A Stochastic Model of Plausibility in Live-Virtual-Constructive Environments

Distributed live-virtual-constructive simulation promises a number of benefits for the test and evaluation community, including reduced costs, access to simulations of limited availability assets, the ability to conduct large-scale multi-service test events, and recapitalization of existing simulation investments. However, geographically distributed systems are subject to fundamental state consistency limitations that make assessing the data quality of live-virtual-constructive experiments difficult. This research presents a data quality model based on the notion of plausible interaction outcomes. This model explicitly accounts for the lack of absolute state consistency in distributed real-time systems and offers system designers a means of estimating data quality and fitness for purpose. Experiments with World of Warcraft player trace data validate the plausibility model and exceedance probability estimates. Additional experiments with synthetic data illustrate the model\u27s use in ensuring fitness for purpose of live-virtual-constructive simulations and estimating the quality of data obtained from live-virtual-constructive experiments

A retrospective analysis of Victorian and South Australian clinical registries for prostate cancer: trends in clinical presentation and management of the disease

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Abstract Background: Prostate cancer (PCa) is the most commonly diagnosed malignancy reported to Australian cancer registries with numerous studies from individual registries summarizing diagnostic and treatment characteristics. The aim of this study was to describe annual trends in clinical and treatment characteristics, and changes in surveillance practice within a large combined cohort of men with PCa in South Australia (SA) and Victoria, Australia in 2008–2013. Methods: Common data items from clinical registries in SA and Victoria were merged to develop a crossjurisdictional dataset consisting of 13,598 men with PCa. Frequencies were used to describe these variables using the National Comprehensive Cancer Network risk of disease progression categories in 10 year age groups. A logistic regression analysis was performed to assess the impact of a number of factors (both individually and together) on the likelihood of men receiving no active treatment within twelve months of the diagnosis (i.e. managed with active surveillance/watchful waiting). Results: Trend analysis showed that over time: (1) men in SA and Victoria are being diagnosed at older age in 2013, 66.1 (SD = 9.7) years compared to 2009 (64.5 (SD = 9.7)); (2) diagnostic methods and characteristics have changed with time; and (3) types of the treatments have changed, with more men having no active treatment. The majority of men were diagnosed with Prostate-Specific Antigen (PSA) <10 ng/mL (66 %) and Grade Group < 4 (65 %). Nearly seventy percent received radical treatment within 12 months of diagnosis, while ~20 % had no active treatment. In 14 % of cases treatment was not recorded or had not commenced. Having no active treatment was strongly associated older age, lower PSA and lower Grade Group at diagnosis, and in 2013 it was offered more frequently (more than 3 times) than in 2009 (OR = 2.63, 95 % CI: 2.16–3.22). Conclusions: Findings of this study provide the first cross-jurisdictional description of PCa characteristics and management in Australia. These findings will provide benchmarking for ongoing monitoring and feedback of disease management and outcomes of PCa through the Prostate Cancer Outcomes Registry–Australia New Zealand to improve evidence-based practice

Greenhouse gas emissions in coffee grown with differing input levels under conventional and organic management

Coffee plays a key role in sustaining millions of livelihoods around the world. Understanding GHG emissions from coffee supply chains is important in evaluating options for climate change mitigation within the sector. We use data from two long-term coffee agroforestry experiments in Costa Rica and Nicaragua to calculate carbon footprints (CF) for coffee and identify emission hotspots within different management systems, levels of inputs and shade types. Management system and input level were the main cause of variation in CFs. Carbon footprints for 1 kg of fresh coffee cherries were between 0.26 and 0.67 kgCO2e for conventional and 0.12 and 0.52 kgCO2e for organic management systems. The main contributor to GHG emissions for all management systems was the inputs of organic and inorganic nitrogen. Nitrous oxide emissions from pruning inputs contributed between 7% and 42 % of CFs. However, these estimates were strongly influenced by the choice of emission factors

Effect of aspirin on cancer incidence and mortality in older adults.

