Institute of Physics Rosario

BACKGROUND: The anti-interleukin (IL) 6 receptor antibody tocilizumab inhibits signalling of IL6, a key cytokine in rheumatoid arthritis (RA) pathogenesis. OBJECTIVE: To evaluate through the AMBITION study the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA for whom previous treatment with methotrexate/biological agents had not failed. METHODS: This 24-week, double-blind, double-dummy, parallel-group study, randomised 673 patients to either tocilizumab 8 mg/kg every 4 weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20 mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab 8 mg/kg. The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 24. RESULTS: The intention-to-treat analysis demonstrated that tocilizumab was better than methotrexate treatment with a higher ACR20 response (69.9 vs 52.5%; p<0.001), and 28-joint Disease Activity Score (DAS28) <2.6 rate (33.6 vs 12.1%) at week 24. Mean high-sensitivity C-reactive protein was within the normal range from week 12 with tocilizumab, whereas levels remained elevated with methotrexate. The incidence of serious adverse events with tocilizumab was 3.8% versus 2.8% with methotrexate (p = 0.50), and of serious infections, 1.4% versus 0.7%, respectively. There was a higher incidence of reversible grade 3 neutropenia (3.1% vs 0.4%) and increased total cholesterol > or =240 mg/dl (13.2% vs 0.4%), and a lower incidence of alanine aminotransferase elevations >3x-<5x upper limit of normal (1.0% vs 2.5%), respectively. CONCLUSION: Tocilizumab monotherapy is better than methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favourable benefit-risk, in patients for whom treatment with methotrexate or biological agents has not previously failed.

High-energy particles are extragalactic Cosmic rays are high-energy particles arriving from space; some have energies far beyond those that human-made particle accelerators can achieve. The sources of higher-energy cosmic rays remain under debate, although we know that lower-energy cosmic rays come from the solar wind. The Pierre Auger Collaboration reports the observation of thousands of cosmic rays with ultrahigh energies of several exa–electron volts (about a Joule per particle), arriving in a slightly dipolar distribution (see the Perspective by Gallagher and Halzen). The direction of the rays indicates that the particles originated in other galaxies and not from nearby sources within our own Milky Way Galaxy. Science , this issue p. 1266 ; see also p. 1240

Ni-CeO2 is a highly efficient, stable and non-expensive catalyst for methane dry reforming at relative low temperatures (700 K). The active phase of the catalyst consists of small nanoparticles of nickel dispersed on partially reduced ceria. Experiments of ambient pressure XPS indicate that methane dissociates on Ni/CeO2 at temperatures as low as 300 K, generating CHx and COx species on the surface of the catalyst. Strong metal-support interactions activate Ni for the dissociation of methane. The results of density-functional calculations show a drop in the effective barrier for methane activation from 0.9 eV on Ni(111) to only 0.15 eV on Ni/CeO2-x (111). At 700 K, under methane dry reforming conditions, no signals for adsorbed CHx or C species are detected in the C 1s XPS region. The reforming of methane proceeds in a clean and efficient way.

We report a study of the distributions of the depth of maximum, ${X}_{\mathrm{max}}$, of extensive air-shower profiles with energies above $1{0}^{17.8}\text{ }\text{ }\mathrm{eV}$ as observed with the fluorescence telescopes of the Pierre Auger Observatory. The analysis method for selecting a data sample with minimal sampling bias is described in detail as well as the experimental cross-checks and systematic uncertainties. Furthermore, we discuss the detector acceptance and the resolution of the ${X}_{\mathrm{max}}$ measurement and provide parametrizations thereof as a function of energy. The energy dependence of the mean and standard deviation of the ${X}_{\mathrm{max}}$ distributions are compared to air-shower simulations for different nuclear primaries and interpreted in terms of the mean and variance of the logarithmic mass distribution at the top of the atmosphere.

