smoke inhalation to establish mechanistic relationships that drive inflammation and to test therapeutic interventions. We show that significant neutrophil recruitment to the lung following burn injury is driven by damage associated molecular patterns (DAMPs); however, this recruitment does not result in improved bacterial clearance following pulmonary infection. To explore the factors that drive inflammation in a clinically relevant direct lung injury model, we developed and validated a novel murine model of acute smoke inhalation. This model mimics granulocyte recruitment, anti-inflammatory cytokine profile, DAMP release, and susceptibility to bacterial infection that are important drivers of outcome in patients. Using this model, we differentiate between correlative and causative inflammatory relationships in ALI. First, we demonstrate that inducible nitric oxide synthase is required for upregulation of interleukin-10 (IL-10), monocyte chemotactic protein 1, and hyaluronic acid (HA) following inhalational injury, but not for bacterial clearance. Thus, we propose that the relationship between elevated IL-10 and the onset of bacterial infection in patients may be correlative rather than causative. Furthermore, we demonstrate that neutrophil recruitment is driven by the chemokine CXCL1 as well as leukotriene B4, and we present data that granulocyte NADPH oxidase (NOX2) rapidly eliminates these signals and prevents excessive inflammation. Finally, we demonstrate that a 50% decrease in early neutrophil recruitment to the lung after smoke inhalation leads to decreased tissue damage and improved outcomes following bacterial challenge. Collectively, these data demonstrate the clinical relevance of our experimental model and suggest that downstream targets of NOX2 activity are promising candidates for accelerating resolution of inflammation in patients.Doctor of Philosoph

    Development of Survey Tool to Evaluate Behavior and Educational Tools Affecting Water Health in Lewiston and Auburn Communities

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    The Androscoggin Valley Stormwater Group (AVSWG) has been tasked with the objective of inducing a reduction or elimination of fertilizers and/or pesticides for 15% of college educated residents between the ages of 35-55 in the cities of Lewiston and Auburn by June, 2018. This demographic was chosen as the target of the outreach program because of their financial stability and their relative willingness to change behavior when compared to other age groups. We produced a survey that targets this same demographic and is meant to evaluate the effectiveness of the AVSWG education outreach program. This deliverable fits into Permit Year 3 of the BMP Adoption Plan. Additionally, we have offered informal evaluation of the BMP adoption plan activities and materials through this tool and through critical evaluation, which also fulfills a compliance task in Permit Year 3

    Towards a fairer reimbursement system for burn patients using cost-sensitive classification

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    The adoption of the Prospective Payment System (PPS) in the UK National Health Service (NHS) has led to the creation of patient groups called Health Resource Groups (HRG). HRGs aim to identify groups of clinically similar patients that share similar resource usage for reimbursement purposes. These groups are predominantly identified based on expert advice, with homogeneity checked using the length of stay (LOS). However, for complex patients such as those encountered in burn care, LOS is not a perfect proxy of resource usage, leading to incomplete homogeneity checks. To improve homogeneity in resource usage and severity, we propose a data-driven model and the inclusion of patient-level costing. We investigate whether a data-driven approach that considers additional measures of resource usage can lead to a more comprehensive model. In particular, a cost-sensitive decision tree model is adopted to identify features of importance and rules that allow for a focused segmentation on resource usage (LOS and patient-level cost) and clinical similarity (severity of burn). The proposed approach identified groups with increased homogeneity compared to the current HRG groups, allowing for a more equitable reimbursement of hospital care costs if adopted.Comment: Joint KDD 2021 Health Day and 2021 KDD Workshop on Applied Data Science for Healthcare: State of XAI and trustworthiness in Healt

    An aeroplane without wings : educational psychology support for a children's home staff team prior to and following a critical incident

