Investigation of Association between PFO Complicated by Cryptogenic Stroke and a Common Variant of the Cardiac Transcription Factor GATA4

Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke

Imaging the Solar Corona from Within: First Results from the Parker Solar Probe Telescope

International audienceParker Solar Probe (PSP) launched in August 2018 is humanity's first probe of a stellar atmosphere. It will make measurements of the near-Sun plasma from 'within' the outer corona with gradually reduced perihelia from its first perihelia of 35 Rs in 2018-19 to 9.8 Rs in 2025. Here we report the results from the imaging observations of the electron and dust corona, whe PSP was 35-54 Rs from the solar surface, taken by the Wide-field Imager for Solar Probe (WISPR). The spacecraft was near-corotating with the solar corona throughout the observing window, which is an unprecedented situation for any type of coronal imaging. Our initial analysis uncovers a long-hypothesized depletion of the primordial dust orbiting near the Sun, reveals the plasma structure of small-scale ejections, and provides a strict test for validating model predictions of the large-scale configuration of the coronal plasma. Thus, WISPR imaging allows the study of near-Sun dust dynamics as the mission progresses. The high-resolution images of small transients, largely unresolved from 1 AU orbits, unravel the sub-structures of small magnetic flux ropes and show that the Sun continually releases helical magnetic fields in the background wind. Finally, WISPR's observations of the coronal streamer evolution confirm the large-scale topology of the solar corona but they also reveal that, as recently predicted, streamers are composed of yet smaller sub-streamers channeling continual density fluctuations at all visible scales

Near-Sun observations of an F-corona decrease and K-corona fine structure

International audienceRemote observations of the solar photospheric light scattered by electrons (the K-corona) and dust (the F-corona or zodiacal light) have been made from the ground during eclipses1 and from space at distances as small as 0.3 astronomical units2-5 to the Sun. Previous observations6-8 of dust scattering have not confirmed the existence of the theoretically predicted dust-free zone near the Sun9-11. The transient nature of the corona has been well characterized for large events, but questions still remain (for example, about the initiation of the corona12 and the production of solar energetic particles13) and for small events even its structure is uncertain14. Here we report imaging of the solar corona15 during the first two perihelion passes (0.16-0.25 astronomical units) of the Parker Solar Probe spacecraft13, each lasting ten days. The view from these distances is qualitatively similar to the historical views from ground and space, but there are some notable differences. At short elongations, we observe a decrease in the intensity of the F-coronal intensity, which is suggestive of the long-sought dust free zone9-11. We also resolve the fine-scale plasma structure of very small eruptions, which are frequently ejected from the Sun. These take two forms: the frequently observed magnetic flux ropes12,16 and the predicted, but not yet observed, magnetic islands17,18 arising from the tearing-mode instability in the current sheet. Our observations of the coronal streamer evolution confirm the large-scale topology of the solar corona, but also reveal that, as recently predicted19, streamers are composed of yet smaller substreamers channelling continual density fluctuations at all visible scales

Supersymmetric localization in two dimensions

This is an introductory review to localization techniques in supersymmetric two-dimensional gauge theories. In particular, we describe how to construct Lagrangians of $\newcommand{\re}{{\rm Re}~} \newcommand{\mat}[1]{\left(\begin{array}{cc}#1\end{array}\right)} \newcommand{\cN}{\mathcal{N}} \cN = (2, 2)$ theories on curved spaces, and how to compute their partition functions and certain correlators on the sphere, the hemisphere and other curved backgrounds. We also describe how to evaluate the partition function of $\newcommand{\re}{{\rm Re}~} \newcommand{\mat}[1]{\left(\begin{array}{cc}#1\end{array}\right)} \newcommand{\cN}{\mathcal{N}} \cN = (0, 2)$ theories on the torus, known as the elliptic genus. Finally we summarize some of the applications, in particular to probe mirror symmetry and other non-perturbative dualities

Ezetimibe added to statin therapy after acute coronary syndromes

BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization ( 6530 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events