Gravity Probe B, launched 20 April 2004, is a space experiment testing two fundamental predictions of Einstein's theory of general relativity (GR), the geodetic and frame-dragging effects, by means ...of cryogenic gyroscopes in Earth orbit. Data collection started 28 August 2004 and ended 14 August 2005. Analysis of the data from all four gyroscopes results in a geodetic drift rate of -6601.8±18.3 mas/yr and a frame-dragging drift rate of -37.2±7.2 mas/yr, to be compared with the GR predictions of -6606.1 mas/yr and -39.2 mas/yr, respectively ("mas" is milliarcsecond; 1 mas=4.848×10(-9) rad).
ABSTRACT Kepler provides light curves of 156,000 stars with unprecedented precision. However, the raw data as they come from the spacecraft contain significant systematic and stochastic errors. These ...errors, which include discontinuities, systematic trends, and outliers, obscure the astrophysical signals in the light curves. To correct these errors is the task of the Presearch Data Conditioning (PDC) module of the Kepler data analysis pipeline. The original version of PDC in Kepler did not meet the extremely high performance requirements for the detection of miniscule planet transits or highly accurate analysis of stellar activity and rotation. One particular deficiency was that astrophysical features were often removed as a side effect of the removal of errors. In this article we introduce the completely new and significantly improved version of PDC which was implemented in Kepler SOC version 8.0. This new PDC version, which utilizes a Bayesian approach for removal of systematics, reliably corrects errors in the light curves while at the same time preserving planet transits and other astrophysically interesting signals. We describe the architecture and the algorithms of this new PDC module, show typical errors encountered in Kepler data, and illustrate the corrections using real light curve examples.
The Gravity Probe B mission provided two new quantitative tests of Einstein's theory of gravity, general relativity (GR), by cryogenic gyroscopes in Earth's orbit. Data from four gyroscopes gave a ...geodetic drift-rate of −6601.8 18.3 marc-s yr−1 and a frame-dragging of −37.2 7.2 marc-s yr−1, to be compared with GR predictions of −6606.1 and −39.2 marc-s yr−1 (1 marc-s = 4.848 × 10−9 radians). The present paper introduces the science, engineering, data analysis, and heritage of Gravity Probe B, detailed in the accompanying 20 CQG papers.
Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach.
To assess ...the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia.
MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015.
Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia.
Two investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Prespecified primary end points were all-cause and cardiovascular mortality.
Twenty-four RCTs comprising 10 159 patients were included. Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density lipoprotein cholesterol levels (mean difference, -47.49% 95% CI, -69.64% to -25.35%; P < 0.001 and other atherogenic lipid fractions, and it reduced all-cause mortality (odds ratio OR, 0.45 CI, 0.23 to 0.86; P = 0.015; heterogeneity P = 0.63; I2 = 0%) and cardiovascular mortality (OR, 0.50 CI, 0.23 to 1.10; P = 0.084; heterogeneity P = 0.78; I2 = 0%). The rate of myocardial infarction was significantly reduced with use of PCSK9 antibodies (OR, 0.49 CI, 0.26 to 0.93; P = 0.030; heterogeneity P = 0.45; I2 = 0%), and increases in the serum creatine kinase level were reduced (OR, 0.72 CI, 0.54 to 0.96; P = 0.026; heterogeneity P = 0.65; I2 = 0%). Serious adverse events did not increase with administration of PCSK9 antibodies.
Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare.
PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.
CRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.
ABSTRACT With the unprecedented photometric precision of the Kepler spacecraft, significant systematic and stochastic errors on transit signal levels are observable in the Kepler photometric data. ...These errors, which include discontinuities, outliers, systematic trends, and other instrumental signatures, obscure astrophysical signals. The presearch data conditioning (PDC) module of the Kepler data analysis pipeline tries to remove these errors while preserving planet transits and other astrophysically interesting signals. The completely new noise and stellar variability regime observed in Kepler data poses a significant problem to standard cotrending methods. Variable stars are often of particular astrophysical interest, so the preservation of their signals is of significant importance to the astrophysical community. We present a Bayesian maximum a posteriori (MAP) approach, where a subset of highly correlated and quiet stars is used to generate a cotrending basis vector set, which is in turn used to establish a range of "reasonable" robust fit parameters. These robust fit parameters are then used to generate a Bayesian prior and a Bayesian posterior probability distribution function (PDF) which, when maximized, finds the best fit that simultaneously removes systematic effects while reducing the signal distortion and noise injection that commonly afflicts simple least-squares (LS) fitting. A numerical and empirical approach is taken where the Bayesian prior PDFs are generated from fits to the light-curve distributions themselves.
