Reducing the weak lensing noise for the gravitational wave Hubble diagram using the non-Gaussianity of the magnification distribution

Gravitational wave sources are a promising cosmological standard candle because their intrinsic luminosities are determined by fundamental physics (and are insensitive to dust extinction). They are, however, affected by weak lensing magnification due to the gravitational lensing from structures along the line of sight. This lensing is a source of uncertainty in the distance determination, even in the limit of perfect standard candle measurements. It is commonly believed that the uncertainty in the distance to an ensemble of gravitational wave sources is limited by the standard deviation of the lensing magnification distribution divided by the square root of the number of sources. Here we show that by exploiting the non-Gaussian nature of the lensing magnification distribution, we can improve this distance determination, typically by a factor of 2--3; we provide a fitting formula for the effective distance accuracy as a function of redshift for sources where the lensing noise dominates.Comment: matches PRD accepted version (expanded description of the cosmological parameter space + minor changes

Nodular fasciitis: a comprehensive, time-correlated investigation of 17 cases

The self-limited nature of nodular fasciitis (NF) is well-known but its precise mechanism has not yet been clarified. We observed that "young" NF (preoperative duration 3 months) (similar to 20%). Thus, we hypothesized that our original observation may reflect a connection with the self-limited nature of NF. Seventeen cases with reliable data concerning the onset were selected, thus approximating the lifetime of each tumor. Besides the USP6 interphase FISH examination, we also checked the most common MYH9-USP6 fusion using RT-PCR. Because of the known pathways of the tumorigenesis of NF, the mRNA level of USP6, TRAIL, IFN-beta, JAK1, STAT1, STAT3, JUN, and CDKN2A was measured using qRT-PCR. Regarding proteins, USP6, p16, p27, TRAIL, and IFN-beta were examined using immunohistochemistry. Targeted gene panel next-generation sequencing (NGS) of three cases was additionally performed. We found a strong negative correlation (p = 0.000) between the lifetime and percentage of USP6 break-apart signals and a strong positive relationship (p = 0.000) between USP6 break-apart signals and mitotic counts. Results of immunostainings, along with qRT-PCR results, favored the previously-suggested USP6-induced negative feedback mechanism through activation of TRAIL and IFN-beta, likely resulting in apoptosis and senescence of tumor cells harboring USP6 fusions. Targeted-NGS resulted in the detection of several variants, but no additional recurrent changes in the pathogenesis of these tumors. We revealed on a cellular level the USP6-induced negative feedback mechanism. In conclusion, we emphasize that in "old" NF, the percentage of USP6 break-apart FISH signals can be as low as 14-27% which can be very important from a differential diagnostic point of view. We emphasize that a careful examination and interpretation of the NGS data is needed before clinical decision-making on treatment.Cancer Signaling networks and Molecular Therapeutic

Identifying Decaying Supermassive Black Hole Binaries from their Variable Electromagnetic Emission

Supermassive black hole binaries (SMBHBs) with masses in the range 10^4-10^7 M_sun/(1+z), produced in galaxy mergers, are thought to complete their coalescence due to the emission of gravitational waves (GWs). The anticipated detection of the GWs by the LISA will constitute a milestone for fundamental physics and astrophysics. While the GW signatures themselves will provide a treasure trove of information, if the source can be securely identified in electromagnetic (EM) bands, this would open up entirely new scientific opportunities, to probe fundamental physics, astrophysics, and cosmology. We discuss several ideas, involving wide-field telescopes, that may be useful in locating electromagnetic counterparts to SMBHBs detected by LISA. In particular, the binary may produce a variable electromagnetic flux, such as a roughly periodic signal due to the orbital motion prior to coalescence, or a prompt transient signal caused by shocks in the circumbinary disk when the SMBHB recoils and "shakes" the disk. We discuss whether these time-variable EM signatures may be detectable, and how they can help in identifying a unique counterpart within the localization errors provided by LISA. We also discuss a possibility of identifying a population of coalescing SMBHBs statistically, in a deep optical survey for periodically variable sources, before LISA detects the GWs directly. The discovery of such sources would confirm that gas is present in the vicinity and is being perturbed by the SMBHB - serving as a proof of concept for eventually finding actual LISA counterparts.Comment: 10 pages with 4 figures; submitted to Classical and Quantum Gravity (special issue for the proceedings of the 7th International LISA Symposium

Advanced localization of massive black hole coalescences with LISA

The coalescence of massive black holes is one of the primary sources of gravitational waves (GWs) for LISA. Measurements of the GWs can localize the source on the sky to an ellipse with a major axis of a few tens of arcminutes to a few degrees, depending on source redshift, and a minor axis which is 2--4 times smaller. The distance (and thus an approximate redshift) can be determined to better than a per cent for the closest sources we consider, although weak lensing degrades this performance. It will be of great interest to search this three-dimensional `pixel' for an electromagnetic counterpart to the GW event. The presence of a counterpart allows unique studies which combine electromagnetic and GW information, especially if the counterpart is found prior to final merger of the holes. To understand the feasibility of early counterpart detection, we calculate the evolution of the GW pixel with time. We find that the greatest improvement in pixel size occurs in the final day before merger, when spin precession effects are maximal. The source can be localized to within 10 square degrees as early as a month before merger at $z = 1$; for higher redshifts, this accuracy is only possible in the last few days.Comment: 11 pages, 4 figures, version published in Classical and Quantum Gravity (special issue for proceedings of 7th International LISA Symposium

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

BACKGROUND AND PURPOSE: Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. METHODS: Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. RESULTS: VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5'-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. CONCLUSIONS: VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)