Effects of cholesterol- or 7-ketocholesterol-containing liposomes on colony-forming ability of cultured cells

AbstractExperiments with cultured Chinese hamster cells showed that incubation of the cells with (phosphatidylcholine + cholesterol + 7-ketocholesterol)-containing liposomes (4:3:1 by weight) during two hours led to a decrease in the colony-forming ability of cells down to zero, while (phosphatidylcholine + cholesterol)-containing liposomes (1:1 by weight) reduce this parameter by 90%. Furthermore, the cholesterol-containing liposomes (without 7-ketocholesterol) induce a decrease in the number of the maximal-site colonies accompanied by the corresponding increase in the number of the middle-size colonies

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Attempt: signs and types

The objective of this study was to analyze what was tempted by direct criminal science. A basic investigation is a dialectical approach to the dissemination of legal phenomena and processes, going through gerais scientific methods (systematic and logical methods, analysis and synthesis) and specific scientific methods. The results will show that the attempted crime was part of the objective side of a certain criminal corpus. The beginning of the attempt may coincide as the beginning of the constitutive act of the crime. Furthermore, an attempt is classified by the implementation of the intention as completed and not completed. And, finally, a special kind of attempt is a "futile attempt."An unsuccessful attempt must be subject to responsibility and qualification, bem as a common attempt

Identification and mitigation of narrow spectral artifacts that degrade searches for persistent gravitational waves in the first two observing runs of Advanced LIGO

International audienceSearches are under way in Advanced LIGO and Virgo data for persistent gravitational waves from continuous sources, e.g. rapidly rotating galactic neutron stars, and stochastic sources, e.g. relic gravitational waves from the Big Bang or superposition of distant astrophysical events such as mergers of black holes or neutron stars. These searches can be degraded by the presence of narrow spectral artifacts (lines) due to instrumental or environmental disturbances. We describe a variety of methods used for finding, identifying and mitigating these artifacts, illustrated with particular examples. Results are provided in the form of lists of line artifacts that can safely be treated as non-astrophysical. Such lists are used to improve the efficiencies and sensitivities of continuous and stochastic gravitational wave searches by allowing vetoes of false outliers and permitting data cleaning

Chasing Gravitational Waves with the Chereknov Telescope Array

Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 2023 (arXiv:2309.08219)2310.07413International audienceThe detection of gravitational waves from a binary neutron star merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this gravitational wave event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a gravitational wave signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. New observing modes and follow-up strategies are being developed for CTA to rapidly cover localization areas of gravitational wave events that are typically larger than the CTA field of view. This work will evaluate and provide estimations on the expected number of of gravitational wave events that will be observable with CTA, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA

Chasing Gravitational Waves with the Chereknov Telescope Array

Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 2023 (arXiv:2309.08219)2310.07413International audienceThe detection of gravitational waves from a binary neutron star merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this gravitational wave event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a gravitational wave signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. New observing modes and follow-up strategies are being developed for CTA to rapidly cover localization areas of gravitational wave events that are typically larger than the CTA field of view. This work will evaluate and provide estimations on the expected number of of gravitational wave events that will be observable with CTA, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA

Performance of a proposed event-type based analysis for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) will be the next-generation observatory in the field of very-high-energy (20 GeV to 300 TeV) gamma-ray astroparticle physics. Classically, data analysis in the field maximizes sensitivity by applying quality cuts on the data acquired. These cuts, optimized using Monte Carlo simulations, select higher quality events from the initial dataset. Subsequent steps of the analysis typically use the surviving events to calculate one set of instrument response functions (IRFs). An alternative approach is the use of event types, as implemented in experiments such as the Fermi-LAT. In this approach, events are divided into sub-samples based on their reconstruction quality, and a set of IRFs is calculated for each sub-sample. The sub-samples are then combined in a joint analysis, treating them as independent observations. This leads to an improvement in performance parameters such as sensitivity, angular and energy resolution. Data loss is reduced since lower quality events are included in the analysis as well, rather than discarded. In this study, machine learning methods will be used to classify events according to their expected angular reconstruction quality. We will report the impact on CTA high-level performance when applying such an event-type classification, compared to the classical procedure

Chasing Gravitational Waves with the Chereknov Telescope Array

Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 2023 (arXiv:2309.08219)2310.07413International audienceThe detection of gravitational waves from a binary neutron star merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this gravitational wave event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a gravitational wave signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. New observing modes and follow-up strategies are being developed for CTA to rapidly cover localization areas of gravitational wave events that are typically larger than the CTA field of view. This work will evaluate and provide estimations on the expected number of of gravitational wave events that will be observable with CTA, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA

A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding