Systematic review and meta-analysis on certolizumab pegol for rheumatoid arthritis in adults

Background The appearance of tumor necrosis factor-alpha (TNFalpha) inhibitors dramatically changed the prognosis of rheumatoid arthritis. Certolizumab pegol (CZP) is a human Fab fragment of anti-TNFalpha monoclonal antibody which is approved for the treatment of rheumatoid arthritis. We performed a systematic review and meta-analysis, with Cochrane methodology, of the effects of CZP in rheumatoid arthritis. Objectives To assess the clinical benefits and harms of CZP in patients with rheumatoid arthritis. Methods We performed a search of electronic database (Cochrane Database, MEDLINE, EMBASE, Web of Knowledge and clinicaltrials.gov) until 26th September 2016. We searched for randomized controlled trials of CZP in rheumatoid arthritis compared to any other agent including placebo. Results 14 trials were included for the meta-analysis, 12 (5422 patients) in the pooled analysis for benefits and 14 (5499 patients) in the pooled analysis for safety. The overall possibility of bias seemed to be low but the quality of the evidence was low due to the risk of attrition bias. With the approved dose - CZP 200 mg subcutaneous every other week with the first three doses of 400 mg - CZP showed statistically significant improvements at 24 weeks compared to placebo in: ACR50 absolute improvement 27% (95% CI 20% to 33%), RR 3.8 (95% CI 2.42 to 5.95) and NNT=4 (95% CI 3 to 8); DAS28 <2.6 - original definition of remission - with RR 3.79 (95% CI 1.90 to 7.56); HAQ with -12% absolute improvement (95% CI -9% to -14%); and erosion score with -0.29% (95% CI -0.42% to -0.17%). There are also data available at 12 weeks with RR of 1.99 (95% CI 1.44 to 2.76) of achieving DAS28<2.6 with CZP 200 mg dose. The proportion of patients achieving DAS28<2.6 was still higher with CZP at 52 weeks with RR of 1.83 (95% CI 1.53 to 2.18). Serious adverse events were more frequent for CZP 200 mg dose with a RR of 1.47 (95% CI 1.13 to 1.91) and NNH of 32. There have been eight adverse events leading to death in CZP 200 mg group versus two in the control group (not statistically significant) and 10 patients developing tuberculosis versus two in the control group (not statistically significant). Conclusions There is low level evidence from randomized controlled trials that CZP as monotherapy or combined with methotrexate improved ACR50, DAS28, HAQ and joint damaged on x-ray. Adverse events were more frequent with active treatment

Development and kinematic verification of a finite element model for the lumbar spine: Application to disc degeneration

The knowledge of the lumbar spine biomechanics is essential for clinical applications. Due to the difficulties to experiment on living people and the irregular results published, simulation based on finite elements (FE) has been developed, making it possible to adequately reproduce the biomechanics of the lumbar spine. A 3D FE model of the complete lumbar spine (vertebrae, discs, and ligaments) has been developed. To verify the model, radiological images (X-rays) were taken over a group of 25 healthy, male individuals with average age of 27.4 and average weight of 78.6 kg with the corresponding informed consent. A maximum angle of 34.40° is achieved in flexion and of 35.58° in extension with a flexion-extension angle of 69.98°. The radiological measurements were 33.94 ± 4.91°, 38.73 ± 4.29°, and 72.67°, respectively. In lateral bending, the maximum angles were 19.33° and 23.40 ± 2.39, respectively. In rotation a maximum angle of 9.96° was obtained. The model incorporates a precise geometrical characterization of several elements (vertebrae, discs, and ligaments), respecting anatomical features and being capable of reproducing a wide range of physiological movements. Application to disc degeneration (L5-S1) allows predicting the affection in the mobility of the different lumbar segments, by means of parametric studies for different ranges of degeneration

