Summary
Background
JTE‐052 is a novel Janus kinase inhibitor presently under clinical development for the topical treatment of atopic dermatitis (AD).
Objectives
To evaluate the efficacy and safety ...of JTE‐052 ointment in Japanese adult patients with AD.
Methods
Patients with moderate‐to‐severe AD were randomized (2: 2: 2: 2: 1: 1) to receive JTE‐052 ointment at 0·25%, 0·5%, 1% or 3%, the vehicle ointment or tacrolimus 0·1% ointment (reference) twice daily for 4 weeks. The primary efficacy end point was the percentage change in modified Eczema Area Severity Index (mEASI) score from baseline at the end of treatment (EOT). Secondary efficacy end points included change from baseline in the pruritus numerical rating scale (NRS) score.
Results
In total, 327 patients were enrolled. At EOT, the least‐squares mean percentage changes from baseline in mEASI score for JTE‐052 at 0·25%, 0·5%, 1% and 3% and the vehicle ointment were −41·7%, −57·1%, −54·9%, −72·9% and −12·2%, respectively. All JTE‐052 groups showed significant reductions of mEASI score vs. the vehicle group (P < 0·001 for all). In the tacrolimus group, the mean percentage change in mEASI score was −62·0%. The JTE‐052 groups also showed significant improvement in other parameters; notably, the pruritus NRS score was reduced as early as day 1 night‐time. JTE‐052 ointment at doses up to 3% was safe and well tolerated.
Conclusions
Topical JTE‐052 markedly and rapidly improved clinical signs and symptoms in Japanese adult patients with moderate‐to‐severe AD, with a favourable safety profile. The study results indicate that topical JTE‐052 is a promising therapeutic option for AD. The trial registration number is JapicCTI‐152887.
What's already known about this topic?
Atopic dermatitis (AD) is a chronic inflammatory skin disease with impaired skin barrier function and pruritus.
The results of some clinical and experimental studies support the concept that inhibition of cytokine signalling via Janus kinase (JAK) may contribute to the improvement of AD.
What does this study add?
Topical JTE‐052, a novel JAK inhibitor, markedly and rapidly improved clinical signs and symptoms in Japanese adult patients with moderate‐to‐severe AD and showed a favourable safety profile.
The study results indicate that topical JTE‐052 is a promising therapeutic option for AD.
Linked Comment: Bissonnette. Br J Dermatol 2018; 178:321.
Plain language summary available online
Respond to this article
In the present study, compressible low-Reynolds-number flow past a stationary isolated sphere was investigated by direct numerical simulations of the Navier–Stokes equations using a body-fitted grid ...with high-order schemes. The Reynolds number based on free-stream quantities and the diameter of the sphere was set to be between 250 and 1000, and the free-stream Mach number was set to be between 0.3 and 2.0. As a result, it was clarified that the wake of the sphere is significantly stabilized as the Mach number increases, particularly at the Mach number greater than or equal to 0.95, but turbulent kinetic energy at the higher Mach numbers conditions is higher than that at the lower Mach numbers conditions of similar flow regimes. A rapid extension of the length of the recirculation region was observed under the transitional condition between the steady and unsteady flows. The drag coefficient increases as the Mach number increases mainly in the transonic regime and its increment is almost due to the increment in the pressure component. In addition, the increment in the drag coefficient is approximately a function of the Mach number and independent of the Reynolds number in the continuum regime. Moreover, the effect of the Mach and Reynolds numbers on the flow properties such as the drag coefficient and flow regime can approximately be characterized by the position of the separation point.
