“Are You a Good Witch or a Bad Witch?”: An Exercise in Suspending Judgment when Interacting with “Difficult” People

Courses: Interpersonal Communication, Health Communication Objectives: In this single-class activity, students gain awareness and practice in suspending judgments about “difficult” people in order to understand the reasoning behind certain objectionable behavior

Presence-Absence Sampling Plans for Stink Bugs (Hemiptera: Pentatomidae) in the Midwest Region of the United States

Stink bugs represent an increasing risk to soybean production in the Midwest region of the United States. The current sampling protocol for stink bugs in this region is tailored for population density estimation and thus is more relevant to research purposes. A practical decision-making framework with more efficient sampling effort for management of herbivorous stink bugs is needed. Therefore, a binomial sequential sampling plan was developed for herbivorous stink bugs in the Midwest region. A total of 146 soybean fields were sampled across 11 states using sweep nets in 2016, 2017, and 2018. The binomial sequential sampling plans were developed using combinations of five tally thresholds at two proportion infested action thresholds to identify those that provided the best sampling outcomes. Final assessment of the operating characteristic curves for each plan indicated that a tally threshold of 3 stink bugs per 25 sweeps, and proportion infested action thresholds of 0.75 and 0.95 corresponding to the action thresholds of 5 and 10 stink bugs per 25 sweeps, provided the optimal balance between highest probability of correct decisions (≥ 99%) and lowest probability of incorrect decisions (≤ 1%). In addition, the average sample size for both plans (18 and 12 sets of 25 sweeps, respectively) was lower than that for the other proposed plans. The binomial sequential sampling plan can reduce the number of sample units required to achieve a management decision, which is important because it can potentially reduce risk/cost of management for stink bugs in soybean in this region

In-Orbit Performance of the GRACE Follow-on Laser Ranging Interferometer

The Laser Ranging Interferometer (LRI) instrument on the Gravity Recovery and Climate Experiment (GRACE) Follow-On mission has provided the first laser interferometric range measurements between remote spacecraft, separated by approximately 220 km. Autonomous controls that lock the laser frequency to a cavity reference and establish the 5 degrees of freedom two-way laser link between remote spacecraft succeeded on the first attempt. Active beam pointing based on differential wave front sensing compensates spacecraft attitude fluctuations. The LRI has operated continuously without breaks in phase tracking for more than 50 days, and has shown biased range measurements similar to the primary ranging instrument based on microwaves, but with much less noise at a level of 1 nm/Hz at Fourier frequencies above 100 mHz. © 2019 authors. Published by the American Physical Society

Quantification of silver nanoparticle uptake and distribution within individual human macrophages by FIB/SEM slice and view

Background Quantification of nanoparticle (NP) uptake in cells or tissues is very important for safety assessment. Often, electron microscopy based approaches are used for this purpose, which allow imaging at very high resolution. However, precise quantification of NP numbers in cells and tissues remains challenging. The aim of this study was to present a novel approach, that combines precise quantification of NPs in individual cells together with high resolution imaging of their intracellular distribution based on focused ion beam/ scanning electron microscopy (FIB/SEM) slice and view approaches. Results We quantified cellular uptake of 75 nm diameter citrate stabilized silver NPs (Ag 75 Cit) into an individual human macrophage derived from monocytic THP-1 cells using a FIB/SEM slice and view approach. Cells were treated with 10 μg/ml for 24 h. We investigated a single cell and found in total 3138 ± 722 silver NPs inside this cell. Most of the silver NPs were located in large agglomerates, only a few were found in clusters of fewer than five NPs. Furthermore, we cross-checked our results by using inductively coupled plasma mass spectrometry and could confirm the FIB/SEM results. Conclusions Our approach based on FIB/SEM slice and view is currently the only one that allows the quantification of the absolute dose of silver NPs in individual cells and at the same time to assess their intracellular distribution at high resolution. We therefore propose to use FIB/SEM slice and view to systematically analyse the cellular uptake of various NPs as a function of size, concentration and incubation time.TU Berlin, Open-Access-Mittel - 201

Microbial mediation of benthic biogenic silica dissolution

Pore water profiles from 24 stations in the South Atlantic (located in the Guinea, Angola, Cape, Guyana, and Argentine basins) show good correlations of oxygen and silicon, suggesting microbially mediated dissolution of biogenic silica. We used simple analytical transport and reaction models to show the tight coupling of the reconstructed process kinetics of aerobic respiration and silicon regeneration. A generic transport and reaction model successfully reproduced the majority of Si pore water profiles from aerobic respiration rates, confirming that the dissolution of biogenic silica (BSi) occurs proportionally to O 2 consumption. Possibly limited to well-oxygenated sediments poor in BSi, benthic Si fluxes can be inferred from O 2 uptake with satisfactory accuracy. Compared to aerobic respiration kinetics, the solubility of BSi emerged as a less influential parameter for silicon regeneration. Understanding the role of bacteria for silicon regeneration requires further investigations, some of which are outlined. The proposed aerobic respiration control of benthic silicon cycling is suitable for benthic–pelagic models. The empirical relation of BSi dissolution to aerobic respiration can be used for regionalization assessments and estimates of the silicon budget to increase the understanding of global primary and export production patterns

Olutasidenib Alone or With Azacitidine in IDH1-Mutated Acute Myeloid Leukaemia and Myelodysplastic Syndrome: Phase 1 Results of a Phase 1/2 Trial

BACKGROUND: Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aims for phase 1 of this phase 1/2 study were to assess the safety, pharmacokinetics, pharmacodynamics, and clinical activity of olutasidenib, as monotherapy or in combination with azacitidine, in patients with acute myeloid leukaemia or myelodysplastic syndrome, harbouring mutant IDH1. METHODS: In this phase 1/2, multicentre, open-label clinical trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia or intermediate, high, or very high risk myelodysplastic syndrome harbouring mutant IDH1 at 18 study sites in the USA, Australia, France, and Spain. Other key eligibility criteria included Eastern Cooperative Oncology Group performance status 0-2 with adequate liver and renal function. The primary outcomes were dose-limiting toxicities and the maximum tolerated dose, maximum evaluated dose, and the recommended phase 2 dose of olutasidenib. Olutasidenib was administered orally in doses of 150 mg once daily, 150 mg twice per day, and 300 mg once daily. Azacitidine (75 mg/m) was administered subcutaneously or intravenously daily for 7 days on, 21 days off. The study was ongoing at the data cutoff (Oct 2, 2019) and is registered with ClinicalTrials.gov, NCT02719574. FINDINGS: Patients were enrolled between Aug 8, 2016, and Nov 14, 2018. 78 patients received olutasidenib as monotherapy (n=32) or in combination with azacitidine (n=46). The median follow-up was 8·3 months (IQR 3·1-13·3) for monotherapy and 10·1 months (4·2-15·3) for combination therapy. 16 (50%) of 32 patients in the monotherapy group and 24 (52%) of 46 patients in the combination therapy group were women. Most patients were White (26 [81%] for monotherapy and 31 [67%] for combination therapy). No dose-limiting toxicities were reported in the dose-escalation cohorts and 150 mg twice per day was declared the recommended phase 2 dose on the basis of safety, pharmacokinetics and pharmacodynamics, and clinical activity. The most common (≥20%) grade 3-4 treatment-emergent adverse events with monotherapy were thrombocytopenia (nine [28%] of 32 patients), febrile neutropenia (seven [22%] of 32), and anaemia (seven [22%] of 32); and with combination therapy were thrombocytopenia (19 [41%] of 46), febrile neutropenia (13 [28%] of 46), neutropenia (13 [28%] of 46), and anaemia (nine [20%] of 46). 11 (34%) of 32 patients in the monotherapy group and nine (20%) of 46 patients in the combination therapy group died (most commonly from disease progression [three (9%) of 32 and four (9%) of 46]). No deaths were considered study-drug related. For patients with relapsed or refractory acute myeloid leukaemia, 41% (95% CI 21-64; nine of 22) receiving monotherapy and 46% (27-67; 12 of 26) receiving combination therapy had an overall response. For treatment-naive patients with acute myeloid leukaemia, 25% (1-81; one of four) receiving monotherapy and 77% (46-95; ten of 13) receiving combination therapy had an overall response. INTERPRETATION: Olutasidenib, with or without azacitidine, was well tolerated and showed meaningful clinical activity in patients with IDH1-mutated acute myeloid leukaemia. The results of this phase 1 study provide rationale for the continued evaluation of olutasidenib in multiple patient populations with myeloid malignancies. FUNDING: Forma Therapeutics