Methods for accurately computing the interaction of molecules with metal surfaces are critical to understanding and thereby improving heterogeneous catalysis. We introduce an implementation of the specific reaction parameter (SRP) approach to density functional theory (DFT) that carries the method forward from a semiquantitative to a quantitative description of the molecule-surface interaction. Dynamics calculations on reactive scattering of hydrogen from the copper (111) surface using an SRP-DFT potential energy surface reproduce data on the dissociative adsorption probability as a function of incidence energy and reactant state and data on rotationally inelastic scattering with chemical accuracy (within approximately 4.2 kilojoules per mole).

We present a combined fit of a simple astrophysical model of UHECR sources to both the energy spectrum and mass composition data measured by the Pierre Auger Observatory. The fit has been performed for energies above 5 10 18 eV, i.e. the region of the all-particle spectrum above the so-called "ankle" feature. The astrophysical model we adopted consists of identical sources uniformly distributed in a comoving volume, where nuclei are accelerated through a rigidity-dependent mechanism. The fit results suggest sources characterized by relatively low maximum injection energies, hard spectra and heavy chemical composition. We also show that uncertainties about physical quantities relevant to UHECR propagation and shower development have a non-negligible impact on the fit results.

Using the data taken at the Pierre Auger Observatory between December 2004 and December 2012, we have examined the implications of the distributions of depths of atmospheric shower maximum (${X}_{\mathrm{max}}$), using a hybrid technique, for composition and hadronic interaction models. We do this by fitting the distributions with predictions from a variety of hadronic interaction models for variations in the composition of the primary cosmic rays and examining the quality of the fit. Regardless of what interaction model is assumed, we find that our data are not well described by a mix of protons and iron nuclei over most of the energy range. Acceptable fits can be obtained when intermediate masses are included, and when this is done consistent results for the proton and iron-nuclei contributions can be found using the available models. We observe a strong energy dependence of the resulting proton fractions, and find no support from any of the models for a significant contribution from iron nuclei. However, we also observe a significant disagreement between the models with respect to the relative contributions of the intermediate components.

OBJECTIVE: To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). METHODS: This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. RESULTS: In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: -0.21; 95% CI -0.35 to -0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). CONCLUSIONS: Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. TRIAL REGISTRATION NUMBER: NCT00988221.

We quantitatively evaluate the contribution of electron-hole pair excitations to the reactive dynamics of H2 on Cu(110) and N2 on W(110), including the six dimensionality of the process in the entire calculation. The interaction energy between molecule and surface is represented by an ab initio six-dimensional potential energy surface. Electron friction coefficients are calculated with density functional theory in a local density approximation. Contrary to previous claims, only minor differences between the adiabatic and nonadiabatic results for dissociative adsorption are found. Our calculations demonstrate the validity of the adiabatic approximation to analyze adsorption dynamics in these two representative systems.

Abstract A new analysis of the data set from the Pierre Auger Observatory provides evidence for anisotropy in the arrival directions of ultra-high-energy cosmic rays on an intermediate angular scale, which is indicative of excess arrivals from strong, nearby sources. The data consist of 5514 events above with zenith angles up to 80° recorded before 2017 April 30. Sky models have been created for two distinct populations of extragalactic gamma-ray emitters: active galactic nuclei from the second catalog of hard Fermi -LAT sources (2FHL) and starburst galaxies from a sample that was examined with Fermi -LAT. Flux-limited samples, which include all types of galaxies from the Swift -BAT and 2MASS surveys, have been investigated for comparison. The sky model of cosmic-ray density constructed using each catalog has two free parameters, the fraction of events correlating with astrophysical objects, and an angular scale characterizing the clustering of cosmic rays around extragalactic sources. A maximum-likelihood ratio test is used to evaluate the best values of these parameters and to quantify the strength of each model by contrast with isotropy. It is found that the starburst model fits the data better than the hypothesis of isotropy with a statistical significance of 4.0 σ , the highest value of the test statistic being for energies above . The three alternative models are favored against isotropy with 2.7 σ –3.2 σ significance. The origin of the indicated deviation from isotropy is examined and prospects for more sensitive future studies are discussed.