G-band Spectral Synthesis in Solar Magnetic Concentrations

Narrow band imaging in the G-band is commonly used to trace the small magnetic field concentrations of the Sun, although the mechanism that makes them bright has remained unclear. We carry out LTE syntheses of the G-band in an assorted set of semi-empirical model magnetic concentrations. The syntheses include all CH lines as well as the main atomic lines within the band-pass. The model atmospheres produce bright G-band spectra having many properties in common with the observed G-band bright points. In particular, the contrast referred to the quiet Sun is about twice the contrast in continuum wavelengths. The agreement with observations does not depend on the specificities of the model atmosphere, rather it holds from single fluxtubes to MIcro-Structured Magnetic Atmospheres. However, the agreement requires that the real G-band bright points are not spatially resolved, even in the best observations. Since the predicted G-band intensities exceed by far the observed values, we foresee a notable increase of contrast of the G-band images upon improvement of the angular resolution. According to the LTE modeling, the G-band spectrum emerges from the deep photosphere that produces the continuum. Our syntheses also predict solar magnetic concentrations showing up in continuum images but not in the G-band . Finally, we have examined the importance of the CH photo-dissociation in setting the amount of G-band absorption. It turns out to play a minor role.Comment: To appear in ApJ, 554 n2 Jun 20, 33 pages and 9 figure

Lactococcus lactis subsp. lactis infection in waterfowl: first confirmation in animals.

We report the first description, confirmed by bacteriologic and molecular (polymerase chain reaction and pulsed-field gel electrophoresis) analysis, of an infection in animals caused by Lactococcus lactis subsp. lactis, affecting waterfowl

When the path is never shortest: a reality check on shortest path biocomputation

Shortest path problems are a touchstone for evaluating the computing performance and functional range of novel computing substrates. Much has been published in recent years regarding the use of biocomputers to solve minimal path problems such as route optimisation and labyrinth navigation, but their outputs are typically difficult to reproduce and somewhat abstract in nature, suggesting that both experimental design and analysis in the field require standardising. This chapter details laboratory experimental data which probe the path finding process in two single-celled protistic model organisms, Physarum polycephalum and Paramecium caudatum, comprising a shortest path problem and labyrinth navigation, respectively. The results presented illustrate several of the key difficulties that are encountered in categorising biological behaviours in the language of computing, including biological variability, non-halting operations and adverse reactions to experimental stimuli. It is concluded that neither organism examined are able to efficiently or reproducibly solve shortest path problems in the specific experimental conditions that were tested. Data presented are contextualised with biological theory and design principles for maximising the usefulness of experimental biocomputer prototypes.Comment: To appear in: Adamatzky, A (Ed.) Shortest path solvers. From software to wetware. Springer, 201

The UHECR-FR0 Radio Galaxy Connection: A Multi-Messenger Study of Energy Spectra/Composition Emission and Intergalactic Magnetic Field Propagation

This study investigates low luminosity Fanaroff-Riley Type 0 (FR0) radio galaxies as a potentially significant source of ultra-high energy cosmic rays (UHECRs). Due to their much higher prevalence in the local universe compared to more powerful radio galaxies (about five times more than FR-1s), FR0s may provide a substantial fraction of the total UHECR energy density. To determine the nucleon composition and energy spectrum of UHECRs emitted by FR0 sources, simulation results from CRPropa3 are fit to Pierre Auger Observatory data. The resulting emission spectral indices, rigidity cutoffs, and nucleon fractions are compared to recent Auger results. The FR0 simulations include the approximately isotropic distribution of FR0 galaxies and various intergalactic magnetic field configurations (including random and structured fields) and predict the fluxes of secondary photons and neutrinos produced during UHECR propagation through cosmic photon backgrounds. This comprehensive simulation allows for investigating the properties of the FR0 sources using observational multi-messenger data.Comment: PoS 444 (38th ICRC) 151

Determination and analysis of in situ spectral aerosol optical properties by a multi-instrumental approach

Continuous in situ measurements of aerosol optical properties were conducted from 29 June to 29 July 2012 in Granada (Spain) with a seven-wavelength Aethalometer, a Multi-Angle Absorption Photometer, and a three-wavelength integrating nephelometer. The aim of this work is to describe a methodology to obtain the absorption coefficients (babs) for the different Aethalometer wavelengths. In this way, data have been compensated using algorithms which best estimate the compensation factors needed. Two empirical factors are used to infer the absorption coefficients from the Aethalometer measurements: C – the parameter describing the enhancement of absorption by particles in the filter matrix due to multiple scattering of light in the filter matrix – and f, the parameter compensating for non-linear loading effects in the filter matrix. Spectral dependence of f found in this study is not very strong. Values for the campaign lie in the range from 1.15 at 370 nm to 1.11 at 950 nm. Wavelength dependence in C proves to be more important, and also more difficult to calculate. The values obtained span from 3.42 at 370 nm to 4.59 at 950 nm. Furthermore, the temporal evolution of the Ångström exponent of absorption (αabs) and the single-scattering albedo (ω0) is presented. On average αabs is around 1.1 ± 0.3, and ω0 is 0.78 ± 0.08 and 0.74 ± 0.09 at 370 and 950 nm, respectively. These are typical values for sites with a predominance of absorbing particles, and the urban measurement site in this study is such. The babs average values are of 16 ± 10 Mm−1 (at 370 nm) and 5 ± 3 Mm−1 (at 950 nm), respectively. Finally, differences between workdays and Sundays have been further analysed, obtaining higher babs and lower ω0 during the workdays than on Sundays as a consequence of the diesel traffic influence.This work was financed jointly by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund through projects CGL2011-24290, CGL2010-18782, CSD2007-00067, and CGL2012-33294; by the Valencia Autonomous Government through project PROMETEO/2010/064; the Andalusia Regional Government through projects P08-RNM-3568 and P10-RNM-6299; and by the Slovenian Ministry of Economic Development and Technology JR-KROP grant 3211-11-000519. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 262254 (ACTRIS). The collaboration of S. Segura in this work was possible thanks to fellowship BES-2010-031626

Morphological stabilization and KPZ scaling by electrochemically induced co-deposition of nanostructured NiW alloy films

We have assessed the stabilizing role that induced co-deposition has in the growth of nanostructured NiW alloy films by electrodeposition on polished steel substrates, under pulsed galvanostatic conditions. We have compared the kinetic roughening properties of NiW films with those of Ni films deposited under the same conditions, as assessed by Atomic Force Microscopy. The surface morphologies of both systems are super-rough at short times, but differ at long times: while a cauliflower-like structure dominates for Ni, the surfaces of NiW films display a nodular morphology consistent with more stable, conformal growth, whose height fluctuations are in the Kardar-Parisi- Zhang universality class of rough two-dimensional interfaces. These differences are explained by the mechanisms controlling surface growth in each case: mass transport through the electrolyte (Ni) and attachment of the incoming species to the growing interface (NiW). Thus, the long-time conformal growth regime is characteristic of electrochemical induced co-deposition under current conditions in which surface kinetics is hindered due to a complex reaction mechanism. These results agree with a theoretical model of surface growth in diffusion-limited systems, in which the key parameter is the relative importance of mass transport with respect to the kinetics of the attachment reaction.Facultad de Ciencias Exacta

Subharmonic bifurcation cascade of pattern oscillations caused by winding number increasing entrainment

Convection structures in binary fluid mixtures are investigated for positive Soret coupling in the driving regime where solutal and thermal contributions to the buoyancy forces compete. Bifurcation properties of stable and unstable stationary square, roll, and crossroll (CR) structures and the oscillatory competition between rolls and squares are determined numerically as a function of fluid parameters. A novel type of subharmonic bifurcation cascade (SC) where the oscillation period grows in integer steps as $n (2\pi)/(\omega)$ is found and elucidated to be an entrainment process.Comment: 7 pages, 4 figure