The peculiar variable X-ray spectrum of the active galactic nucleus PKS 2005-489

PKS 2005-489 is a well-known, bright southern BL Lac object that has been detected up to TeV energies. In a low-flux state it exhibits the expected multiwavelength double-peaked spectrum in the radio -- $\gamma$-ray band. The high-flux state shows extreme flux variations in the X-ray band with a hardening as well as a peculiar curved feature in the spectrum. Thus far, PKS 2005-489 is the only source to exhibit such a feature. To study the X-ray variability further, we obtained the first hard X-ray spectrum of the source with NuSTAR. We compare quasi-simultaneous radio, optical, UV, soft and hard X-ray, and $\gamma$-ray data of PKS 2005-489 to archival data in order to study its broadband behavior. We find a very consistent quiet state in the SED, with little variation in spectral shape or flux between the 2012 and 2020 data. A possible explanation for the peculiar X-ray spectrum in the flaring state is an additional component in the jet, possibly accelerated via magnetic reconnection, that is not co-spatial to the low-flux state emission region

Search for Gamma-Ray and neutrino coincidences using HAWC and ANTARES data

In the quest for high-energy neutrino sources, the Astrophysical Multimessenger Observatory Network (AMON) has implemented a new search by combining data from the High Altitude Water Cherenkov (HAWC) observatory and the Astronomy with a Neutrino Telescope and Abyss environmental RESearch (ANTARES) neutrino telescope. Using the same analysis strategy as in a previous detector combination of HAWC and IceCube data, we perform a search for coincidences in HAWC and ANTARES events that are below the threshold for sending public alerts in each individual detector. Data were collected between July 2015 and February 2020 with a livetime of 4.39 years. Over this time period, 3 coincident events with an estimated false-alarm rate of <1 coincidence per year were found. This number is consistent with background expectations.Peer ReviewedPostprint (published version

Reliability of Eye Tracking and Pupillometry Measures in Individuals with Fragile X Syndrome

Recent insight into the underlying molecular and cellular mechanisms of fragile X syndrome (FXS) has led to the proposal and development of new pharmaceutical treatment strategies, and the initiation of clinical trials aimed at correcting core symptoms of the developmental disorder. Consequently, there is an urgent and critical need for outcome measures that are valid for quantifying specific symptoms of FXS and that are consistent across time. We used eye tracking to evaluate test–retest reliability of gaze and pupillometry measures in individuals with FXS and we demonstrate that these measures are viable options for assessing treatment-specific outcomes related to a core behavioral feature of the disorder

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Rapid variability of Markarian 421 during extreme flaring as seen through the eyes of XMM-Newton

By studying the variability of blazars across the electromagnetic spectrum, it is possible to resolve the underlying processes responsible for rapid flux increases, so-called flares. We report on an extremely bright X-ray flare in the high-peaked BL Lacertae object Markarian 421 (Mrk 421) that occurred simultaneously with enhanced γ-ray activity detected at very high energies by First G-APD Cherenkov Telescope on 2019 June 9. We triggered an observation with XMM-Newton, which observed the source quasi-continuously for 25 h. We find that the source was in the brightest state ever observed using XMM-Newton, reaching a flux of 2.8 × 10-9 over an energy range of 0.3-10 keV. We perform a spectral and timing analysis to reveal the mechanisms of particle acceleration and to search for the shortest source-intrinsic time-scales. Mrk 421 exhibits the typical harder-when-brighter behaviour throughout the observation and shows a clock-wise hysteresis pattern, which indicates that the cooling dominates over the acceleration process. While the X-ray emission in different sub-bands is highly correlated, we can exclude large time lags as the computed z-transformed discrete correlation functions are consistent with a zero lag. We find rapid variability on time-scales of 1 ks for the 0.3-10 keV band and down to 300 s in the hard X-ray band (4-10 keV). Taking these time-scales into account, we discuss different models to explain the observed X-ray flare, and find that a plasmoid-dominated magnetic reconnection process is able to describe our observation best.ISSN:0035-8711ISSN:1365-296

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

BackgroundTranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.MethodsWe did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.FindingsBetween July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).InterpretationWe found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.</div