Design of a nasal spray based on cardiospermum halicacabum extract loaded in phospholipid vesicles enriched with gelatin or chondroitin sulfate

The extract of Cardiospermum halicacabum L. (C. halicacabum) obtained from flower, leaf and vine was loaded into modified phospholipid vesicles aiming at obtaining sprayable, biocompatible and effective nasal spray formulations for the treatment of nasopharyngeal diseases. Penetration enhancer-containing vesicles (PEVs) and hyalurosomes were formulated, and stabilized by adding a commercial gelatin from fish (20 mg/mL) or chondroitin sulfate from catshark cartilages (Scyliorhi-nus canicula, 20 mg/mL). Cryo-TEM images confirmed the formation of spherical vesicles, while photon correlation spectroscopy analysis disclosed the formation of small and negatively-charged vesicles. PEVs were the smaller vesicles (~100 nm) along with gelatin-hyalurosomes (~120 nm), while chondroitin-PEVs and chondroitin-hyalurosomes were larger (~160 nm). Dispersions prepared with chondroitin sulfate were more homogeneous, as the polydispersity index was ~0.15. The in vitro analysis of the droplet size distribution, average velocity module and spray cone angle suggested a good spray-ability and deposition of formulations in the nasal cavity, as the mean diameter of the droplets was in the range recommended by the Food and Drug Administration for nasal targets. The spray plume analysis confirmed the ability of PEVs, gelatin-PEVs, hyalurosomes and gelatin-hyalurosomes to be atomized in fine droplets homogenously distributed in a full cone plume, with an angle ranging from 25 to 30◦ . Moreover, vesicles were highly biocompatible and capable of protecting the epithelial cells against oxidative damage, thus preventing the inflammatory state

Burn mass casualty incidents in Europe: A European response plan within the European Union Civil Protection Mechanism

Background: Burn care is centralized in highly specialized burn centers in Europe. These centers are of limited capacity and may be overwhelmed by a sudden surge in case of a burn mass casualty incident. Prior incidents in Europe and abroad have sustained high standards of care through well-orchestrated responses to share the burden of care in several burn centers. A burn mass casualty incident in Romania in 2015 sparked an initiative to strengthen the existing EU mechanisms. This paper aims to provide insight into developing a response plan for burn mass casualties within the EU Civil Protection Mechanism. Methods: The European Burns Association drafted medical guidelines for burn mass casualty incidents based on a literature review and an in-depth analysis of the Romanian incident. An online questionnaire surveyed European burn centers and EU States for burn mass casualty preparedness. Results: The Romanian burn mass casualty in 2015 highlighted the lack of a burn-specific mechanism, leading to the late onset of international transfers. In Europe, 71% of respondents had existing mass casualty response plans, though only 35% reported having a burn-specific plan. A burns response plan for burn mass casualties was developed and adopted as a Commission staff working document in preparation for further implementation. The plan builds on the existing Union Civil Protection Mechanism framework and the standards of the WHO Emergency Medical Teams initiative to provide 1) burn assessment teams for specialized in-hospital triage of patients, 2) specialized burn care across European burn centers, and 3) medevac capacities from participating states. Conclusion: The European burn mass casualty response plan could enable the delivery of high-level burn care in the face of an overwhelming incident in an affected European country. Further steps for integration and implementation of the plan within the Union Civil Protection Mechanism framework are needed.publishedVersio

MAGIC observations of MWC 656, the only known Be/BH system

Context: MWC 656 has recently been established as the first observationally detected high-mass X-ray binary system containing a Be star and a black hole (BH). The system has been associated with a gamma-ray flaring event detected by the AGILE satellite in July 2010. Aims: Our aim is to evaluate if the MWC 656 gamma-ray emission extends to very high energy (VHE > 100 GeV) gamma rays. Methods. We have observed MWC 656 with the MAGIC telescopes for $\sim$23 hours during two observation periods: between May and June 2012 and June 2013. During the last period, observations were performed contemporaneously with X-ray (XMM-Newton) and optical (STELLA) instruments. Results: We have not detected the MWC 656 binary system at TeV energies with the MAGIC Telescopes in either of the two campaigns carried out. Upper limits (ULs) to the integral flux above 300 GeV have been set, as well as differential ULs at a level of $\sim$5% of the Crab Nebula flux. The results obtained from the MAGIC observations do not support persistent emission of very high energy gamma rays from this system at a level of 2.4% the Crab flux.Comment: Accepted for publication in A&A. 5 pages, 2 figures, 2 table

The major upgrade of the MAGIC telescopes, Part II: A performance study using observations of the Crab Nebula

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent a series of upgrades, involving the exchange of the MAGIC-I camera and its trigger system, as well as the upgrade of the readout system of both telescopes. We use observations of the Crab Nebula taken at low and medium zenith angles to assess the key performance parameters of the MAGIC stereo system. For low zenith angle observations, the standard trigger threshold of the MAGIC telescopes is ~50GeV. The integral sensitivity for point-like sources with Crab Nebula-like spectrum above 220GeV is (0.66+/-0.03)% of Crab Nebula flux in 50 h of observations. The angular resolution, defined as the sigma of a 2-dimensional Gaussian distribution, at those energies is < 0.07 degree, while the energy resolution is 16%. We also re-evaluate the effect of the systematic uncertainty on the data taken with the MAGIC telescopes after the upgrade. We estimate that the systematic uncertainties can be divided in the following components: < 15% in energy scale, 11-18% in flux normalization and +/-0.15 for the energy spectrum power-law slope.Comment: 21 pages, 25 figures, accepted for publication in Astroparticle Physic

Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes

The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between October 2009 and April 2011. Analysis of this data sample using the latest improvements in the MAGIC stereoscopic software provided an unprecedented precision of spectral and night-by-night light curve determination at gamma rays. We derived a differential spectrum with a single instrument from 50 GeV up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC results, combined with Fermi-LAT data, show a flat and broad Inverse Compton peak. The overall fit to the data between 1 GeV and 30 TeV is not well described by a log-parabola function. We find that a modified log-parabola function with an exponent of 2.5 instead of 2 provides a good description of the data ($\chi^2=35/26$). Using systematic uncertainties of red the MAGIC and Fermi-LAT measurements we determine the position of the Inverse Compton peak to be at (53 $\pm$ 3stat + 31syst -13syst) GeV, which is the most precise estimation up to date and is dominated by the systematic effects. There is no hint of the integral flux variability on daily scales at energies above 300 GeV when systematic uncertainties are included in the flux measurement. We consider three state- of-the-art theoretical models to describe the overall spectral energy distribution of the Crab Nebula. The constant B-field model cannot satisfactorily reproduce the VHE spectral measurements presented in this work, having particular difficulty reproducing the broadness of the observed IC peak. Most probably this implies that the assumption of the homogeneity of the magnetic field inside the nebula is incorrect. On the other hand, the time-dependent 1D spectral model provides a good fit of the new VHE results when considering a 80 {\mu}G magnetic field. However, it fails to match the data when including the morphology of the nebula at lower wavelengths.Comment: accepted by JHEAp, 9 pages, 6 figure

MAGIC detection of short-term variability of the high-peaked BL Lac object 1ES 0806+524

The high-frequency-peaked BL Lac (HBL) 1ES 0806+524 (z = 0.138) was discovered in VHE $\gamma$ rays in 2008. Until now, the broad-band spectrum of 1ES 0806+524 has been only poorly characterized, in particular at high energies. We analysed multiwavelength observations from $\gamma$ rays to radio performed from 2011 January to March, which were triggered by the high activity detected at optical frequencies. These observations constitute the most precise determination of the broad-band emission of 1ES 0806+524 to date. The stereoscopic MAGIC observations yielded a $\gamma$-ray signal above 250 GeV of $(3.7 \pm 0.7)$ per cent of the Crab Nebula flux with a statistical significance of 9.9 $\sigma$. The multiwavelength observations showed significant variability in essentially all energy bands, including a VHE $\gamma$-ray flare that lasted less than one night, which provided unprecedented evidence for short-term variability in 1ES 0806+524. The spectrum of this flare is well described by a power law with a photon index of $2.97 \pm 0.29$ between $\sim$150 GeV and 1 TeV and an integral flux of $(9.3 \pm 1.9)$ per cent of the Crab Nebula flux above 250 GeV. The spectrum during the non-flaring VHE activity is compatible with the only available VHE observation performed in 2008 with VERITAS when the source was in a low optical state. The broad-band spectral energy distribution can be described with a one-zone Synchrotron Self Compton model with parameters typical for HBLs, indicating that 1ES 0806+524 is not substantially different from the HBLs previously detected.Comment: 12 pages, 8 figures, 3 tables, accepted 2015 April 20 for publication in Monthly Notices of the Royal Astronomical Society Main Journa

Detection of bridge emission above 50 GeV from the Crab pulsar with the MAGIC telescopes

The Crab pulsar is the only astronomical pulsed source detected at very high energy (VHE, E>100GeV) gamma-rays. The emission mechanism of VHE pulsation is not yet fully understood, although several theoretical models have been proposed. In order to test the new models, we measured the light curve and the spectra of the Crab pulsar with high precision by means of deep observations. We analyzed 135 hours of selected MAGIC data taken between 2009 and 2013 in stereoscopic mode. In order to discuss the spectral shape in connection with lower energies, 4.6 years of {\it Fermi}-LAT data were also analyzed. The known two pulses per period were detected with a significance of $8.0 \sigma$ and $12.6 \sigma$. In addition, significant emission was found between the two pulses with $6.2 \sigma$. We discovered the bridge emission above 50 GeV between the two main pulses. This emission can not be explained with the existing theories. These data can be used for testing new theoretical models.Comment: 5 pages, 4 figure

Probing the very-high-energy gamma-ray spectral curvature in the blazar PG 1553+113 with the MAGIC telescopes

PG 1553+113 is a very-high-energy (VHE, $E>100\,\mathrm{GeV}$) $\gamma$-ray emitter classified as a BL Lac object. Its redshift is constrained by intergalactic absorption lines in the range $0.4<z<0.58$. The MAGIC telescopes have monitored the source's activity since 2005. In early 2012, PG 1553+113 was found in a high-state, and later, in April of the same year, the source reached its highest VHE flux state detected so far. Simultaneous observations carried out in X-rays during 2012 April show similar flaring behaviour. In contrast, the $\gamma$-ray flux at $E<100\,\mathrm{GeV}$ observed by Fermi-LAT is compatible with steady emission. In this paper, a detailed study of the flaring state is presented. The VHE spectrum shows clear curvature, being well fitted either by a power law with an exponential cut-off or by a log-parabola. A simple power-law fit hypothesis for the observed shape of the PG 1553+113 VHE $\gamma$-ray spectrum is rejected with a high significance (fit probability P=2.6 $\times 10^{-6}$). The observed curvature is compatible with the extragalactic background light (EBL) imprint predicted by current generation EBL models assuming a redshift $z\sim0.4$. New constraints on the redshift are derived from the VHE spectrum. These constraints are compatible with previous limits and suggest that the source is most likely located around the optical lower limit, $z=0.4$, based on the detection of Ly$\alpha$ absorption. Finally, we find that the synchrotron self-Compton (SSC) model gives a satisfactory description of the observed multi-wavelength spectral energy distribution during the flare.Comment: 13 pages, 7 figures, accepted for publication in MNRA

First broadband characterization and redshift determination of the VHE blazar MAGIC J2001+439

We aim to characterize the broadband emission from 2FGL J2001.1+4352, which has been associated with the unknown-redshift blazar MG4 J200112+4352. Based on its gamma-ray spectral properties, it was identified as a potential very high energy (VHE; E > 100 GeV) gamma-ray emitter. The source was observed with MAGIC first in 2009 and later in 2010 within a multi-instrument observation campaign. The MAGIC observations yielded 14.8 hours of good quality stereoscopic data. The object was monitored at radio, optical and gamma-ray energies during the years 2010 and 2011. The source, named MAGIC J2001+439, is detected for the first time at VHE with MAGIC at a statistical significance of 6.3 {\sigma} (E > 70 GeV) during a 1.3-hour long observation on 2010 July 16. The multi-instrument observations show variability in all energy bands with the highest amplitude of variability in the X-ray and VHE bands. We also organized deep imaging optical observations with the Nordic Optical Telescope in 2013 to determine the source redshift. We determine for the first time the redshift of this BL Lac object through the measurement of its host galaxy during low blazar activity. Using the observational evidence that the luminosities of BL Lac host galaxies are confined to a relatively narrow range, we obtain z = 0.18 +/- 0.04. Additionally, we use the Fermi-LAT and MAGIC gamma-ray spectra to provide an independent redshift estimation, z = 0.17 +/- 0.10. Using the former (more accurate) redshift value, we adequately describe the broadband emission with a one-zone SSC model for different activity states and interpret the few-day timescale variability as produced by changes in the high-energy component of the electron energy distribution.Comment: 17 pages, 15 figures, Accepted for publication in A&

The 2009 multiwavelength campaign on Mrk 421: Variability and correlation studies

We performed a 4.5-month multi-instrument campaign (from radio to VHE gamma rays) on Mrk421 between January 2009 and June 2009, which included VLBA, F-GAMMA, GASP-WEBT, Swift, RXTE, Fermi-LAT, MAGIC, and Whipple, among other instruments and collaborations. Mrk421 was found in its typical (non-flaring) activity state, with a VHE flux of about half that of the Crab Nebula, yet the light curves show significant variability at all wavelengths, the highest variability being in the X-rays. We determined the power spectral densities (PSD) at most wavelengths and found that all PSDs can be described by power-laws without a break, and with indices consistent with pink/red-noise behavior. We observed a harder-when-brighter behavior in the X-ray spectra and measured a positive correlation between VHE and X-ray fluxes with zero time lag. Such characteristics have been reported many times during flaring activity, but here they are reported for the first time in the non-flaring state. We also observed an overall anti-correlation between optical/UV and X-rays extending over the duration of the campaign. The harder-when-brighter behavior in the X-ray spectra and the measured positive X-ray/VHE correlation during the 2009 multi-wavelength campaign suggests that the physical processes dominating the emission during non-flaring states have similarities with those occurring during flaring activity. In particular, this observation supports leptonic scenarios as being responsible for the emission of Mrk421 during non-flaring activity. Such a temporally extended X-ray/VHE correlation is not driven by any single flaring event, and hence is difficult to explain within the standard hadronic scenarios. The highest variability is observed in the X-ray band, which, within the one-zone synchrotron self-Compton scenario, indicates that the electron energy distribution is most variable at the highest energies.Comment: Accepted for publication in A&A, 18 pages, 14 figures (v2 has a small modification in the acknowledgments, and also corrects a typo in the field "author" in the metadata