450 research outputs found
Ustekinumab for the treatment of moderateâtoâsevere plaque psoriasis in paediatric patients (â„ 6 to < 12 years of age): efficacy, safety, pharmacokinetic and biomarker results from the openâlabel CADMUS Jr study
Background Limited options are available for treatment of paediatric psoriasis. Objectives To evaluate the efficacy and safety of ustekinumab in paediatric patients with psoriasis (>= 6 to = 60 to 100 kg: 90 mg) administered by subcutaneous injection at weeks 0 and 4, then every 12 weeks through week 40. Study endpoints (all at week 12) included the proportions of patients achieving a Physician's Global Assessment score of cleared/minimal (PGA 0/1) and >= 75%/90% improvement in Psoriasis Area and Severity Index (PASI 75/90), and change in Children's Dermatology Life Quality Index (CDLQI). Serum ustekinumab concentrations, antidrug antibodies and cytokine levels were measured through week 52. Safety was evaluated through week 56. Results In total, 44 patients (median age 9 center dot 5 years) received at least one dose of ustekinumab. Three patients discontinued the study agent through week 40. At week 12, 77% of patients achieved PGA 0/1, 84% achieved PASI 75 and 64% achieved PASI 90 response. The mean change in CDLQI was -6 center dot 3. Trough serum ustekinumab concentrations reached steady state at weeks 28-52. The incidence of antidrug antibodies was 10% (n = 4). Mean serum concentrations of interleukin-17A/F and interleukin-22 were significantly reduced at weeks 12 and 52. Overall, 34 patients (77%) had at least one adverse event and three (7%) had a serious adverse event. Conclusions Ustekinumab effectively treated moderate-to-severe psoriasis in paediatric patients, and no new safety concerns were identified.
What is already known about this topic? Ustekinumab is approved for use in adolescents (>= 12 to = 18 years) with moderate-to-severe psoriasis.
What does this study add? Ustekinumab effectively treats moderate-to-severe psoriasis in paediatric patients (>= 6 to < 12 years of age), with no new safety concerns
Striped antiferromagnetic order and electronic properties of stoichiometric LiFeAs from first-principles calculations
We investigate the structural, electronic, and magnetic properties of
stoichiometric LiFeAs by using state-of-the-arts first-principles method. We
find the magnetic ground-state by comparing the total energies among all the
possible magnetic orders. Our calculated internal positions of Li and As are in
good agreement with experiment. Our results show that stoichiometric LiFeAs has
almost the same striped antiferromagnetic spin order as other FeAs-based parent
compounds and tetragonal FeSe do, and the experimental fact that no magnetic
phase transition has been observed at finite temperature is attributed to the
tiny inter-layer spin coupling
Realistic D-Brane Models on Warped Throats: Fluxes, Hierarchies and Moduli Stabilization
We describe the construction of string theory models with semirealistic
spectrum in a sector of (anti) D3-branes located at an orbifold singularity at
the bottom of a highly warped throat geometry, which is a generalisation of the
Klebanov-Strassler deformed conifold. These models realise the Randall-Sundrum
proposal to naturally generate the Planck/electroweak hierarchy in a concrete
string theory embedding, and yielding interesting chiral open string spectra.
We describe examples with Standard Model gauge group (or left-right symmetric
extensions) and three families of SM fermions, with correct quantum numbers
including hypercharge. The dilaton and complex structure moduli of the geometry
are stabilised by the 3-form fluxes required to build the throat. We describe
diverse issues concerning the stabilisation of geometric Kahler moduli, like
blow-up modes of the orbifold singularities, via D term potentials and gauge
theory non-perturbative effects, like gaugino condensation. This local
geometry, once embedded in a full compactification, could give rise to models
with all moduli stabilised, and with the potential to lead to de Sitter vacua.
Issues of gauge unification, proton stability, supersymmetry breaking and
Yukawa couplings are also discussed.Comment: 46 pages, 13 figures (figures 3 and 13 corrected
A probabilistic method for the operation of three-phase unbalanced active distribution networks
YesThis paper proposes a probabilistic multi-objective optimization method for the operation of three-phase distribution networks incorporating active network management (ANM) schemes including coordinated voltage control and adaptive power factor control. The proposed probabilistic method incorporates detailed modelling of three-phase distribution network components and considers different operational objectives. The method simultaneously minimizes the total energy losses of the lines from the point of view of distribution network operators (DNOs) and maximizes the energy generated by photovoltaic (PV) cells considering ANM schemes and network constraints. Uncertainties related to intermittent generation of PVs and load demands are modelled by probability density functions (PDFs). Monte Carlo simulation method is employed to use the generated PDFs. The problem is solved using É-constraint approach and fuzzy satisfying method is used to select the best solution from the Pareto optimal set. The effectiveness of the proposed probabilistic method is demonstrated with IEEE 13- and 34- bus test feeders
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC
Measurements of inclusive jet suppression in heavy ion collisions at the LHC
provide direct sensitivity to the physics of jet quenching. In a sample of
lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated
luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with
a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the
transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the
anti-kt algorithm with values for the distance parameter that determines the
nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of
the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp.
Jet production is found to be suppressed by approximately a factor of two in
the 10% most central collisions relative to peripheral collisions. Rcp varies
smoothly with centrality as characterized by the number of participating
nucleons. The observed suppression is only weakly dependent on jet radius and
transverse momentum. These results provide the first direct measurement of
inclusive jet suppression in heavy ion collisions and complement previous
measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables,
submitted to Physics Letters B. All figures including auxiliary figures are
available at
http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02
Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% for TBLH-BMD, and 39% for TB-LM, with a shared genetic component of 43%. We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: _WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5_. Variants in the _TOM1L2/SREBF1_ locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that _SREBF1_ is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass
A hierarchy of heuristic-based models of crowd dynamics
International audienceWe derive a hierarchy of kinetic and macroscopic models from a noisy variant of the heuristic behavioral Individual-Based Model of Moussaid et al, PNAS 2011, where the pedestrians are supposed to have constant speeds. This IBM supposes that the pedestrians seek the best compromise between navigation towards their target and collisions avoidance. We first propose a kinetic model for the probability distribution function of the pedestrians. Then, we derive fluid models and propose three different closure relations. The first two closures assume that the velocity distribution functions are either a Dirac delta or a von Mises-Fisher distribution respectively. The third closure results from a hydrodynamic limit associated to a Local Thermodynamical Equilibrium. We develop an analogy between this equilibrium and Nash equilibia in a game theoretic framework. In each case, we discuss the features of the models and their suitability for practical use
Measurement of the Group Velocity of Light in Sea Water at the ANTARES Site
The group velocity of light has been measured at eight different wavelengths
between 385 nm and 532 nm in the Mediterranean Sea at a depth of about 2.2 km
with the ANTARES optical beacon systems. A parametrisation of the dependence of
the refractive index on wavelength based on the salinity, pressure and
temperature of the sea water at the ANTARES site is in good agreement with
these measurements.Comment: 14 pages, 5 figure
- âŠ