74 research outputs found
In vivo dual RNA-seq reveals that neutrophil recruitment underlies differential tissue tropism of Streptococcus pneumoniae.
Streptococcus pneumoniae is a genetically diverse human-adapted pathogen commonly carried asymptomatically in the nasopharynx. We have recently shown that a single nucleotide polymorphism (SNP) in the raffinose pathway regulatory gene rafR accounts for a difference in the capacity of clonally-related strains to cause localised versus systemic infection. Using dual RNA-seq, we show that this SNP affects expression of bacterial genes encoding multiple sugar transporters, and fine-tunes carbohydrate metabolism, along with extensive rewiring of host transcriptional responses to infection, particularly expression of genes encoding cytokine and chemokine ligands and receptors. The data predict a crucial role for differential neutrophil recruitment (confirmed by in vivo neutrophil depletion and IL-17 neutralization) indicating that early detection of bacteria by the host in the lung environment is crucial for effective clearance. Thus, dual RNA-seq provides a powerful tool for understanding complex host-pathogen interactions and reveals how a single bacterial SNP can drive differential disease outcomes
State of the world’s plants and fungi 2020
Kew’s State of the World’s Plants and Fungi project provides assessments of our current knowledge of the diversity of plants and fungi on Earth, the global threats that they face, and the policies to safeguard them. Produced in conjunction with an international scientific symposium, Kew’s State of the World’s Plants and Fungi sets an important international standard from which we can annually track trends in the global status of plant and fungal diversity
Neutrino interaction vertex reconstruction in DUNE with Pandora deep learning
The Pandora Software Development Kit and algorithm libraries perform reconstruction of neutrino interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at the Deep Underground Neutrino Experiment, which will operate four large-scale liquid argon time projection chambers at the far detector site in South Dakota, producing high-resolution images of charged particles emerging from neutrino interactions. While these high-resolution images provide excellent opportunities for physics, the complex topologies require sophisticated pattern recognition capabilities to interpret signals from the detectors as physically meaningful objects that form the inputs to physics analyses. A critical component is the identification of the neutrino interaction vertex. Subsequent reconstruction algorithms use this location to identify the individual primary particles and ensure they each result in a separate reconstructed particle. A new vertex-finding procedure described in this article integrates a U-ResNet neural network performing hit-level classification into the multi-algorithm approach used by Pandora to identify the neutrino interaction vertex. The machine learning solution is seamlessly integrated into a chain of pattern-recognition algorithms. The technique substantially outperforms the previous BDT-based solution, with a more than 20% increase in the efficiency of sub-1 cm vertex reconstruction across all neutrino flavours
Global Retinoblastoma Presentation and Analysis by National Income Level
Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved
Experience in Surveillance of the Prestress of Concrete Reactor Vessels at Wylfa Nuclear Power Station
Value co-creation in Shari'ah-compliant banking: a Saudi Arabian case study
This paper argues that Shari'ah-compliant Islamic banking is essentially a value co-creation business model that illustrates attributes associated with the emerging service-dominant logic paradigm. The underpinning Shari'ah philosophy of minimising ‘usage’ of one party by another results in the sharing of profit, losses, risk and the promotion of interest-free principles. Islamic banks that follow Shari'ah traditions endeavour to co-create value with their business and corporate customers in a manner that would resonate with the proponents of service-dominant logic. The authors argue that Shari'ah-compliant business models may be more appropriate for today’s volatile and socio-economic climate, evidencing their potential via business case examples. Shari'ah-compliant Islamic financing, such as ÎukËk (Islamic bonds), istiÎnÉÑ (construction finance), murÉbaÍah (commodity trade finance), muÌÉrabah (finance trusteeship), mushÉrakah (joint venture) and ijÉrah (Islamic leasing), is generally based on a business relationship and partnership approach. Such approaches are now gaining popularity and offer those engaged in service exchange the opportunity to co-create value or at least mutual benefit
Spatially explicit model of wintering common loons:Conservation implications
Common loons Gavia immer are a conservation concern in New England due to a variety of anthropogenic factors, yet little is known about biotic and abiotic environmental factors determining their wintering distribution and abundance in nearshore and offshore waters. The primary objective of this study was to develop a spatially explicit abundance model of wintering common loons in the maritime waters of southern New England (USA) that could inform decisions about offshore development. Aerial line-transect surveys were conducted throughout a 3800 km2 study area off the coast of Rhode Island during the winters of 2010-2011 and 2011-2012. A density surface model (DSM) approach was used to account for imperfect detection and incorporate spatially explicit environmental covariates. Common loon densities were greatest in waters 2 mg m). The DSM predicted 5047 (95% CI = 3993-6379) common loons in the study area during winter, which suggests this region provides key habitat for this species in eastern North America. This study highlights important areas for common loons in the region, suggests key biotic (primary productivity as measured by long-term chl a surface concentrations) and abiotic covariates (water depth) driving the spatial distribution and abundance of common loons in southern New England, and identifies sites that should be considered for protection from offshore development, including offshore wind facilities
A spatial conservation prioritization approach for protecting marine birds given proposed offshore wind energy development
There are currently no offshore wind energy developments (OWEDs) in North America, although numerous OWEDs have been proposed along the Atlantic Coast. Development pressure has been a catalyst for marine spatial planning (MSP) to identify suitable areas for OWED. However, integrating complex ecological information to guide OWED siting remains a substantial challenge. We developed spatial distribution models of marine birds from aerial surveys that we conducted from 2010 to 2012 throughout a 3800km2 area off the coast of Rhode Island. For seven groups of marine birds, we constructed either a density surface model or a presence-absence model that incorporated relevant environmental covariates. We integrated our spatial models, along with uncertainty, using spatial conservation prioritization (SCP) software. This identified sites with high marine bird conservation priority that aided evaluation of proposed OWED sites. We found that shallow nearshore waters had the highest conservation priority overall, but we also detected key offshore areas of high priority. Hypothetical OWEDs placed in conservation priority areas significantly reduced the overall distribution of focal species. Currently proposed OWED sites are located in areas of relatively low conservation priority and so would not substantially reduce the overall distribution of marine birds. This SCP approach when combined with quantitative models of bird distribution given relevant environmental covariates provides a robust framework that satisfies the principles of ecosystem-based MSP. Thus, this combined SCP-distribution modeling framework should be extremely helpful to decision makers as they evaluate proposed siting locations of OWEDs in the context of a dynamic marine system. © 2013 Elsevier Ltd
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