Objectives We evaluated the prognostic value of myocardial flow reserve (MFR) using rubidium-82 (82 Rb) positron emission tomography (PET) in patients assessed for ischemia. Background The clinical ...value of MFR quantification using82 Rb PET beyond relative myocardial perfusion imaging remains uncertain. Methods We prospectively enrolled 704 consecutive patients; 677 (96%) completed follow-up (median 387 days interquartile range: 375 to 416 days). Patients were divided into 4 groups: I, normal summed stress score (SSS) (<4) and normal myocardial flow reserve (MFR) (>2); II, normal SSS and MFR <2; III, SSS ≥4 and MFR ≥2; IV, SSS ≥4 and MFR <2. Results For patients with a normal SSS and those with an abnormal SSS, there were significant differences in outcomes for hard events (cardiac death and myocardial infarction) between patients with MFR ≥2 and those with MFR <2 (I: 1.3% vs. II: 2% p = 0.029; III: 1.1% vs. IV: 11.4% p = 0.05) and for major adverse cardiac events (MACE) (p = 0.003 and p < 0.001, respectively). In the adjusted Cox model, MFR was an independent predictor of hard events (hazard ratio: 3.3; 95% confidence interval: 1.1 to 9.5; p = 0.029) and MACE (hazard ratio: 2.4, 95% confidence interval: 1.4 to 4.4, p = 0.003). The incremental prognostic value of the MFR over the SSS was demonstrated by comparing the adjusted SSS model with and without the MFR for hard events (p = 0.0197) and MACE (p = 0.002). Conclusions MFR quantified using82 Rb PET predicts hard cardiac events and MACE independent of the SSS and other parameters. Routine assessment of82 Rb PET–quantified MFR could improve risk stratification for patients being investigated for ischemia.
ABSTRACT
Some core-collapse supernovae are likely to be efficient cosmic ray accelerators up to the PeV range, and therefore, to potentially play an important role in the overall Galactic cosmic ray ...population. The TeV gamma-ray domain can be used to study particle acceleration in the multi-TeV and PeV range. This motivates the study of the detectability of such supernovae by current and future gamma-ray facilities. The gamma-ray emission of core-collapse supernovae strongly depends on the level of the two-photon annihilation process: high-energy gamma-ray photons emitted at the expanding shock wave following the supernova explosion can interact with soft photons from the supernova photosphere through the pair production channel, thereby strongly suppressing the flux of gamma-rays leaving the system. In the case of SN 1993J, whose photospheric and shock-related parameters are well measured, we calculate the temporal evolution of the expected gamma-ray attenuation by accounting for the temporal and geometrical effects. We find the attenuation to be of about 10 orders of magnitude in the first few days after the supernova explosion. The probability of detection of a supernova similar to SN 1993J with the Cherenkov Telescope Array is highest if observations are performed either earlier than 1 d, or later than 10 d after the explosion, when the gamma-ray attenuation decreases to about two orders of magnitude.
Context. The breakthrough developments of Cherenkov telescopes in the past decade have led to angular resolution of 0.1° and an unprecedented sensitivity. This has allowed the current generation of ...Cherenkov telescopes (H.E.S.S., MAGIC, and VERITAS) to discover a population of supernova remnants (SNRs) radiating in very-high-energy (VHE; E > 100 GeV) γ-rays. A number of those VHE SNRs exhibit a shell-type morphology that is spatially coincident with the shock front of the SNR. Aims. The members of this VHE shell SNR club are RX J1713.7−3946, RX J0852.0−4622, RCW 86, SN 1006, and HESS J1731−347. The last two objects have been poorly studied in high-energy (HE; 0.1 < E < 100 GeV) γ-rays and need to be investigated in order to draw the overall picture of this class of SNRs and to constrain the characteristics of the underlying population of accelerated particles. Methods. Using 6 years of Fermi-LAT P7 reprocessed data, we studied the GeV counterpart of the SNRs HESS J1731−347 and SN 1006. The two SNRs are not detected in the data set, and given that there is no hint of detection, we do not expect any detection in coming years from the SNRs. However in both cases, we derived upper limits that significantly constrain the γ-ray emission mechanism and can rule out a standard hadronic scenario with a confidence level >5σ. Results. With this Fermi analysis, we now have a complete view of the HE to VHE γ-ray emission of TeV shell SNRs. All five sources have a hard HE photon index (Γ < 1.8), which suggests a common scenario where the bulk of the emission is produced by accelerated electrons radiating from radio to VHE γ-rays through synchrotron and inverse Compton processes. In addition when correcting for the distance, all SNRs show a surprisingly similar γ-ray luminosity supporting the idea of a common emission mechanism. While the γ-ray emission is likely to be leptonic-dominated at the scale of the whole SNR, this does not rule out efficient hadron acceleration in those objects.
