8 research outputs found

    Active Internet Traffic Filtering: Real-time Response to Denial of Service Attacks

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    Denial of Service (DoS) attacks are one of the most challenging threats to Internet security. An attacker typically compromises a large number of vulnerable hosts and uses them to flood the victim's site with malicious traffic, clogging its tail circuit and interfering with normal traffic. At present, the network operator of a site under attack has no other resolution but to respond manually by inserting filters in the appropriate edge routers to drop attack traffic. However, as DoS attacks become increasingly sophisticated, manual filter propagation becomes unacceptably slow or even infeasible. In this paper, we present Active Internet Traffic Filtering, a new automatic filter propagation protocol. We argue that this system provides a guaranteed, significant level of protection against DoS attacks in exchange for a reasonable, bounded amount of router resources. We also argue that the proposed system cannot be abused by a malicious node to interfere with normal Internet operation. Finally, we argue that it retains its efficiency in the face of continued Internet growth.Comment: Briefly describes the core ideas of AITF, a protocol for facing Denial of Service Attacks. 6 pages lon

    Evaluation of network coding techniques for a sniper detection application

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    This paper experimentally studies the reliability and delay of flooding based multicast protocols for a sniper detection application. In particular using an emulator it studies under which conditions protocols based on network coding deliver performance improvements compared to classic flooding. It then presents an implementation of such protocols on mobile phones

    Development and validation of SCOPE score: a clinical score to predict progression of COVID-19 pneumonia to severe respiratory failure

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    Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions

    Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial

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    Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1 alpha/beta inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR >= 6 ng ml(-1), 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an IL-1 alpha/beta inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor

    Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: a subgroup analysis of the SAVE-MORE randomised trialResearch in context

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    Summary: Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22–0.50; CCI 9 ng/mL, OR: 0.35, 95% CI 0.19–0.66; suPAR 6–9 ng/mL, OR: 0.35, 95% CI 0.24–0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25–0.66; and patients <65 years, OR: 0.29, 95% CI 0.19–0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28–0.57) and 0.46 (95% CI 0.32–0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment. Interpretation: Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90. Funding: Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB

    Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial

    No full text
    Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1 alpha/beta inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR &gt;= 6 ng ml(-1), 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P &lt; 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter. The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an IL-1 alpha/beta inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor
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