Electrochemical Boron-Doped Diamond Film Microcells Micromachined with Femtosecond Laser: Application to the Determination of Water Framework Directive Metals

Planar electrochemical microcells were micromachined in a microcrystalline boron-doped diamond (BDD) thin layer using a femtosecond laser (Photo 1). The electrochemical performances of the new laser-machined BDD microcell were assessed by differential pulse anodic stripping voltammetry (DPASV) determinations, at nM level, of the four heavy metal ions of the European Water Framework Directive (WFD): Cd(II), Ni(II), Pb(II), Hg(II). The results are compared with those of previously published BDD electrodes [1]. The calculated detection limits are 0.4 nM, 6.8 nM and 5.5 nm 2.3 nM, and the linearities go up to 35nM, 97nM, 48nM and 5nM for respectively Cd(II), Ni(II) Pb(II) and Hg(II). The detection limits meet with the environmental quality standard of the WFD for three of the four metals. It was shown that the four heavy metals could be detected simultaneously, in the concentration ratio usually measured in sewage or runoff waters

Ionospheric response modeling under eclipse conditions: Evaluation of 14 December 2020, total solar eclipse prediction over the South American sector

In this work, we evaluate the SUPIM-INPE model prediction of the 14 December 2020, total solar eclipse over the South American continent. We compare the predictions with data from multiple instruments for monitoring the ionosphere and with different obscuration percentages (i.e., Jicamarca, 12.0°S, 76.8°W, 17%; Tucumán 26.9°S, 65.4° W, 49%; Chillán 36.6°S, 72.0°W; and Bahía Blanca, 38.7°S, 62.3°W, reach 95% obscuration) due to the eclipse. The analysis is done under total eclipse conditions and non-total eclipse conditions. Results obtained suggest that the model was able to reproduce with high accuracy both the daily variation and the eclipse impacts of E and F1 layers in the majority of the stations evaluated (except in Jicamarca station). The comparison at the F2 layer indicates small differences (<7.8%) between the predictions and observations at all stations during the eclipse periods. Additionally, statistical metrics reinforce the conclusion of a good performance of the model. Predicted and calibrated Total Electron Content (TEC, using 3 different techniques) are also compared. Results show that, although none of the selected TEC calibration methods have a good agreement with the SUPIM-INPE prediction, they exhibit similar trends in most of the cases. We also analyze data from the Jicamarca Incoherent Scatter Radar (ISR), and Swarm-A and GOLD missions. The electron temperature changes observed in ISR and Swarm-A are underestimated by the prediction. Also, important changes in the O/N2 ratio due to the eclipse, have been observed with GOLD mission data. Thus, future versions of the SUPIM-INPE model for eclipse conditions should consider effects on thermospheric winds and changes in composition, specifically in the O/N2 ratio

A dose escalating phase i study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies

Background Integrin signaling is an attractive target for anti-cancer treatment. GLPG0187 is a broad spectrum integrin receptor antagonist (IRA). GLPG0187 inhibited tumor growth and metastasis in mouse models. Methods We aimed to determine the Recommended Phase II Dose (RP2D) and to assess safety and tolerability of continuous i.v. infusion in patients with advanced malignant solid tumors. Anticipated dose levels were 20, 40, 80, 160, 320, and 400 mg/day in a modified 3 + 3 design. Plasma concentrations of GLPG0187 were assessed to characterize the pharmacokinetics (PK). C-terminal telopeptide of type I collagen (CTX) was used as pharmacodynamics marker. Results Twenty patients received GLPG0187. No dose limiting toxicities (DLTs) were observed. The highest possible and tested dose was 400 mg/day. Fatigue was the most frequently reported side effect (25 %). Recurrent Port-A-Cath-related infections and skin toxicity suggest cutaneous integrin inhibition. No dose-dependent toxicity could be established. PK analysis showed a short average distribution (0.16 h) and elimination (3.8 h) half-life. Continuous infusion resulted in dose proportional PK profiles. We observed decreases in serum CTX levels independent of the dose given, suggesting target engagement at the lowest dose level tested. Single agent treatment did not result in tumor responses. Conclusions GLPG0187 was well tolerated with a dose-proportional PK profile upon continuous infusion. No formal maximal tolerated dose could be established. GLPG0187 showed signs of target engagement with a favourable toxicity profile. However, continuous infusion of GLPG0187 failed to show signs of monotherapy efficacy