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Abstract Despite an increasing desire to use historical cohorts as “synthetic” controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012–2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.

Abstract Compared with the extensively used ester‐based electrolyte, the hard carbon (HC) electrode is more compatible with the ether‐based counterpart in sodium‐ion batteries, which can lead to improved cycling stability and robust rate capability. However, the impact of salt anion on the electrochemical performance of HC electrodes has yet to be fully understood. In this study, the anionic chemistry in regulating the stability of electrolytes and the performance of sodium‐ion batteries have been systematically investigated. This work shows discrepancies in the reductive stability of the anionic group, redox kinetics, and component/structure of solid electrolyte interface (SEI) with different salts (NaBF4, NaPF6, and NaSO3CF3) in the typical ether solvent (diglyme). Particularly, the density functional theory calculation manifests the preferred decomposition of PF6− due to the reduced reductive stability of anions in the solvation structure, thus leading to the formation of NaF‐rich SEI. Further investigation on redox kinetics reveals that the NaPF6/diglyme can induce the fast ionic diffusion dynamic and low charge transfer barrier for HC electrode, thus resulting in superior sodium storage performance in terms of rate capability and cycling life, which outperforms those of NaBF4/diglyme and NaSO3CF3/diglyme. Importantly, this work offers valuable insights for optimizing the electrochemical behaviors of electrode materials by regulating the anionic group in the electrolyte.

With the rapid growth in renewable energy, researchers worldwide are trying to expand energy storage technologies. The development of beyond-lithium battery technologies has accelerated in recent years, amid concerns regarding the sustainability of battery materials. However, the absence of suitable high-performance materials has hampered the development of the next-generation battery systems. MXenes, a family of 2D transition metal carbides and/or nitrides, have drawn significant attention recently for electrochemical energy storage, owing to their unique physical and chemical properties. The extraordinary electronic conductivity, compositional diversity, expandable crystal structure, superior hydrophilicity, and rich surface chemistries make MXenes promising materials for electrode and other components in rechargeable batteries. This report especially focuses on the recent MXene applications as novel electrode materials and functional separator modifiers in rechargeable batteries beyond lithium. In particular, we highlight the recent advances of surface and structure engineering strategies for improving the electrochemical performance of the MXene-based materials, including surface termination modifications, heteroatom doping strategies, surface coating, interlayer space changes, nanostructure engineering, and heterostructures and secondary materials engineering. Finally, perspectives for building future sustainable rechargeable batteries with MXenes and MXene-based composite materials are presented based upon material design and a fundamental understanding of the reaction mechanisms.

Abstract Clear‐air turbulence (CAT) is hazardous to aircraft and is projected to intensify in response to future climate change. However, our understanding of past CAT trends is currently limited, being derived largely from outdated reanalysis data. Here we analyze CAT trends globally during 1979–2020 in a modern reanalysis data set using 21 diagnostics. We find clear evidence of large increases around the midlatitudes at aircraft cruising altitudes. For example, at an average point over the North Atlantic, the total annual duration of light‐or‐greater CAT increased by 17% from 466.5 hr in 1979 to 546.8 hr in 2020, with even larger relative changes for moderate‐or greater CAT (increasing by 37% from 70.0 to 96.1 hr) and severe‐or‐greater CAT (increasing by 55% from 17.7 to 27.4 hr). Similar increases are also found over the continental USA. Our study represents the best evidence yet that CAT has increased over the past four decades.

Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53 mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis and TP53, FLT3 or RB1 alterations associated with poor survival. Targetable signaling mutations were present in 45% of cases and included recurrent mutations of ALK and NTRK1, the latter of which drives erythroid leukemogenesis sensitive to TRK inhibition. This genomic landscape of AEL provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted therapies in this high-risk leukemia.

Radiosonde descent profiles have been available from tens of stations for several years now – mainly from Vaisala RS41 radiosondes. They have been compared with the ascent profiles, with ECMWF short-range forecasts and with co-located radio occultation retrievals. Over this time, our understanding of the data has grown, and the comparison has also shed some light on radiosonde ascent data. The fall rate is very variable and is an important factor, with high fall rates being associated with temperature biases, especially at higher altitudes. Ascent winds are affected by pendulum motion; on average, descent winds are less affected by pendulum motion and are smoother. It is plausible that the true wind variability in the vertical lies between that shown by ascent and descent profiles. This discrepancy indicates the need for reference wind measurements. With current processing, the best results are for radiosondes with parachutes and pressure sensors. Some of the wind, temperature and humidity data are now assimilated in the ECMWF forecast system.

To advance our understanding of the stratosphere, high-quality observational datasets of the stratosphere are needed. It is commonplace that reanalysis datasets are used to conduct stratospheric studies. However, the accuracy of these reanalyses at these heights is hard to infer due to a lack of in situ measurements. Satellite measurements provide one source of temperature information. As some satellite information is already assimilated into reanalyses, the direct comparison of satellite temperatures to the reanalysis is not truly independent. Stratospheric lidars use Rayleigh scattering to measure density in the middle and upper atmosphere, allowing temperature profiles to be derived for altitudes from 30 km (where Mie scattering due to stratospheric aerosols becomes negligible) to 80–90 km (where the signal-to-noise ratio begins to drop rapidly). The Network for the Detection of Atmospheric Composition Change (NDACC) contains several lidars at different latitudes that have measured atmospheric temperatures since the 1970s, resulting in a long-running upper-stratospheric temperature dataset. These temperature datasets are useful for validating reanalysis datasets in the stratosphere, as they are not assimilated into reanalyses. Here, stratospheric temperature data from lidars in the Northern Hemisphere between 1990–2017 were compared with the European Centre for Medium-Range Weather Forecasts ERA-Interim and ERA5 reanalyses. To give confidence to any bias found, temperature data from NASA's EOS Microwave Limb Sounder were also compared to ERA-Interim and ERA5 at points over the lidar sites. In ERA-Interim a cold bias of −3 to −4 K between 10 and 1 hPa was found when compared to both measurement systems. Comparisons with ERA5 found a small bias of magnitude 1 K which varies between cold and warm bias with height between 10 and 1 hPa, indicating a good thermal representation of the middle atmosphere up to 1 hPa. A further comparison was undertaken looking at the temperature bias by year to see the effects of the assimilation of the Advanced Microwave Sounding Unit-A (AMSU-A) satellite data and the Constellation Observing System for Meteorology, Ionosphere, and Climate GPS Radio Occultation (COSMIC GPSRO) data on stratospheric temperatures within the aforementioned ERA analyses. It was found that ERA5 was sensitive to the introduction of COSMIC GPSRO in 2007 with the reduction of the cold bias above 1 hPa. In addition to this, the introduction of AMSU-A data caused variations in the temperature bias between 1–10 hPa between 1997–2008.

Modifying droplet behavior has wide applications, from removing pathogens to increasing rainfall. In an environmental experiment, negative charge release is demonstrated to influence a natural fog. During charge emission, the average mass concentration of 1 μm droplets increased by 95.3%. For smaller droplets, concentrations during charge emission exceeded those without charge emission at the 99% confidence level. This is consistent with charge both facilitating formation of small droplets and inhibiting their evaporation. Physics-based droplet modification has immediate relevance to weather modification and, conceivably, pathogen control, without the introduction of additional chemical materials.

The Earth and atmosphere are in constant motion. Volcanoes, glaciers, earthquakes, thunderstorms, and even the aurora borealis produce powerful low-frequency sounds known as infrasound. Infrasound is constantly passing through our atmosphere at frequencies of less than 20 Hz, below the range of human hearing, which is effectively an inaudible symphony. Inspired by wanting to allow physical access to this natural phenomenon, a collaboration between the worlds of contemporary art and meteorology has been developed. This led to a project called hertz, named after the 19th century physicist Heinrich Hertz, whose surname provides the scientific unit (Hz) for frequency. Hertz explores the manifestation of the hidden vibrations of our own planet and the secret harmonies of our stars. The manifestation of the hidden vibrations of our own planet was principally achieved using a subwoofer and furniture adapted to vibrate to the amplitude of infrasonic waves from pre-recorded sources and in real time. The project's motivations are to explore new methods for experiencing and re-engaging with parts of our planet through this phenomenon. Hertz has had a UK national tour in which 7000 people interacted with the piece, of which approximately 85 % felt more reconnected to the environment after interacting with the installation. This paper describes the concepts, creative ideas, technology, and science behind the project. It addresses its development, including the steps to make it accessible for all, and examines its impact on those who created and interacted with the work.

