Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over 5 years of therapy in a phase 3b and subsequent postmarketing observational study.

INTRODUCTION: Patients with active rheumatoid arthritis who had failed at least one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab (ADA) in the ReAct study with the option to continue treatment for 5 years in ReAlise. The purpose of this study was to evaluate the long-term safety and effectiveness of ADA as prescribed from the first injection in ReAct to the last observation in ReAlise. METHODS: Patients received ADA alone or in combination with DMARDs according to usual clinical care practices. Adverse events (AEs) were tabulated by five time windows after the first ADA injection. Effectiveness measures included achievement of low disease activity (LDA), defined as Simplified Disease Activity Index (SDAI) ≤11, or remission, (REM), defined as SDAI ≤3.3. RESULTS: Of the 6,610 ReAct patients, 3,435 (52%) continued in ReAlise. At baseline in ReAct, mean age was 54 years, mean DAS28 was 6.0 and mean HAQ DI was 1.64. The mean treatment duration was 1,016 days, representing 18,272 patient-years (PYs) of ADA exposure. Overall incidence rates of serious AEs and serious infections were 13.8 and 2.8 events (E)/100 PYs, respectively. Serious AEs occurred most frequently in the first 6 months and deceased thereafter. Standardised mortality ratio was 0.71 (95% CI 0.57 to 0.87) and standardised incidence ratio for malignancies was 0.64 (95% CI 0.53 to 0.76). LDA was achieved by 50% and REM by 21% of patients at last observation. CONCLUSIONS: Results of this large observational study of ADA in routine clinical practice were consistent with controlled trials, with no new safety concerns during a follow-up of more than 5 years. Effectiveness of ADA was maintained during long-term observation. TRIAL REGISTRATION: NCT00448383, NCT0023488

An Explanation for the Observed Weak Size Evolution of Disk Galaxies

Surveys of distant galaxies with the Hubble Space Telescope and from the ground have shown that there is only mild evolution in the relationship between radial size and stellar mass for galactic disks from z~1 to the present day. Using a sample of nearby disk-dominated galaxies from the Sloan Digital Sky Survey (SDSS), and high redshift data from the GEMS (Galaxy Evolution from Morphology and SEDs) survey, we investigate whether this result is consistent with theoretical expectations within the hierarchical paradigm of structure formation. The relationship between virial radius and mass for dark matter halos in the LCDM model evolves by about a factor of two over this interval. However, N-body simulations have shown that halos of a given mass have less centrally concentrated mass profiles at high redshift. When we compute the expected disk size-stellar mass distribution, accounting for this evolution in the internal structure of dark matter halos and the adiabatic contraction of the dark matter by the self-gravity of the collapsing baryons, we find that the predicted evolution in the mean size at fixed stellar mass since z~1 is about 15-20 percent, in good agreement with the observational constraints from GEMS. At redshift z~2, the model predicts that disks at fixed stellar mass were on average only 60% as large as they are today. Similarly, we predict that the rotation velocity at a given stellar mass (essentially the zero-point of the Tully-Fisher relation) is only about 10 percent larger at z~1 (20 percent at z~2) than at the present day.Comment: 13 pages, 6 figures, accepted for publication in ApJ. Revised in response to referee's comments to improve clariry. Results are unchange

GEMS: The Size Evolution of Disk Galaxies

We combine HST imaging from the GEMS survey with photometric redshifts from COMBO-17 to explore the evolution of disk-dominated galaxies since z<1.1. The sample is comprised of all GEMS galaxies with Sersic indices n<2.5, derived from fits to the galaxy images. We account fully for selection effects through careful analysis of image simulations; we are limited by the depth of the redshift and HST data to the study of galaxies with absolute magnitudes M(V)10. We find strong evolution in the magnitude-size scaling relation for galaxies with M(V)<-20, corresponding to a brightening of 1 mag per sqarcsec in rest-frame V-band by z=1. Yet, disks at a given absolute magnitude are bluer and have lower stellar mass-to-light ratios at z=1 than at the present day. As a result, our findings indicate weak or no evolution in the relation between stellar mass and effective disk size for galaxies with log(M)>10 over the same time interval. This is strongly inconsistent with the most naive theoretical expectation, in which disk size scales in proportion to the halo virial radius, which would predict that disks are a factor of two denser at fixed mass at z=1. The lack of evolution in the stellar mass-size relation is consistent with an ``inside-out'' growth of galaxy disks on average (galaxies increasing in size as they grow more massive), although we cannot rule out more complex evolutionary scenarios.Comment: 22 pages, 16 figures, submitted to Ap

