Stratospheric X‐rays detected at mid‐latitudes with a miniaturized balloon‐borne microscintillator‐PiN diode system

A miniaturized scintillator (“microscintillator”), was flown on a meteorological radiosonde to observe energetic particles in the lower atmosphere. A PiN diode was used to measure the light from the microscintillator to count rates and energies of ionizing radiation from the ground up to the stratosphere (32 km). The flight, over the southern UK on August 27, 2018, occurred during a geomagnetic storm. Low-energy (50–150 keV) particles in the stratosphere were detected in addition to the usual signal from higher-energy cosmic rays. Unusually for these miniaturized radiosonde systems, which are designed to be disposable, the payload was retrieved. This allowed for re-calibration of the microscintillator, which confirmed the low-energy particle detection. Laboratory tests excluded thermal effects on the microscintillator instrument as the origin of the signal. Data from the NOAA POES spacecraft offer the explanation that the microscintillator detected bremstrahhlung X-rays from energetic electron precipitation (EEP). EEP events may affect weather and climate through a range of physical mechanisms, and this midlatitude observation, well away from the auroral oval, extends the region over which meteorological effects of EEPs need to be assessed. Our findings underline the value of balloon measurements in providing rapid response to space weather events. The energy-discriminating and altitude-sensitive capability of the microscintillator augments spacecraft observations from below

Meteorological source variability in atmospheric gravity wave parameters derived from a tropical infrasound station

Gravity waves are an important part of the momentum budget of the atmosphere. Despite this, parameterizations of gravity wave spectra in atmospheric models are poorly constrained. Gravity waves are formed by jet streams, flow over topography and convection, all of which produce pressure perturbations as they propagate over the Earth’s surface, detectable by microbarometer arrays used for sensing infrasound. In this study, observations of gravity waves between 2007 and 2011 at an infrasound station in the Ivory Coast, West Africa are combined with meteorological data to calculate parameters such as intrinsic phase speed and wavenumber. Through spectral analysis, the seasonal and daily variations in all gravity wave parameters are examined. The gravity wave back azimuth varies with the migration of the Inter-Tropical Convergence Zone, a region of intense convection, supporting previous studies. Daily variations in gravity wave arrivals at the station can be linked to two distinct convective cycles over the land and ocean. This was achieved by combining the gravity wave parameters with lightning strikes detected by the Met Office’s Arrival Time Difference lightning detection system. Noise generated by turbulence in the middle of the day was found to attenuate smaller pressure amplitude gravity waves, artificially amplifying the daily variations in some gravity wave parameters. Detection of daily and seasonal variations in gravity wave parameters has the potential be used to improve the representation of gravity wave spectra in atmospheric models

Saharan dust plume charging observed over the UK

A plume of Saharan dust and Iberian smoke was carried across the southern UK on 16th October 2017, entrained into an Atlantic cyclone which had originated as Hurricane Ophelia. The dust plume aloft was widely noticed as it was sufficiently dense to redden the visual appearance of the sun. Time series of backscatter from ceilometers at Reading and Chilbolton show two plumes: one carried upwards to 2.5 km, and another below 800m into the boundary layer, with a clear slot between. Steady descent of particles at about 50 cms−1 continued throughout the morning, and coarse mode particles reached the surface. Plumes containing dust are frequently observed to be strongly charged,often through frictional effects. This plume passed over atmospheric electric field sensors at Bristol, Chilbolton and Reading. Consistent measurements at these three sites indicated negative plume charge. The lower edge plume charge density was (−8.0±3.3) nCm−2, which is several times greater than that typical for stratiform water clouds, implying an active in situ charge generation mechanism such as turbulent triboelectrification. A meteorological radiosonde measuring temperature and humidity was launched into the plume at 1412 UTC, specially instrumented with charge and turbulence sensors. This detected charge in the boundary layer and in the upper plume region, and strong turbulent mixing was observed throughout the atmosphere’s lowest 4 km. The clear slot region, through which particles sedimented, was anomalously dry compared with modelled values, with water clouds forming intermittently in the air beneath. Electrical aspects of dust should be included in numerical models, particularly the charge-related effects on cloud microphysical properties, to accurately represent particle behaviour and transport

