Can Sgr A* flares reveal the molecular gas density PDF?

Illumination of dense gas in the Central Molecular Zone (CMZ) by powerful X-ray flares from Sgr A* leads to prominent structures in the reflected emission that can be observed long after the end of the flare. By studying this emission we learn about past activity of the supermassive black hole in our Galactic Center and, at the same time, we obtain unique information on the structure of molecular clouds that is essentially impossible to get by other means. Here we discuss how X-ray data can improve our knowledge of both sides of the problem. Existing data already provide: i) an estimate of the flare age, ii) a model-independent lower limit on the luminosity of Sgr A* during the flare and iii) an estimate of the total emitted energy during Sgr A* flare. On the molecular clouds side, the data clearly show a voids-and-walls structure of the clouds and can provide an almost unbiased probe of the mass/density distribution of the molecular gas with the hydrogen column densities lower than few $10^{23}\;{\rm cm^{-2}}$. For instance, the probability distribution function of the gas density $PDF(\rho)$ can be measured this way. Future high energy resolution X-ray missions will provide the information on the gas velocities, allowing, for example a reconstruction of the velocity field structure functions and cross-matching the X-ray and molecular data based on positions and velocities.Comment: 13 pages, 7 figures; Accepted for publication in MNRA

Not that long time ago in the nearest galaxy: 3D slice of molecular gas revealed by a 110 years old flare of Sgr A*

A powerful outburst of X-ray radiation from the supermassive black hole Sgr A* at the center of the Milky Way is believed to be responsible for the illumination of molecular clouds in the central ~100 pc of the Galaxy (Sunyaev et al., 1993, Koyama et al., 1996). The reflected/reprocessed radiation comes to us with a delay corresponding to the light propagation time that depends on the 3D position of molecular clouds with respect to Sgr A*. We suggest a novel way of determining the age of the outburst and positions of the clouds by studying characteristic imprints left by the outburst in the spatial and time variations of the reflected emission. We estimated the age of the outburst that illuminates the Sgr A molecular complex to be ~110 yr. This estimate implies that we see the gas located ~10 pc further away from us than Sgr A*. If the Sgr B2 complex is also illuminated by the same outburst, then it is located ~130 pc closer than our Galactic Center. The outburst was short (less than a few years) and the total amount of emitted energy in X-rays is $\displaystyle \sim 10^{48}\rho_3^{-1}$ erg, where $\rho_3$ is the mean hydrogen density of the cloud complex in units of $10^3 {\rm cm^{-3}}$. Energetically, such fluence can be provided by a partial tidal disruption event or even by a capture of a planet. Further progress in more accurate positioning and timing of the outburst should be possible with future X-ray polarimetric observations and long-term systematic observations with Chandra and XMM-Newton. A few hundred-years long X-ray observations would provide a detailed 3D map of the gas density distribution in the central $\sim 100$ pc region.Comment: 10 pages, 7 figures, accepted for publication in MNRA

Polarization and long-term variability of Sgr A* X-ray echo

We use a model of the molecular gas distribution within ~100 pc from the center of the Milky Way (Kruijssen, Dale & Longmore) to simulate time evolution and polarization properties of the reflected X-ray emission, associated with the past outbursts from Sgr A*. While this model is too simple to describe the complexity of the true gas distribution, it illustrates the importance and power of long-term observations of the reflected emission. We show that the variable part of X-ray emission observed by Chandra and XMM from prominent molecular clouds is well described by a pure reflection model, providing strong support of the reflection scenario. While the identification of Sgr A* as a primary source for this reflected emission is already a very appealing hypothesis, a decisive test of this model can be provided by future X-ray polarimetric observations, that will allow placing constraints on the location of the primary source. In addition, X-ray polarimeters (like, e.g., XIPE) have sufficient sensitivity to constrain the line-of-sight positions of molecular complexes, removing major uncertainty in the model.Comment: 17 pages, 10 figures, accepted for publication in MNRA

Probing 3D Density and Velocity Fields of ISM in Centers of Galaxies with Future X-Ray Observations

Observations of bright and variable "reflected" X-ray emission from molecular clouds located within inner hundred parsec of our Galaxy have demonstrated that the central supermassive black hole, Sgr A*, experienced short and powerful flares in the past few hundred years. These flares offer a truly unique opportunity to determine 3D location of the illuminated clouds (with ~10 pc accuracy) and to reveal their internal structure (down to 0.1 pc scales). Short duration of the flare(s), combined with X-rays high penetration power and insensitivity of the reflection signal to thermo- and chemo-dynamical state of the gas, ensures that the provided diagnostics of the density and velocity fields is unbiased and almost free of the projection and opacity effects. Sharp and sensitive snapshots of molecular gas accessible with aid of future X-ray observatories featuring large collecting area and high angular (arcsec-level) and spectral (eV-level) resolution cryogenic bolometers will present invaluable information on properties of the supersonic turbulence inside the illuminated clouds, map their shear velocity field and allow cross-matching between X-ray data and velocity-resolved emission of various molecular species provided by ALMA and other ground-based facilities. This will highlight large and small-scale dynamics of the dense gas and help uncovering specifics of the ISM lifecycle and high-mass star formation under very extreme conditions of galactic centers. While the former is of particular importance for the SMBH feeding and triggering AGN feedback, the latter might be an excellent test case for star formation taking place in high-redshift galaxies.Comment: White paper submitted to the Astro2020 Decadal Surve

