Near-field speckle-scanning-based x-ray imaging

The x-ray near-field speckle-scanning concept is an approach recently introduced to obtain absorption, phase, and dark-field images of a sample. In this paper, we present ways of recovering from a sample its ultrasmall-angle x-ray scattering distribution using numerical deconvolution. We also show how to access the 2D phase gradient signal from random step scans, the latter having the potential to elude the flat-field correction error. Each feature is explained theoretically and demonstrated experimentally at a synchrotron x-ray facility.Comment: 8 figures, 9 page

FORGE: An eLearning Framework for Remote Laboratory Experimentation on FIRE Testbed Infrastructure

The Forging Online Education through FIRE (FORGE) initiative provides educators and learners in higher education with access to world-class FIRE testbed infrastructure. FORGE supports experimentally driven research in an eLearning environment by complementing traditional classroom and online courses with interactive remote laboratory experiments. The project has achieved its objectives by defining and implementing a framework called FORGEBox. This framework offers the methodology, environment, tools and resources to support the creation of HTML-based online educational material capable accessing virtualized and physical FIRE testbed infrastruc- ture easily. FORGEBox also captures valuable quantitative and qualitative learning analytic information using questionnaires and Learning Analytics that can help optimise and support student learning. To date, FORGE has produced courses covering a wide range of networking and communication domains. These are freely available from FORGEBox.eu and have resulted in over 24,000 experiments undertaken by more than 1,800 students across 10 countries worldwide. This work has shown that the use of remote high- performance testbed facilities for hands-on remote experimentation can have a valuable impact on the learning experience for both educators and learners. Additionally, certain challenges in developing FIRE-based courseware have been identified, which has led to a set of recommendations in order to support the use of FIRE facilities for teaching and learning purposes

MRI channel flows in vertically-stratified models of accretion disks

Simulations of the magnetorotational instability (MRI) in 'unstratified' shearing boxes exhibit powerful coherent flows, whereby the fluid vertically splits into countermoving planar jets or `channels'. Channel flows correspond to certain axisymmetric linear MRI modes, and their preponderance follows from the remarkable fact that they are approximate nonlinear solutions of the MHD equations in the limit of weak magnetic fields. We show in this paper, analytically and with one-dimensional numerical simulations, that this property is also shared by certain axisymmetric MRI modes in vertically-stratified shearing boxes. These channel flows rapidly capture significant amounts of magnetic and kinetic energy, and thus are vulnerable to secondary shear instabilities. We examine these parasites in the vertically stratified context, and estimate the maximum amplitudes that channels attain before they are destroyed. These estimates suggest that a dominant channel flow will usually drive the disk's magnetic field to thermal strengths. The prominence of these flows and their destruction place enormous demands on simulations, but channels in their initial stages also offer a useful check on numerical codes. These benchmarks are especially valuable given the increasing interest in the saturation of the stratified MRI. Lastly we speculate on the potential connection between 'run-away' channel flows and outburst behaviour in protostellar and dwarf nova disks.Comment: 17 pages, 12 figures. MNRAS, accepted

Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors

BACKGROUND Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors. METHODS Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR). RESULTS As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3-79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16-49) for all patients. In all patients, the 24-week disease control rate was 73% (95% CI: 54-87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45-100), 56% (95% CI: 38-74), and 85% (95% CI: 71-99), respectively. Median time to response was 1.9 months (range 1.0-3.8 months). Duration of treatment ranged from 1.2-31.3+ months. Treatment-related adverse events were reported for 20 patients, with Grade 3-4 in 3 patients. No new safety signals were identified. CONCLUSIONS In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació