Antimicrobial resistance, an update from the ward: Increased incidence of new potential pathogens and site of infection-specific antibacterial resistances

In order to monitor the spread of antimicrobial resistance, the European Union requires hospitals to be equipped with infection control centers. With this aim, we analyzed 1583 bacterial strains isolated from samples of different origin from patients with community-onset and nosocomial infections in a public tertiary University Hospital on the outskirts of Turin, Italy. Statistical analyses of the isolates (source, type) and their antimicrobial resistance (AMR) were performed. The survey revealed infections associated with bacterial species considered as not-commensal and not-pathogenic, hence potentially emerging as new threats for human health. Conversely to the general observation of nosocomial strains being more resistant to antibiotics compared to community-acquired strains, nosocomial strains isolated in this study were more resistant only to 1/42 tested antibiotics (tetracycline). By adopting an ecological approach, we observed that blood infections are associated with the broadest range of species compared to infections affecting other areas and we obtained clear indications on the antibiotics that should be preferred in the treatment of infections at specific body sites. Future investigations carried out on a larger geographical scale will clarify whether these indications are limited to the geographical region investigated over this study, or whether the same trends are visible at national or international level

Anomalies in low-energy Gamma-Ray Burst spectra with the Fermi Gamma-Ray Burst Monitor

A Band function has become the standard spectral function used to describe the prompt emission spectra of gamma-ray bursts (GRBs). However, deviations from this function have previously been observed in GRBs detected by BATSE and in individual GRBs from the \textit{Fermi} era. We present a systematic and rigorous search for spectral deviations from a Band function at low energies in a sample of the first two years of high fluence, long bursts detected by the \textit{Fermi} Gamma-Ray Burst Monitor (GBM). The sample contains 45 bursts with a fluence greater than 2$\times10^{-5}$ erg / cm$^{2}$ (10 - 1000 keV). An extrapolated fit method is used to search for low-energy spectral anomalies, whereby a Band function is fit above a variable low-energy threshold and then the best fit function is extrapolated to lower energy data. Deviations are quantified by examining residuals derived from the extrapolated function and the data and their significance is determined via comprehensive simulations which account for the instrument response. This method was employed for both time-integrated burst spectra and time-resolved bins defined by a signal to noise ratio of 25 $\sigma$ and 50 $\sigma$. Significant deviations are evident in 3 bursts (GRB\,081215A, GRB\,090424 and GRB\,090902B) in the time-integrated sample ($\sim$ 7%) and 5 bursts (GRB\,090323, GRB\,090424, GRB\,090820, GRB\,090902B and GRB\,090926A) in the time-resolved sample ($\sim$ 11%).} The advantage of the systematic, blind search analysis is that it can demonstrate the requirement for an additional spectral component without any prior knowledge of the nature of that extra component. Deviations are found in a large fraction of high fluence GRBs; fainter GRBs may not have sufficient statistics for deviations to be found using this method

Synchrotron Cooling in Energetic Gamma-Ray Bursts Observed by the Fermi Gamma-Ray Burst Monitor

We study the time-resolved spectra of eight GRBs observed by Fermi GBM in its first five years of mission, with 1 keV - 1 MeV fluence $f>1.0\times10^{-4}$ erg cm$^{-2}$ and signal-to-noise level $\text{S/N}\geq10.0$ above 900 keV. We aim to constrain in detail the spectral properties of GRB prompt emission on a time-resolved basis and to discuss the theoretical implications of the fitting results in the context of various prompt emission models. We perform time-resolved spectral analysis using a variable temporal binning technique according to optimal S/N criteria, resulting in a total of 299 time-resolved spectra. We fit the Band function to all spectra and obtain the distributions for the low-energy power-law index $\alpha$, the high-energy power-law index $\beta$, the peak energy in the observed $\nu F_\nu$ spectrum $E_\text{p}$, and the difference between the low- and high-energy power-law indices $\Delta s=\alpha-\beta$. Using the distributions of $\Delta s$ and $\beta$, the electron population index $p$ is found to be consistent with the "moderately fast" scenario which fast- and slow-cooling scenarios cannot be distinguished. We also apply a physically motivated synchrotron model, which is a triple power-law with constrained power-law indices and a blackbody component, to test for consistency with a synchrotron origin for the prompt emission and obtain the distributions for the two break energies $E_\text{b,1}$ and $E_\text{b,2}$, the middle segment power-law index $\beta$, and the Planck function temperature $kT$. A synchrotron model is found consistent with the majority of time-resolved spectra for these eight energetic Fermi GBM bursts with good high-energy photon statistics, as long as both the cooling and injection break are included and the leftmost spectral slope is lifted either by inclusion of a thermal component or when an evolving magnetic field is accounted for.Comment: 20 pages, 7 figures, 8 tables, accepted for publication in A&

DO the FERMI GAMMA-RAY BURST MONITOR and SWIFT BURST ALERT TELESCOPE SEE the SAME SHORT GAMMA-RAY BURSTS?

