Clinical effectiveness of cefiderocol for the treatment of bloodstream infections due to carbapenem-resistant Acinetobacter baumannii during the COVID-19 era: a single center, observational study.

BACKGROUND: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI). MATERIALS/METHODS: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW). RESULTS: Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival. CONCLUSIONS: CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.

Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

Bounds on Lorentz Invariance Violation from MAGIC Observation of GRB 190114C.

On January 14, 2019, the Major Atmospheric Gamma Imaging Cherenkov telescopes detected GRB 190114C above 0.2 TeV, recording the most energetic photons ever observed from a gamma-ray burst. We use this unique observation to probe an energy dependence of the speed of light in vacuo for photons as predicted by several quantum gravity models. Based on a set of assumptions on the possible intrinsic spectral and temporal evolution, we obtain competitive lower limits on the quadratic leading order of speed of light modification.

Compact radio emission indicates a structured jet was produced by a binary neutron star merger.

The binary neutron star merger event GW170817 was detected through both electromagnetic radiation and gravitational waves. Its afterglow emission may have been produced by either a narrow relativistic jet or an isotropic outflow. High-spatial-resolution measurements of the source size and displacement can discriminate between these scenarios. We present very-long-baseline interferometry observations, performed 207.4 days after the merger by using a global network of 32 radio telescopes. The apparent source size is constrained to be smaller than 2.5 milli-arc seconds at the 90% confidence level. This excludes the isotropic outflow scenario, which would have produced a larger apparent size, indicating that GW170817 produced a structured relativistic jet. Our rate calculations show that at least 10% of neutron star mergers produce such a jet.

Signatures of a jet cocoon in early spectra of a supernova associated with a γ-ray burst.

Long γ-ray bursts are associated with energetic, broad-lined, stripped-envelope supernovae1,2 and as such mark the death of massive stars. The scarcity of such events nearby and the brightness of the γ-ray burst afterglow, which dominates the emission in the first few days after the burst, have so far prevented the study of the very early evolution of supernovae associated with γ-ray bursts3. In hydrogen-stripped supernovae that are not associated with γ-ray bursts, an excess of high-velocity (roughly 30,000 kilometres per second) material has been interpreted as a signature of a choked jet, which did not emerge from the progenitor star and instead deposited all of its energy in a thermal cocoon4. Here we report multi-epoch spectroscopic observations of the supernova SN 2017iuk, which is associated with the γ-ray burst GRB 171205A. Our spectra display features at extremely high expansion velocities (around 115,000 kilometres per second) within the first day after the burst5,6. Using spectral synthesis models developed for SN 2017iuk, we show that these features are characterized by chemical abundances that differ from those observed in the ejecta of SN 2017iuk at later times. We further show that the high-velocity features originate from the mildly relativistic hot cocoon that is generated by an ultra-relativistic jet within the γ-ray burst expanding and decelerating into the medium that surrounds the progenitor star7,8. This cocoon rapidly becomes transparent9 and is outshone by the supernova emission, which starts to dominate the emission three days after the burst.

Spectroscopic identification of r-process nucleosynthesis in a double neutron-star merger.

The merger of two neutron stars is predicted to give rise to three major detectable phenomena: a short burst of γ-rays, a gravitational-wave signal, and a transient optical-near-infrared source powered by the synthesis of large amounts of very heavy elements via rapid neutron capture (the r-process). Such transients, named 'macronovae' or 'kilonovae', are believed to be centres of production of rare elements such as gold and platinum. The most compelling evidence so far for a kilonova was a very faint near-infrared rebrightening in the afterglow of a short γ-ray burst at redshift z = 0.356, although findings indicating bluer events have been reported. Here we report the spectral identification and describe the physical properties of a bright kilonova associated with the gravitational-wave source GW170817 and γ-ray burst GRB 170817A associated with a galaxy at a distance of 40 megaparsecs from Earth. Using a series of spectra from ground-based observatories covering the wavelength range from the ultraviolet to the near-infrared, we find that the kilonova is characterized by rapidly expanding ejecta with spectral features similar to those predicted by current models. The ejecta is optically thick early on, with a velocity of about 0.2 times light speed, and reaches a radius of about 50 astronomical units in only 1.5 days. As the ejecta expands, broad absorption-like lines appear on the spectral continuum, indicating atomic species produced by nucleosynthesis that occurs in the post-merger fast-moving dynamical ejecta and in two slower (0.05 times light speed) wind regions. Comparison with spectral models suggests that the merger ejected 0.03 to 0.05 solar masses of material, including high-opacity lanthanides.

