The very faint hard state of the persistent neutron star X-ray binary SLX 1737-282 near the Galactic centre

We report on a detailed study of the spectral and temporal properties of the neutron star low mass X-ray binary SLX 1737-282, which is located only ~1degr away from Sgr A. The system is expected to have a short orbital period, even within the ultra-compact regime, given its persistent nature at low X-ray luminosities and the long duration thermonuclear burst that it has displayed. We have analysed a Suzaku (18 ks) observation and an XMM-Newton (39 ks) observation taken 7 years apart. We infer (0.5-10 keV) X-ray luminosities in the range 3-6 x10^35erg s-1, in agreement with previous findings. The spectra are well described by a relatively cool (kTbb = 0.5 keV) black body component plus a Comptonized emission component with {\Gamma} ~1.5-1.7. These values are consistent with the source being in a faint hard state, as confirmed by the ~ 20 per cent fractional root mean square amplitude of the fast variability (0.1 - 7 Hz) inferred from the XMM-Newton data. The electron temperature of the corona is >7 keV for the Suzaku observation, but it is measured to be as low as ~2 keV in the XMM-Newton data at higher flux. The latter is significantly lower than expected for systems in the hard state. We searched for X-ray pulsations and imposed an upper limit to their semi-amplitude of 2 per cent (0.001 - 7 Hz). Finally, we investigated the origin of the low frequency variability emission present in the XMM-Newton data and ruled out an absorption dip origin. This constraint the orbital inclination of the system to 65 degr unless the orbital period is longer than 11 hr (i.e. the length of the XMM-Newton observation).Comment: 7 pages, 4 figures, 1 table. Accepted for publication in MNRA

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

Clinically Significant Drug Interactions Between Psychotropic Agents and Repurposed COVID-19 Therapies

As many patients with underlying psychiatric disorders may be infected with COVID-19, and COVID-19-affected subjects may frequently experience a new onset of psychiatric manifestations, concomitant use of psychotropic medications and COVID-19 therapies is expected to be highly likely and raises concerns of clinically relevant drug interactions. In this setting, four major mechanisms responsible for drug interactions involving psychotropic agents and COVID-19 therapies may be identified: (1) pharmacokinetic drug–drug interactions mainly acting on cytochrome P450; (2) pharmacodynamic drug–drug interactions resulting in additive or synergistic toxicity; (3) drug–disease interactions according to stage and severity of the disease; and (4) pharmacogenetic issues associated with polymorphisms of cytochrome P450 isoenzymes. In this review, we summarise the available literature on relevant drug interactions between psychotropic agents and COVID-19 therapies, providing practical clinical recommendations and potential management strategies according to severity of illness and clinical scenario

A pilot project to limit the human impacts on the fragile antarctic biota: Mitigation of a runway through vegetation transplantation

Background: Antarctica is among the world\u2019s last great wildernesses, but the anthropogenic activities and associated infrastructures threaten its fragile biota. We quantify the impact of the construction of a 2200 m long gravel runway airstrip for airfreight operations of the Italian research station on vegetation ecosystems at Boulder Clay (continental Antarctica). We propose a pilot project to mitigate this impact through the transplantation of vegetation from the runway to safe sites. Methods: A vegetation field survey was performed through phytosociological relev\ue9s and vegetation mapping and data were analyzed through multivariate analysis. Results: We quantify the destructive impact of the runway construction on the flora and vegetation of Boulder Clay. Based on vegetation characteristics, 28 priority areas were transplanted from the runway to safe sites, with 89% of survival. Conclusions: To our knowledge, this is the first time that vegetation transplantation was performed in Antarctica to mitigate the consequences of human actions, as formerly it was used only for scientific experiments. This pilot project provides a tool to support management decisions, involving the quantitative evaluation of the infrastructure impacts and showing the suitability of practical mitigation actions. This pilot project proposes a practical tool exportable to all Antarctica and beyond and suggests to link the permissions\u2019 release for the new infrastructures in Antarctica to the realization of specific conservation and mitigation actions

Coinage metal exciplexes with helium atoms: a theoretical study of M*(2L)Hen (M = Cu, Ag, Au; L = P,D)

The structure and energetics of exciplexes M*(2L)He n (M = Cu, Ag and Au; L = P and D) in their vibrational ground state are studied by employing diffusion Monte Carlo (DMC). Interaction potentials between the excited coinage metals and He atoms are built using the Diatomics-in-Molecule (DIM) approach and ab initio potential curves for the M(2L)-He dimers. Extending our previous work [Cargnoni et al., J. Phys. Chem. A, 2011, 115, 7141], we computed the dimer potential for Au in the 2P and 2D states, as well for Cu and Ag in the 2D state, employing basis set superposition error-corrected Configuration Interaction calculations. We found that the 2\u3a0 potential correlating with the 2P state of Au is substantially less binding than for Ag and Cu, a trend well supported by the M+ ionic radiuses. Conversely, the interaction potentials between a (n - 1)d 9ns2 2D metal and He present a very weak dependency on M itself or the projection of the angular momentum along the dimer axis. This is due to the screening exerted by the ns2 electrons on the hole in the (n - 1)d shell. Including the spin-orbit coupling perturbatively in the DIM energy matrix has a major effect on the lowest potential energy surface of the 2P manifold, the one for Cu allowing the formation of a "belt" of five He atoms while the one for Au being completely repulsive. Conversely, spin-orbit coupling has only a weak effect on the 2D manifold due to the nearly degenerate nature of the diatomic potentials. Structural and energetic results from DMC have been used to support experimental indications for the formation of metastable exciplexes or the opening of non-radiative depopulation channels in bulk and cold gaseous He