SUMMARY
Reconstruction of the distribution of ground motion due to an earthquake is one of the key technologies for the prediction of seismic damage to infrastructure. Particularly, the immediate ...reconstruction of the spatially continuous wavefield is valuable for decision-making of disaster response decisions in the initial phase. For a fast and accurate reconstruction, utilization of prior information is essential. In fluid mechanics, full-state recovery, which recovers the full state from sparse observation using a data-driven model reduced-order model, is actively used. In this study, the framework developed in the field of fluid mechanics is applied to seismic wavefield reconstruction. A seismic wavefield reconstruction framework based on compressed sensing using the data-driven reduced-order model (ROM) is proposed and its characteristics are investigated through numerical experiments. The data-driven ROM is generated from the data set of the wavefield using the singular value decomposition. The spatially continuous seismic wavefield is reconstructed from the sparse and discrete observation and the data-driven ROM. The observation sites used for reconstruction are effectively selected by the sensor optimization method for linear inverse problems based on a greedy algorithm. The proposed framework was applied to simulation data of theoretical waveform with the subsurface structure of the horizontally stratified three layers. The validity of the proposed method was confirmed by the reconstruction based on the noise-free observation. Since the ROM of the wavefield is used as prior information, the reconstruction error is reduced to an approximately lower error bound of the present framework, even though the number of sensors used for reconstruction is limited and randomly selected. In addition, the reconstruction error obtained by the proposed framework is much smaller than that obtained by the Gaussian process regression. For the numerical experiment with noise-contaminated observation, the reconstructed wavefield is degraded due to the observation noise, but the reconstruction error obtained by the present framework with all available observation sites is close to a lower error bound, even though the reconstructed wavefield using the Gaussian process regression is fully collapsed. Although the reconstruction error is larger than that obtained using all observation sites, the number of observation sites used for reconstruction can be reduced while minimizing the deterioration and scatter of the reconstructed data by combining it with the sensor optimization method. Hence, a better and more stable reconstruction of the wavefield than randomly selected observation sites can be realized, even if the reconstruction is carried out with a smaller number of observations with observation noise, by combining it with the sensor optimization method.
Ever since the first image of a coral reef was captured in 1885, people worldwide have been accumulating images of coral reefscapes that document the historic conditions of reefs. However, these ...innumerable reefscape images suffer from perspective distortion, which reduces the apparent size of distant taxa, rendering the images unusable for quantitative analysis of reef conditions. Here we solve this century-long distortion problem by developing a novel computer-vision algorithm, ReScape, which removes the perspective distortion from reefscape images by transforming them into top-down views, making them usable for quantitative analysis of reef conditions. In doing so, we demonstrate the first-ever ecological application and extension of inverse-perspective mapping-a foundational technique used in the autonomous-driving industry. The ReScape algorithm is composed of seven functions that (1) calibrate the camera lens, (2) remove the inherent lens-induced image distortions, (3) detect the scene's horizon line, (4) remove the camera-roll angle, (5) detect the transformable reef area, (6) detect the scene's perspective geometry, and (7) apply brute-force inverse-perspective mapping. The performance of the ReScape algorithm was evaluated by transforming the perspective of 125 reefscape images. Eighty-five percent of the images had no processing errors and of those, 95% were successfully transformed into top-down views. ReScape was validated by demonstrating that same-length transects, placed increasingly further from the camera, became the same length after transformation. The mission of the ReScape algorithm is to (i) unlock historical information about coral-reef conditions from previously unquantified periods and localities, (ii) enable citizen scientists and recreational photographers to contribute reefscape images to the scientific process, and (iii) provide a new survey technique that can rigorously assess relatively large areas of coral reefs, and other marine and even terrestrial ecosystems, worldwide. To facilitate this mission, we compiled the ReScape algorithm into a free, user-friendly App that does not require any coding experience. Equipped with the ReScape App, scientists can improve the management and prediction of the future of coral reefs by uncovering historical information from reefscape-image archives and by using reefscape images as a new, rapid survey method, opening a new era of coral-reef monitoring.
Nitrogen fixation in temperate oceans is a potentially important, but poorly understood process that may influence the marine nitrogen budget. This study determined seasonal variations in nitrogen ...fixation and the diazotroph community within the euphotic zone in the temperate coastal region of the northwestern North Pacific. Nitrogen fixation as high as 13.6 nmol N L−1 d−1 was measured from early summer to fall when the surface temperature exceeded 14.2 °C (but was lower than 24.3 °C) and the surface nitrate concentration was low (≤ 0.30 μM), although we also detected nitrogen fixation in subsurface layers (42–62 m) where nitrate concentrations were high (> 1 μM). Clone library analysis results indicated that nifH gene sequences were omnipresent throughout the investigation period. During the period when nitrogen fixation was detected (early summer to fall), the genes affiliated with UCYN-A, Trichodesmium, and γ-proteobacterial phylotype γ-24774A11 were frequently recovered. In contrast, when nitrogen fixation was undetectable (winter to spring), many sequences affiliated with Cluster III diazotrophs (putative anaerobic bacteria) were recovered. Quantitative PCR analysis revealed that UCYN-A was relatively abundant from early to late summer compared with Trichodesmium and γ-24774A11, whereas Trichodesmium abundance was the highest among the three groups during fall.
