High Zn content of Randall's plaque: A μ-X-ray fluorescence investigation

Kidney stone disease, or nephrolithiasis, is a common ailment. Among the different risk factors usually associated with nephrolithiasis are dehydration, metabolic defects (especially with regard to calcium and oxalate). The presence of a mineral deposit at the surface of the renal papilla (termed Randall's plaque) has all been recently underlined. Of note, Randall's plaque is made of the calcium phosphate, carbapatite, and serves as a nucleus for kidney stone formation. The process by which apatite nanocrystals nucleate and form Randall's plaque remains unclear. This paper deals with the possible relationship between trace elements and the formation of this mineral. The investigation has been performed on a set of Randall's plaques, extracted from human kidney stones, through μ-X-ray diffraction and μ-X-ray fluorescence analyses in order to determine the chemical composition of the plaque as well as the nature and the amount of trace elements. Our data provide evidence that Zn levels are dramatically increased in carbapatite of RP by comparison to carbapatite in kidney stones, suggesting that calcified deposits within the medullar interstitium are a pathological process involving a tissue reaction. Further studies, perhaps including the investigation of biomarkers for inflammation, are necessary for clarifying the role of Zn in Randall's plaque formation

Differentiable Collision Detection: a Randomized Smoothing Approach

Collision detection appears as a canonical operation in a large range of robotics applications from robot control to simulation, including motion planning and estimation. While the seminal works on the topic date back to the 80s, it is only recently that the question of properly differentiating collision detection has emerged as a central issue, thanks notably to the ongoing and various efforts made by the scientific community around the topic of differentiable physics. Yet, very few solutions have been suggested so far, and only with a strong assumption on the nature of the shapes involved. In this work, we introduce a generic and efficient approach to compute the derivatives of collision detection for any pair of convex shapes, by notably leveraging randomized smoothing techniques which have shown to be particularly adapted to capture the derivatives of non-smooth problems. This approach is implemented in the HPP-FCL and Pinocchio ecosystems, and evaluated on classic datasets and problems of the robotics literature, demonstrating few micro-second timings to compute informative derivatives directly exploitable by many real robotic applications including differentiable simulation.Comment: 7 pages, 6 figures, 2 table

Who Is In Charge, and Who Should Be? The Disciplinary Role of the Commander in Military Justice Systems

BackgroundStandard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma. MethodsWe randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival. ResultsA total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P=0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P=0.049) and 33.9% and 30.1% at 2 years (P=0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%). ConclusionsThe addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo.

Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine

Galunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor, blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein) and TGF-β-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments included chemokine, cytokine, and T cell subsets alterations. 158 patients were randomized to galunisertib plus lomustine (n = 79), galunisertib (n = 39) and placebo+lomustine (n = 40). In 127 of these patients, tissue was adequate for central pathology review and biomarker work. Isocitrate dehydrogenase (IDH1) negative glioblastoma patients with baseline pSMAD2+ in cytoplasm had median overall survival (OS) 9.5 months vs. 6.9 months for patients with no tumor pSMAD2 expression (p = 0.4574). Eight patients were IDH1 R132H+ and had a median OS of 10.4 months compared to 6.9 months for patients with negative IDH1 R132H (p = 0.5452). IDH1 status was associated with numerically higher plasma macrophage-derived chemokine (MDC/CCL22), higher whole blood FOXP3, and reduced tumor CD3+ T cell counts. Compared to the baseline, treatment with galunisertib monotherapy preserved CD4+ T cell counts, eosinophils, lymphocytes, and the CD4/CD8 ratio. The T-regulatory cell compartment was associated with better OS with MDC/CCL22 as a prominent prognostic marker. View Full-Tex

PROX-QP: Yet another Quadratic Programming Solver for Robotics and beyond

International audienceQuadratic programming (QP) has become a core modelling component in the modern engineering toolkit. This is particularly true for simulation, planning and control in robotics. Yet, modern numerical solvers have not reached the level of efficiency and reliability required in practical applications where speed, robustness, and accuracy are all necessary. In this work, we introduce a few variations of the well-established augmented Lagrangian method, specifically for solving QPs, which include heuristics for improving practical numerical performances. Those variants are embedded within an open-source software which includes an efficient C++ implementation, a modular API, as well as best-performing heuristics for our test-bed. Relying on this framework, we present a benchmark studying the practical performances of modern optimization solvers for convex QPs on generic and complex problems of the literature as well as on common robotic scenarios. This benchmark notably highlights that this approach outperforms modern solvers in terms of efficiency, accuracy and robustness for small to medium-sized problems, while remaining competitive for higher dimensions

VLTI status update: a decade of operations and beyond

We present the latest update of the European Southern Observatory's Very Large Telescope interferometer (VLTI). The operations of VLTI have greatly improved in the past years: reduction of the execution time; better offering of telescopes configurations; improvements on AMBER limiting magnitudes; study of polarization effects and control for single mode fibres; fringe tracking real time data, etc. We present some of these improvements and also quantify the operational improvements using a performance metric. We take the opportunity of the first decade of operations to reflect on the VLTI community which is analyzed quantitatively and qualitatively. Finally, we present briefly the preparatory work for the arrival of the second generation instruments GRAVITY and MATISSE.Comment: 10 pages, 7 figures, Proceedings of the SPIE, 9146-1

High-flow oxygen therapy versus noninvasive ventilation: a randomised physiological crossover study of alveolar recruitment in acute respiratory failure.

High-flow nasal cannula (HFNC) oxygen therapy has recently shown clinical benefits in hypoxaemic acute respiratory failure (ARF) patients, while the value of noninvasive ventilation (NIV) remains debated. The primary end-point was to compare alveolar recruitment using global end-expiratory electrical lung impedance (EELI) between HFNC and NIV. Secondary end-points compared regional EELI, lung volumes (global and regional tidal volume variation (V (T))), respiratory parameters, haemodynamic tolerance, dyspnoea and patient comfort between HFNC and NIV, relative to face mask (FM). A prospective randomised crossover physiological study was conducted in patients with hypoxaemic ARF due to pneumonia. They received alternately HFNC, NIV and FM. 16 patients were included. Global EELI was 4083 with NIV and 2921 with HFNC (p=0.4). Compared to FM, NIV and HFNC significantly increased global EELI by 1810.5 (95% CI 857-2646) and 826 (95% CI 399.5-2361), respectively. Global and regional V (T) increased significantly with NIV compared to HFNC or FM, but not between HFNC and FM. NIV yielded a significantly higher pulse oxygen saturation/inspired oxygen fraction ratio compared to HFNC (p=0.03). No significant difference was observed between HFNC, NIV and FM for dyspnoea. Patient comfort score with FM was not significantly different than with HFNC (p=0.1), but was lower with NIV (p=0.001). This study suggests a potential benefit of HFNC and NIV on alveolar recruitment in patients with hypoxaemic ARF. In contrast with HFNC, NIV increased lung volumes, which may contribute to overdistension and its potentially deleterious effect in these patients

Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419)

Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined. Methods: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumours, prognostic factors were analysed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich. Results: At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterised) had been registered. In the IDH wildtype population, median age was 56 years (range 24-78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumours with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% confidence interval [95% CI] 7.9-11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p < 0.001) and had a high rate (48.8%) of MGMT promoter-unmethylated tumours. Conclusions: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma