Standard treatment for higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myeloid leukemia is azacitidine. In single arm studies, adding lenalidomide had been ...suggested to improve outcomes. The ALLG MDS4 phase II trial randomized such patients to standard azacitidine or combination azacitidine (75mg/m
/d days 1 to 5) with lenalidomide (10mg days 1-21 of 28-day cycle from cycle 3) to assess clinical benefit (alive without progressive disease) at 12 months. A total of 160 patients were enrolled; median age 70.7 years (range 42.5-87.2), 31.3% female with 14% chronic myelomonocytic leukemia, 12% acute myeloid leukemia and 74% myelodysplastic syndromes. Adverse events were similar in both arms. There was excellent delivery of protocol therapy (median azacitidine cycles 11 both arms) with few dose reductions, delays or early cessations. At median follow up 33.1 months (range 0.7-59.5), the rate of clinical benefit at 12 months was 65% azacitidine arm and 54% lenalidomide+azacitidine arm (
=0.2). There was no difference in clinical benefit between each arm according to WHO diagnostic subgroup or IPSS-R. Overall response rate was 57% in azacitidine arm and 69% in lenalidomide+azacitidine (
=0.14). There was no difference in progression- free or overall survival between the arms (each
>0.12). Although the combination of lenalidomide and azacitidine was tolerable, there was no improvement in clinical benefit, response rates or overall survival in higher risk myelodysplastic syndrome, chronic myelomonocytic leukemia or low blast acute myeloid leukemia patients compared to treatment with azacitidine alone. This trial was registered at
as
.
Abstract
The properties of the population of merging binary black holes encode some of the uncertain physics underlying the evolution of massive stars in binaries. The binary black hole merger rate ...and chirp-mass distribution are being measured by ground-based gravitational-wave detectors. We consider isolated binary evolution, and explore how accurately the physical model can be constrained with such observations by applying the Fisher information matrix to the merging black hole population simulated with the rapid binary-population synthesis code COMPAS. We investigate variations in four COMPAS parameters: common-envelope efficiency, kick-velocity dispersion and mass-loss rates during the luminous blue variable, and Wolf–Rayet stellar-evolutionary phases. We find that ∼1000 observations would constrain these model parameters to a fractional accuracy of a few per cent. Given the empirically determined binary black hole merger rate, we can expect gravitational-wave observations alone to place strong constraints on the physics of stellar and binary evolution within a few years. Our approach can be extended to use other observational data sets; combining observations at different evolutionary stages will lead to a better understanding of stellar and binary physics.
In response to societal grand challenges, professors have unique opportunities to effect change, repurposing their expertise to deploy relevant, timely, practical, and research-backed knowledge for ...the betterment of communities. Drawing on scholarship on postcrisis organizing, entrepreneurial hustle, and social entrepreneurship, we provide a firsthand, real-time case description of a three-day “virtual idea blitz” organized in response to the COVID-19 crisis. The event was organized and executed in less than a week and ultimately involved 200 individuals, including entrepreneurs, coders, medical doctors, venture capitalists, industry professionals, students, and professors from around the world. By the end of the weekend, 21 ideas with corresponding pitches were developed in five thematic areas: health needs, education, small businesses, community, and purchasing. We describe how the community was rapidly rallied, and we discuss the key learning outcomes of this spontaneous entrepreneurial endeavor. We provide evidence from participants and mentors that showcases the value of the time-compressed virtual idea blitz in accelerating social entrepreneurial action. We offer practical guidance to academic, community, and professional institutions that would like to replicate or build upon our approach to stimulate the formation of community and to coordinate efforts to thwart the ongoing threat of COVID-19, as well as other societal challenges that might emerge in the future.
We extend the entrepreneurship literature to include positive psychological capital — an individual or organization's level of psychological resources consisting of hope, optimism, resilience, and ...confidence — as a salient signal in crowdfunding. We draw from the costless signaling literature to argue that positive psychological capital language usage enhances crowdfunding performance. We examine 1726 crowdfunding campaigns from Kickstarter, finding that entrepreneurs conveying positive psychological capital experience superior fundraising performance. Human capital moderates this relationship while social capital does not, suggesting that costly signals may, at times, enhance the influence of costless signals. Post hoc analyses suggest findings generalize across crowdfunding types, but not to IPOs.
•Positive psychological capital rhetoric is a key costless signal in crowdfunding.•Human capital signals moderate psychological capital-performance relationship.•Costly signals increase importance of costless signals in crowdfunding.•Findings generalize across reward-based and social crowdfunding, but not to IPOs.