In the present study, a compressible low-Reynolds-number flow over a circular cylinder was investigated using a low-density wind tunnel with time-resolved schlieren visualizations and pressure and ...force measurements. The Reynolds number ( $Re$ ) based on freestream quantities and the diameter of a circular cylinder was set to be between 1000 and 5000, and the freestream Mach number ( $M$ ) between 0.1 and 0.5. As a result, we have clarified the effect of $M$ on the aerodynamic characteristics of flow over a circular cylinder at $Re=O(10^{3})$ . The results of the schlieren visualization showed that the trend of $M$ effect on the flow field, that are the release location of the Kármán vortices, the Strouhal number of vortex shedding and the maximum width of the recirculation, is changed at approximately $Re=3000$ . In addition, the spanwise phase difference of the surface pressure fluctuation was captured by the measurement using pressure-sensitive paint at approximately $Re=3000$ of higher- $M$ cases. The observed spanwise phase difference is considered to relate to the spanwise phase difference of the vortex shedding due to the oblique instability wave on the separated shear layer caused by the compressibility effects. The Strouhal number of the vortex shedding is influenced by $M$ and $Re$ , and those effects are nonlinear. However, the effects of $M$ and $Re$ can approximately be characterized by the maximum width of the recirculation. In addition, the $M$ effect on the drag coefficient can be characterized by the maximum width of the recirculation region and the Prandtl–Glauert transformation.
SUMMARY
The ‘big’ seismic data not only acquired by seismometers but also acquired by vibrometers installed in buildings and infrastructure and accelerometers installed in smartphones will be ...certainly utilized for seismic research in the near future. Since it is impractical to utilize all the seismic big data in terms of the computational cost, methods which can select observation sites depending on the purpose are indispensable. We propose an observation site selection method for the accurate reconstruction of the seismic wavefield by process-driven approaches. The proposed method selects observation sites suitable for accurately estimating physical model parameters such as subsurface structures and source information to be input into a numerical simulation of the seismic wavefield. The seismic wavefield is reconstructed by the numerical simulation using the parameters estimated based on the observed signals at only observation sites selected by the proposed method. The observation site selection in the proposed method is based on the sensitivity of each observation site candidate to the physical model parameters; the matrix corresponding to the sensitivity is constructed by approximately calculating the derivatives based on the simulations, and then, observation sites are selected by evaluating the quantity of the sensitivity matrix based on the D-optimality criterion proposed in the optimal design of experiments. In this study, physical knowledge on the sensitivity to the parameters such as seismic velocity, layer thickness, and hypocentre location was obtained by investigating the characteristics of the sensitivity matrix. Furthermore, the effectiveness of the proposed method was shown by verifying the accuracy of seismic wavefield reconstruction using the observation sites selected by the proposed method.
This paper proposes a multi-agent approach to power system restoration. The proposed system consists of a number of bus agents (BAGS) and a single facilitator agent (FAG). BAG is developed to decide ...a suboptimal target configuration after a fault occurrence by interacting with other BAGS based on only locally available information, while FAG is to act as a manager in the decision process. The interaction of several simple agents leads to a dynamic system, allowing efficient approximation of a solution. Simulation results have demonstrated that this method is able to reach suboptimal target configurations, which are favorably compared with those obtained by a mathematical programming approach.
The Serpens South embedded cluster, which is located in the constricted part of a long, filamentary, infrared dark cloud, is believed to be in a very early stage of cluster formation. We present ...results of near-infrared (JHKs) polarization observations of the filamentary cloud. Our polarization measurements of near-infrared point sources indicate a well-ordered global magnetic field that is perpendicular to the main filament, implying that the magnetic field is likely to have controlled the formation of the main filament. On the other hand, the sub-filaments, which converge on the central part of the cluster, tend to run along the magnetic field. The global magnetic field appears to be curved in the southern part of the main filament. Such morphology is consistent with the idea that the global magnetic field is distorted by gravitational contraction along the main filament toward the northern part, which contains larger mass. Applying the Chandrasekhar-Fermi method, the magnetic field strength is roughly estimated to be a few X100 Delta *mG, suggesting that the filamentary cloud is close to magnetically critical.
PDF