Chemical and microbiological characterization of an aged PCB-contaminated soil.

This study was aimed at complex characterization of three soil samples (bulk soil, topsoil and rhizosphere soil) from a site historically contaminated with polychlorinated biphenyls (PCB). The bulk soil was the most highly contaminated, with a PCB concentration of 705.95 mg kg(-1), while the rhizosphere soil was the least contaminated (169.36 mg kg(-1)). PCB degradation intermediates, namely chlorobenzoic acids (CBAs), were detected in all the soil samples, suggesting the occurrence of microbial transformation processes over time. The higher content of organic carbon in the topsoil and rhizosphere soil than in the bulk soil could be linked to the reduced bioaccessibility (bioavailability) of these chlorinated pollutants. However, different proportions of the PCB congener contents and different bioaccessibility of the PCB homologues indicate microbial biotransformation of the compounds. The higher content of organic carbon probably also promoted the growth of microorganisms, as revealed by phospholipid fatty acid (PFLA) quantification. Tag-encoded pyrosequencing analysis showed that the bacterial community structure was significantly similar among the three soils and was predominated by Proteobacteria (44-48%) in all cases. Moreover, analysis at lower taxonomic levels pointed to the presence of genera (Sphingomonas, Bulkholderia, Arthrobacter, Bacillus) including members with reported PCB removal abilities. The fungal community was mostly represented by Basidiomycota and Ascomycota, which accounted for >80% of all the sequences detected in the three soils. Fungal taxa with biodegradation potential (Paxillus, Cryptococcus, Phoma, Mortierella) were also found. These results highlight the potential of the indigenous consortia present at the site as a starting point for PCB bioremediation processes.

Pyrosequencing reveals the effect of mobilizing agents and lignocellulosic substrate amendment on microbial community composition in a real industrial PAH-polluted soil.

Bacterial and fungal biodiversity throughout different biostimulation and bioaugmentation treatments applied to an industrial creosote-polluted soil were analyzed by means of polyphasic approach in order to gain insight into the microbial community structure and dynamics. Pyrosequencing data obtained from initial creosote polluted soil (after a biopiling step) revealed that Alpha and Gammaproteobacteria were the most abundant bacterial groups, whereas Fusarium and Scedosporium were the main fungal genera in the contaminated soil. At the end of 60-days laboratory scale bioremediation assays, pyrosequencing and DGGE data showed that (i) major bacterial community shifts were caused by the type of mobilizing agent added to the soil and, to a lesser extent, by the addition of lignocellulosic substrate; and (ii) the presence of the non-ionic surfactant (Brij 30) hampered the proliferation of Actinobacteria (Mycobacteriaceae) and Bacteroidetes (Chitinophagaceae) and, in the absence of lignocellulosic substrate, also impeded polycyclic aromatic hydrocarbons (PAHs) degradation. The results show the importance of implementing bioremediation experiments combined with microbiome assessment to gain insight on the effect of crucial parameters (e.g. use of additives) over the potential functions of complex microbial communities harbored in polluted soils, essential for bioremediation success.

Black hole physics. Black hole lightning due to particle acceleration at subhorizon scales.

Supermassive black holes with masses of millions to billions of solar masses are commonly found in the centers of galaxies. Astronomers seek to image jet formation using radio interferometry but still suffer from insufficient angular resolution. An alternative method to resolve small structures is to measure the time variability of their emission. Here we report on gamma-ray observations of the radio galaxy IC 310 obtained with the MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes, revealing variability with doubling time scales faster than 4.8 min. Causality constrains the size of the emission region to be smaller than 20% of the gravitational radius of its central black hole. We suggest that the emission is associated with pulsar-like particle acceleration by the electric field across a magnetospheric gap at the base of the radio jet.

Ecotoxicity and biodegradability of new brominated flame retardants: a review.

