Phoenix: DGA-Based Botnet Tracking and Intelligence

Abstract. Modern botnets rely on domain-generation algorithms (DGAs) to build resilient command-and-control infrastructures. Given the prevalence of this mechanism, recent work has focused on the anal-ysis of DNS traffic to recognize botnets based on their DGAs. While previous work has concentrated on detection, we focus on supporting intelligence operations. We propose Phoenix, a mechanism that, in ad-dition to telling DGA- and non-DGA-generated domains apart using a combination of string and IP-based features, characterizes the DGAs behind them, and, most importantly, finds groups of DGA-generated domains that are representative of the respective botnets. As a result, Phoenix can associate previously unknown DGA-generated domains to these groups, and produce novel knowledge about the evolving behavior of each tracked botnet. We evaluated Phoenix on 1,153,516 domains, in-cluding DGA-generated domains from modern, well-known botnets: with-out supervision, it correctly distinguished DGA- vs. non-DGA-generated domains in 94.8 percent of the cases, characterized families of domains that belonged to distinct DGAs, and helped researchers “on the field” in gathering intelligence on suspicious domains to identify the correct botnet.

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51

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

Extracorporeal Life Support in Myocardial Infarction: New Highlights

Background and Objectives: Cardiogenic shock (CS) is a potentially severe complication following acute myocardial infarction (AMI). The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in these patients has risen significantly over the past two decades, especially when conventional treatments fail. Our aim is to provide an overview of the role of VA-ECMO in CS complicating AMI, with the most recent literature highlights. Materials and Methods: We have reviewed the current VA-ECMO practices with a particular focus on CS complicating AMI. The largest studies reporting the most significant results, i.e., overall clinical outcomes and management of the weaning process, were identified in the PubMed database from 2019 to 2024. Results: The literature about the use of VA-ECMO in CS complicating AMI primarily has consisted of observational studies until 2019, generating the need for randomized controlled trials. The EURO-SHOCK trial showed a lower 30-day all-cause mortality rate in patients receiving VA-ECMO compared to those receiving standard therapy. The ECMO-CS trial compared immediate VA-ECMO implementation with early conservative therapy, with a similar mortality rate between the two groups. The ECLS-SHOCK trial, the largest randomized controlled trial in this field, found no significant difference in mortality at 30 days between the ECMO group and the control group. Recent studies suggest the potential benefits of combining left ventricular unloading devices with VA-ECMO, but they also highlight the increased complication rate, such as bleeding and vascular issues. The routine use of VA-ECMO in AMI complicated by CS cannot be universally supported due to limited evidence and associated risks. Ongoing trials like the Danger Shock, Anchor, and Recover IV trials aim to provide further insights into the management of AMI complicated by CS. Conclusions: Standardizing the timing and indications for initiating mechanical circulatory support (MCS) is crucial and should guide future trials. Multidisciplinary approaches tailored to individual patient needs are essential to minimize complications from unnecessary MCS device initiation

Neuromuscular block monitoring by smartphone application (i-TOF© system): an observational pilot study

Abstract Neuromuscular block monitoring is recommended by international guidelines to improve myorelaxation during surgery and reduce the risk of postoperative residual curarization. We conducted a pilot study to verify the efficacy of i-TOF, a wireless neuromuscular monitoring device connectable to a smartphone, comparing it with TOF WATCH SX. We enrolled 53 patients who underwent general anesthesia. For each patient, we recorded by both devices, in different time intervals, train-of-four (TOF) count/ratio after induction to general anesthesia (TI0–TI3) and during recovery (TR0–TR3). Moreover, post-tetanic count (PTC) was evaluated during deep neuromuscular block (TP0–TP2). We noticed no significant differences between the devices in recorded mean values of TOF ratio, TOF count, and PTC analyzed at time intervals for every phase of general anesthesia, although the i-TOF tends to an underestimation compared to TOF WATCH SX. For each patient, data sessions were successfully recorded by a smartphone. This aspect could be relevant for clinicians in order to have a stored proof of good clinical practice to be added on anesthesiologist records. By our results, i-TOF demonstrates a comparable efficacy to TOF WATCH SX, suggesting that it could be a proven alternative to standard devices for neuromuscular block monitoring. Further studies are needed to confirm our findings

CoFeed: privacy-preserving Web search recommendation based on collaborative aggregation of interest feedback

