Pathophysiological mechanisms of statin‐associated myopathies: possible role of the ubiquitin‐proteasome system

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All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe

The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band

Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations

The LOFT mission concept: a status update

The Large Observatory For x-ray Timing (LOFT) is a mission concept which was proposed to ESA as M3 and M4 candidate in the framework of the Cosmic Vision 2015-2025 program. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument and the uniquely large field of view of its wide field monitor, LOFT will be able to study the behaviour of matter in extreme conditions such as the strong gravitational field in the innermost regions close to black holes and neutron stars and the supra-nuclear densities in the interiors of neutron stars. The science payload is based on a Large Area Detector (LAD, >8m2 effective area, 2-30 keV, 240 eV spectral resolution, 1 degree collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g., GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the current technical and programmatic status of the mission

MAGIC and H.E.S.S. detect VHE gamma rays from the blazar OT081 for the first time: a deep multiwavelength study

https://pos.sissa.it/395/815/pdfPublished versio

Comparison of clinical outcomes between genders following antihypertensive therapy: A Meta-analysis

Numerous studies have reported sex and gender differences in the prevalence and treatment of cardiovascular diseases. However, sex differences in the therapy of hypertension have not been completely examined

Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: A meta-analysis of 16 randomized controlled treatment arms

Abstract AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging class of low-density lipoprotein cholesterol (LDL-C)-lowering agents. In spite of their known effects on lipids, the impact of these drugs on systemic inflammation is less known. We aimed to investigate the effect of PCSK9 inhibitors on high-sensitivity C-reactive protein (hs-CRP) levels through a meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search of Medline, SCOPUS and Google Scholar was conducted up to December 2015 to identify RCTs assessing changes in hs-CRP concentrations during treatment with PCSK9 inhibitors. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. RESULTS: Sixteen treatment arms, with a total of 2546 participants, were included. Random-effects meta-analysis did not show any significant effect of PCSK9 inhibitors on hs-CRP levels (WMD: 0.002 mg l(-1) , CI: -0.017, 0.021; P = 0.807; I(2) = 37.26%). This effect size was robust, not sensitive to any single study, and not affected by the type of PCSK9 inhibitor (evolocumab: WMD: 0.002 mg l(-1) , CI: -0.02, 0.02; P = 0.855; alirocumab WMD: 0.15 mg l(-1) , CI: -0.11, 0.40; P = 0.259; I(2) = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l(-1) , CI: -0.20, 0.46; P = 0.433; I(2) = 55.19%; monthly: WMD: 0.003 mg l(-1) , CI: -0.01, 0.01; P = 0.59; I(2) = 0%). Random-effects meta-regression did not suggest any association of changes in hs-CRP levels with changes in plasma LDL-C concentrations (P = 0.697) or cumulative dosage of the drug (P = 0.980). CONCLUSIONS: This meta-analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs-CRP concentrations

Pathophysiological mechanisms of statin‐associated myopathies: possible role of the ubiquitin‐proteasome system

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The blazar TXS 0506+056 associated with a high-energy neutrino: insights into extragalactic jets and cosmic ray acceleration

International audienceA neutrino with energy ∼290 TeV, IceCube-170922A, was detected in coincidence with the BL Lac object TXS 0506+056 during enhanced gamma-ray activity, with chance coincidence being rejected at ∼3σ level. We monitored the object in the very-high-energy (VHE) band with the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes for ∼41 hr from 1.3 to 40.4 days after the neutrino detection. Day-timescale variability is clearly resolved. We interpret the quasi-simultaneous neutrino and broadband electromagnetic observations with a novel one-zone lepto-hadronic model, based on interactions of electrons and protons co-accelerated in the jet with external photons originating from a slow-moving plasma sheath surrounding the faster jet spine. We can reproduce the multiwavelength spectra of TXS 0506+056 with neutrino rate and energy compatible with IceCube-170922A, and with plausible values for the jet power of . The steep spectrum observed by MAGIC is concordant with internal γγ absorption above ∼100 GeV entailed by photohadronic production of a ∼290 TeV neutrino, corroborating a genuine connection between the multi-messenger signals. In contrast to previous predictions of predominantly hadronic emission from neutrino sources, the gamma-rays can be mostly ascribed to inverse Compton upscattering of external photons by accelerated electrons. The X-ray and VHE bands provide crucial constraints on the emission from both accelerated electrons and protons. We infer that the maximum energy of protons in the jet comoving frame can be in the range ∼1014 – 1018 eV