Brominated flame retardants (BFRs) have been routinely used as additives in a number of consumer products for several decades in order to reduce the risk of fire accidents. Concerns about the massive use of these substances have increased due to their possible toxicity, endocrine disrupting properties and occurrence in almost all the environmental compartments, including humans and wildlife organisms. Several conventional BFRs (e.g. polybrominated diphenylethers (PBDE)) have been included in the list of Persistent Organic Pollutants and their use has been restricted because of their established toxicity and environmental persistence. Over the past few years, these compounds have been replaced with "new" BFRs (NBFRs). Despite the fact that NBFRs are different chemical molecules than traditional BFRs, most of physical-chemical properties (e.g. aromatic moiety, halogen substitution, lipophilic character) are common to both groups; therefore, their fate in the environment is potentially similar to the banned BFRs. Therefore, this article has been compiled to summarize the published scientific data regarding the biodegradability of the most widely used NBFRs, a key factor in their potential persistency in the environment, and their ecotoxicological effects on humans and test organisms. The data reviewed here document that the mechanisms through NBFRs exibit their ecotoxicity and the processes leading to their biotransformation in the environment are still poorly understood. Thus emphasis is placed on the need for further research in these areas is therefore emphasized, in order to avoid the massive use of further potentially harmful and recalcitrant substances of anthropogenic origin.

Circular polarization in the optical afterglow of GRB 121024A.

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

GRB 130427A: a nearby ordinary monster.

Long-duration gamma-ray bursts (GRBs) are an extremely rare outcome of the collapse of massive stars and are typically found in the distant universe. Because of its intrinsic luminosity (L ~ 3 × 10(53) ergs per second) and its relative proximity (z = 0.34), GRB 130427A reached the highest fluence observed in the γ-ray band. Here, we present a comprehensive multiwavelength view of GRB 130427A with Swift, the 2-meter Liverpool and Faulkes telescopes, and by other ground-based facilities, highlighting the evolution of the burst emission from the prompt to the afterglow phase. The properties of GRB 130427A are similar to those of the most luminous, high-redshift GRBs, suggesting that a common central engine is responsible for producing GRBs in both the contemporary and the early universe and over the full range of GRB isotropic energies.

Chlorobenzoic acid degradation by Lentinus (Panus) tigrinus: in vivo and in vitro mechanistic study-evidence for P-450 involvement in the transformation.

Aim of this work was to investigate the ability of Lentinus (Panus) tigrinus to degrade and detoxify a chlorobenzoate (CBA) mixture composed of mono-, di- and tri-chlorinated isomers. The degradation process was investigated as a function of both the growing medium (i.e. low N Kirk's and malt extract-glucose medium) and cultivation conditions (i.e. stationary and shaken cultures). The majority of CBAs were quantitatively degraded within the early 15 d from spiking with the notable exception of the double ortho-chlorinated compounds, 2,6-di-, 2,3,6-tri- and 2,4,6-tri-CBA. Analysis of the degradation intermediates indicated the occurrence of side chain reduction, hydroxylation and methylation reactions. Although CBAs stimulated laccase production, in vitro experiments with a purified L. tigrinus laccase isoenzyme demonstrated its inability to participate in the initial attack on CBAs even in the presence of redox mediators; similar results were found with a Mn-peroxidase isoenzyme. Conversely, prompt degradation was observed upon 1h incubation of CBAs with a purified microsomal fraction containing cytochrome P-450 monooxygenase. The nature of some reaction products (i.e. hydroxylated derivatives), the dependency of the reaction on NADPH and its susceptibility to either CO or piperonyl butoxide inhibition confirmed the involvement of L. tigrinus cytochrome P-450 in the early steps of CBA degradation.

Comparative assessment of bioremediation approaches to highly recalcitrant PAH degradation in a real industrial polluted soil.

