Clinical effects of natalizumab on multiple sclerosis appear early in treatment course

In clinical practice natalizumab is typically used in patients who have experienced breakthrough disease during treatment with interferon beta (IFNβ) or glatiramer acetate. In these patients it is important to reduce disease activity as quickly as possible. In a phase II study, differences between natalizumab and placebo in MRI outcomes reflecting inflammatory activity were evident after the first infusion and maintained through a 6-month period, suggesting a rapid onset of natalizumab treatment effects. To explore how soon after natalizumab initiation clinical effects become apparent, annualized relapse rates per 3-month period and time to first relapse were analyzed in the phase III AFFIRM study (natalizumab vs. placebo) and in the multinational Tysabri® Observational Program (TOP). In AFFIRM, natalizumab reduced the annualized relapse rate within 3months of treatment initiation compared with placebo in the overall population (0.30 vs. 0.71; p<0.0001) and in patients with highly active disease (0.30 vs. 0.94; p=0.0039). The low annualized relapse rate was maintained throughout the 2-year study period, and the risk of relapse in AFFIRM patients treated with natalizumab was reduced [hazard ratio against placebo 0.42 (95% CI 0.34-0.52); p<0.0001]. Rapid reductions in annualized relapse rate also occurred in TOP (baseline 1.99 vs. 0-3months 0.26; p<0.0001). Natalizumab resulted in rapid, sustained reductions in disease activity in both AFFIRM and in clinical practice. This decrease in disease activity occurred within the first 3months of treatment even in patients with more active diseas

Mercury DPM: fast, flexible particle simulations in complex geometries part II: applications

MercuryDPM is a particle-simulation software developed open-source by a global network of researchers. It was designed ​ab initio to simulate realistic geometries and materials, thus it contains several unique features not found in any other particle simulation software. These features have been discussed in a companion paper published in the DEM7 conference proceedings; here we present several challenging setups implemented in MercuryDPM ​ . Via these setups, we demonstrate the unique capability of the code to simulate and analyse highly complex geotechnical and industrial applications.These tups implemented include complex geometries such as (i) a screw conveyor, (ii) steady-state inflow conditions for chute flows, (iii) a confined conveyor belt to simulate a steady-state breaking wave, and(iii)aquasi-2D cylindrical slice to efficiently study shear flows.​MercuryDPM is also parallel, which we showcase via a multi-million particle simulations of a rotating drum. We further demonstrate how to simulate complex particle interactions, including: (i)deformable, charged clay particles; and (ii) liquid bridges and liquid migration in wet particulates, (iii) non-spherical particles implemented via superquadrics. Finally, we show how to analyse and complex systems using the unique micro-macro mapping (coarse-graining) tool MercuryCG

A large margin algorithm for automated segmentation of white matter hyperintensity

Precise detection and quantification of white matter hyperintensity (WMH) is of great interest in studies of neurological and vascular disorders. In this work, we propose a novel method for automatic WMH segmentation with both supervised and semi-supervised large margin algorithms provided by the framework. The proposed algorithms optimize a kernel based max-margin objective function which aims to maximize the margin between inliers and outliers. We show that the semi-supervised learning problem can be formulated to learn a classifier and label assignment simultaneously, which can be solved efficiently by an iterative algorithm. The model is learned first via the supervised approach and then fine-tuned on a target image by using the semi-supervised algorithm. We evaluate our method on 88 brain fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images from subjects with vascular disease. Quantitative evaluation of the proposed approach shows that it outperforms other well known methods for WMH segmentation

Comparative return of imports into the state of Negri Sembilan during the years, 1916 and 1915.

Supplement to the F.M.S Government Gazette, May 11th, 1917. It also contains 'Comparative return of exports into the state of Negri Sembilan during the years, 1916 and 1915'

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Effectiveness of Lucid Dreaming Practice on Waking Task Performance: A Scoping Review of Evidence and Meta-Analysis

A lucid dream is a dream during which the dreamer becomes aware of the fact that they are experiencing a dream. The higher awareness and cognitive traits which accompany lucid dreams offer individuals a unique opportunity to use this practice to rehearse waking skills. This scoping review aimed to summarise existing evidence on the effectiveness of lucid dreaming practice (LDP) on the performance of waking skills and employed a meta-analytical approach to estimate an overall effect of LDP. A total of seven studies were reviewed. Findings indicate that LDP can improve waking performance of motor tasks of a variety of nature with an overall medium positive effect size of .483 (p=.095). LDP environments appear to be suitable for the practice of such tasks however practitioners should be aware that perception may at times be distorted from wakefulness. Dream distractions may also be encountered which may impair dream practice and have a negative effect on subsequent performance. A lack of empirical evidence within the literature was identified. Challenges with conducting LDP research are discussed and recommendations for future research are proposed