Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.

BACKGROUND: Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are common in urothelial carcinoma and may be associated with lower sensitivity to immune interventions. Erdafitinib, a tyrosine kinase inhibitor of FGFR1-4, has shown antitumor activity in preclinical models and in a phase 1 study involving patients with FGFR alterations. METHODS: In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified FGFR alterations. All the patients had a history of disease progression during or after at least one course of chemotherapy or within 12 months after neoadjuvant or adjuvant chemotherapy. Prior immunotherapy was allowed. We initially randomly assigned the patients to receive erdafitinib in either an intermittent or a continuous regimen in the dose-selection phase of the study. On the basis of an interim analysis, the starting dose was set at 8 mg per day in a continuous regimen (selected-regimen group), with provision for a pharmacodynamically guided dose escalation to 9 mg. The primary end point was the objective response rate. Key secondary end points included progression-free survival, duration of response, and overall survival. RESULTS: A total of 99 patients in the selected-regimen group received a median of five cycles of erdafitinib. Of these patients, 43% had received at least two previous courses of treatment, 79% had visceral metastases, and 53% had a creatinine clearance of less than 60 ml per minute. The rate of confirmed response to erdafitinib therapy was 40% (3% with a complete response and 37% with a partial response). Among the 22 patients who had undergone previous immunotherapy, the confirmed response rate was 59%. The median duration of progression-free survival was 5.5 months, and the median duration of overall survival was 13.8 months. Treatment-related adverse events of grade 3 or higher, which were managed mainly by dose adjustments, were reported in 46% of the patients; 13% of the patients discontinued treatment because of adverse events. There were no treatment-related deaths. CONCLUSIONS: The use of erdafitinib was associated with an objective tumor response in 40% of previously treated patients who had locally advanced and unresectable or metastatic urothelial carcinoma with FGFR alterations. Treatment-related grade 3 or higher adverse events were reported in nearly half the patients. (Funded by Janssen Research and Development; BLC2001 ClinicalTrials.gov number, NCT02365597.).

Enhanced light trapping in solar cells using snow globe coating.

A novel method, snow globe coating, is found to show significant enhancement of the short circuit current JSC (35%) when applied as a scattering back reflector for polycrystalline silicon thin-film solar cells. The coating is formed from high refractive index titania particles without containing binder and gives close to 100% reflectance for wavelengths above 400 nm. Snow globe coating is a physicochemical coating method executable in pH neutral media. The mild conditions of this process make this method applicable to many different types of solar cells.

Modeling of the laser polarization as control parameter in self-organized surface pattern.

To shed light on nanopattern formation upon femtosecond laser ablation, an adopted surface erosion model is developed, based on the description for ion beam sputtering. In particular, the dependence of generated patterns on the laser polarization is taken into account. We find that an asymmetry in deposition and dissipation of incident laser energy results in a respective dependence of coefficients in a nonlinear equation of the Kuramoto-Sivashinsky type. Surface morphologies obtained by this model for different polarization of the laser beam are presented and the time evolution of the nanopattern is discussed. A comparison of these numerical results with experimental data shows an excellent agreement. Dependence of femtosecond laser induced formation on the polarization of the incident beam within an adopted surface erosion model is considered. A continuum theory of erosion by polarized laser radiation is developed. We exploit the similarity to ion-beam sputtering and extend a corresponding model for laser ablation by including laser polarization. This yields a respective dependence of coefficients in a nonlinear equation of the Kuramoto-Sivashinsky type. We present the surface morphologies obtained by this model for different polarization of the laser beam and discuss a time evolution of the nanopattern. These numerical results are in a good agreement with numerous experimental data. We show that the correlation of ripples orientation with laser polarization can be described within a model where the polarization causes the breaking of symmetry at the surface. Our results support the non-linear self-organization mechanism of pattern formation on the surface of solids.

Overall survival in patients with metastatic renal cell carcinoma in Russia, Kazakhstan, and Belarus: a report from the RENSUR3 registry.

BACKGROUND: Real-world data describing outcomes of treatment among metastatic renal cell carcinoma (mRCC) patients are limited and heterogeneous. AIM: RENSUR3 registry study assessed real-world data on the use of therapies in mRCC and overall survival (OS) in Russia, Kazakhstan, and Belarus. METHODS: Patients were included in the retrospective multicenter registry study. To be eligible, patients were required to have mRCC diagnosed from January 2015 to January 2016. Anonymized data were collected through an online registry. The outcomes of interest were patient characteristics, treatment patterns, and OS. RESULTS: 1094 mRCC patients were identified. Mean age was 62.3 (SD, 11.2) years. Four hundred and forty-four (41%) patients were 65 years and older. Primary tumor has not been removed in 503 (46%) patients. Subtype of RCC based on WHO classification (clear-cell or other) has been reported in 402 (37%) patients. In total, 595 (54.4%) patients received systemic therapy for metastatic disease. 58% of elderly patients (≥65) were not treated compared to 37% of younger patients. Cytokines and targeted therapy were used in 298 (50.1%) and 297 (49.9%) of 595 treated patients, respectively. Median OS was 11.9 months (95% CI 10.9-12.9). The 1- and 3-year OS rates were 49.6% and 19.3%. CONCLUSIONS: Half of patients received no systemic therapy or had only cytokines for mRCC in Russia, Kazakhstan, and Belarus, which doubtless negatively affected OS in this population. Novel therapies should be considered as life prolonging and a priority.

Role of Kuroshio Current in fish resource variability off southwest Japan.

Western boundary currents in the subtropics play a pivotal role in transporting warm water from the tropics that contribute to development of highly diverse marine ecosystem in the coastal regions. As one of the western boundary currents in the North Pacific, the Kuroshio Current (hereafter the Kuroshio) exerts great influences on biological resource variability off southwest Japan, but few studies have examined physical processes that attribute the coastal fish resource variability to the basin-scale Kuroshio variability. Using the high-quality fish catch data and high-resolution ocean reanalysis results, this study identifies statistical links of interannual fish resource variability off Sukumo Bay, Shikoku island of Japan, to subsurface ocean temperature variability in the Kuroshio. The subsurface ocean temperature variability off the south of Sukumo Bay exhibits vertically coherent structure with sea-surface height variability, which originates from the westward-propagating oceanic Rossby waves generated through surface wind anomalies in the Northwest Pacific. Although potential sources of the atmospheric variability remain unclarified, the remotely-induced oceanic Rossby waves contribute to fish resource variability off Sukumo Bay. These findings have potential applications to other coastal regions along the western boundary currents in the subtropics where the westward-propagating oceanic Rossby waves may contribute to coastal ocean temperature variability.

Assimilation of the seabird and ship drift data in the north-eastern sea of Japan into an operational ocean nowcast/forecast system.

At the present time, ocean current is being operationally monitored mainly by combined use of numerical ocean nowcast/forecast models and satellite remote sensing data. Improvement in the accuracy of the ocean current nowcast/forecast requires additional measurements with higher spatial and temporal resolution as expected from the current observation network. Here we show feasibility of assimilating high-resolution seabird and ship drift data into an operational ocean forecast system. Data assimilation of geostrophic current contained in the observed drift leads to refinement in the gyre mode events of the Tsugaru warm current in the north-eastern sea of Japan represented by the model. Fitting the observed drift to the model depends on ability of the drift representing geostrophic current compared to that representing directly wind driven components. A preferable horizontal scale of 50 km indicated for the seabird drift data assimilation implies their capability of capturing eddies with smaller horizontal scale than the minimum scale of 100 km resolved by the satellite altimetry. The present study actually demonstrates that transdisciplinary approaches combining bio-/ship- logging and numerical modeling could be effective for enhancement in monitoring the ocean current.

Polycrystalline silicon thin-film solar cells with plasmonic-enhanced light-trapping.

One of major approaches to cheaper solar cells is reducing the amount of semiconductor material used for their fabrication and making cells thinner. To compensate for lower light absorption such physically thin devices have to incorporate light-trapping which increases their optical thickness. Light scattering by textured surfaces is a common technique but it cannot be universally applied to all solar cell technologies. Some cells, for example those made of evaporated silicon, are planar as produced and they require an alternative light-trapping means suitable for planar devices. Metal nanoparticles formed on planar silicon cell surface and capable of light scattering due to surface plasmon resonance is an effective approach. The paper presents a fabrication procedure of evaporated polycrystalline silicon solar cells with plasmonic light-trapping and demonstrates how the cell quantum efficiency improves due to presence of metal nanoparticles. To fabricate the cells a film consisting of alternative boron and phosphorous doped silicon layers is deposited on glass substrate by electron beam evaporation. An Initially amorphous film is crystallised and electronic defects are mitigated by annealing and hydrogen passivation. Metal grid contacts are applied to the layers of opposite polarity to extract electricity generated by the cell. Typically, such a ~2 µm thick cell has a short-circuit current density (Jsc) of 14-16 mA/cm(2), which can be increased up to 17-18 mA/cm(2) (~25% higher) after application of a simple diffuse back reflector made of a white paint. To implement plasmonic light-trapping a silver nanoparticle array is formed on the metallised cell silicon surface. A precursor silver film is deposited on the cell by thermal evaporation and annealed at 23°C to form silver nanoparticles. Nanoparticle size and coverage, which affect plasmonic light-scattering, can be tuned for enhanced cell performance by varying the precursor film thickness and its annealing conditions. An optimised nanoparticle array alone results in cell Jsc enhancement of about 28%, similar to the effect of the diffuse reflector. The photocurrent can be further increased by coating the nanoparticles by a low refractive index dielectric, like MgF(2;), and applying the diffused reflector. The complete plasmonic cell structure comprises the polycrystalline silicon film, a silver nanoparticle array, a layer of MgF(2;), and a diffuse reflector. The Jsc for such cell is 21-23 mA/cm(2), up to 45% higher than Jsc of the original cell without light-trapping or ~25% higher than Jsc for the cell with the diffuse reflector only.