Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe ...plaque psoriasis.
In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points).
The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept.
Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).
In this paper, we combine inertial sensing and sensor network technology to create a pedestrian dead reckoning system. The core of the system is a lightweight sensor-and-wireless-embedded device ...called NavMote that is carried by a pedestrian. The NavMote gathers information about pedestrian motion from an integrated magnetic compass and accelerometers. When the NavMote comes within range of a sensor network (composed of NetMotes), it downloads the compressed data to the network. The network relays the data via a RelayMote to an information center where the data are processed into an estimate of the pedestrian trajectory based on a dead reckoning algorithm. System details including the NavMote hardware/software, sensor network middleware services, and the dead reckoning algorithm are provided. In particular, simple but effective step detection and step length estimation methods are implemented in order to reduce computation, memory, and communication requirements on the Motes. Static and dynamic calibrations of the compass data are crucial to compensate the heading errors. The dead reckoning performance is further enhanced by wireless telemetry and map matching. Extensive testing results show that satisfactory tracking performance with relatively long operational time is achieved. The paper also serves as a brief survey on pedestrian navigation systems, sensors, and techniques.
Traditional stock market prediction approaches commonly utilize the historical price-related data of the stocks to forecast their future trends. As the Web information grows, recently some works try ...to explore financial news to improve the prediction. Effective indicators, e.g., the events related to the stocks and the people’s sentiments toward the market and stocks, have been proved to play important roles in the stocks’ volatility, and are extracted to feed into the prediction models for improving the prediction accuracy. However, a major limitation of previous methods is that the indicators are obtained from only a single source whose reliability might be low, or from several data sources but their interactions and correlations among the multi-sourced data are largely ignored.
In this work, we extract the events from Web news and the users’ sentiments from social media, and investigate their joint impacts on the stock price movements via a coupled matrix and tensor factorization framework. Specifically, a tensor is firstly constructed to fuse heterogeneous data and capture the intrinsic relations among the events and the investors’ sentiments. Due to the sparsity of the tensor, two auxiliary matrices, the stock quantitative feature matrix and the stock correlation matrix, are constructed and incorporated to assist the tensor decomposition. The intuition behind is that stocks that are highly correlated with each other tend to be affected by the same event. Thus, instead of conducting each stock prediction task separately and independently, we predict multiple correlated stocks simultaneously through their commonalities, which are enabled via sharing the collaboratively factorized low rank matrices between matrices and the tensor. Evaluations on the China A-share stock data and the HK stock data in the year 2015 demonstrate the effectiveness of the proposed model.
CUORE sensitivity to $$0\nu \beta \beta $$ decay Alduino, C.; Alfonso, K.; Artusa, D. R. ...
European physical journal. C, Particles and fields,
08/2017, Letnik:
77, Številka:
8
Journal Article
Recenzirano
Odprti dostop
We report a study of the CUORE sensitivity to neutrinoless double beta (0νββ) decay. We used a Bayesian analysis based on a toy Monte Carlo (MC) approach to extract the exclusion sensitivity to the ...0νββ decay half-life (T1/20ν) at 90% credibility interval (CI) – i.e. the interval containing the true value of T1/20ν with 90% probability – and the 3σ discovery sensitivity. We consider various background levels and energy resolutions, and describe the influence of the data division in subsets with different background levels. If the background level and the energy resolution meet the expectation, CUORE will reach a 90% CI exclusion sensitivity of 2·1025 year with 3 months, and 9·1025 year with 5 years of live time. Under the same conditions, the discovery sensitivity after 3 months and 5 years will be 7·1024 year and 4·1025 year, respectively.
ABSTRACT We describe directed searches for continuous gravitational waves (GWs) in data from the sixth Laser Interferometer Gravitational-wave Observatory (LIGO) science data run. The targets were ...nine young supernova remnants not associated with pulsars; eight of the remnants are associated with non-pulsing suspected neutron stars. One target's parameters are uncertain enough to warrant two searches, for a total of 10. Each search covered a broad band of frequencies and first and second frequency derivatives for a fixed sky direction. The searches coherently integrated data from the two LIGO interferometers over time spans from 5.3-25.3 days using the matched-filtering -statistic. We found no evidence of GW signals. We set 95% confidence upper limits as strong (low) as 4 × 10−25 on intrinsic strain, 2 × 10−7 on fiducial ellipticity, and 4 × 10−5 on r-mode amplitude. These beat the indirect limits from energy conservation and are within the range of theoretical predictions for neutron-star ellipticities and r-mode amplitudes.
Patients with acute kidney injury frequently have pulmonary complications. Similarly ischemic acute kidney injury or bilateral nephrectomy in rodents causes lung injury characterized by pulmonary ...edema, increased pulmonary capillary leak and interstitial leukocyte infiltration. Interleukin-6 is a pro-inflammatory cytokine that is increased in the serum of patients with acute kidney injury and predicts mortality. Here we found that lung neutrophil infiltration, myeloperoxidase activity, the neutrophil chemokines KC and MIP-2 and capillary leak all increased within 4h following acute kidney injury in wild-type mice. These pathologic factors were reduced in interleukin-6-deficient mice following acute kidney injury or bilateral nephrectomy. The lungs of mutant mice had reduced KC but MIP-2 was similar to that of wild type mice. Wild-type mice, treated with an interleukin-6 inactivating antibody, had decreased lung myeloperoxidase activity and KC levels following acute kidney injury. Our study shows that interleukin-6 contributes to lung injury following acute kidney injury.
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