Measuring ionizing radiation in the atmosphere with a new balloon-borne detector

Increasing interest in energetic particle effects on weather and climate has motivated development of a miniature scintillator-based detector intended for deployment on meteorological radiosondes or unmanned airborne vehicles. The detector was calibrated with laboratory gamma sources up to 1.3 MeV, and known gamma peaks from natural radioactivity of up to 2.6 MeV. The specifications of our device in combination with the performance of similar devices suggest that it will respond to up to 17 MeV gamma rays. Laboratory tests show the detector can measure muons at the surface, and it is also expected to respond to other ionizing radiation including, for example, protons, electrons (>100 keV) and energetic helium nuclei from cosmic rays or during space weather events. Its estimated counting error is ±10%. Recent tests, when the detector was integrated with a meteorological radiosonde system, and carried on a balloon to ~25 km altitude, identified the transition region between energetic particles near the surface, which are dominated by terrestrial gamma emissions, to higher-energy particles in the free troposphere

Consistent dust electrification from Arabian Gulf sea breezes

The Arabian Gulf region experiences regular thermally driven sea breeze circulations which occur all year round, penetrating hundreds of kilometres inland. As a sea breeze front moves inland, substantial electric fields are generated by separation of charged desert dust. In the first surface electric field measurements made in the United Arab Emirates (UAE), consistent and repeatable substantial electric field changes with magnitudes up to 7 kV m-1 have been detected at Al Ain (170 km from the western coast), during 80 separate sea breeze events in 2018. Every sea breeze frontal passage shows the same characteristic signature of a transient maximum peak in electric field lasting tens of minutes. Electric field changes during these events were always negative (i.e. enhancing the existing negative “fair weather” electric field), in contrast to many other reported observations in dust storms in which conditions were less repeatable. The regular and substantial dust electrification found demonstrates that accurate representation of dust in climate and weather models requires electrical effects to be addressed, both in the generation process, and by considering aggregates in radiative transfer calculations as electrically aligned rather than randomly ordered. Furthermore, satellite aerosol retrievals are affected by the changed attenuation of electromagnetic radiation when dust particles are charged, for which corrections may be needed

A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study

Se trata de la publicación del estudio de fase 3 ASPEN que comparó en pacientes con macro-globulinemia de Waldenström (WM) la eficacia y la seguridad de ibrutinib, un inhibidor de la tirosi-na quinasa Bruton (BTK) de primera generación, familia que ha demostrado ser un tratamiento eficaz en estos pacientes, frente a zanubrutinib, un nuevo inhibidor de BTK de 2ª generación, altamente selectivo. Los pacientes con enfermedad MYD88L265P se asignaron al azar 1:1 al tratamiento con ibrutinib o zanubrutinib. El criterio principal de valoración fue la proporción de pa-cientes que lograron una respuesta completa (RC) o una respuesta parcial muy buena (RPMB) mediante una revisión independiente. Los criterios secundarios clave de valoración incluyeron la tasa de respuesta mayor (RM), la supervivencia libre de progresión (SLP), la duración de la res-puesta (DR), la carga de la enfermedad y la seguridad. Se randomizaron 201 pacientes y 199 recibieron al menos 1 dosis del tratamiento del estudio. Veintinueve (28%) pacientes tratados con zanubrutinib y 19 (19%) pacientes tratados con ibrutinib lograron una RPMB, diferencia que no alcanzó la significación estadística (P = 0,09). Las RM fueron del 77% y del 78%, respectivamen-te. No se alcanzó la mediana de DR y SLP, ya que el 84% y el 85% de los pacientes tratados con ibrutinib y zanubrutinib estaban libres de progresión a los 18 meses. La fibrilación auricular, hema-tomas, diarrea, edema periférico, hemorragia, espasmos musculares y neumonía, así como los eventos adversos que condujeron a interrumpir el tratamiento, fueron menos frecuentes entre los receptores de zanubrutinib. La incidencia de neutropenia fue mayor con zanubrutinib, aunque las tasas de infección de grado ≥3 fueron similares en ambos grupos (1,2 y 1,1 eventos por 100 me-ses-persona). Estos resultados demuestran que zanubrutinib e ibrutinib son altamente efectivos en el tratamiento de la WM, pero zanubrutinib se asoció con menor toxicidad y una tendencia hacia una mejor calidad de respuesta y menos toxicidad, particularmente toxicidad cardiovascular.[EN]Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.BeiGene CoBeiGene C

