Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial

<div><p>Background</p><p>Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts.</p><p>Methods</p><p>The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637.</p><p>Results</p><p>Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment.</p><p>Conclusions</p><p>The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01144637" target="_blank">NCT01144637</a></p></div

Gravitational Lensing Signature of Long Cosmic Strings

The gravitational lensing by long, wiggly cosmic strings is shown to produce a large number of lensed images of a background source. In addition to pairs of images on either side of the string, a number of small images outline the string due to small-scale structure on the string. This image pattern could provide a highly distinctive signature of cosmic strings. Since the optical depth for multiple imaging of distant quasar sources by long strings may be comparable to that by galaxies, these image patterns should be clearly observable in the next generation of redshift surveys such as the Sloan Digital Sky Survey.Comment: 4 pages, revtex with 3 postscript figures include

Millimeter and sub-millimeter atmospheric performance at Dome C combining radiosoundings and ATM synthetic spectra

The reliability of astronomical observations at millimeter and sub-millimeter wavelengths closely depends on a low vertical content of water vapor as well as on high atmospheric emission stability. Although Concordia station at Dome C (Antarctica) enjoys good observing conditions in this atmospheric spectral windows, as shown by preliminary site-testing campaigns at different bands and in, not always, time overlapped periods, a dedicated instrument able to continuously determine atmospheric performance for a wide spectral range is not yet planned. In the absence of such measurements, in this paper we suggest a semi-empirical approach to perform an analysis of atmospheric transmission and emission at Dome C to compare the performance for 7 photometric bands ranging from 100 GHz to 2 THz. Radiosoundings data provided by the Routine Meteorological Observations (RMO) Research Project at Concordia station are corrected by temperature and humidity errors and dry biases and then employed to feed ATM (Atmospheric Transmission at Microwaves) code to generate synthetic spectra in the wide spectral range from 100 GHz to 2 THz. To quantify the atmospheric contribution in millimeter and sub-millimeter observations we are considering several photometric bands in which atmospheric quantities are integrated. The observational capabilities of this site at all the selected spectral bands are analyzed considering monthly averaged transmissions joined to the corresponding fluctuations. Transmission and pwv statistics at Dome C derived by our semi-empirical approach are consistent with previous works. It is evident the decreasing of the performance at high frequencies. We propose to introduce a new parameter to compare the quality of a site at different spectral bands, in terms of high transmission and emission stability, the Site Photometric Quality Factor.Comment: accepted to MNRAS with minor revision

The statistics of wide-separation lensed quasars

The absence of any wide-separation gravitational lenses in the Large Bright Quasar Survey is used to place limits on the population of cluster-sized halos in the universe, and hence constrain a number of cosmological parameters. The results agree with previous investigations in strongly ruling out the standard cold dark matter model but they are consistent with low-density universes in which the primordial fluctuation spectrum matches both cluster abundances and cosmic microwave background measurements. These conclusions are essentially independent of the cosmological constant, which is in stark contrast to the statistics of galaxy lenses. The constraints presented here are nullified if clusters have core radii of more than 10 kpc, but are free of a number of potential systematic errors, due to the homogeneity of the data.Comment: MNRAS, in press; 7 pages, 8 figure

A reflection origin for the soft and hard X-ray excess of Ark 120

Over the last few years several models have been proposed to interpret the widespread soft excess observed in the X-ray spectra of type 1 active galactic nuclei (AGN). In particular, reflection from the photoionized accretion disc blurred by relativistic effects has proven to be successful in reproducing both the spectral shape and the variability pattern of many sources. As a further test to this scenario we present the analysis of a recent ~100 ks long Suzaku observation of Arakelian 120, a prototypical 'bare' Seyfert 1 galaxy in which no complex absorption system is expected to mimic a soft excess or mask the intrinsic properties of this key component. We show that a reflection model allowing for both warm/blurred and cold/distant reprocessing provides a self-consistent and convincing interpretation of the broadband X-ray emission of Ark 120, also characterized by a structured iron feature and a high-energy hump. Although warm absorbers, winds/outflows and multiple Comptonizing regions may play significant roles in sources with more spectral complexity, this case study adds evidence to the presence of blurred disc reflection as a basic component of the X-ray spectra of type 1 AGN.Comment: 11 pages, 6 figures, accepted for publication in MNRA