An increase in the level of nitric oxide (NO) plays a key role in regulating the human cardiovascular system (lowering blood pressure, improving blood flow), glycemic control in type 2 diabetes, and ...may help enhance exercise capacity in healthy individuals (including athletes). This molecule is formed by endogenous enzymatic synthesis and the intake of inorganic nitrate (NO
) from dietary sources. Although one of the most well-known natural sources of NO
in the daily diet is beetroot (
), this review also explores other plant sources of NO
with comparable concentrations that could serve as ergogenic aids, supporting exercise performance or recovery in healthy individuals. The results of the analysis demonstrate that red spinach (
spp.) and green spinach (
) are alternative natural sources rich in dietary NO
. The outcomes of the collected studies showed that consumption of selected alternative sources of inorganic NO
could support physical condition. Red spinach and green spinach have been shown to improve exercise performance or accelerate recovery after physical exertion in healthy subjects (including athletes).
CRISPR screens provide large-scale assessment of cellular gene functions. Pooled libraries typically consist of several single guide RNAs (sgRNAs) per gene, for a large number of genes, which are ...transduced in such a way that every cell receives at most one sgRNA, resulting in the disruption of a single gene in that cell. This approach is often used to investigate effects on cellular fitness, by measuring sgRNA abundance at different time points. Comparing gene knockout effects between different cell populations is challenging due to variable cell-type specific parameters and between replicates variation. Failure to take those into account can lead to inflated or false discoveries.
We propose a new, flexible approach called ShrinkCRISPR that can take into account multiple sources of variation. Impact on cellular fitness between conditions is inferred by using a mixed-effects model, which allows to test for gene-knockout effects while taking into account sgRNA-specific variation. Estimates are obtained using an empirical Bayesian approach. ShrinkCRISPR can be applied to a variety of experimental designs, including multiple factors. In simulation studies, we compared ShrinkCRISPR results with those of drugZ and MAGeCK, common methods used to detect differential effect on cell fitness. ShrinkCRISPR yielded as many true discoveries as drugZ using a paired screen design, and outperformed both drugZ and MAGeCK for an independent screen design. Although conservative, ShrinkCRISPR was the only approach that kept false discoveries under control at the desired level, for both designs. Using data from several publicly available screens, we showed that ShrinkCRISPR can take data for several time points into account simultaneously, helping to detect early and late differential effects.
ShrinkCRISPR is a robust and flexible approach, able to incorporate different sources of variations and to test for differential effect on cell fitness at the gene level. These improve power to find effects on cell fitness, while keeping multiple testing under the correct control level and helping to improve reproducibility. ShrinkCrispr can be applied to different study designs and incorporate multiple time points, making it a complete and reliable tool to analyze CRISPR screen data.