We report a measurement of the proton-air cross section for particle production at the center-of-mass energy per nucleon of 57 TeV. This is derived from the distribution of the depths of shower maxima observed with the Pierre Auger Observatory: systematic uncertainties are studied in detail. Analyzing the tail of the distribution of the shower maxima, a proton-air cross section of $[505\ifmmode\pm\else\textpm\fi{}22(\mathrm{stat}{)}_{\ensuremath{-}36}^{+28}(\mathrm{syst})]\text{ }\text{ }\mathrm{mb}$ is found.

The Pierre Auger collaboration reports new results bearing on the composition of cosmic rays. The muon number of air showers, created by cosmic rays and measured by the collaboration, is intriguingly at odds with all theoretical models, posing a challenge to our current understanding of the mass composition of cosmic rays.

Cross sections for electron emission in the energy range from $2--300\mathrm{eV}$ were measured for $60\mathrm{MeV}/u$ ${\mathrm{Kr}}^{34+}$ ions impacting on ${\mathrm{H}}_{2}$. Model calculations are introduced to guide the search for interference effects in the electron spectra produced by the coherent emission of electrons from the two H atoms in analogy with Young's two-slit experiment. Experimentally, a full sinusoidal-like oscillation was observed in the energy range up to $250\mathrm{eV}$ in good agreement with the calculations. The oscillatory structure is found to be similar for the observation angles $20\ifmmode^\circ\else\textdegree\fi{}$, $30\ifmmode^\circ\else\textdegree\fi{}$, $150\ifmmode^\circ\else\textdegree\fi{}$, and $160\ifmmode^\circ\else\textdegree\fi{}$.

Ultrahigh energy cosmic ray air showers probe particle physics at energies beyond the reach of accelerators. Here we introduce a new method to test hadronic interaction models without relying on the absolute energy calibration, and apply it to events with primary energy 6-16 EeV (E_{CM}=110-170 TeV), whose longitudinal development and lateral distribution were simultaneously measured by the Pierre Auger Observatory. The average hadronic shower is 1.33±0.16 (1.61±0.21) times larger than predicted using the leading LHC-tuned models EPOS-LHC (QGSJetII-04), with a corresponding excess of muons.

We study numerically, using a one-dimensional Heisenberg model coupled to the lattice in the adiabatic approximation, the spin-Peierls transition in the linear ${\mathrm{Cu}}^{2+}$ spin-1/2 chains in the inorganic compound ${\mathrm{CuGeO}}_{3}$, which has been recently observed experimentally. We suggest that the magnetic susceptibility, the temperature dependence of the spin gap, and the spin-Peierls transition temperature of this material can be reasonably described by including nearest and next-nearest-neighbor antiferromagnetic interactions along the chain. We estimate that the nearest-neighbor exchange parameter J is approximately 160 K, and that the next-nearest-neighbor exchange parameter is approximately 0.36J.

We analyze the distribution of arrival directions of ultra-high energy cosmic rays recorded at the Pierre Auger Observatory in 10 years of operation. The data set, about three times larger than that used in earlier studies, includes arrival directions with zenith angles up to $80^\circ$, thus covering from $-90^\circ$ to $+45^\circ$ in declination. After updating the fraction of events correlating with the active galactic nuclei (AGNs) in the Véron-Cetty and Véron catalog, we subject the arrival directions of the data with energies in excess of 40 EeV to different tests for anisotropy. We search for localized excess fluxes and for self-clustering of event directions at angular scales up to $30^\circ$ and for different threshold energies between 40~EeV and 80~EeV. We then look for correlations of cosmic rays with celestial structures both in the Galaxy (the Galactic Center and Galactic Plane) and in the local Universe (the Super-Galactic Plane). We also examine their correlation with different populations of nearby extragalactic objects: galaxies in the 2MRS catalog, AGNs detected by Swift-BAT, radio galaxies with jets and the Centaurus~A galaxy. None of the tests shows a statistically significant evidence of anisotropy. The strongest departures from isotropy (post-trial probability ${\sim}1.4$\%) are obtained for cosmic rays with $E&gt;58$~EeV in rather large windows around Swift AGNs closer than 130~Mpc and brighter than $10^{44}$~erg/s (18$^\circ$ radius) and around the direction of Centaurus~A (15$^\circ$ radius).

Using computational techniques, it is shown that pairing is a robust property of hole-doped antiferromagnetic insulators. In one dimension and for two-leg ladder systems, a BCS-like variational wave function with long-bond spin singlets and a Jastrow factor provides an accurate representation of the ground state of the t-J model, even though strong quantum fluctuations destroy the off-diagonal superconducting long-range order in this case. However, in two dimensions it is argued-and numerically confirmed using several techniques, especially quantum Monte Carlo-that quantum fluctuations are not strong enough to suppress superconductivity.

The transformation of methane into methanol or higher alcohols at moderate temperature and pressure conditions is of great environmental interest and remains a challenge despite many efforts. Extended surfaces of metallic nickel are inactive for a direct CH4 → CH3OH conversion. This experimental and computational study provides clear evidence that low Ni loadings on a CeO2(111) support can perform a direct catalytic cycle for the generation of methanol at low temperature using oxygen and water as reactants, with a higher selectivity than ever reported for ceria-based catalysts. On the basis of ambient pressure X-ray photoemission spectroscopy and density functional theory calculations, we demonstrate that water plays a crucial role in blocking catalyst sites where methyl species could fully decompose, an essential factor for diminishing the production of CO and CO2, and in generating sites on which methoxy species and ultimately methanol can form. In addition to water-site blocking, one needs the effects of metal–support interactions to bind and activate methane and water. These findings should be considered when designing metal/oxide catalysts for converting methane to value-added chemicals and fuels.

We report a measurement of the energy spectrum of cosmic rays for energies above 2.5×1018 eV based on 215,030 events recorded with zenith angles below 60°. A key feature of the work is that the estimates of the energies are independent of assumptions about the unknown hadronic physics or of the primary mass composition. The measurement is the most precise made hitherto with the accumulated exposure being so large that the measurements of the flux are dominated by systematic uncertainties except at energies above 5×1019 eV. The principal conclusions are:\n(1) The flattening of the spectrum near 5×1018 eV, the so-called “ankle,” is confirmed.\n(2) The steepening of the spectrum at around 5×1019 eV is confirmed.\n(3) A new feature has been identified in the spectrum: in the region above the ankle the spectral index γ of the particle flux (∝E−γ) changes from 2.51±0.03 (stat)±0.05 (syst) to 3.05±0.05 (stat)±0.10 (syst) before changing sharply to 5.1±0.3 (stat)±0.1 (syst) above 5×1019 eV.\n(4) No evidence for any dependence of the spectrum on declination has been found other than a mild excess from the Southern Hemisphere that is consistent with the anisotropy observed above 8×1018 eV.

The results of core-level photoemission indicate that Ni-CeO2(111) surfaces with small or medium coverages of nickel are able to activate methane at 300 K, producing adsorbed CHx and COx (x = 2, 3) groups. Calculations based on density functional theory predict a relatively low activation energy of 0.6–0.7 eV for the cleavage of the first C–H bond in the adsorbed methane molecule. Ni and O centers of ceria work in a cooperative way in the dissociation of the C–H bond at room temperature, where a low Ni loading is crucial for the catalyst activity and stability. The strong electronic perturbations in the Ni nanoparticles produced by the ceria supports of varying natures, such as stoichiometric and reduced, result in a drastic change in their chemical properties toward methane adsorption and dissociation as well as the dry reforming of methane reaction. The coverage of Ni has a drastic effect on the ability of the system to dissociate methane and catalyze the dry re-forming process.