Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3)

OBJECTIVE: To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents. METHODS: Patients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks. RESULTS: At week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%; p=0.0295 and p \u3c 0.0001, respectively), and mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (-0.20) versus placebo (-0.07; p=0.0073). In patients with baseline psoriasis body surface area involvement \u3e /=3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%; p=0.0098) at week 16. At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment. Most adverse events were mild to moderate in severity; the most common were diarrhoea, nausea, headache and upper respiratory tract infection. CONCLUSIONS: Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. Apremilast was generally well tolerated and demonstrated an acceptable safety profile. TRIAL REGISTRATION NUMBER: NCT01212770

Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis

Background & Aims New oral therapeutic agents are needed for patients with ulcerative colitis (UC) who are unresponsive or intolerant to conventional therapy. Methods We performed a double-blind, phase 2 trial of adults with active UC for 3 months or more who were naive to biologic therapy or had been failed by, could not tolerate, or had contraindications to conventional therapies. The study was performed at 61 sites in 14 countries (screening from January 2015 through May 2017). Patients were randomly assigned to groups given apremilast 30 mg (n = 57), apremilast 40 mg (n = 55), or placebo (n = 58) twice daily for 12 weeks; patients were then randomly assigned to groups that received apremilast, 30 or 40 mg twice daily, for an additional 40 weeks. Endoscopies were performed and biopsies were collected during the screening phase, at week 12, and at week 52. Blood and fecal samples were also collected and analyzed throughout the study. The primary endpoint was clinical remission at week 12, defined as a total Mayo score of 2 or less, with no individual subscore above 1. Results Clinical remission was achieved at week 12 by 31.6% of patients in the 30 mg apremilast group and 12.1% of patients in the placebo group (P = .01). However, only 21.8% of patients in the 40 mg apremilast group achieved clinical remission at week 12 (P = .27 compared with placebo). Differences in clinical remission between the 30 mg and 40 mg apremilast groups were associated with differences in endoscopic improvement. Both apremilast groups had similar improvements from baseline in Mayo score components (stool frequency score, rectal bleeding score, physician's global assessment). The 30 mg and 40 mg apremilast groups had greater median percent reductions in C-reactive protein (measured by a high-sensitivity blood test) and fecal calprotectin through week 12 than the placebo group. At week 52, clinical remission was achieved by 40.4% of patients initially assigned to the apremilast 30 mg group and 32.7% of patients initially assigned to the apremilast 40 mg group. The most frequent apremilast-associated adverse events were headache and nausea. Conclusions Although the primary endpoint of clinical remission was not met in this phase 2 trial, a greater proportion of patients with active UC who received apremilast (30 mg or 40 mg) had improvements in clinical and endoscopic features, and markers of inflammation, at 12 weeks. Clinical remission was maintained to week 52 in up to 40% of patients who continued apremilast until that time point. ClinicalTrials.gov no: NCT0228941

Strain-Controlled Spin Wave Excitation and Gilbert Damping in Flexible Co2FeSi Films Activated by Femtosecond Laser Pulse

The dynamic response of magnetic order to optical excitation at sub-picosecond scale has offered an intriguing alternative for magnetism manipulation. Such ultrafast optical manipulation of magnetism has become a fundamental challenging topic with high implications for future spintronics. Here, this study demonstrates such manipulation in Co2FeSi films grown on flexible polyimide substrate, and demonstrates how the magneto-optical interaction can be modified by using strain engineering which in turn triggers the excitation of both dipolar and exchange spin waves modes. Furthermore, Gilbert damping and spin-orbit coupling in Co2FeSi can both be tuned significantly by altering the magnitude and type of applied strain, suggesting an appealing way to manipulate spin wave propagation. These results develop the optical manipulation magnetism into the field of spin wave dynamics, and open a new direction in the application of spin orbitronics and magnonics devices using strain engineering

Speckle Noise Suppression Based on Empirical Mode Decomposition and Improved Anisotropic Diffusion Equation

Existing methods to eliminate the laser speckle noise in quantitative phase imaging always suffer from the loss of detailed phase information and the resolution reduction in the reproduced image. To overcome these problems, this paper proposes a speckle noise suppression method based on empirical mode decomposition. Our proposed method requires only one image without additional equipment and avoids the complicated process of searching the optimal processing parameters. In this method, we use empirical mode decomposition to highlight the high frequency information of the interference image and use the Canny operator to perform edge detection, so the diffusion denoising process is guided by high-precision detection results to achieve better results. To validate the performance of our proposed method, the phase maps processed by our proposed method are compared with the phase maps processed by the improved anisotropic diffusion equation method with edge detection, the mean filter method and the median filter method. The experimental results show that the method proposed in this paper not only has a better denoising effect but also preserves more details and achieves higher phase reconstruction accuracy

Suppressing the zero-frequency component of hologram with Hilbert-Huang transform in single-shot off-axis holography

This paper proposes a method based on Hilbert-Huang transform to suppress the zero-frequency component of holograms with only one shot. It can effectively improve the quality of reconstructed phase objects

Deciding Your Own Anonymity: User-Oriented Node Selection in I2P

With the development of Internet applications, anonymous communication technology plays a very significant role in protecting personal privacy. As one of the most popular anonymous communication systems, I2P provides strong anonymity through its encryption and communication schemes. However, I2P does not consider the users' preferences, which is difficult to meet the individual demands of specific users and then allows them to decide their anonymity. Thus, this paper proposes two novel user-oriented node selection algorithms that can effectively enhance the anonymity or reduce the communication delay over the I2P network. In order to choose proper nodes, we also investigate key factors to evaluate the nodes. Then, the basic node selection algorithm (BNSA) is proposed to group routing nodes and provide high-performance node candidates. Based on BNSA, the geographic-diversity-oriented node selection algorithm (GDNSA) and the communication-delay-oriented node selection algorithm (CDNSA) are proposed. These can improve the anonymity or communication performance of the I2P network. The GDNSA increases the attack difficulty by establishing tunnels that span multiple regions. In the meantime, the CDNSA reduces the communication delay of the tunnel by selecting the next hop node with the lowest communication delay. Finally, the mathematical analysis and experimental results show that the GDNSA has good resistance to collusion attacks, and the CDNSA reduces the communication delay in spite of weakening a little anonymity. 2018 IEEE.This work was supported in part by the National Natural Science Foundation of China under Grant 61771166 and in part by the National Key Research & Development Plan of China under Grant 2016QY05X1000.Scopus2-s2.0-8505671476