A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa.

The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo. Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to 3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2, MIP-1β/CCL4, IL-6, TNF-α, IL-1Ra, and IL-10 occurred on day 1. A signature explaining 68% of cytokine/chemokine vaccine-response variability was identified. Its score was higher in HD versus LD vaccinees and was associated positively with vaccine viremia and negatively with cytopenia. It was higher in vaccinees with injection-site pain, fever, myalgia, chills, and headache; higher scores reflected increasing severity. In contrast, HD vaccinees who subsequently developed arthritis had lower day 1 scores than other HD vaccinees. Vaccine dose did not influence the signature despite its influence on specific outcomes. The Geneva-derived signature associated strongly (ρ = 0.97) with that of a cohort of 75 vaccinees from a parallel trial in Lambaréné, Gabon. Its score in Geneva HD vaccinees with subsequent arthritis was significantly lower than that in Lambaréné HD vaccinees, none of whom experienced arthritis. This signature, which reveals monocytes' critical role in rVSV-ZEBOV immunogenicity and safety across doses and continents, should prove useful in assessments of other vaccines

An optically stimulated superconducting-like phase in K3C60 far above equilibrium Tc

The control of non-equilibrium phenomena in complex solids is an important research frontier, encompassing new effects like light induced superconductivity. Here, we show that coherent optical excitation of molecular vibrations in the organic conductor K3C60 can induce a non-equilibrium state with the optical properties of a superconductor. A transient gap in the real part of the optical conductivity and a low-frequency divergence of the imaginary part are measured for base temperatures far above equilibrium Tc=20 K. These findings underscore the role of coherent light fields in inducing emergent order.Comment: 40 pages, 23 figure

The White Dwarf Luminosity Functions from the Pan-STARRS 1 3π Steradian Survey

A large sample of white dwarfs is selected by both proper motion and colours from the Pan-STARRS 1 3{\pi} Steradian Survey Processing Version 2 to construct the White Dwarf Luminosity Functions of the discs and halo in the solar neighbourhood. Four-parameter astrometric solutions were recomputed from the epoch data. The generalised maximum volume method is then used to calculate the density of the populations. After removal of crowded areas near the Galactic plane and centre, the final sky area used by this work is 7.833 sr, which is 83% of the 3{\pi} sky and 62% of the whole sky. By dividing the sky using Voronoi tessellation, photometric and astrometric uncertainties are recomputed at each step of the integration to improve the accuracy of the maximum volume. Interstellar reddening is considered throughout the work. We find a disc-to-halo white dwarf ratio of about 100

The inevitable youthfulness of known high-redshift radio galaxies

Radio galaxies can be seen out to very high redshifts, where in principle they can serve as probes of the early evolution of the Universe. Here we show that for any model of radio-galaxy evolution in which the luminosity decreases with time after an initial rapid increase (that is, essentially all reasonable models), all observable high-redshift radio-galaxies must be seen when the lobes are less than 10^7 years old. This means that high-redshift radio galaxies can be used as a high-time-resolution probe of evolution in the early Universe. Moreover, this result helps to explain many observed trends of radio-galaxy properties with redshift [(i) the `alignment effect' of optical emission along radio-jet axes, (ii) the increased distortion in radio structure, (iii) the decrease in physical sizes, (iv) the increase in radio depolarisation, and (v) the increase in dust emission] without needing to invoke explanations based on cosmology or strong evolution of the surrounding intergalactic medium with cosmic time, thereby avoiding conflict with current theories of structure formation.Comment: To appear in Nature. 4 pages, 2 colour figures available on request. Also available at http://www-astro.physics.ox.ac.uk/~km

A 5 item version of the Compliance Questionnaire for Rheumatology (CQR5) successfully identifies low adherence to DMARDs

© 2013 Hughes et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedTaking DMARDs as prescribed is an essential part of self-management for patients with Rheumatoid Arthritis. To date, the Compliance Questionnaire for Rheumatology (CQR) is the only self-report adherence measure created specifically for and validated in rheumatic diseases. However, the factor structure of the CQR has not been reported and it can be considered lengthy at 19 items. The aim of this study was to test the factor structure of the CQR and reduce the number of items whilst retaining robust explanation of non-adherence to DMARDs. Such a reduction would increase the clinical utility of the scale, to identify patients with sub-optimal adherence to DMARDs in the clinic as well as for research purposes.Peer reviewe

Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella henselae

Bartonella henselae, the agent of cat scratch disease and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis, contains to date two groups of described pathogenicity factors: adhesins and type IV secretion systems. Bartonella adhesin A (BadA), the Trw system and possibly filamentous hemagglutinin act as promiscous or specific adhesins, whereas the virulence locus (Vir)B/VirD4 type IV secretion system modulates a variety of host cell functions. BadA mediates bacterial adherence to endothelial cells and extracellular matrix proteins and triggers the induction of angiogenic gene programming. The VirB/VirD4 type IV secretion system is responsible for, e.g., inhibition of host cell apoptosis, bacterial persistence in erythrocytes, and endothelial sprouting. The Trw-conjugation system of Bartonella spp. mediates host-specific adherence to erythrocytes. Filamentous hemagglutinins represent additional potential pathogenicity factors which are not yet characterized. The exact molecular functions of these pathogenicity factors and their contribution to an orchestral interplay need to be analyzed to understand B. henselae pathogenicity in detail