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    Outcomes for looked after children and young people tend to be poor across numerous domains. To address this, some children's homes in England are supported by educational psychologists using Pillars of Parenting. This 'Emotional Warmth' approach is based on the theoretical and empirical knowledge base of applied psychology. It has been shown to have a positive impact on the lives of looked after children and young people (Cameron, 2017; Cameron & Das, 2019). This paper shares the story of a traumatic incident which occurred in a children's home supported by a Pillars of Parenting psychologist consultant. Using the strong relationships built up with staff through Pillars of Parenting sessions, other tools were used to provide support for staff over two meetings. This support was given in the lead up to this event and following it. Prior to the incident, the psychologist consultant used the MAPS tool to help staff acknowledge their gifts and plan for a positive future. A critical incident response to the event was provided by two educational psychologists using a bespoke process shared in this paper. Anecdotal evidence suggests that this support was appreciated and beneficial

    Isoprene and monoterpene emissions from alder, aspen and spruce short rotation forest plantations in the UK

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    An expansion of bioenergy has been proposed to help reduce fossil-fuel greenhouse gas emissions, and short-rotation forestry (SRF) can contribute to this expansion. However, SRF plantations could also be sources of biogenic volatile organic compound (BVOC) emissions, which can impact atmospheric air quality. In this study, emissions of isoprene and 11 monoterpenes from the branches and forest floor of hybrid aspen, Italian alder and Sitka spruce stands in an SRF field trial in central Scotland were measured during two years (2018–2019) and used to derive emission potentials for different seasons. Sitka spruce was included as a comparison as it is the most extensive plantation species in the UK. Winter and spring emissions of isoprene and monoterpenes were small compared to those in summer. Sitka spruce had a standardised mean emission rate of 15 µgCg−1h−1 for isoprene in the dry and warm summer of 2018 – more than double the emissions in 2019. However, standardised mean isoprene emissions from hybrid aspen were similar across both years, approximately 23 µgCg−1h−1, and standardised mean isoprene emissions from Italian alder were very low. Mean standardised total monoterpene emissions for these species followed a similar pattern of higher standardised emissions in the warmer year: Sitka spruce emitting 4.5 and 2.3 µgCg−1h−1 for 2018 and 2019, aspen emitting 0.3 and 0.09 µgCg−1h−1, and Italian alder emitting 1.5 and 0.2 µgCg−1h−1, respectively. In contrast to these foliage emissions, the forest floor was only a small source of monoterpenes, typically 1 or 2 orders of magnitude lower than foliage emissions on a unit of ground area basis. Estimates of total annual emissions from each plantation type per hectare were derived using the MEGAN 2.1 model. The modelled total BVOC (isoprene and monoterpenes) emissions of SRF hybrid aspen plantations were approximately half those of Sitka spruce for plantations of the same age. Italian alder SRF emissions were 20 times smaller than from Sitka spruce. The expansion of bioenergy plantations to 0.7 Mha has been suggested for the UK to help achieve net-zero greenhouse gas emissions by 2050. The model estimates show that, with such an expansion, total UK BVOC emissions would increase between <1 % and 35 %, depending on the tree species planted. Whereas increases might be small on a national scale, regional increases might have a larger impact on local air quality

    Guidelines and considerations for the use of system suitability and quality control samples in mass spectrometry assays applied in untargeted clinical metabolomic studies

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    Background Quality assurance (QA) and quality control (QC) are two quality management processes that are integral to the success of metabolomics including their application for the acquisition of high quality data in any high-throughput analytical chemistry laboratory. QA defines all the planned and systematic activities implemented before samples are collected, to provide confidence that a subsequent analytical process will fulfil predetermined requirements for quality. QC can be defined as the operational techniques and activities used to measure and report these quality requirements after data acquisition. Aim of review This tutorial review will guide the reader through the use of system suitability and QC samples, why these samples should be applied and how the quality of data can be reported. Key scientific concepts of review System suitability samples are applied to assess the operation and lack of contamination of the analytical platform prior to sample analysis. Isotopically-labelled internal standards are applied to assess system stability for each sample analysed. Pooled QC samples are applied to condition the analytical platform, perform intra-study reproducibility measurements (QC) and to correct mathematically for systematic errors. Standard reference materials and long-term reference QC samples are applied for inter-study and inter-laboratory assessment of data
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