The Kepler mission has to date found almost 6000 planetary transit-like signals, utilizing three years of data for over 170,000 stars at extremely high photometric precision. Due to its design, ...contamination from eclipsing binaries, variable stars, and other transiting planets results in a significant number of these signals being false positives (Fps). We find that 685 Kepler Objects of Interest (KOIs)-12% of all those analyzed-are FPs as a result of contamination, due to 409 unique parent sources. Of these, 118 have not previously been identified by other methods. Comparing single-planet candidate KOIs to multi-planet candidate KOIs, we find an observed FP fraction due to contamination of 16% and 2.4% respectively, bolstering the existing evidence that multi-planet KOIs are significantly less likely to be Fps. We expect FP KOIs to become more frequent when analyzing more quarters of Kepler data, and note that many of them will not be able to be identified based on Kepler data alone.
The number of individuals referred for coronary artery bypass grafting (CABG) with preoperative atrial fibrillation (AF) is reported to be 8% to 20%. Atrial fibrillation is a known marker of ...high-risk patients as it was repeatedly found to negatively influence survival. Therefore, when performing surgical revascularization, consideration should be given to the concomitant treatment of the arrhythmia, the clinical consequences of the arrhythmia itself, and the selection of adequate surgical techniques. This state-of-the-art review aimed to provide a comprehensive analysis of the current understanding of, advancements in, and optimal strategies for CABG in patients with underlying AF. The following topics are considered: stroke prevention, prophylaxis and occurrence of postoperative AF, the role of surgical ablation and left atrial appendage occlusion, and an on-pump vs off-pump strategy. Multiple acute complications can occur in patients with preexisting AF undergoing CABG, each of which can have a significant effect on patient outcomes. Long-term results in these patients and the future perspectives of this scientific area were also addressed. Preoperative arrhythmia should always be considered for surgical ablation because such an approach improves prognosis without increasing perioperative risk. While planning a revascularization strategy, it should be noted that although off-pump coronary artery bypass provides better short-term outcomes, conventional on-pump approach may be beneficial at long-term follow-up. By collecting the current evidence, addressing knowledge gaps, and offering practical recommendations, this state-of-the-art review serves as a valuable resource for clinicians involved in the management of patients with AF undergoing CABG, ultimately contributing to improved outcomes and enhanced patient care.
Rearrangements of o-tolyl aryl ethers, amines, and sulfides with the Grubbs–Stoltz reagent (Et3SiH + KOtBu) were recently announced, in which the ethers were converted to o-hydroxydiarylmethanes, ...while the (o-tol)(Ar)NH amines were transformed into dihydroacridines. Radical mechanisms were proposed, based on prior evidence for triethylsilyl radicals in this reagent system. A detailed computational investigation of the rearrangements of the aryl tolyl ethers now instead supports an anionic Truce–Smiles rearrangement, where the initial benzyl anion can be formed by either of two pathways: (i) direct deprotonation of the tolyl methyl group under basic conditions or (ii) electron transfer to an initially formed benzyl radical. By contrast, the rearrangements of o-tolyl aryl amines depend on the nature of the amine. Secondary amines undergo deprotonation of the N-H followed by a radical rearrangement, to form dihydroacridines, while tertiary amines form both dihydroacridines and diarylmethanes through radical and/or anionic pathways. Overall, this study highlights the competition between the reactive intermediates formed by the Et3SiH/KOtBu system.
Abstract
Background
The prognosis for Li–Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development ...of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients.
Methods
In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated.
Results
The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup “SHH_3” (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively).
Conclusions
LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients.
Graphical Abstract
Graphical Abstract
The Chandra X-Ray Observatory observed the Crab Nebula and pulsar during orbital calibration. Zeroth-order images with the High-Energy Transmission Grating (HETG) readout by the Advanced CCD Imaging ...Spectrometer spectroscopy array (ACIS-S) show a striking richness of X-ray structure at a resolution comparable to that of the best ground-based visible-light observations. The HETG-ACIS-S images reveal, for the first time, an X-ray inner ring within the X-ray torus, the suggestion of a hollow-tube structure for the torus, and X-ray knots along the inner ring and (perhaps) along the inward extension of the X-ray jet. Although complicated by instrumental effects and the brightness of the Crab Nebula, the spectrometric analysis shows systematic variations of the X-ray spectrum throughout the nebula.
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