ABSTRACT To uniformly determine the properties of supernova remnants (SNRs) at high energies, we have developed the first systematic survey at energies from 1 to 100 GeV using data from the Fermi ...Large Area Telescope (LAT). Based on the spatial overlap of sources detected at GeV energies with SNRs known from radio surveys, we classify 30 sources as likely GeV SNRs. We also report 14 marginal associations and 245 flux upper limits. A mock catalog in which the positions of known remnants are scrambled in Galactic longitude allows us to determine an upper limit of 22% on the number of GeV candidates falsely identified as SNRs. We have also developed a method to estimate spectral and spatial systematic errors arising from the diffuse interstellar emission model, a key component of all Galactic Fermi LAT analyses. By studying remnants uniformly in aggregate, we measure the GeV properties common to these objects and provide a crucial context for the detailed modeling of individual SNRs. Combining our GeV results with multiwavelength (MW) data, including radio, X-ray, and TeV, we demonstrate the need for improvements to previously sufficient, simple models describing the GeV and radio emission from these objects. We model the GeV and MW emission from SNRs in aggregate to constrain their maximal contribution to observed Galactic cosmic rays.
Aims.
Among the
γ
-ray sources discovered at high and very-high energies, a large fraction still lack a clear identification. In particular, the H.E.S.S. Galactic Plane Survey (HGPS) revealed 78 TeV ...sources among which 47 are not clearly associated with a known object. Multiwavelength data can help identify the origin of the very-high energy
γ
-ray emission, although some bright TeV sources have been detected without clear counterparts. We present a multiwavelength approach to constrain the origin of the emission from unidentified HGPS sources.
Methods.
We present a generic pipeline that explores a large database of multiwavelength archival data toward any region in the Galactic plane. Along with a visual inspection of the retrieved multiwavelength observations to search for faint and uncataloged counterparts, we derive a radio spectral index that helps disentangle thermal from nonthermal emission and a mean magnetic field through X-ray and TeV data in case of a leptonic scenario. We also search for a spectral connection between the GeV and the TeV regimes with the
Fermi
-LAT cataloged sources that may be associated with the unidentified HGPS source. We complete the association procedure with catalogs of known objects (supernova remnants, pulsar wind nebulae, H
II
regions, etc.) and with the source catalogs from instruments whose data are retrieved.
Results.
The method is applied on two unidentified sources, namely HESS J1427−608 and HESS J1458−608, for which the multiwavelength constraints favor the pulsar wind nebula (PWN) scenario. We model their broadband nonthermal spectra in a leptonic scenario with a magnetic field
B
≲ 10
μ
G, which is consistent with that obtained from ancient PWNe. We place both sources within the context of the TeV PWN population to estimate the spin-down power and the characteristic age of the putative pulsar. We also shed light on two possibly significant
γ
-ray excesses in the HGPS: the first is located in the south of the unidentified source HESS J1632−478 and the second is spatially coincident with the synchrotron-emitting supernova remnant G28.6−0.1. The multiwavelength counterparts found toward both
γ
-ray excesses make these promising candidates for being new very-high energy
γ
-ray sources.
The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new ...observations from an unprecedented gamma-ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies (& GSIM;100 GeV) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant gamma-ray excess is found in the search region of the 2014-2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section (sigma v). Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach (sigma v) values of 3.7 x 10-26 cm3 s-1 for 1.5 TeV DM mass in the W+W- annihilation channel, and 1.2 x 10-26 cm3 s-1 for 0.7 TeV DM mass in the tau+tau- annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based gamma-ray observations thus probe (sigma v) values expected from thermal-relic annihilating TeV DM particles.
In this paper, we report on the fourth soft gamma-ray source catalog obtained with the IBIS gamma-ray imager on board the INTEGRAL satellite. The scientific data set is based on more than 70 Ms of ...high-quality observations performed during the first five and a half years of the Core Program and public observations. Compared to previous IBIS surveys, this catalog includes a substantially increased coverage of extragalactic fields, and comprises more than 700 high-energy sources detected in the energy range 17-100 keV, including both transients and faint persistent objects that can only be revealed with longer exposure times. A comparison is provided with the latest Swift/BAT survey results. Based on observations with INTEGRAL, an ESA project with instruments and Science Data Centre funded by ESA member states (especially the PI countries: Denmark, France, Germany, Italy, Switzerland, Spain), Czech Republic, and Poland, and with the participation of Russia and the USA.
Purpose
Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone ...reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans.
Methods
PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review.
Results
Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements.
Conclusion
Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.
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