Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

Background Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. Methods In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. Results In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. Conclusions Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.

All-optical SR flip-flop based on SOA-MZI switches monolithically integrated on a generic InP platform

At the dawning of the exaflop era, High Performance Computers are foreseen to exploit integrated all-optical elements, to overcome the speed limitations imposed by electronic counterparts. Drawing from the well-known Memory Wall limitation, imposing a performance gap between processor and memory speeds, research has focused on developing ultra-fast latching devices and all-optical memory elements capable of delivering buffering and switching functionalities at unprecedented bit-rates. Following the master-slave configuration of electronic Flip-Flops, coupled SOA-MZI based switches have been theoretically investigated to exceed 40 Gb/s operation, provided a short coupling waveguide. However, this flip-flop architecture has been only hybridly integrated with silica-on-silicon integration technology exhibiting a total footprint of 45x12 mm2 and intra-Flip-Flop coupling waveguide of 2.5cm, limited at 5 Gb/s operation. Monolithic integration offers the possibility to fabricate multiple active and passive photonic components on a single chip at a close proximity towards, bearing promises for fast all-optical memories. Here, we present for the first time a monolithically integrated all-optical SR Flip-Flop with coupled master-slave SOA-MZI switches. The photonic chip is integrated on a 6x2 mm2 die as a part of a multi-project wafer run using library based components of a generic InP platform, fiber-pigtailed and fully packaged on a temperature controlled ceramic submount module with electrical contacts. The intra Flip-Flop coupling waveguide is 5 mm long, reducing the total footprint by two orders of magnitude. Successful flip flop functionality is evaluated at 10 Gb/s with clear open eye diagram, achieving error free operation with a power penalty of 4dB

Monolithically integrated all-optical SOA-based SR Flip-Flop on InP platform

In this paper, we demonstrate for the first time a monolithically integrated InP All-Optical Flip-Flop (FF) based on optical coupled SOA-MZI switches. The experimental proof of principle demonstrated successful error free operation of SR-FF functionality at 5 Gb/s

Optical static RAM cell using a monolithically integrated InP Flip-Flop and wavelength-encoded signals

We experimentally demonstrate successful optical static RAM cell operation with READ/WRITE at 5Gbps and I/O wavelength diversity capabilities. The RAM cell incorporates an integrated SOA-MZI Access Gate and a monolithic InP Flip-Flop with coupled switches

Use of amorphous silicon for the design of a photonic crystal based MZ modulator at 1.55μm

The design of an amorphous silicon based Mach-Zehnder electro-optic modulator integrated into a two-dimensional (2D) photonic crystal (PhC) has been designed for wavelengths of ~1.55 μ m. The numerical analysis has been performed by using a finite-difference time domain (FDTD) based simulation tool. The design of the PhC-based MZ Modulator relies on the exploitation of the refractive index tunability of the hydrogenated amorphous silicon (a-Si:H) for the fabrication of PhC waveguides requiring minimum critical technological processes

Design of amorphous silicon photonic crystal-based M-Z modulator operating at 1.55 μm

The design of an amorphous silicon-based Mach-Zehnder electro-optic modulator including two guiding pi-n structures integrated inside a two-dimensional (2-D) photonic crystal (PhC) working at 1.55 μm, is reported. Electrically induced free carrier dispersion effect in this photonic material with a very cost-effective technology, is investigated for modulation. Our numerical analysis, performed by a time-domain (FDTD)-based software, proves that the voltage-length product can be remarkably reduced by taking advantage of both the strong PhC confinement and the wide refractive index tunability of amorphous silicon

Hydrodynamic conditions in front of a vertical wall with an overhanging horizontal cantilever slab

Transforming wave heights from offshore to the shoreline is the first step of any coastal engineering work. Wave breaking is analyzed to understand hydrodynamic conditions. For vertical breakwaters and sea walls, wave reflection is an important process that affects the determination of the wave height. Many of the design formulas presented in the literature depend on empirical studies based on the structures tested. In this study, the hydrodynamic conditions in front of a vertical wall with an overhanging horizontal cantilever slab with a foreshore slope of 1/20 are determined experimentally under regular wave conditions to assess the applicability of the formulas of Goda (2000) for predicting the nearshore wave height and breaker index equation (Goda, 2010). The selection of wave measurements used to determine the design wave height, the reflection coefficients, and wave breaking is also analyzed, and the reflection equations are derived from the dataset covering different breaker types. Small-scale tests show that the incident wave height is a good representative of the design wave height and that the values predicted by Goda are in good agreement with actual measurements. However, the predicted H-max values are overestimated. In addition, the inception of the wave breaking point is postponed because of the reflection and/or turbulence left over from preceding waves, which is an effect of the vertical wall. At higher water levels, the effect of the vertical wall on the inception point becomes more significant

Loads on Entrance platforms for off-shore wind turbines

The present paper gives an overview of the performed large scale tests in GWK, Hannover, for studying wave run up generated forces on wind turbine entrance platforms. The run-up height and velocity was measured by use of high speed video recordings supplemented by some wave gauges mounted on the pile. Hereafter, the run up generated impact forces were measured on two types of grates and solid plate. The pressure distribution was also measured for the solid plate. In addition to this the wave generated backfilling of an initial scour hole and the strength of the backfilling soil was studied. The purpose of all the tests was to study scale effects related to the above items by comparison with small scale tests and also to present new guidelines for desig