Sensation Seeking and Gambling Behavior in Adolescence: Can Externalizing Problems Moderate This Relationship?

Gambling is a widespread phenomenon during adolescence. Among different risk factors involved in the onset of adolescent gambling behaviors, one factor that is studied is the sensation seeking personality trait. However, the literature is heterogeneous and a direct relationship between sensation seeking and gaming behaviors has not always been highlighted. This suggests that the relationship can be influenced by other factors. In particular, we explored the moderating role of externalizing problems in this relationship. A total of 363 adolescents (232 males and 131 females) aged 14 to 20 (M = 16.35, SD = 1.36) completed a battery of questionnaires aimed to assess their gambling behaviors, as well as the levels of externalizing problems and sensation seeking. The results showed that sensation seeking was associated with gambling severity, but this relationship was significant when externalizing problems were high and medium. On the contrary, when externalizing problems were low, the relationship between sensation seeking and gambling severity was not significant. Overall, sensation seeking in adolescence can favor the implementation of risk behaviors, such as gambling, but only in association with the presence of externalizing problems. Limitations, strengths, and social and clinical implications of the present study are discussed

Iron K-alpha echoes from the circumnuclear disk orbiting Sgr A*

Molecular clouds in the Galactic center (GC) reprocess radiation from past outbursts of nearby high-energy sources, generating a bright Fe K-alpha fluorescence at 6.4 keV. The closest clouds to the GC are only $\simeq 1.5$ pc from Sgr A*, forming a torus-like structure known as the circumnuclear disk (CND). The study of fluorescence emission can lead to a characterization of the illuminating source(s), the reflecting clouds, and the global geometry of such a system lying in the GC. The primary purpose of our study is to analyze possible fluorescence signals arising in the CND. This signal would allow us to constrain the CND's physical properties and the source-reflector system's geometry. By exploiting the last $\simeq 20$ years of XMM-Newton observations of the GC, we studied the variability of the Fe K-alpha line in the region around Sgr A*. We identified regions with a flux excess and computed the spectrum therein. We then derived the hydrogen column density of the CND after relating the intensity of the 6.4 keV line to the total energy emitted by known transient sources in the region. Starting from data collected in 2019, we find significant line excesses in a region compatible with the eastern portion of the CND. The echo radiation can be linked to the 2013 outburst of the magnetar SGR J1745-2900. We derive a mean effective hydrogen column density of the CND in the eastern region of $\simeq 10^{23}$ cm$^{-2}$. The scenario depicted is physically plausible, given the luminosity, the position of the illuminating source, and the expected density of the CND.Comment: 15 pages, 18 figures, to be published in Astronomy & Astrophysic

Probing variability patterns of the Fe K line complex in bright nearby AGNs

The unprecedented sensitivity of current X-ray telescopes allows for the first time to address the issue of the Fe K line complex variability patterns in bright, nearby AGNs. We examine XMM-Newton observations of the brightest sources of the FERO sample of radio-quiet type 1 AGNs with the aim of characterizing the temporal behaviour of Fe K complex features. A systematic mapping of residual flux above and below the continuum in the 4-9 keV range is performed in the time vs energy domain, with the purpose of identifying interesting spectral features in the three energy bands: 5.4-6.1 keV, 6.1-6.8 keV and 6.8-7.2 keV, corresponding respectively to the redshifted, rest frame and blueshifted or highly ionized Fe Kalpha line bands. The variability significance is assessed by extracting light curves and comparing them with MonteCarlo simulations. The time-averaged profile of the Fe K complex revealed spectral complexity in several observations. Red- and blue-shifted components (either in emission or absorption) were observed in 30 out of 72 observations, with an average ~90 eV for emission and ~ -30 eV for absorption features. We detected significant line variability (with confidence levels ranging between 90% and 99.7%) within at least one of the above energy bands in 26 out of 72 observations on time scales of ~6-30 ks. Reliability of these features has been carefully calculated using this sample and has been assessed at ~3sigma confidence level. This work increases the currently scanty number of detections of variable, energy shifted, Fe lines and confirms the reliability of the claimed detections. We found that the distribution of detected features is peaked at high variability significances in the red- and blue-shifted energy bands, suggesting an origin in a relativistically modified accretion flow.Comment: Accepted for publication in Astronomy & Astrophysic

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