We report on the creation of bosonic NaCs molecules in their absolute rovibrational ground state via stimulated Raman adiabatic passage. We create ultracold gases with up to 22 000 dipolar NaCs ...molecules at a temperature of 300(50) nK and a peak density of 1.0(4)×10^{12} cm^{-3}. We demonstrate comprehensive quantum state control by preparing the molecules in a specific electronic, vibrational, rotational, and hyperfine state. We measure the ground state ac polarizability at 1064 nm along with the two-body loss rate, which we find to be universal. Employing the tunability and strength of the permanent electric dipole moment of NaCs, we induce dipole moments of up to 2.6 D at a dc electric field of 2.1(2) kV/cm and demonstrate strong microwave coupling between the two lowest rotational states with a Rabi frequency of 2π×45 MHz. A large electric dipole moment, accessible at relatively small electric fields, makes ultracold gases of NaCs molecules well suited for the exploration of strongly interacting phases of dipolar quantum matter.
The recent advanced LIGO detections of gravitational waves from merging binary black holes enhance the prospect of exploring binary evolution via gravitational-wave observations of a population of ...compact-object binaries. In the face of uncertainty about binary formation models, model-independent inference provides an appealing alternative to comparisons between observed and modelled populations. We describe a procedure for clustering in the multidimensional parameter space of observations that are subject to significant measurement errors. We apply this procedure to a mock data set of population-synthesis predictions for the masses of merging compact binaries convolved with realistic measurement uncertainties, and demonstrate that we can accurately distinguish subpopulations of binary neutron stars, binary black holes, and mixed neutron star-black hole binaries with tens of observations.
Abstract
We present a study of two-photon pathways for the transfer of NaCs molecules to their rovibrational ground state. Starting from NaCs Feshbach molecules, we perform bound-bound excited state ...spectroscopy in the wavelength range from 900 nm to 940 nm, covering more than 30 vibrational states of the
c
3
Σ
+
,
b
3
Π
, and
B
1
Π
electronic states. Analyzing the rotational substructure, we identify the highly mixed
c
3
Σ
1
+
|
v
=
22
⟩
∼
b
3
Π
1
|
v
=
54
⟩
state as an efficient bridge for stimulated Raman adiabatic passage. We demonstrate transfer into the NaCs ground state with an efficiency of up to 88(4)%. Highly efficient transfer is critical for the realization of many-body quantum phases of strongly dipolar NaCs molecules and high fidelity detection of single molecules, for example, in spin physics experiments in optical lattices and quantum information experiments in optical tweezer arrays.
A key knowledge gap blocking development of effective therapeutics for Alzheimer’s disease (AD) is the lack of understanding of how amyloid beta (Aβ) peptide and pathological forms of the tau protein ...cooperate in causing disease phenotypes. Within a mouse tau-deficient background, we probed the molecular, cellular, and behavioral disruption triggered by the influence of wild-type human tau on human Aβ-induced pathology. We find that Aβ and tau work cooperatively to cause a hyperactivity behavioral phenotype and to cause downregulation of transcription of genes involved in synaptic function. In both our mouse model and human postmortem tissue, we observe accumulation of pathological tau in synapses, supporting the potential importance of synaptic tau. Importantly, tau reduction in the mice initiated after behavioral deficits emerge corrects behavioral deficits, reduces synaptic tau levels, and substantially reverses transcriptional perturbations, suggesting that lowering synaptic tau levels may be beneficial in AD.
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•Aβ and tau work together to cause behavioral and transcriptional deficits in mice•In mice with Aβ and tau, glial gene expression increases and synaptic genes decrease•Tau is present in synaptic terminals in APP/PS1+Tau mice and human Alzheimer brain•In mice, lowering tau levels improves cognition and restores gene expression
One of the mysteries of Alzheimer’s disease is how the two key pathological proteins, amyloid beta and tau, interact. Pickett et al. use a mouse model to show that these proteins cooperate to change behavior and gene expression and that these phenotypes recover when tau levels are lowered.
A survey has been conducted of the resonance data available in the major evaluated libraries for a range of mid-mass isotopes. Although many isotopes have data derived from experimental measurements ...and rigorous analyses, the data for some others, particularly for isotopes that are unstable, are purely theoretically generated, e.g. via the use of the TARES code.
A subsequent project has developed a suite of automated tools to rapidly inspect the resonance data available for a specified isotope. These tools calculate a range of values and distributions for the available data (e.g. cumulative number of resonances versus neutron energy) and use a comparison against expected theoretical values (e.g. a Porter-Thomas distribution) to suggest their physical validity or otherwise.
The motivation for this study, the tools developed, and results for a number of isotopes, are presented in this paper.
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