Isotropic Luminosity Indicators in a Complete AGN Sample

The [O IV] 25.89 micron line has been shown to be an accurate indicator of active galactic nucleus (AGN) intrinsic luminosity in that it correlates well with hard (10-200 keV) X-ray emission. We present measurements of [O IV] for 89 Seyfert galaxies from the unbiased Revised Shapley-Ames (RSA) sample. The [O IV] luminosity distributions of obscured and unobscured Seyferts are indistinguishable, indicating that their intrinsic AGN luminosities are quite similar and that the RSA sample is well suited for tests of the unified model. In addition, we analyze several commonly used proxies for AGN luminosity, including [O III] 5007 A, 6 cm radio, and 2-10 keV X-ray emission. We find that the radio luminosity distributions of obscured and unobscured AGNs show no significant difference, indicating that radio luminosity is a useful isotropic luminosity indicator. However, the observed [O III] and 2-10 keV luminosities are systematically smaller for obscured Seyferts, indicating that they are not emitted isotropically.Comment: Updated to match version published in ApJ. 9 pages, 4 figure

The Spectral Energy Distribution and Emission-Line properties of the NLS1 Galaxy Arakelian 564

We present the intrinsic spectral energy distribution (SED) of the NLS1 Arakelian 564, constructed with contemporaneous data obtained during a multi-wavelength, multi-satellite observing campaign in 2000 and 2001. We compare it with that of the NLS1 Ton S180 and with those obtained for BLS1s to infer how the relative accretion rates vary among the Sy1 population. Although the peak of the SED is not well constrained, most of the energy is emitted in the 10-100 eV regime, constituting roughly half of the emitted energy in the optical/X-ray ranges. This is consistent with a primary spectral component peaking in the extreme UV/soft X-ray band, and disk-corona models, hence high accretion rates. Indeed, we estimate that \dot{m}~1. We examine the emission lines in its spectrum, and we constrain the physical properties of the line-emitting gas through photoionization modeling. The line-emitting gas is characterized by log n~11 and log U~0, and is stratified around log U~0. Our estimate of the radius of the H\beta-emitting region ~10 \pm 2 lt-days is consistent with the radius-luminosity relationships found for Sy1 galaxies. We also find evidence for super-solar metallicity in this NLS1. We show that the emission lines are not good diagnostics for the underlying SEDs and that the absorption line studies offer a far more powerful tool to determine the ionizing continuum of AGNs, especially if comparing the lower- and higher-ionization lines.Comment: 15 pages, 10 figures; accepted for publication in The Astrophysical Journal, LaTeX emulateapj.st

Optical Identification of the ASCA Large Sky Survey

We present results of optical identification of the X-ray sources detected in the ASCA Large Sky Survey. Optical spectroscopic observations were done for 34 X-ray sources which were detected with the SIS in the 2-7 keV band above 3.5 sigma. The sources are identified with 30 AGNs, 2 clusters of galaxies, and 1 galactic star. Only 1 source is still unidentified. The flux limit of the sample corresponds to 1 x 10^{-13} erg s^{-1} cm^{-2} in the 2-10 keV band. Based on the sample, the paper discusses optical and X-ray spectral properties of the AGNs, contribution of the sources to the Cosmic X-ray Background, and redshift and luminosity distributions of the AGNs. An interesting result is that the redshift distribution of the AGNs suggests a deficiency of high-redshift (0.5 10^{44} erg s^{-1}) absorbed narrow-line AGNs (so called type 2 QSOs).Comment: Accepted for publication in ApJ. 57 pages with 13 figures, 9 JPG plates, 5 additional PS tables. Original EPS plates (gzipped format ~1Mbyte/plate) and TeX tables are available from ftp://ftp.kusastro.kyoto-u.ac.jp/pub/akiyama/0001289

Hard X-ray Variability of AGN

Aims: Active Galactic Nuclei are known to be variable throughout the electromagnetic spectrum. An energy domain poorly studied in this respect is the hard X-ray range above 20 keV. Methods: The first 9 months of the Swift/BAT all-sky survey are used to study the 14 - 195 keV variability of the 44 brightest AGN. The sources have been selected due to their detection significance of >10 sigma. We tested the variability using a maximum likelihood estimator and by analysing the structure function. Results: Probing different time scales, it appears that the absorbed AGN are more variable than the unabsorbed ones. The same applies for the comparison of Seyfert 2 and Seyfert 1 objects. As expected the blazars show stronger variability. 15% of the non-blazar AGN show variability of >20% compared to the average flux on time scales of 20 days, and 30% show at least 10% flux variation. All the non-blazar AGN which show strong variability are low-luminosity objects with L(14-195 keV) < 1E44 erg/sec. Conclusions: Concerning the variability pattern, there is a tendency of unabsorbed or type 1 galaxies being less variable than the absorbed or type 2 objects at hardest X-rays. A more solid anti-correlation is found between variability and luminosity, which has been previously observed in soft X-rays, in the UV, and in the optical domain.Comment: 9 pages, 7 figures, accepted for publication in A&