A low-inclination neutral Trans-Neptunian Object in a extreme orbit

We present photometric observations and numerical simulations of 2016 SD$_{106}$, a low inclination ($i=4.8^{\circ}$) extreme trans-Neptunian Object with a large semi-major axis ($a=350$ au) and perihelion ($q= 42.6$ au). This object possesses a peculiar neutral color of $g-r = 0.45\pm0.05$ and $g-i=0.72\pm0.06$, in comparison with other distant trans-Neptunian objects, all of which have moderate-red to ultra-red colors. A numerical integration based on orbital fitting on astrometric data covering eight years of arc confirms that 2016 SD$_{106}$ is a metastable object without significant scattering evolution. Each of the clones survived at the end of the 1 Gyr simulation. However, very few neutral objects with inclinations $<5^{\circ}$ have been found in the outer solar system, even in the main Kuiper belt. Furthermore, most mechanisms which lift perihelion distances are expected to produce a very low number of extreme objects with inclinations $<5^{\circ}$. We thus explored the possibility that a hypothetical distant planet could increase the production of such objects. Our simulations show that no 2016 SD$_{106}$-like orbits can be produced from three Kuiper belt populations tested (i.e. plutinos, twotinos, and Haumea Family) without the presence of an hypothetical planet, while a few similar orbits can be obtained with it; however, the presence of the additional planet produces a wide range of large semimajor-axis / large perihelion objects, in apparent contradiction with the observed scarcity of objects in those regions of phase space. Future studies may determine if there is a connection between the existence of a perihelion gap and a particular orbital configuration of an hypothetical distant planet.Comment: 10 pages, 4 figures, 1 tables, accepted for publication in the ApJ Letter

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

One-pot cascade reactions using fructose-6-phosphate aldolase: Efficient synthesis of D-arabinose 5-phosphate, D-fructose 6-phosphate and analogues

One-pot multienzymatic reactions have been performed for the synthesis of 1-deoxy-D-fructose 6-phosphate, 1,2-dideoxy-D-arabino-hept-3-ulose 7-phosphate, D-fructose 6-phosphate and D-arabinose 5-phosphate. The whole synthetic strategy is based on an aldol addition reaction catalysed by fructose-6-phosphate aldolase (FSA) as a key step of a three or four enzymes-catalysed cascade reaction. The four known donors for FSA - dihydroxyacetone (DHA), hydroxyacetone (HA), 1-hydroxy-2-butanone (HB) and glycolaldehyde (GA) - were used with D-glyceraldehyde 3-phosphate as acceptor substrate. The target phosphorylated sugars were obtained in good to excellent yields and high purity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Peer Reviewe

OSSOS. XII. Variability Studies of 65 Trans-Neptunian Objects Using the Hyper Suprime-Cam

We present variability measurements and partial light curves of Trans-Neptunian Objects (TNOs) from a two-night pilot study using Hyper Suprime-Cam (HSC) on the Subaru Telescope (Maunakea, Hawai'i, USA). Subaru's large aperture (8-m) and HSC's large field of view (1.77 square degrees) allow us to obtain measurements of multiple objects with a range of magnitudes in each telescope pointing. We observed 65 objects with m_r = 22.6--25.5 mag in just six pointings, allowing 20--24 visits of each pointing over the two nights. Our sample, all discovered in the recent Outer Solar System Origins Survey (OSSOS), span absolute magnitudes H_r = 6.2--10.8 mag and thus investigates smaller objects than previous light curve projects have typically studied. Our data supports the existence of a correlation between light curve amplitude and absolute magnitude seen in other works, but does not support a correlation between amplitude and orbital inclination. Our sample includes a number of objects from different dynamical populations within the trans-Neptunian region, but we do not find any relationship between variability and dynamical class. We were only able to estimate periods for 12 objects in the sample and found that a longer baseline of observations is required for reliable period analysis. We find that 31 objects (just under half of our sample) have variability greater than 0.4 magnitudes during all of the observations; in smaller 1.25 hr, 1.85 hr and 2.45 hr windows, the median variability is 0.13, 0.16 and 0.19 mags, respectively. The fact that variability on this scale is common for small TNOs has important implications for discovery surveys (such as OSSOS or the Large Synoptic Survey Telescope) and color measurements.Comment: 49 pages, 14 figures, 7 table

Optimal currency area theory and monetary integration in the Andean and Caribbean regions

In this article, the author analyses the prospects for monetary integration in the Andean and Caribbean regions and stresses the regional specificities that should be taken into account. He points to the necessity to combine economic, political economy and institutional approaches to assess scenarios for monetary integration. The author also argues that the application of optimum currency area theory to regions with specific characteristics (in many respects different from the EU) might produce positive feed-back effects for the development of OCA theory itself, highlighting specific aspects and implications of the same theory and stimulating theoretical research.optimum currency areas, monetary integration, Andean region, Caribbean,

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software