Inestabilidad lateral crónica de tobillo: hallazgos artroscópicos y resultados tras reparación mediante técnica de Karlsson

ObjetivoRecoger los resultados obtenidos asociando la artroscopia diagnóstico-terapéutica a la técnica propuesta por Karlsson.Material y métodoSe revisaron retrospectivamente 11 casos tratados entre diciembre de 2004 y julio de 2009 mediante cirugía artroscópica de tobillo asociada a la técnica de Karlsson. La media de edad fue de 25 años (rango 13-45). Primero se realizó la artroscopia y posteriormente el abordaje lateral para la reparación ligamentosa. El ligamento peroneo-calcáneo se reparó en los 4 casos en que se objetivó su lesión. Se valoró la funcionalidad según la escala de la American Orthopaedic Foot and Ankle Society (AOFAS) y el grado de satisfacción subjetiva. Se recogieron las complicaciones.ResultadosTras un seguimiento medio de 11 meses, valoramos 11 pacientes cuya puntuación media según la AOFAS fue de 84 puntos. La valoración subjetiva fue excelente en 7 casos, buena en 2 y mala en 2. Como complicaciones, hubo 2 casos de síndrome de dolor regional complejo (SDRC) y un paciente tuvo que ser reintervenido con técnica de Castaing II.ConclusionesConsideramos que la asociación de la artroscopia previa a la realización de la reconstrucción para el tratamiento de la inestabilidad crónica constituye una maniobra útil para el diagnóstico de patologías articulares asociadas, aportando información importante para el pronóstico funcional de la articulación.AimsThe purpose of this study is to evaluate the result of diagnostic and therapeutic arthroscopy in association with Karlsson technique.Material And MethodsBetween 2004 and 2009, 11 patients were operated by ankle arthroscopic surgery associated with Karlsson technique. The mean age was 25 years (range 13-45). Arthroscopy was performed first and secondly the lateral approach to ligament repair. Peroneal-calcaneal ligament wasn injuried and repaired in 4 cases. AOFAS scale was used for clinical and functional evaluation, and patients were asked about subjective satisfaction. Complications were recorded.ResultsAt a mean follow-up of 11 months the mean final score was 84 points on the AOFAS scale. The subjective assessment was excellent in 7 cases, good in 2 and poor in 2. There were 2 cases of CRPS and one patient was reoperated by Castaing II technique.ConclusionsWe believe that the association of arthroscopy prior to the reconstruction is useful for associated joint lesion diagnosis, providing important information for the functional prognosis of the joint

Gamma-ray and radio tests of the e+e- excess from DM annihilations

PAMELA and ATIC recently reported an excess in e+e- cosmic rays. We show that if it is due to Dark Matter annihilations, the associated gamma-ray flux and the synchrotron emission produced by e+e- in the galactic magnetic field violate HESS and radio observations of the galactic center and HESS observations of dwarf Spheroidals, unless the DM density profile is significantly less steep than the benchmark NFW and Einasto profiles.Comment: 16 pages, 4 figures; v2: normalizations fixed in Table 2 and typos corrected (no changes in the analysis nor the results), some references and comments added; v3: minor additions, matches published versio

Changes in Glucose and Glutamine Lymphocyte Metabolisms Induced by Type I Interferon α