High recalcitrant characteristics and low bioavailability rates due to aging processes can hinder high molecular weight polycyclic aromatic hydrocarbons (HMW-PAHs) bioremediation in real industrial polluted soils. With the aim of reducing the residual fraction of total petroleum hydrocarbons (TPH) and (HMW-PAHs) in creosote-contaminated soil remaining after a 180-d treatment in a pilot-scale biopile, either biostimulation (BS) of indigenous microbial populations with a lignocellulosic substrate (LS) or fungal bioaugmentation with two strains of white-rot fungi (WRF) (i.e., Trametes versicolor and Lentinus tigrinus) were comparatively tested. The impact of bivalent manganese ions and two mobilizing agents (MAs) (i.e., Soybean Oil and Brij 30) on the degradation performances of biostimulated and bioaugmented microcosms was also compared. The results reveal soil colonization by both WRF strains was clearly hampered by an active native soil microbiota. In fact, a proper enhancement of native microbiota by means of LS amendment promoted the highest biodegradation of HMW-PAHs, even of those with five aromatic rings after 60 days of treatment, but HMW-PAH-degrading bacteria were specifically inhibited when non-ionic surfactant Brij 30 was amended. Effects of bioaugmentation and other additives such as non-ionic surfactants on the degrading capability of autochthonous soil microbiota should be evaluated in polluted soils before scaling up the remediation process at field scale.

The unusual gamma-ray burst GRB 101225A explained as a minor body falling onto a neutron star.

The tidal disruption of a solar-mass star around a supermassive black hole has been extensively studied analytically and numerically. In these events, the star develops into an elongated banana-shaped structure. After completing an eccentric orbit, the bound debris falls into the black hole, forming an accretion disk and emitting radiation. The same process may occur on planetary scales if a minor body passes too close to its star. In the Solar System, comets fall directly into our Sun or onto planets. If the star is a compact object, the minor body can become tidally disrupted. Indeed, one of the first mechanisms invoked to produce strong gamma-ray emission involved accretion of comets onto neutron stars in our Galaxy. Here we report that the peculiarities of the 'Christmas' gamma-ray burst (GRB 101225A) can be explained by a tidal disruption event of a minor body around an isolated Galactic neutron star. This would indicate either that minor bodies can be captured by compact stellar remnants more frequently than occurs in the Solar System or that minor-body formation is relatively easy around millisecond radio pulsars. A peculiar supernova associated with a gamma-ray burst provides an alternative explanation.

Relativistic jet activity from the tidal disruption of a star by a massive black hole.

Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.

GRB 090423 at a redshift of z approximately 8.1.

Gamma-ray bursts (GRBs) are produced by rare types of massive stellar explosion. Their rapidly fading afterglows are often bright enough at optical wavelengths that they are detectable at cosmological distances. Hitherto, the highest known redshift for a GRB was z = 6.7 (ref. 1), for GRB 080913, and for a galaxy was z = 6.96 (ref. 2). Here we report observations of GRB 090423 and the near-infrared spectroscopic measurement of its redshift, z = 8.1(-0.3)(+0.1). This burst happened when the Universe was only about 4 per cent of its current age. Its properties are similar to those of GRBs observed at low/intermediate redshifts, suggesting that the mechanisms and progenitors that gave rise to this burst about 600,000,000 years after the Big Bang are not markedly different from those producing GRBs about 10,000,000,000 years later.

Observation of pulsed gamma-rays above 25 GeV from the Crab pulsar with MAGIC.

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 giga-electron volts. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 giga-electron volts, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.

Broadband observations of the naked-eye gamma-ray burst GRB 080319B.

Long-duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of massive stars. Previous early optical observations of even the most exceptional GRBs (990123 and 030329) lacked both the temporal resolution to probe the optical flash in detail and the accuracy needed to trace the transition from the prompt emission within the outflow to external shocks caused by interaction with the progenitor environment. Here we report observations of the extraordinarily bright prompt optical and gamma-ray emission of GRB 080319B that provide diagnostics within seconds of its formation, followed by broadband observations of the afterglow decay that continued for weeks. We show that the prompt emission stems from a single physical region, implying an extremely relativistic outflow that propagates within the narrow inner core of a two-component jet.

Very-high-energy gamma rays from a distant quasar: how transparent is the universe?

The atmospheric Cherenkov gamma-ray telescope MAGIC, designed for a low-energy threshold, has detected very-high-energy gamma rays from a giant flare of the distant Quasi-Stellar Radio Source (in short: radio quasar) 3C 279, at a distance of more than 5 billion light-years (a redshift of 0.536). No quasar has been observed previously in very-high-energy gamma radiation, and this is also the most distant object detected emitting gamma rays above 50 gigaelectron volts. Because high-energy gamma rays may be stopped by interacting with the diffuse background light in the universe, the observations by MAGIC imply a low amount for such light, consistent with that known from galaxy counts.