278 research outputs found

    Hematopoietic stem and progenitor cells are present in healthy gingiva tissue

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    Hematopoietic stem cells reside in the bone marrow, where they generate the effector cells that drive immune responses. However, in response to inflammation, some hematopoietic stem and progenitor cells (HSPCs) are recruited to tissue sites and undergo extramedullary hematopoiesis. Contrasting with this paradigm, here we show residence and differentiation of HSPCs in healthy gingiva, a key oral barrier in the absence of overt inflammation. We initially defined a population of gingiva monocytes that could be locally maintained; we subsequently identified not only monocyte progenitors but also diverse HSPCs within the gingiva that could give rise to multiple myeloid lineages. Gingiva HSPCs possessed similar differentiation potentials, reconstitution capabilities, and heterogeneity to bone marrow HSPCs. However, gingival HSPCs responded differently to inflammatory insults, responding to oral but not systemic inflammation. Combined, we highlight a novel pathway of myeloid cell development at a healthy barrier, defining a gingiva-specific HSPC network that supports generation of a proportion of the innate immune cells that police this barrier

    Return to employment following critical illness and its association with psychosocial outcomes: a systematic review and meta-analysis

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    Background: Patients who survive critical illness have well-defined physical, cognitive, emotional, and familial problems. However, the impact of these problems on survivors’ ability to return to work and other financial outcomes are less clear. Objective: To determine the financial and employment consequences of an intensive care stay, we performed a systematic review and meta-analysis. Data Source We searched MEDLINE, Embase, and CINAHL (1970-2018). All study designs except narrative reviews, case reports, case control studies, and editorials were included. Included studies assessed financial outcomes in patients admitted to critical care, and their caregivers. Data Extraction: Two reviewers independently applied eligibility criteria, assessed quality and extracted data. The primary outcome reported was return to employment among those previously employed. We also examined financial stress and the impact financial outcomes had on quality of life and psychosocial health. Data Synthesis: From 5765 eligible abstracts, 51 studies were included, which provided data on 858 caregivers/family members and 7267 patients. Forty-two papers reported on patient outcomes and 11 papers on caregiver/family members. Two papers included data from both patients and caregivers/family members. Return to employment was the most commonly reported financial outcome for critical care survivors. The pooled estimate for return to employment—among those who were employed prior to critical illness—was 33% (95% CI: 21%-48%), 55% (95% CI: 45%-64%) and 56% (95% CI: 45%-66%) at 3, 6, and 12 months, respectively. Across the studies included in this review, there was a positive association with psychosocial health if patients returned to employment. This included improved health related quality of life and fewer depressive symptoms. With caregivers/family members, six studies reported changes to employment such as reduced hours and lost earnings. Conclusions: Following critical illness, many patients who were previously employed do not return to work, even one year later. This new job loss is associated with worse health related quality of life amongst survivors and worse psychological function amongst survivors and caregivers/family members. More interventional research is required to understand how best to support employability after critical illness