In lymphocytes (LY), the well-documented antiproliferative effects of IFN-α are associated with inhibition of protein synthesis, decreased amino acid incorporation, and cell cycle arrest. However, the effects of this cytokine on the metabolism of glucose and glutamine in these cells have not been well investigated. Thus, mesenteric and spleen LY of male Wistar rats were cultured in the presence or absence of IFN-α, and the changes on glucose and glutamine metabolisms were investigated. The reduced proliferation of mesenteric LY was accompanied by a reduction in glucose total consumption (35%), aerobic glucose metabolism (55%), maximal activity of glucose-6-phosphate dehydrogenase (49%), citrate synthase activity (34%), total glutamine consumption (30%), aerobic glutamine consumption (20.3%) and glutaminase activity (56%). In LY isolated from spleen, IFNα also reduced the proliferation and impaired metabolism. These data demonstrate that in LY, the antiproliferative effects of IFNα are associated with a reduction in glucose and glutamine metabolisms

PPPC 4 DM ID: A Poor Particle Physicist Cookbook for Dark Matter Indirect Detection

We provide ingredients and recipes for computing signals of TeV-scale Dark Matter annihilations and decays in the Galaxy and beyond. For each DM channel, we present the energy spectra of electrons and positrons, antiprotons, antideuterons, gamma rays, neutrinos and antineutrinos e, mu, tau at production, computed by high-statistics simulations. We estimate the Monte Carlo uncertainty by comparing the results yielded by the Pythia and Herwig event generators. We then provide the propagation functions for charged particles in the Galaxy, for several DM distribution profiles and sets of propagation parameters. Propagation of electrons and positrons is performed with an improved semi-analytic method that takes into account position-dependent energy losses in the Milky Way. Using such propagation functions, we compute the energy spectra of electrons and positrons, antiprotons and antideuterons at the location of the Earth. We then present the gamma ray fluxes, both from prompt emission and from Inverse Compton scattering in the galactic halo. Finally, we provide the spectra of extragalactic gamma rays. All results are available in numerical form and ready to be consumed.Comment: 57 pages with many figures and tables. v4: updated to include a 125 higgs boson, computation and discussion of extragalactic spectra corrected, some other typos fixed; all these corrections and updates are reflected on the numerical ingredients available at http://www.marcocirelli.net/PPPC4DMID.html they correspond to Release 2.

Proyecto “Turmicultura”: Cultivo de trufas del desierto contra el cambio climático y para el desarrollo rural

Publishe

Evolutionary factors affecting the cross-species utility of newly developed microsatellite markers in seabirds

Microsatellite loci are ideal for testing hypotheses relating to genetic segregation at fine spatio-temporal scales. They are also conserved among closely related species, making them potentially useful for clarifying interspecific relationships between recently diverged taxa. However, mutations at primer binding sites may lead to increased non-amplification, or disruptions that may lead to decreased polymorphism in non-target species. Furthermore, high mutation rates and constraints on allele size may also lead, with evolutionary time, to an increase in convergently evolved allele size classes, biasing measures of interspecific genetic differentiation. Here, we used next-generation sequencing to develop microsatellite markers from a shotgun genome sequence of the sub-Antarctic seabird, the thin-billed prion (Pachyptila belcheri), that we tested for cross-species amplification in other Pachyptila and related sub-Antarctic species. We found that heterozygosity decreased and the proportion of non-amplifying loci increased with phylogenetic distance from the target species. Surprisingly, we found that species trees estimated from interspecific FST provided better approximations of mtDNA relationships among the studied species than those estimated using DC, even though FST was more affected by null alleles. We observed a significantly non-linear second order polynomial relationship between microsatellite and mtDNA distances. We propose that the loss of linearity with increasing mtDNA distance stems from an increasing proportion of homoplastic allele size classes that are identical in state, but not identical by descent. Therefore, despite high cross-species amplification success and high polymorphism among the closely related Pachyptila species, we caution against the use of microsatellites in phylogenetic inference among distantly related taxa

Semicosimplicial DGLAs in deformation theory

We identify Cech cocycles in nonabelian (formal) group cohomology with Maurer-Cartan elements in a suitable L-infinity algebra. Applications to deformation theory are described.Comment: Largely rewritten. Abstract modified. 15 pages, Latex, uses xy-pi