Compact binary system mergers are expected to generate gravitational radiation detectable by ground-based interferometers. A subset of these, the merger of a neutron star with another neutron star or a black hole, are also the most popular model for the production of short gamma-ray bursts (GRBs). The Swift Burst Alert Telescope (BAT) and the Fermi Gamma-ray Burst Monitor (GBM) trigger on short GRBs (SGRBs) at rates that reflect their relative sky exposures, with the BAT detecting 10 per year compared to about 45 for GBM. We examine the SGRB populations detected by Swift BAT and Fermi GBM. We find that the Swift BAT triggers on weaker SGRBs than Fermi GBM, providing they occur close to the center of the BAT field of view, and that the Fermi GBM SGRB detection threshold remains flatter across its field of view. Overall, these effects combine to give the instruments the same average sensitivity, and account for the SGRBs that trigger one instrument but not the other. We do not find any evidence that the BAT and GBM are detecting significantly different populations of SGRBs. Both instruments can detect untriggered SGRBs using ground searches seeded with time and position. The detection of SGRBs below the on-board triggering sensitivities of Swift BAT and Fermi GBM increases the possibility of detecting and localizing the electromagnetic counterparts of gravitational wave (GW) events seen by the new generation of GW detectors

Vesicular glutamate release from feeder-free hiPSC-derived neurons

Human-induced pluripotent stem cells (hiPSCs) represent one of the main and powerful tools for the in vitro modeling of neurological diseases. Standard hiPSC-based protocols make use of animal-derived feeder systems to better support the neuronal differentiation process. Despite their efficiency, such protocols may not be appropriate to dissect neuronal specific properties or to avoid interspecies contaminations, hindering their future translation into clinical and drug discovery approaches. In this work, we focused on the optimization of a reproducible protocol in feeder-free conditions able to generate functional glutamatergic neurons. This protocol is based on a generation of neuroprecursor cells differentiated into human neurons with the administration in the culture medium of specific neurotrophins in a Geltrex-coated substrate. We confirmed the efficiency of this protocol through molecular analysis (upregulation of neuronal markers and neurotransmitter receptors assessed by gene expression profiling and expression of the neuronal markers at the protein level), morphological analysis, and immunfluorescence detection of pre-synaptic and post-synaptic markers at synaptic boutons. The hiPSC-derived neurons acquired Ca2+-dependent glutamate release properties as a hallmark of neuronal maturation. In conclusion, our study describes a new methodological approach to achieve feeder-free neuronal differentiation from hiPSC and adds a new tool for functional characterization of hiPSC-derived neurons

An Observed Correlation Between Thermal and Non-Thermal Emission in Gamma-Ray Bursts

Recent observations by the $Fermi$ Gamma-ray Space Telescope have confirmed the existence of thermal and non-thermal components in the prompt photon spectra of some Gamma-ray bursts (GRBs). Through an analysis of six bright Fermi GRBs, we have discovered a correlation between the observed photospheric and non-thermal $\gamma$-ray emission components of several GRBs using a physical model that has previously been shown to be a good fit to the Fermi data. From the spectral parameters of these fits we find that the characteristic energies, $E_{\rm p}$ and $kT$, of these two components are correlated via the relation $E_{\rm p} \propto T^{\alpha}$ which varies from GRB to GRB. We present an interpretation in which the value of index $\alpha$ indicates whether the jet is dominated by kinetic or magnetic energy. To date, this jet composition parameter has been assumed in the modeling of GRB outflows rather than derived from the data

Heterodimer of A2A and Oxytocin Receptors Regulating Glutamate Release in Adult Striatal Astrocytes

Background: Roles of astrocytes in the modulatory effects of oxytocin (OT) in central nervous system are increasingly considered. Nevertheless, OT effects on gliotransmitter release have been neglected. Methods: In purified astrocyte processes from adult rat striatum, we assessed OT receptor (OTR) and adenosine A2A receptor expression by confocal analysis. The effects of receptors activation on glutamate release from the processes were evaluated; A2A-OTR heteromerization was assessed by co-immunoprecipitation and PLA. Structure of the possible heterodimer of A2A and OT receptors was estimated by a bioinformatic approach. Results: Both A2A and OT receptors were expressed on the same astrocyte processes. Evidence for A2A-OTR receptor-receptor interaction was obtained by measuring the release of glutamate: OT inhibited the evoked glutamate release, while activation of A2A receptors, per se ineffective, abolished the OT effect. Biochemical and bio-physical evidence for A2A-OTR heterodimers on striatal astrocytes was also obtained. The residues in the transmembrane domains 4 and 5 of both receptors are predicted to be mainly involved in the heteromerization. Conclusions: When considering effects of OT in striatum, modulation of glutamate release from the astrocyte processes and of glutamatergic synapse functioning, and the interaction with A2A receptors on the astrocyte processes should be taken into consideration

The 3rd Fermi GBM Gamma-Ray Burst Catalog: The First Six Years

Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two gamma-ray bursts (GRB) every three days. Here we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years, through the middle of July 2014. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux and fluence are derived. The latter two quantities are calculated for the 50-300~keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBM's low-energy NaI(Tl) detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fitted by a two-component model with short-hard and long-soft bursts, than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center (HEASARC).Comment: 225 pages, 13 figures and 8 tables. Accepted for publication in Astrophysical Journal Supplement 201