    The Global Landsat Archive: Status, Consolidation, and Direction

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    New and previously unimaginable Landsat applications have been fostered by a policy change in 2008 that made analysis-ready Landsat data free and open access. Since 1972, Landsat has been collecting images of the Earth, with the early years of the program constrained by onboard satellite and ground systems, as well as limitations across the range of required computing, networking, and storage capabilities. Rather than robust on-satellite storage for transmission via high bandwidth downlink to a centralized storage and distribution facility as with Landsat-8, a network of receiving stations, one operated by the U.S. government, the other operated by a community of International Cooperators (ICs), were utilized. ICs paid a fee for the right to receive and distribute Landsat data and over time, more Landsat data was held outside the archive of the United State Geological Survey (USGS) than was held inside, much of it unique. Recognizing the critical value of these data, the USGS began a Landsat Global Archive Consolidation (LGAC) initiative in 2010 to bring these data into a single, universally accessible, centralized global archive, housed at the Earth Resources Observation and Science (EROS) Center in Sioux Falls, South Dakota. The primary LGAC goals are to inventory the data held by ICs, acquire the data, and ingest and apply standard ground station processing to generate an L1T analysis-ready product. As of January 1, 2015 there were 5,532,454 images in the USGS archive. LGAC has contributed approximately 3.2 million of those images, more than doubling the original USGS archive holdings. Moreover, an additional 2.3 million images have been identified to date through the LGAC initiative and are in the process of being added to the archive. The impact of LGAC is significant and, in terms of images in the collection, analogous to that of having had twoadditional Landsat-5 missions. As a result of LGAC, there are regions of the globe that now have markedly improved Landsat data coverage, resulting in an enhanced capacity for mapping, monitoring change, and capturing historic conditions. Although future missions can be planned and implemented, the past cannot be revisited, underscoring the value and enhanced significance of historical Landsat data and the LGAC initiative. The aim of this paper is to report the current status of the global USGS Landsat archive, document the existing and anticipated contributions of LGAC to the archive, and characterize the current acquisitions of Landsat-7 and Landsat-8. Landsat-8 is adding data to the archive at an unprecedented rate as nearly all terrestrial images are now collected. We also offer key lessons learned so far from the LGAC initiative, plus insights regarding other critical elements of the Landsat program looking forward, such as acquisition, continuity, temporal revisit, and the importance of continuing to operationalize the Landsat program

    Association between fruit and vegetable intakes and mental health in the australian diabetes obesity and lifestyle cohort

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    Increasing prevalence of mental health disorders within the Australian population is a serious public health issue. Adequate intake of fruits and vegetables (FV), dietary fibre (DF) and resistant starch (RS) is associated with better mental and physical health. Few longitudinal studies exist exploring the temporal relationship. Using a validated food frequency questionnaire, we examined baseline FV intakes of 5845 Australian adults from the AusDiab study and estimated food group-derived DF and RS using data from the literature. Perceived mental health was assessed at baseline and 5 year follow up using SF-36 mental component summary scores (MCS). We conducted baseline cross-sectional analysis and prospective analysis of baseline dietary intake with perceived mental health at 5 years. Higher baseline FV and FV-derived DF and RS intakes were associated with better 5 year MCS (p \u3c 0.001). A higher FV intake (754 g/d vs. 251 g/d, Q4 vs. Q1) at baseline had 41% lower odds (OR = 0.59: 95% CI 0.46–0.75) of MCS below population average ( \u3c 47) at 5 year follow up. Findings were similar for FV-derived DF and RS. An inverse association was observed with discretionary food-derived DF and RS. This demonstrates the association between higher intakes of FV and FV-derived DF and RS with better 5 year mental health outcomes. Further RCTs are necessary to understand mechanisms that underlie this association including elucidation of causal effects

    Successful treatment of HIV-associated multicentric Castleman's disease and multiple organ failure with rituximab and supportive care: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Multicentric Castleman's Disease (MCD), a lymphoproliferative disorder associated with Human Herpes Virus-8 (HHV-8) infection, is increasing in incidence amongst HIV patients. This condition is associated with lymphadenopathy, polyclonal gammopathy, hepato-splenomegaly and systemic symptoms. A number of small studies have demonstrated the efficacy of the anti-CD20 monoclonal antibody, rituximab, in treating this condition.</p> <p>Case presentation</p> <p>We report the case of a 46 year old Zambian woman who presented with pyrexia, diarrhoea and vomiting, confusion, lymphadenopathy, and renal failure. She rapidly developed multiple organ failure following the initiation of treatment of MCD with rituximab. Following admission to intensive care (ICU), she received prompt multi-organ support. After 21 days on the ICU she returned to the haematology medical ward, and was discharged in remission from her disease after 149 days in hospital.</p> <p>Conclusion</p> <p>Rituximab, the efficacy of which has thus far been examined predominantly in patients <it>outside </it>the ICU, in conjunction with extensive organ support was effective treatment for MCD with associated multiple organ failure. There is, to our knowledge, only one other published report of its successful use in an ICU setting, where it was combined with cyclophosphamide, adriamycin and prednisolone. Reports such as ours support the notion that critically unwell patients with HIV and haematological disease <it>can </it>benefit from intensive care.</p