Chronic lymphocytic leukaemia Australasian consensus practice statement

Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in Australia and New Zealand (ANZ). Considerable changes to diagnostic and management algorithms have occurred within the last decade. The availability of next-generation sequencing and measurable residual disease assessment by flow cytometry allow for advanced prognostication and response assessments. Novel therapies, including inhibitors of Bruton's tyrosine kinase (BTKi) and B-cell lymphoma 2 (BCL2) inhibitors, have transformed the treatment landscape for both treatment-naïve and relapsed/refractory disease, particularly for patients with high-risk genetic aberrations. Recommendations regarding appropriate supportive management continue to evolve, and special considerations are required for patients with CLL with respect to the global SARS-CoV-2 pandemic. The unique funding and treatment environments in Australasia highlight the need for specific local guidance with respect to the investigation and management of CLL. This consensus practice statement was developed by a broadly representative group of ANZ experts in CLL with endorsement by peak haematology bodies, with a view to providing this standardised guidance

Applications of electrified dust and dust devil electrodynamics to Martian atmospheric electricity

Atmospheric transport and suspension of dust frequently brings electrification, which may be substantial. Electric fields of 10 kVm-1 to 100 kVm-1 have been observed at the surface beneath suspended dust in the terrestrial atmosphere, and some electrification has been observed to persist in dust at levels to 5 km, as well as in volcanic plumes. The interaction between individual particles which causes the electrification is incompletely understood, and multiple processes are thought to be acting. A variation in particle charge with particle size, and the effect of gravitational separation explains to, some extent, the charge structures observed in terrestrial dust storms. More extensive flow-based modelling demonstrates that bulk electric fields in excess of 10 kV m-1 can be obtained rapidly (in less than 10 s) from rotating dust systems (dust devils) and that terrestrial breakdown fields can be obtained. Modelled profiles of electrical conductivity in the Martian atmosphere suggest the possibility of dust electrification, and dust devils have been suggested as a mechanism of charge separation able to maintain current flow between one region of the atmosphere and another, through a global circuit. Fundamental new understanding of Martian atmospheric electricity will result from the ExoMars mission, which carries the DREAMS (Dust characterization, Risk Assessment, and Environment Analyser on the Martian Surface)-MicroARES (Atmospheric Radiation and Electricity Sensor) instrumentation to Mars in 2016 for the first in situ measurements

Improving outcomes for patients with lymphoma: design and development of the Australian and New Zealand Lymphoma and Related Diseases Registry

Background Lymphoma is a malignancy of lymphocytes and lymphoid tissues comprising a heterogeneous group of diseases, with up to 80 entities now described. Lymphoma is the 6th most common cancer in Australia, affecting patients of all ages, with rising incidence rates. With the proliferation of efficacious novel agents, therapeutic strategies are increasingly diverse and survival is improving. There is a clear need for contemporary robust and detailed data on diagnostic, investigational and management strategies for this disease in Australia, New Zealand and worldwide, to inform and benchmark local and international standards of care. Clinical quality registries can provide these data, and support development of strategies to address variations in management, including serving as platforms for clinical trials and other research activities. The Lymphoma and Related Diseases Registry (LaRDR) was developed to capture details of patient demographics, disease characteristics, and management throughout their disease course and therapy and to develop outcome benchmarks nationally and internationally for lymphoma. This report describes the aims, development and implementation of the LaRDR, as well as challenges addressed in the process. Methods The LaRDR was established in 2016 as a multicentre, collaborative project at sites across Australia with a secure online database which collects prospective data on patients with a new diagnosis of lymphoma or chronic lymphocytic leukaemia (CLL). LaRDR development required multidisciplinary participation including specialist haematology, information technology, and biostatistical support, as well as secure funding. Here we describe the database development, data entry, ethics approval process, registry governance and support for participating sites and the coordinating centre. Results To date more than 5,300 patients have been enrolled from 28 sites in Australia and New Zealand. Multiple challenges arose during the development, which we describe, along with approaches used to overcome them. Several confirmed international collaborations are now in place, and the registry is providing valuable data for clinicians, researchers, industry and government, including through presentations of results at major national and international conferences. Conclusion Challenges in establishing the LaRDR have been successfully overcome and the registry is now a valuable resource for lymphoma clinicians, researchers, health economists and others in Australia, New Zealand and globally