A 1.5-million-year record of orbital and millennial climate variability in the North Atlantic

Climate during the last glacial period was marked by abrupt instability on millennial timescales that included large swings of temperature in and around Greenland (Daansgard-Oeschger events) and smaller, more gradual changes in Antarctica (AIM events). Less is known about the existence and nature of similar variability during older glacial periods, especially during the early Pleistocene when glacial cycles were dominantly occurring at 41 kyr intervals compared to the much longer and deeper glaciations of the more recent period. Here, we report a continuous millennially resolved record of stable isotopes of planktic and benthic foraminifera at IODP Site U1385 (the "Shackleton Site") from the southwestern Iberian margin for the last 1.5 million years, which includes the Middle Pleistocene Transition (MPT). Our results demonstrate that millennial climate variability (MCV) was a persistent feature of glacial climate, both before and after the MPT. Prior to 1.2 Ma in the early Pleistocene, the amplitude of MCV was modulated by the 41 kyr obliquity cycle and increased when axial tilt dropped below 23.5° and benthic δ18O exceeded ∼3.8 ‰ (corrected to Uvigerina), indicating a threshold response to orbital forcing. Afterwards, MCV became focused mainly on the transitions into and out of glacial states (i.e. inceptions and terminations) and during times of intermediate ice volume. After 1.2 Ma, obliquity continued to play a role in modulating the amplitude of MCV, especially during times of glacial inceptions, which are always associated with declining obliquity. A non-linear role for obliquity is also indicated by the appearance of multiples (82, 123 kyr) and combination tones (28 kyr) of the 41 kyr cycle. Near the end of the MPT (∼0.65 Ma), obliquity modulation of MCV amplitude wanes as quasi-periodic 100 kyr and precession power increase, coinciding with the growth of oversized ice sheets on North America and the appearance of Heinrich layers in North Atlantic sediments. Whereas the planktic δ18O of Site U1385 shows a strong resemblance to Greenland temperature and atmospheric methane (i.e. Northern Hemisphere climate), millennial changes in benthic δ18O closely follow the temperature history of Antarctica for the past 800 kyr. The phasing of millennial planktic and benthic δ18O variation is similar to that observed for MIS 3 throughout much of the record, which has been suggested to mimic the signature of the bipolar seesaw - i.e. an interhemispheric asymmetry between the timing of cooling in Antarctica and warming in Greenland. The Iberian margin isotopic record suggests that bipolar asymmetry was a robust feature of interhemispheric glacial climate variations for at least the past 1.5 Ma despite changing glacial boundary conditions. A strong correlation exists between millennial increases in planktic δ18O (cooling) and decreases in benthic δ13C, indicating that millennial variations in North Atlantic surface temperature are mirrored by changes in deep-water circulation and remineralization of carbon in the abyssal ocean. We find strong evidence that climate variability on millennial and orbital scales is coupled across different timescales and interacts in both directions, which may be important for linking internal climate dynamics and external astronomical forcing

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

High Altitude Supersonic Decelerator Test Vehicle

The Low Density Supersonic Decelerator (LDSD) project is tasked by NASA's Office of the Chief Technologist (OCT) to advance the state of the art in Mars entry and descent technology in order to allow for larger payloads to be delivered to Mars at higher altitudes with better accuracy. The project will develop a 33.5 m Do Supersonic Ringsail (SSRS) parachute, 6m attached torus, robotic class Supersonic Inflatable Aerodynamic Decelerator (SIAD-R), and an 8 m attached isotensoid, exploration class Supersonic Inflatable Aerodynamic Decelerator (SIAD-E). The SSRS and SIAD-R should be brought to TRL-6, while the SIAD-E should be brought to TRL-5. As part of the qualification and development program, LDSD must perform a Mach-scaled Supersonic Flight Dynamics Test (SFDT) in order to demonstrate successful free flight dynamic deployments at Mars equivalent altitude, of all three technologies. In order to perform these tests, LDSD must design and build a test vehicle to deliver all technologies to approximately 180,000 ft and Mach 4, deploy a SIAD, free fly to approximately Mach 2, deploy the SSRS, record high-speed and high-resolution imagery of both deployments, as well as record data from an instrumentation suite capable of characterizing the technology induced vehicle dynamics. The vehicle must also be recoverable after splashdown into the ocean under a nominal flight, while guaranteeing forensic data protection in an off nominal catastrophic failure of a test article that could result in a terminal velocity, tumbling water impact

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ):Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.</p

Observations of clouds, aerosols, precipitation, and surface radiation over the Southern Ocean: An overview of CAPRICORN, MARCUS, MICRE and SOCRATES

International audienc