Immunomodulation with romiplostim as a second-line strategy in primary immune thrombocytopenia: The iROM study.

Thrombopoietin receptor agonists (TPO-RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first-line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end-points included the sustained remission off-treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)-4, IL-9 and IL-17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor-β levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation

Numerical models of collisions between core-collapse supernovae and circumstellar shells

Recent observations of luminous Type IIn supernovae (SNe) provide compelling evidence that massive circumstellar shells surround their progenitors. In this paper we investigate how the properties of such shells influence the SN lightcurve by conducting numerical simulations of the interaction between an expanding SN and a circumstellar shell ejected a few years prior to core collapse. Our parameter study explores how the emergent luminosity depends on a range of circumstellar shell masses, velocities, geometries, and wind mass-loss rates, as well as variations in the SN mass and energy. We find that the shell mass is the most important parameter, in the sense that higher shell masses (or higher ratios of M_shell/M_SN) lead to higher peak luminosities and higher efficiencies in converting shock energy into visual light. Lower mass shells can also cause high peak luminosities if the shell is slow or if the SN ejecta are very fast, but only for a short time. Sustaining a high luminosity for durations of more than 100 days requires massive circumstellar shells of order 10 M_sun or more. This reaffirms previous comparisons between pre-SN shells and shells produced by giant eruptions of luminous blue variables (LBVs), although the physical mechanism responsible for these outbursts remains uncertain. The lightcurve shape and observed shell velocity can help diagnose the approximate size and density of the circumstellar shell, and it may be possible to distinguish between spherical and bipolar shells with multi-wavelength lightcurves. These models are merely illustrative. One can, of course, achieve even higher luminosities and longer duration light curves from interaction by increasing the explosion energy and shell mass beyond values adopted here.Comment: Accepted for publication in MNRAS. Tables of numerical results (SN lightcurves and velocities) to be published online. (Updated to fix figures

Nonresonant Semileptonic Heavy Quark Decay

In both the large N_c limit and the valence quark model, semileptonic decays are dominated by resonant final states. Using Bjorken's sum rule in an "unquenched" version of the quark model, I demonstrate that in the heavy quark limit nonresonant final states should also be produced at a significant rate. By calculating the individual strengths of a large number of exclusive two-body nonresonant channels, I show that the total rate for such processes is highly fragmented. I also describe some very substantial duality-violating suppression factors which reduce the inclusive nonresonant rate to a few percent of the total semileptonic rate for the finite quark masses of B decay, and comment on the importance of nonresonant decays as testing grounds for very basic ideas on the structure, strength, and significance of the quark-antiquark sea and on quark-hadron duality in QCD.Comment: 51 pages, 2 Postscript figure

The role of FAIR nanosafety data and nanoinformatics in achieving the UN sustainable development goals: the NanoCommons experience†

The increasing focus on open and FAIR (Findable, Accessible, Interoperable and Re-useable) data is driving a step-change in how research communities and governments think about data and knowledge, and the potential for re-use of data. It has long been recognised that international data sharing is essential for regulatory harmonisation and commercialisation, via the Mutual Acceptance of Data (MAD) principle of the Organisation for Economic Cooperation and Development (OECD) for example. However, it is interesting to note that despite the power of data and data-driven software to support the achievement of the United Nations Sustainable Development Goals (UN SDGs), there appears to be limited awareness of how nanomaterials environmental health and safety (nano EHS) data can drive progress towards many of the SDGs. The goal of the NanoCommons research infrastructure project was to increase FAIRness and impact of nanoEHS data through development of services, including data shepherding to support researchers across the data life cycle and tools such as user-friendly nanoinformatics predictive models. We surveyed both service providers and service users on their ideas regarding how nanoEHS data might support the SDGs, and discovered a significant lack of awareness of the SDGs in general, and the potential for impact from NanoCommons tools and services. To address this gap, a workshop on the SDGs was prepared and delivered to support the NanoCommons service providers to understand the SDGs and how nanosafety data and nanoinformatics can support their achievement. Following the workshop, providers were invited to update their questionnaire responses. The results from the workshop discussions are presented, along with a summary of the 12 SDGs identified where increasingly accessible nanoEHS data will have a significant impact, and the 5 that are indirectly benefited along with some recommendations for EU-funded projects on how they can maximise and monitor their contributions to the SDGs

Decay constants, semi-leptonic and non-leptonic decays in a Bethe-Salpeter Model

We evaluate the decay constants for the B and $D$ mesons and the form factors for the semileptonic decays of the B meson to $D$ and $D^*$ mesons in a Bethe-Salpeter model. From data we extract $V_{cb}=0.039 \pm 0.002$ from ${\bar B} \to D^* l {\bar{\nu}}$ and $V_{cb}=0.037 \pm 0.004$ from ${\bar B} \to D l {\bar{\nu}}$ decays. The form factors are then used to obtain non-leptonic decay partial widths for $B\to D \pi (K)$ and $B \to D D (D_s)$ in the factorization approximation.Comment: 15 Pages, 3 Postscript figures (available also from [email protected]

Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands.

Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems

Observed Fractions of Core-Collapse Supernova Types and Initial Masses of their Single and Binary Progenitor Stars

We analyse observed fractions of core-collapse SN types from the Lick Observatory SN Search, and we discuss corresponding implications for massive star evolution. For a standard IMF, observed fractions of SN types cannot be reconciled with expectations of single-star evolution. The mass range of WR stars that shed their H envelopes via their own mass loss accounts for less than half the observed fraction of SNeIbc. Progenitors of SNeIbc must extend to a much lower range of initial masses than classical WR stars, and we argue that most SNIbc and SNIIb progenitors must arise from binary Roche-lobe overflow. SNeIc still trace higher mass and metallicity, because line-driven winds in the WR stage remove the He layer and propel the transition from SNIb to Ic. Less massive progenitors of SNeIb and IIb may not be classical WR stars; they may be underluminous with weak winds, possibly hidden by overluminous mass-gainer companions that appear as B[e] supergiants or related objects having aspherical circumstellar material. The remaining SN types (II-P, II-L, and IIn) are redistributed across the full range of initial mass. We consider direct collapse to black holes without visible SNe, but find this problematic. Major areas of remaining uncertainty are (1) the influence of binary separation, rotation, and metallicity, (2) mass differences in progenitors of SNeIIn compared to SNeII-L and II-P, and (3) SNeIc arising from single stars with eruptive mass loss, its dependence on metallicity, and how it relates to diversity within the SNIc subclass. (abridged)Comment: MNRAS accepted, 18 pages, 8 Figures, 1 color figur

B --> D(D^*) Form Factors in a Bethe-Salpeter model

We calculate the form factors for the semileptonic decays of the $B$ meson to $D$ and $D^*$ mesons in a Bethe-Salpeter model. We show that our model is consistent with the constraints of Heavy Quark Effective Theory (HQET) and we extract the matrix elements that represent the $1/m_Q$ corrections to the form factors in HQET. With available data, we obtain $V_{cb}$=$(31.9 \pm 1.4)\times10^{-3}$.Comment: 15 pages, 5 figure