BACKGROUND: ASPirin in Reducing Events in the Elderly (ASPREE), a randomized double-blind placebo-controlled trial (RCT) of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast prior RCTs, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. METHODS: 19,114 Australian and U.S. community-dwelling participants aged 70+ years (U.S. minorities 65+ years) without cardiovascular disease, dementia or physical disability were randomized and followed for a median of 4.7 years. Fatal and non-fatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. RESULTS: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (HR = 1.04, 95% CI = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). CONCLUSIONS: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and thus, suggest caution with its use in this age group

Validation of the surgical fear questionnaire in adult patients waiting for elective surgery

Objectives: Because existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ. Methods: Based on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (N = 3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis. Results: EFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1-4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5-10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbach's alpha) was between 0.765-0.920 (SFQ-total), 0.766-0.877 (SFQ-s), and 0.628-0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity. Discussion: The SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.This study was conducted with departmental funding and supported by a grant from The Netherlands Organisation for Scientific Research (Zon-MW, http://www.zonmw.nl/en/), grant no. 110000007. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Serum Proteome and Ursodeoxycholic Acid Response in Primary Biliary Cholangitis.

Funder: UK‐PBC MRC Stratified MedicineFunder: Pfizer; Id: http://dx.doi.org/10.13039/100004319BACKGROUND AND AIMS: Stratified therapy has entered clinical practice in primary biliary cholangitis (PBC), with routine use of second-line therapy in nonresponders to first-line therapy with ursodeoxycholic acid (UDCA). The mechanism for nonresponse to UDCA remains, however, unclear and we lack mechanistic serum markers. The UK-PBC study was established to explore the biological basis of UDCA nonresponse in PBC and identify markers to enhance treatment. APPROACH AND RESULTS: Discovery serum proteomics (Olink) with targeted multiplex validation were carried out in 526 subjects from the UK-PBC cohort and 97 healthy controls. In the discovery phase, untreated PBC patients (n = 68) exhibited an inflammatory proteome that is typically reduced in scale, but not resolved, with UDCA therapy (n = 416 treated patients). Nineteen proteins remained at a significant expression level (defined using stringent criteria) in UDCA-treated patients, six of them representing a tightly linked profile of chemokines (including CCL20, known to be released by biliary epithelial cells (BECs) undergoing senescence in PBC). All showed significant differential expression between UDCA responders and nonresponders in both the discovery and validation cohorts. A linear discriminant analysis, using serum levels of C-X-C motif chemokine ligand 11 and C-C motif chemokine ligand 20 as markers of responder status, indicated a high level of discrimination with an AUC of 0.91 (CI, 0.83-0.91). CONCLUSIONS: UDCA under-response in PBC is characterized by elevation of serum chemokines potentially related to cellular senescence and was previously shown to be released by BECs in PBC, suggesting a potential role in the pathogenesis of high-risk disease. These also have potential for development as biomarkers for identification of high-risk disease, and their clinical utility as biomarkers should be evaluated further in prospective studies

Polarized blazar X-rays imply particle acceleration in shocks

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization—the only range available until now—probe extended regions of the jet containing particles that left the acceleration site days to years earlier1,2,3, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree ΠX of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock

X-ray Polarization Observations of BL Lacertae

Blazars are a class of jet-dominated active galactic nuclei with a typical double-humped spectral energy distribution. It is of common consensus the Synchrotron emission to be responsible for the low frequency peak, while the origin of the high frequency hump is still debated. The analysis of X-rays and their polarization can provide a valuable tool to understand the physical mechanisms responsible for the origin of high-energy emission of blazars. We report the first observations of BL Lacertae performed with the Imaging X-ray Polarimetry Explorer ({IXPE}), from which an upper limit to the polarization degree $\Pi_X<$12.6\% was found in the 2-8 keV band. We contemporaneously measured the polarization in radio, infrared, and optical wavelengths. Our multiwavelength polarization analysis disfavors a significant contribution of proton synchrotron radiation to the X-ray emission at these epochs. Instead, it supports a leptonic origin for the X-ray emission in BL Lac.Comment: 17 pages, 5 figures, accepted for publication in ApJ

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe