Dust observations with antenna measurements and its prospects for observations with Parker Solar Probe and Solar Orbiter

The electric and magnetic field instrument suite FIELDS on board the NASA Parker Solar Probe and the radio and plasma waves instrument RPW on the ESA Solar Orbiter mission that explore the inner heliosphere are sensitive to signals generated by dust impacts. Dust impacts have been observed using electric field antennas on spacecraft since the 1980s and the method was recently used with a number of space missions to derive dust fluxes. Here, we consider the details of dust impacts, subsequent development of the impact generated plasma and how it produces the measured signals. We describe empirical approaches to characterise the signals and compare these in a qualitative discussion of laboratory simulations to predict signal shapes for spacecraft measurements in the inner solar system. While the amount of charge production from a dust impact will be higher near the Sun than observed in the interplanetary medium before, the amplitude of pulses is determined by the recovery behaviour that is different near the Sun since it varies with the plasma environment

Combination romidepsin and azacitidine therapy is well tolerated and clinically active in adults with high‐risk acute myeloid leukaemia ineligible for intensive chemotherapy

Azacitidine (AZA) is important in the management of patients with acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. Romidepsin (ROM) is a histone deacetylase inhibitor which synergises with AZA in vitro. The ROMAZA trial established the maximum tolerated dose (MTD) of combined ROM/AZA therapy in patients with AML, as ROM 12 mg/m2 on Days 8 and 15, with AZA 75 mg/m2 administered for 7/28 day cycle. Nine of the 38 (23·7%) patients treated at the MTD were classified as responders by Cycle 6 (best response: complete remission [CR]/incomplete CR n = 7, partial response n = 2). Correlative next‐generation sequencing studies demonstrated important insights into therapy resistance

Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia : a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT

Background: Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning. Methods: In this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18-72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors. Results: In 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02-1.39), 1.26 (1.1-1.44), and 1.51 (1.26-1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62-0.90), 0.70 (0.60-0.82), and 0.60 (0.49-0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI group, and with higher RI in the chemotherapy group. TBI-based conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients. Conclusions: In this large study, we confirmed that patients who are MRD-negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI-based conditioning in the myeloablative setting.Peer reviewe

Impact of route and adequacy of nutritional intake on outcomes of allogeneic haematopoietic cell transplantation for haematologic malignancies.

BACKGROUND: Allogeneic haematopoietic cell transplantation (HCT) is often associated with poor oral intake due to painful mucositis and gastrointestinal sequalae that occur following a preparative regimen of intensive chemotherapy and/or total body radiation. Although attractive to assume that optimal nutrition improves HCT outcomes, there are limited data to support this. It is also unclear whether artificial nutrition support should be provided as enteral tube feeding or parenteral nutrition (PN). METHODS: We analysed day-100 non-relapse mortality (NRM), incidence of acute graft-versus-host disease (GvHD), acute gastrointestinal GvHD, 5-year survival and GvHD-free/relapse-free survival (GRFS) according to both route and adequacy of nutritional intake prior to neutrophil engraftment, together with other known prognostic factors, in a retrospective cohort of 484 patients who underwent allogeneic HCT for haematologic malignancy between 2000 and 2014. RESULTS: Multivariate analyses showed increased NRM with inadequate nutrition (hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.2-7.2) and adequate PN (HR 2.9; 95% CI 1.6-5.4) compared to adequate enteral nutrition (EN) both P < .001. There were increased incidences of gastrointestinal GvHD of any stage and all GvHD ≥ grade 2 in patients who received PN (odds ratio (OR) 2.0; 95% CI 1.2-3.3; P = .006, and OR 1.8; 95% CI 1.1-3.0; P = .018, respectively), compared to adequate EN. Patients who received adequate PN and inadequate nutrition also had reduced probabilities of survival and GRFS at 5 years. CONCLUSION: Adequate EN during the early transplantation course is associated with reduced NRM, improved survival and GRFS at 5 years. Furthermore, adequate EN is associated with lower incidence of overall and gut acute GvHD than PN, perhaps because of its ability to maintain mucosal integrity, modulate the immune response to intensive chemo/radiotherapy and support the gastrointestinal tract environment, including gut microflora

One-Year Analysis of Dust Impact-Like Events Onto the MMS Spacecraft

We present an analysis of 1‐year data of dust impacts observed on two of the Earth‐orbiting Magnetospheric Multiscale mission (MMS) spacecraft. The dust impact signals were identified in observations of the electric field probes and were registered simultaneously by monopole and dipole configurations of the instrument. This unique setup allows us to reliably identify changes in the spacecraft potential as candidates for dust impacts. We present a detailed study of the properties of the pulses generated by the dust impacts and show the influence of the local plasma environment (spacecraft location in the Earth magnetosphere) on signals generated by dust impacts and their detection. We discuss the credibility of impact identification and possible sources of signal misinterpretation. We find a total of 784 observed events that we can interpret as dust impacts and that we use to derive a dust flux. We show that MMS1 registered 0.7 and MMS3 0.8 dust impact‐like events per hour. This corresponds to dust flux of 2.5–6 × 10−5 m−2 s−1