12,903 research outputs found

    Direct Numerical Simulation of decaying two-dimensional turbulence in a no-slip square box using Smoothed Particle Hydrodynamics

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    This paper explores the application of SPH to a Direct Numerical Simulation (DNS) of decaying turbulence in a two-dimensional no-slip wall-bounded domain. In this bounded domain, the inverse energy cascade, and a net torque exerted by the boundary, result in a spontaneous spin up of the fluid, leading to a typical end state of a large monopole vortex that fills the domain. The SPH simulations were compared against published results using a high accuracy pseudo-spectral code. Ensemble averages of the kinetic energy, enstrophy and average vortex wavenumber compared well against the pseudo-spectral results, as did the evolution of the total angular momentum of the fluid. However, while the pseudo-spectral results emphasised the importance of the no-slip boundaries as generators of long lived coherent vortices in the flow, no such generation was seen in the SPH results. Vorticity filaments produced at the boundary were always dissipated by the flow shortly after separating from the boundary layer. The kinetic energy spectrum of the SPH results was calculated using a SPH Fourier transform that operates directly on the disordered particles. The ensemble kinetic energy spectrum showed the expected k-3 scaling over most of the inertial range. However, the spectrum flattened at smaller length scales (initially less than 7.5 particle spacings and growing in size over time), indicating an excess of small-scale kinetic energy

    Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies

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    Introduction: This analysis was conducted to assess the tolerability, safety, and efficacy of brivaracetam (BRV) for adjunctive treatment of focal (partial-onset) seizures in patients aged ā‰„65 years. Methods: Safety/tolerability and efficacy data for patients aged ā‰„65 years were pooled from three randomized, double-blind, placebo-controlled, fixed-dose Phase III studies (NCT00490035, NCT00464269, and NCT01261325). Data were pooled by treatment group: placebo or the proposed therapeutic dose range of 50ā€“200 mg/day: BRV 50, 100, 200 mg/day. Results: Thirty-two patients aged ā‰„65 years were randomized to placebo or BRV 50ā€“200 mg/day. Of these, 30 patients (93.8%) completed their respective study. In the safety population (n = 32), 87.5% placebo- vs 73.3% BRV-treated patients reported treatment-emergent adverse events (TEAEs) during the treatment period; most commonly, headache (25.0% vs 12.5%), paresthesia (0% vs 12.5%), and somnolence (50.0% vs 12.5%) for placebo- vs BRV-treated patients, respectively. During the treatment period, drug-related TEAEs were reported by 62.5% of placebo- vs 53.3% of BRV-treated patients, and serious TEAEs (SAEs) were reported by 0% of placebo- and 4.2% of BRV-treated patients; there were no drug-related SAEs and no deaths. Three SAEs (placebo 1/8; BRV 2/24) and two deaths (placebo 1/8; BRV 1/24) occurred in the post-treatment period. In the efficacy population (n = 31), median percent reduction from baseline in focal seizure frequency/28 days was 14.0% for placebo vs 25.5%, 49.6%, and 74.9% for BRV 50, 100, and 200 mg/day, respectively. The ā‰„50% responder rate was 14.3% for placebo vs 25.0%, 50.0%, and 66.7% for BRV 50, 100, and 200 mg/day, respectively. Conclusions: Safety/tolerability and efficacy findings in this small subgroup of older patients treated with adjunctive BRV are consistent with those observed in the much larger overall pooled population. BRV may be a suitable adjunctive treatment for older patients with uncontrolled focal seizures. Further larger studies in this population are warranted

    Post-Therapeutic Thyroid Reserve: Thyroid Reserve in Euthyroid Patients After Ablative Therapy for Diffuse Toxic Goiter

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    Thyroid reserve was measured in 41 patients who were euthyroid 5 to 15 years after therapy for diffuse toxic goiter. Twenty-one of them had been treated by 131I, 20 by surgery and 10 were normal controls. All had a PBI (protein bound iodine) and 3-hour thyroidal 131I uptake. The same parameters of function were measured again 24 hours after they were given 10 units of thyroid stimulating hormone (TSH) intramuscularly. Only two patients in each treatment group responded with normal elevation of both the PBI and 131I uptake. In 52% of the 131I-treated patients and in 55% of those surgically treated there was no significant increase in either PBI or thyroidal iodine uptake. These results suggest that current efforts to reduce the early post 131I incidence of hypothyroidism may result in a long-term reduction of this complication as well and make this group comparable to those treated surgically. It is certain, however, that no patient receiving either therapy should be dismissed from continuing medical followup

    Estimation from Pairwise Comparisons: Sharp Minimax Bounds with Topology Dependence

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    Data in the form of pairwise comparisons arises in many domains, including preference elicitation, sporting competitions, and peer grading among others. We consider parametric ordinal models for such pairwise comparison data involving a latent vector wāˆ—āˆˆRdw^* \in \mathbb{R}^d that represents the "qualities" of the dd items being compared; this class of models includes the two most widely used parametric models--the Bradley-Terry-Luce (BTL) and the Thurstone models. Working within a standard minimax framework, we provide tight upper and lower bounds on the optimal error in estimating the quality score vector wāˆ—w^* under this class of models. The bounds depend on the topology of the comparison graph induced by the subset of pairs being compared via its Laplacian spectrum. Thus, in settings where the subset of pairs may be chosen, our results provide principled guidelines for making this choice. Finally, we compare these error rates to those under cardinal measurement models and show that the error rates in the ordinal and cardinal settings have identical scalings apart from constant pre-factors.Comment: 39 pages, 5 figures. Significant extension of arXiv:1406.661

    cDNA-RNA subtractive hybridization reveals increased expression of mycocerosic acid synthase in intracellular Mycobacterium bovis BCG.

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    Identifying genes that are differentially expressed by Mycobacterium bovis BCG after phagocytosis by macrophages will facilitate the understanding of the molecular mechanisms of host cell-intracellular pathogen interactions. To identify such genes a cDNA-total RNA subtractive hybridization strategy has been used that circumvents the problems both of limited availability of bacterial RNA from models of infection and the high rRNA backgrounds in total bacterial RNA. The subtraction products were used to screen a high-density gridded Mycobacterium tuberculosis genomic library. Sequence data were obtained from 19 differential clones, five of which contained overlapping sequences for the gene encoding mycocerosic acid synthase (mas). Mas is an enzyme involved in the synthesis of multi-methylated long-chain fatty acids that are part of phthiocerol dimycocerosate, a major component of the complex mycobacterial cell wall. Northern blotting and primer extension data confirmed up-regulation of mas in intracellular mycobacteria and also revealed a putative extended -10 promoter structure and a long untranslated upstream region 5' of the mas transcripts, containing predicted double-stranded structures. Furthermore, clones containing overlapping sequences for furB, groEL-2, rplE and fadD28 were identified and the up-regulation of these genes was confirmed by Northern blot analysis. The cDNA-RNA subtractive hybridization enrichment and high density gridded library screening, combined with selective extraction of bacterial mRNA represents a valuable approach to the identification of genes expressed during intra-macrophage residence for bacteria such as M. bovis BCG and the pathogenic mycobacterium, M. tuberculosis
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