Search engines essentially rely on the structure of the graph of hyperlinks. Although accurate for the main trend, this is not effective when some query is ambiguous. Leveraging semantic information by the mean of interest matching allows proposing complementary results that are tailored to the user's expectations. This paper proposes a collaborative search companion system, CoFeed, that collects user search queries and that considers feedback to build user-centric and document-centric profiling information. Over time, the system constructs ranked collections of elements that maintain the required information diversity and enhance the user search experience by presenting additional results tailored to the user's interest space. This collaborative search companion requires a supporting architecture adapted to large user populations generating high request loads. To that end, it integrates mechanisms for ensuring scalability and load balancing of the service under varying loads and user interest distributions. Moreover, collecting the recommendation data poses the problem of users' privacy, and the bias one peer can induce to the system by sending fake recommendations. To that end, CoFeed ensures both publisher anonymity and rate limitation. With the former, the origin of the data is never known by the server that processes it, even if several servers collude to spy on some user. The latter, combined with decoupled authentication, allows to minimize the influence of cheating peers sending fake recommendations. Experiments with a deployed prototype highlight the efficiency of the system by analyzing improvement in search relevance, computational cost, scalability and load balancing. Copyright (c) 2011 John Wiley & Sons, Ltd

Perioperative Right Ventricular Dysfunction and Abnormalities of the Tricuspid Valve Apparatus in Patients Undergoing Cardiac Surgery

Right ventricular (RV) dysfunction frequently occurs after cardiac surgery and is linked to adverse postoperative outcomes, including mortality, reintubation, stroke, and prolonged ICU stays. While various criteria using echocardiography and hemodynamic parameters have been proposed, a consensus remains elusive. Distinctive RV anatomical features include its thin wall, which presents a triangular shape in a lateral view and a crescent shape in a cross-sectional view. Principal causes of RV dysfunction after cardiac surgery encompass ischemic reperfusion injury, prolonged ischemic time, choice of cardioplegia and its administration, cardiopulmonary bypass weaning characteristics, and preoperative risk factors. Post-left ventricular assist device (LVAD) implantation RV dysfunction is common but often transient, with a favorable prognosis upon resolution. There is an ongoing debate regarding the benefits of concomitant surgical repair of the RV in the presence of regurgitation. According to the literature, the gold standard techniques for assessing RV function are cardiac magnetic resonance imaging and hemodynamic assessment using thermodilution. Echocardiography is widely favored for perioperative RV function evaluation due to its accessibility, reproducibility, non-invasiveness, and cost-effectiveness. Although other techniques exist for RV function assessment, they are less common in clinical practice. Clinical management strategies focus on early detection and include intravenous drugs (inotropes and vasodilators), inhalation drugs (pulmonary vasodilators), ventilator strategies, volume management, and mechanical support. Bridging research gaps in this field is crucial to improving clinical outcomes associated with RV dysfunction in the near future

Current European practice in immune tolerance induction therapy in patients with haemophilia and inhibitors

The management of patients with inhibitors is an important challenge in haemophilia care. The lack of randomized controlled trials means that clinical decisions are generally based on subjective opinions, and purchasers' attention is likely to focus on the costs of treatment. In order to assess the current management of inhibitor patients and use of immune tolerance induction therapy (ITI) in Europe, we performed a survey within a European network of 21 comprehensive care centres from 14 countries (the European Haemophilia Therapy Standardisation Board). The survey identified a total of 381 patients with inhibitors attending the centres, 211 (55.4%) of whom had never been exposed to ITI. Between 1998 and 2003, the centres performed 233 procedures and 114 (48.9%) were successful. The survey demonstrated that dosing, which is the time to start and stop the ITI, the type of concentrate to use and the definition of success varied among the centres. Well-designed trials are warranted to guide decision-making, but in the absence of these studies we have developed consensus guidance for the management of inhibitor patients based on current clinical practice, as identified by the survey, and review of the literature

Current use of by-passing agents in Europe in the management of acute bleeds in patients with haemophilia and inhibitors.

The ultimate goal of treatment for patients with inhibitory antibodies should be to permanently eradicate the inhibitor by immune tolerance induction therapy (ITI). However, ITI procedures fail in a substantial number of patients and in many countries ITI is not even offered owing to its high cost. How patients with inhibitors are managed in different European countries is evaluated with a special focus on the use of by-passing agents, i.e. recombinant FVIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC), as well as the type of monitoring performed. Investigators from 22 large haemophilia centres participating within the network of the European Haemophilia Therapy Standardisation Board (EHTSB) were asked to complete a questionnaire. rFVIIa was routinely used in all centres for both children and adults at dosages ranging from 90 to 250 mug kg(-1) at an interval of 2-4 h. aPCC was used in 85% of the centres in adults and in 25% of the centres in children with haemophilia A at dosages of 50-100 IU kg(-1) every 6-12 h. The corresponding figures for children and adults with haemophilia B were 40% and 15% of the centres, respectively. Higher dosages of both agents were considered in the case of life-threatening bleeds. General recommendations were developed, based on the information provided by the survey. The results clearly indicate the need for well-designed comparative studies to optimize the use of by-passing agents