Strategies for early prediction and timely recognition of drug-induced liver injury: The case of cyclin-dependent kinase 4/6 inhibitors

The idiosyncratic nature of drug-induced liver injury (Dili) represents a current challenge for drug developers, regulators and clinicians. The myriad of agents (including medications, herbals, and dietary supplements) with recognized Dili potential not only strengthens the importance of the post-marketing phase, when urgent withdrawal sometimes occurs for rare unanticipated liver toxicity, but also shows the imperfect predictivity of pre-clinical models and the lack of validated biomarkers beyond traditional, non-specific liver function tests. After briefly reviewing proposed key mechanisms of Dili, we will focus on drug-related risk factors (physiochemical and pharmacokinetic properties) recently proposed as predictors of Dili and use cyclin-dependent kinase 4/6 inhibitors, relatively novel oral anticancer medications approved for breast cancer, as a case study to discuss the feasibility of early detection of Dili signals during drug development: published data from pivotal clinical trials, unpublished post-marketing reports of liver adverse events, and pharmacokinetic properties will be used to provide a comparative evaluation of their liver safety and gain insight into drug-related risk factors likely to explain the observed differences

3C 33: another case of photoionized soft X-ray emission in radio galaxies

All the observations available in the Chandra and XMM-Newton archives have been used to investigate the X-ray spectral properties of 3C 33. In this paper is presented a complete X-ray analysis of the nuclear emission of this narrow line radio galaxy. The broad band spectrum of 3C 33 is complex. The hard part resembles that of Seyfert 2 galaxies, with a heavily obscured nuclear continuum (N_H~10^23 cm^-2) and a prominent Fe Kalpha line. This represents the nuclear radiation directly observed in transmission through a cold circumnuclear gas. On the other hand an unabsorbed continuum plus emission lines seem to fit well the soft part of the spectrum (0.5-2 keV) suggesting that the jet does not significantly contribute to the X-ray emission. We discuss the possible collisional or photoionized origin of the gas that emits the soft X-ray lines. Our results, strengthened by optical spectroscopy favor the photoionization scenario.Comment: 7 pages, 5 figures, accepted for publication in A&

Relationship between adverse drug reactions to antibacterial agents and the Klebsiella pneumoniae carbapenemase-producing (KPC) Klebsiella pneumoniae outbreak: Insight from a pharmacovigilance study

Background: The management of Klebsiella pneumoniae carbapenemase producing (KPC) infections represents a major challenge. Several safety and efficacy concerns are shared by available antibiotics used in KPC infections, leading to the occurrence of serious adverse drug reactions (ADRs), with ceftazidime-avibactam possibly showing a more favourable risk-benefit profile. We investigated the potential impact of resistance on ADR reports in countries with different prevalence of KPC isolates (Italy vs. United Kingdom [UK]), and described safety profile of newer and older antibiotics used in KPC infections. Methods: Three spontaneous reporting systems (SRSs) with different features (Italy, UK and worldwide FAERS) were used to describe safety profiles of colistin, meropenem, tigecycline, gentamicin and ceftazidime-avibactam in terms of System Organ Class and Preferred Term level. ADRs were plotted with prevalence of KPC isolates in Italy and UK. A comparison between before-after the KPC outbreak period (1999-2008 vs. 2009-2018) of overall and serious ADRs for selected antibiotics in each SRS was performed. Relationship between total and serious number of ADR reports per year and KPC isolates per year after KPC outbreak (2009-2017) was investigated for both Italy and UK. Results: A total of 16,329 ADR reports were collected in the three SRSs, with meropenem (42.6%) and gentamicin (36.9%) having the highest number of reports. Significant increase in total and serious ADR reports after the KPC outbreak compared to previous 10 years was found for colistin, meropenem and gentamicin (p < 0.01). No significant increase in tigecycline ADRs was reported in FAERS and UK database. Unexpected safety signals involving selected antibiotics were not detected. Significant positive relationship between overall and serious ADR reports and KPC isolates per year for both Italy (p < 0.01; p = 0.005) and UK (p = 0.032; p = 0.013) was found. Conclusion: KPC outbreak led to significant increase in ADRs to selected antibiotics, and a close relationship with antimicrobial resistance was found, both in countries with high and low resistance rate. New safety signals were not detected for selected agents. Active surveillance should be maintained to promptly identify unexpected safety issues

Dapagliflozin and cardiovascular outcomes: anything else to DECLARE?

Introduction: Individuals with type 2 diabetes mellitus (T2DM) have increased cardiovascular risk with regulatory agencies requiring cardiovascular outcome trials (CVOTs) for the approval of new antidiabetic drugs. Areas covered: In this paper, the authors critically discuss the background, trial design, results and implications of a recent CVOT [NCT01730534; DECLARE-TIMI 58 study], which demonstrated that dapagliflozin was non-inferior to placebo in terms of major adverse cardiovascular events, and superior for the occurrence of hospitalization for heart failure (HF) and composite renal endpoints, thus confirming the cardiovascular benefit of sodium-glucose co-transporter-2 (SGLT2) inhibitors. No statistically-significant effects were found for amputations, fractures, and stroke (debated safety issues having emerged in previous CVOTs). Expert opinion: DECLARE-TIMI 58 is the longest (4.2 years of follow up), largest (>17,000 participants) and most inclusive (only 41% of individuals with established atherosclerotic cardiovascular disease) CVOT raising the debate towards SGLT2 inhibitor therapy in primary prevention and the potential use of these drugs also in patients with HF without T2DM and other subpopulations