    Lipidomic risk score independently and cost-effectively predicts risk of future type 2 diabetes: results from diverse cohorts

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    Background: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening. Methods: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The LRS derived from SAFHS as well as its recalibrated version were validated in an independent cohort from Australia--the AusDiab cohort. The participants were T2D-free at baseline and followed for 9197 person-years in the SAFHS cohort (n = 771) and 5930 person-years in the AusDiab cohort (n = 644). Statistically and clinically improved T2D prediction was evaluated with established statistical parameters in both cohorts. Modeling studies were conducted to determine whether the use of LRS would be cost-effective for T2D screening. The main outcome measures included accuracy and incremental value of the LRS over routinely used clinical predictors of T2D risk; validation of these results in an independent cohort and cost-effectiveness of including LRS in screening/intervention programs for T2D. Results: The LRS was based on plasma concentration of dihydroceramide 18:0, lysoalkylphosphatidylcholine 22:1 and triacyglycerol 16:0/18:0/18:1. The score predicted future T2D independently of prediabetes with an accuracy of 76%. Even in the subset of initially euglycemic individuals, the LRS improved T2D prediction. In the AusDiab cohort, the LRS continued to predict T2D significantly and independently. When combined with risk-stratification methods currently used in clinical practice, the LRS significantly improved the model fit (p \u3c 0.001), information content (p \u3c 0.001), discrimination (p \u3c 0.001) and reclassification (p \u3c 0.001) in both cohorts. Modeling studies demonstrated that LRS-based risk-stratification combined with metformin supplementation for high-risk individuals was the most cost-effective strategy for T2D prevention. Conclusions: Considering the novelty, incremental value and cost-effectiveness of LRS it should be used for risk-stratification of future T2D

    NightShift simulation to train newly qualified doctors in non-technical skills: a feasibility study

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    There is growing evidence of greater rates of morbidity and mortality in hospitals during out-of-hours shifts, which appears to be exacerbated during the period in which newly qualified doctors commence work. In order to combat this issue, an online simulation of a night shift was developed and trialled in order to improve the non-technical skills of newly qualified doctors and, ultimately, improve clinical outcomes. A randomised feasibility trial of the electronic training simulation was performed with medical students (n=30) at the end of their training and in the initial weeks of working at a large teaching hospital. The study showed that participants in the intervention group completed their non-urgent tasks more rapidly than the control group: mean (SD) time to complete a non-urgent task of 85.1 (50.1) versus 157.6 (90.4) minutes, p=0.027. This difference persisted using linear regression analysis, which was undertaken using rota and task volume as independent cofactors (p=0.028). This study shows the potential for simulation technologies to improve non-technical skills

    Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19.

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    COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints

    Rare Charm Decays in the Standard Model and Beyond

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    We perform a comprehensive study of a number of rare charm decays, incorporating the first evaluation of the QCD corrections to the short distance contributions, as well as examining the long range effects. For processes mediated by the cu+c\to u\ell^+\ell^- transitions, we show that sensitivity to short distance physics exists in kinematic regions away from the vector meson resonances that dominate the total rate. In particular, we find that Dπ+D\to\pi\ell^+\ell^- and Dρ+D\to\rho\ell^+\ell^- are sensitive to non-universal soft-breaking effects in the Minimal Supersymmetric Standard Model with R-parity conservation. We separately study the sensitivity of these modes to R-parity violating effects and derive new bounds on R-parity violating couplings. We also obtain predictions for these decays within extensions of the Standard Model, including extensions of the Higgs, gauge and fermion sectors, as well as models of dynamical electroweak symmetry breaking.Comment: 45 pages, typos fixed, discussions adde
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