A tethered-balloon system (TBS) has been developed and is being operated by Sandia National Laboratories (SNL) on behalf of the U.S. Department of Energy's (DOE) Atmospheric Radiation Measurement (ARM) User Facility in order to collect in situ atmospheric measurements within mixed-phase Arctic clouds. Periodic tethered-balloon flights have been conducted since 2015 within restricted airspace at ARM's Advanced Mobile Facility 3 (AMF3) in Oliktok Point, Alaska, as part of the AALCO (Aerial Assessment of Liquid in Clouds at Oliktok), ERASMUS (Evaluation of Routine Atmospheric Sounding Measurements using Unmanned Systems), and POPEYE (Profiling at Oliktok Point to Enhance YOPP Experiments) field campaigns. The tethered-balloon system uses helium-filled 34 m3 helikites and 79 and 104 m3 aerostats to suspend instrumentation that is used to measure aerosol particle size distributions, temperature, horizontal wind, pressure, relative humidity, turbulence, and cloud particle properties and to calibrate ground-based remote sensing instruments. Supercooled liquid water content (SLWC) sondes using the vibrating-wire principle, developed by Anasphere Inc., were operated at Oliktok Point at multiple altitudes on the TBS within mixed-phase clouds for over 200 h. Sonde-collected SLWC data were compared with liquid water content derived from a microwave radiometer, Ka-band ARM zenith radar, and ceilometer at the AMF3, as well as liquid water content derived from AMF3 radiosonde flights. The in situ data collected by the Anasphere sensors were also compared with data collected simultaneously by an alternative SLWC sensor developed at the University of Reading, UK; both vibrating-wire instruments were typically observed to shed their ice quickly upon exiting the cloud or reaching maximum ice loading. Temperature sensing measurements distributed with fiber optic tethered balloons were also compared with AMF3 radiosonde temperature measurements. Combined, the results indicate that TBS-distributed temperature sensing and supercooled liquid water measurements are in reasonably good agreement with remote sensing and radiosonde-based measurements of both properties. From these measurements and sensor evaluations, tethered-balloon flights are shown to offer an effective method of collecting data to inform and constrain numerical models, calibrate and validate remote sensing instruments, and characterize the flight environment of unmanned aircraft, circumventing the difficulties of in-cloud unmanned aircraft flights such as limited flight time and in-flight icing.

BACKGROUND:Multiple myeloma (MM) is a hematological malignancy characterized by the clonal expansion of malignant plasma cells. Though durable remissions are possible, MM is considered incurable, with relapse occurring in almost all patients. There has been limited data reported on the lipid metabolism changes in plasma cells during MM progression. Here, we evaluated the feasibility of concurrent lipidomics and proteomics analyses from patient plasma cells, and report these data on a limited number of patient samples, demonstrating the feasibility of the method, and establishing hypotheses to be evaluated in the future. METHODS:Plasma cells were purified from fresh bone marrow aspirates using CD138 microbeads. Proteins and lipids were extracted using a bi-phasic solvent system with methanol, methyl tert-butyl ether, and water. Untargeted proteomics, untargeted and targeted lipidomics were performed on 7 patient samples using liquid chromatography-mass spectrometry. Two comparisons were conducted: high versus low risk; relapse versus newly diagnosed. Proteins and pathways enriched in the relapsed group was compared to a public transcriptomic dataset from Multiple Myeloma Research Consortium reference collection (n = 222) at gene and pathways level. RESULTS:From one million purified plasma cells, we were able to extract material and complete untargeted (~6000 and ~3600 features in positive and negative mode respectively) and targeted lipidomics (313 lipids), as well as untargeted proteomics analysis (~4100 reviewed proteins). Comparative analyses revealed limited differences between high and low risk groups (according to the standard clinical criteria), hence we focused on drawing comparisons between the relapsed and newly diagnosed patients. Untargeted and targeted lipidomics indicated significant down-regulation of phosphatidylcholines (PCs) in relapsed MM. Although there was limited overlap of the differential proteins/transcripts, 76 significantly enriched pathways in relapsed MM were common between proteomics and transcriptomics data. Further evaluation of transcriptomics data for lipid metabolism network revealed enriched correlation of PC, ceramide, cardiolipin, arachidonic acid and cholesterol metabolism pathways to be exclusively correlated among relapsed but not in newly-diagnosed patients. CONCLUSIONS:This study establishes the feasibility and workflow to conduct integrated lipidomics and proteomics analyses on patient-derived plasma cells. Potential lipid metabolism changes associated with MM relapse warrant further investigation.

Understanding rainfall in arid and water-scarce regions is central to the efficient use of water resources in agriculture, irrigation, and domestic food security. This work presents a new dataset with which to study precipitation processes in arid regions, utilising two years (2018–2020) of ceilometer observations made at Al Ain International Airport in the desert region of Al Ain, United Arab Emirates (UAE), where the annual rainfall is 76 mm. Ceilometer data provide a novel method by which to study both the evolution of water droplets from the cloud base down to the surface and the local circumstances required for rain to successfully reach the surface. In this work, we explore how successful precipitation depends on the initial size of the droplets and the thermodynamic profile below the cloud. For 64 of the 105 rain events, the droplet diameters ranged from 0.60 to 3.75 mm, with a mean of 1.84 mm. We find that smaller droplets, higher cloud bases, reduced cloud depths, and colder cloud bases all act to prevent successful precipitation, instead yielding virga (28 out of the 105 rain generating events). We identify how these multiple regional factors combine—specifically, we identify clouds deeper than 2.9 km, droplet diameters greater than 2 mm, and a midpoint below-cloud RH profile greater than 50%—to give successful rainfall, which may ultimately lead to more efficient rainfall enhancing measures, such as cloud seeding.

Abstract. The proportion of patients with acute myeloid leukemia (AML) cured is increased by administering high-dose cytarabine (HiDAC). It remains uncertain whether to administer HiDAC as induction or consolidation, and whether ≥1 cycle of HiDAC is required. Our retrospective study of 416 adult AML patients, excluding good risk cytogenetics, compared a single cycle of HiDAC-based therapy followed by 2 cycles of standard-dose cytarabine (SDAC) (HiDAC induction cohort) with SDAC-based chemotherapy followed by 2 cycles of HiDAC-based chemotherapy (HiDAC consolidation cohort). Complete remission (CR) rate was greater in the HiDAC induction cohort (90% vs 78%, P

The structure of ferroelectric 0.06LiNbO3-0.94K0.5Na0.5NbO3 (KNNL6) was investigated by the neutron total scattering method in the temperature range of 290–773 K. The Rietveld analysis using the powder neutron diffraction data in the range of 290–773 K indicates transition from a two-phase (monoclinic and tetragonal) mixture at room temperature to tetragonal and cubic phases at higher temperatures. However, characterization of the local structure by the pair distribution function (PDF) method indicates that the local structure (r ≲ 10 Å) stays monoclinic over the same temperature range. Besides, the local oxygen octahedral distortion exhibits smaller changes with temperature than what is observed for the long-range average structure.

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.

The GAUDI study assessed safety and preliminary efficacy of induction therapy with obinutuzumab plus chemotherapy, followed by maintenance therapy with obinutuzumab alone, in previously untreated patients with follicular lymphoma. Assignment to chemotherapy was decided on a per-center basis before the patients’ enrollment. Patients (n=81) received four to six cycles of obinutuzumab plus bendamustine every 4 weeks or six to eight cycles of obinutuzumab plus CHOP every 3 weeks. Patients with an end-of-treatment response were eligible for obinutuzumab maintenance therapy every 3 months for 2 years or until disease progression. Induction treatment was completed by 90% of patients in the obinutuzumab plus bendamustine group and 95% in the obinutuzumab plus CHOP group, while maintenance was completed by 81% and 72% of patients, respectively. All patients experienced at least one adverse event during induction, most commonly infusion-related reactions (58%), the majority of which were grade 1/2. The most common hematologic adverse event was grade 3/4 neutropenia (36% during induction and 7% during maintenance). One treatment-related death occurred during the maintenance phase. At the end of induction, 94% of patients had achieved an overall response, with complete response based on computed tomography in 36%. The progression-free survival rate at 36 months was 90% in the obinutuzumab plus bendamustine group and 84% in the obinutuzumab plus CHOP group. These results demonstrate that induction therapy with obinutuzumab plus bendamustine or obinutuzumab plus CHOP, followed by obinutuzumab maintenance, is associated with tolerable safety and promising efficacy. This study is registered at ClinicalTrials.gov as NCT00825149.