248 research outputs found

    Competing risk bias in prognostic models predicting hepatocellular carcinoma occurrence: impact on clinical decision making

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    Existing models predicting hepatocellular carcinoma (HCC) occurrence do not account for competing risk events and, thus, may overestimate the probability of HCC. Our goal was to quantify this bias for patients with cirrhosis and cured hepatitis C. We analyzed a nationwide cohort of patients with cirrhosis and cured hepatitis C infection from Scotland. Two HCC prognostic models were developed: (1) a Cox regression model ignoring competing risk events and (2) a Fine-Gray regression model accounting for non-HCC mortality as a competing risk. Both models included the same set of prognostic factors used by previously developed HCC prognostic models. Two predictions were calculated for each patient: first, the 3-year probability of HCC predicted by model 1 and second, the 3-year probability of HCC predicted by model 2. The study population comprised 1629 patients with cirrhosis and cured HCV, followed for 3.8 years on average. A total of 82 incident HCC events and 159 competing risk events (ie, non-HCC deaths) were observed. The mean predicted 3-year probability of HCC was 3.37% for model 1 (Cox) and 3.24% for model 2 (Fine-Gray). For most patients (76%), the difference in the 3-year probability of HCC predicted by model 1 and model 2 was minimal (ie, within 0 to ±0.3%). A total of 2.6% of patients had a large discrepancy exceeding 2%; however, these were all patients with a 3-year probability exceeding >5% in both models. Prognostic models that ignore competing risks do overestimate the future probability of developing HCC. However, the degree of overestimation—and the way it is patterned—means that the impact on HCC screening decisions is likely to be modest

    MAVS Signaling Is Required for Preventing Persistent Chikungunya Heart Infection and Chronic Vascular Tissue Inflammation

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    Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cardiac cells to define the mechanisms of CHIKV heart infection. Using an immunocompetent mouse model of CHIKV infection as well as human primary cardiac cells, we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts. In immunocompetent mice, CHIKV is cleared from cardiac tissue without significant damage through the induction of a local type I interferon response from both infected and non-infected cardiac cells. Using mice deficient in major innate immunity signaling components, we found that signaling through the mitochondrial antiviral-signaling protein (MAVS) is required for viral clearance from the heart. In the absence of MAVS signaling, persistent infection leads to focal myocarditis and vasculitis of the large vessels attached to the base of the heart. Large vessel vasculitis was observed for up to 60 days post infection, suggesting CHIKV can lead to vascular inflammation and potential long-lasting cardiovascular complications. This study provides a model of CHIKV cardiac infection and mechanistic insight into CHIKV-induced heart disease, underscoring the importance of monitoring cardiac function in patients with CHIKV infections

    OSSOS. IX. Two Objects in Neptune's 9: 1 Resonance - Implications for Resonance Sticking in the Scattering Population

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    We discuss the detection in the Outer Solar System Origins Survey (OSSOS) of two objects in Neptune's distant 9:1 mean motion resonance at semimajor axis a 130a\approx~130~au. Both objects are securely resonant on 10~Myr timescales, with one securely in the 9:1 resonance's leading asymmetric libration island and the other in either the symmetric or trailing asymmetric island. These objects are the largest semimajor axis objects with secure resonant classifications, and their detection in a carefully characterized survey allows for the first robust resonance population estimate beyond 100~au. The detection of these objects implies a 9:1 resonance population of 1.1×1041.1\times10^4 objects with Hr<8.66H_r<8.66 (D  100D~\gtrsim~100~km) on similar orbits (95\% confidence range of 0.43×104\sim0.4-3\times10^4). Integrations over 4~Gyr of an ensemble of clones spanning these objects' orbit fit uncertainties reveal that they both have median resonance occupation timescales of 1\sim1~Gyr. These timescales are consistent with the hypothesis that these objects originate in the scattering population but became transiently stuck to Neptune's 9:1 resonance within the last 1\sim1~Gyr of solar system evolution. Based on simulations of a model of the current scattering population, we estimate the expected resonance sticking population in the 9:1 resonance to be 1000-4500 objects with Hr<8.66H_r<8.66; this is marginally consistent with the OSSOS 9:1 population estimate. We conclude that resonance sticking is a plausible explanation for the observed 9:1 population, but we also discuss the possibility of a primordial 9:1 population, which would have interesting implications for the Kuiper belt's dynamical history.Comment: accepted for publication in A

    Progress report no. 5

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    Includes bibliographical referencesProgress report; June 30, 1974U.S. Atomic Energy Commission contract AT(11-1)225

    The promise of digital healthcare technologies

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    Digital health technologies have been in use for many years in a wide spectrum of healthcare scenarios. This narrative review outlines the current use and the future strategies and significance of digital health technologies in modern healthcare applications. It covers the current state of the scientific field (delineating major strengths, limitations, and applications) and envisions the future impact of relevant emerging key technologies. Furthermore, we attempt to provide recommendations for innovative approaches that would accelerate and benefit the research, translation and utilization of digital health technologies
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