Weak-Field Gravity of Revolving Circular Cosmic Strings

A weak-field solution of Einstein's equations is constructed. It is generated by a circular cosmic string revolving in its plane about the centre of the circle. (The revolution is introduced to prevent the string from collapsing.) This solution exhibits a conical singularity, and the corresponding deficit angle is the same as for a straight string of the same linear energy density, irrespective of the angular velocity of the string.Comment: 13 pages, LaTe

A Model for Emission from Jets in X-ray Binaries: Consequences of a Single Acceleration Episode

There are strong evidence for powerful jets in the low/hard state of black-hole X-ray binaries (BHXRBs). Here, we present a model in which electrons are accelerated once at the base of the jet, and are cooled by synchrotron emission and possible adiabatic energy losses. The accelerated electrons assume a Maxwellian distribution at low energies and possible energetic power law tail. These assumptions yield to a wealth of spectra, which we study in details. We identify critical values of the magnetic field, and five transition frequencies in the spectra. In particular, we show that: (I) the decay of the magnetic field along the jet enables, for wide jets, production of flat radio spectra without the need for electrons re-acceleration along the jet. (II) An increase of the magnetic field above a critical value of ~10^5 G leads to a sharp decrease in the flux at the radio band, while the flux at higher frequencies saturates to a constant value. (III) For strong magnetic field, the flux decays in the optical/UV band as F_nu ~ nu^{-1/2}, irrespective of the electrons initial distribution. (IV) For B_0 ~ 10^4 G, the X-ray flux gradually steepens. (V) With adiabatic energy losses, flat spectrum can be obtained only at a limited frequency range, and under certain conditions (VI) For narrow jets, r(x) ~ x^{alpha} with alpha < 1/2, flat radio spectrum cannot be obtained. We provide full description of the spectrum in the different scenarios, and show that our model is consistent with the key observed properties of BHXRBs.Comment: Slightly shortened; references added; accepted for publication in Ap

The VIMOS VLT Deep Survey: Evolution of the non-linear galaxy bias up to z=1.5

We present the first measurements of the Probability Distribution Function (PDF) of galaxy fluctuations in the VIMOS-VLT Deep Survey (VVDS) cone, covering 0.4x0.4 deg between 0.4<z<1.5. The second moment of the PDF, i.e. the rms fluctuations of the galaxy density field, is with good approximation constant over the full redshift baseline investigated: we find that, in redshift space, sigma_8 for galaxies brighter than M=-20+5log h has a mean value of 0.94\pm0.07 in the redshift interval 0.7<z<1.5. The third moment, i.e. the skewness, increases with cosmic time: we find that the probability of having underdense regions is greater at z~0.7 than it was at z~1.5. By comparing the PDF of galaxy density contrasts with the theoretically predicted PDF of mass fluctuations we infer the redshift-, density-, and scale-dependence of the biasing function b(z, \delta, R) between galaxy and matter overdensities up to redshift z=1.5. Our results can be summarized as follows: i) the galaxy bias is an increasing function of redshift: evolution is marginal up to z~0.8 and more pronounced for z>0.8; ii) the formation of bright galaxies is inhibited below a characteristic mass-overdensity threshold whose amplitude increases with redshift and luminosity; iii) the biasing function is non linear in all the redshift bins investigated with non-linear effects of the order of a few to 10% on scales >5Mpc.Comment: 30 pages, 17 figs, Accepted by A&

Batrachochytrium dendrobatidis Shows High Genetic Diversity and Ecological Niche Specificity among Haplotypes in the Maya Mountains of Belize

The amphibian pathogen Batrachochytrium dendrobatidis (Bd) has been implicated in amphibian declines around the globe. Although it has been found in most countries in Central America, its presence has never been assessed in Belize. We set out to determine the range, prevalence, and diversity of Bd using quantitative PCR (qPCR) and sequencing of a portion of the 5.8 s and ITS1-2 regions. Swabs were collected from 524 amphibians of at least 26 species in the protected areas of the Maya Mountains of Belize. We sequenced a subset of 72 samples that had tested positive for Bd by qPCR at least once; 30 samples were verified as Bd. Eight unique Bd haplotypes were identified in the Maya Mountains, five of which were previously undescribed. We identified unique ecological niches for the two most broadly distributed haplotypes. Combined with data showing differing virulence shown in different strains in other studies, the 5.8 s - ITS1-2 region diversity found in this study suggests that there may be substantial differences among populations or haplotypes. Future work should focus on whether specific haplotypes for other genomic regions and possibly pathogenicity can be associated with haplotypes at this locus, as well as the integration of molecular tools with other ecological tools to elucidate the ecology and pathogenicity of Bd