Rb-Sr and single - zircon grain 207Pb / 206Pb chronology of the Monesterio granodiorite and related migmatites. Evidence of a Late Cambrian melting event in the Ossa-Morena Zone, Iberian Massif

The Monesterio granodiorite, a small granodioritic body placed in a migmatitic complex in the SW of the Olivenza-Monesterio antiform, is a key plutonic body to understanding the relationships among the magmatism, metamorphism, and deformation in the Ossa-Morena Zone, SW Iberian Massif. We dated the granodiorite with the single zircon stepwise-evaporation 207Pb/206Pb method, and the related migmatization event with the Rb-Sr method on leucosomes. Our results indicate that the Monesterio granodiorite crystallised at 510 ± 7 Ma and its protolith had a component with Upper Proterozoic zircons with a minimum age of 1696 Ma. Leucosomes give a Rb-Sr age of 511 ± 40 Ma (MSWD =1,7) with initial 87Sr/86Sr =0.70914 ± 0.00048. The lower initial 87Sr/86Sr of the granodiorite and its calc-alkaline chemistry precludes it from having derived from the same protolith as the migmatites. The existence of different magmatic bodies in the Ossa-Morena Zone with ages clustering around 500-510 Ma reveals the existence of a significant melting event during the Late Cambrian that involved protoliths with very different geochemical and isotopic signatures.La granodiorita de Monesterio es un pequeño cuerpo emplazado en un complejo migmatítico en el SO del antiforme Olivenza-Monesterio, importante para entender las relaciones entre magmatismo, metamorfismo y deformación en la Zona de Ossa-Morena. Se ha datado la granodiorita por el método de evaporación secuencial de 207Pb/206Pb en cristal único de circón y los leucosomes de las migmatitas circundantes por el método Rb-Sr. Los datos indican una edad de cristalización de la granodiorita de 510 ± 4 Ma y un posible protolito Proterozoico Superior con una edad mínima de ∼1.700 Ma, obtenida a partir de núcleos heredados de los circones analizados. Los leucosomes dan una edad Rb-Sr de 511 ± 40 Ma, con una relación 87Sr/86Sr=0,70914 ± 0,00048. La relación inicial de 87Sr/86Sr en la granodiorita (∼0,7049) es mucho más baja que en los leucosomes, lo que junto con su naturaleza calcoalcalina indica que no derivan del mismo protolito. La existencia en la zona de Ossa-Morena de diferentes cuerpos magmáticos con edades en tomo a 500-510 Ma, indica un evento de fusión importante durante el Cámbrico Superior desarrollado sobre protolitos con características geoquímicas e isotópicas muy diferentes

A revised Ordovician age for the Miranda do Douro orthogneiss, Portugal. Zircon U-Pb ion-microprobe and LA-ICPMS dating

The Miranda do Douro orthogneiss was believed to be the oldest magmatic rock of the Central Iberian Zone, on the base of a U-Pb discordia upper intercept of 618 ± 9 Ma. Nevertheless, new ion-microprobe and LA-ICPMS U-Pb zircon dating revealed that the crystallization age was 483 ± 3 Ma. The orthogneiss also contains a 605 ± 13 Ma zircon population that indicates that the source-rock for the Ordovician magma was Pan-African. Moreover, a few ~3.17 Ga zircon grains were also recorded. These grains are the oldest found so far in Iberia, and its occurrence would suggest the involvement of an Archean crust in the Pan-African orogeny

IgG 3 + B cells are associated with the development of multiple sclerosis

Objectives Disease‐modifying therapies (DMTs) targeting B cells are amongst the most effective for preventing multiple sclerosis (MS) progression. IgG3 antibodies and their uncharacterised B‐cell clones are predicted to play a pathogenic role in MS. Identifying subsets of IgG3+ B cells involved in MS progression could improve diagnosis, could inform timely disease intervention and may lead to new DMTs that target B cells more specifically. Methods We designed a 31‐parameter B‐cell‐focused mass cytometry panel to interrogate the role of peripheral blood IgG3+ B cells in MS progression of two different patient cohorts: one to investigate the B‐cell subsets involved in conversion from clinically isolated syndrome (CIS) to MS; and another to compare MS patients with inactive or active stages of disease. Each independent cohort included a group of non‐MS controls. Results Nine distinct CD20+IgD−IgG3+ B‐cell subsets were identified. Significant changes in the proportion of CD21+CD24+CD27−CD38− and CD27+CD38hiCD71hi memory B‐cell subsets correlated with changes in serum IgG3 levels and time to conversion from CIS to MS. The same CD38− double‐negative B‐cell subset was significantly elevated in MS patients with active forms of the disease. A third CD21+CD24+CD27+CD38− subset was elevated in patients with active MS, whilst narrowband UVB significantly reduced the proportion of this switched‐memory B‐cell subset. Conclusion We have identified previously uncharacterised subsets of IgG3+ B cells and shown them to correlate with autoimmune attacks on the central nervous system (CNS). These results highlight the potential for therapies that specifically target IgG3+ B cells to impact MS progression

The distinct stellar-to-halo mass relations of satellite and central galaxies: Insights from the IllustrisTNG simulations

We study the stellar-to-halo mass relation (SHMR) for central and satellite galaxies with total dynamical masses above 1010.5 M⊙ using the suite of cosmological magnetohydrodynamical simulations IllustrisTNG. In particular, we quantify environmental effects on satellite populations from TNG50, TNG100, and TNG300 located within the virial radius of group- and clusterlike hosts with total masses of 1012-15.2 M⊙. At fixed stellar mass, the satellite SHMR exhibits a distinct shift towards lower dynamical mass compared to the SHMR of centrals. Conversely, at fixed dynamical mass, satellite galaxies appear to have larger stellar-to-total mass fractions than centrals by up to a factor of a few. The systematic deviation from the central SHMR is larger for satellites in more massive hosts, at smaller cluster-centric distances, with earlier infall times, and that inhabits higher local density environments; moreover, it is in place already at early times (z 2). Systematic environmental effects might contribute to the perceived galaxy-to-galaxy variation in the measured SHMR when galaxies cannot be separated into satellites and centrals. The SHMR of satellites exhibits a larger scatter than centrals (by up to ∼0.8 dex), over the whole range of dynamical mass. The shift of the satellite SHMR results mostly from tidal stripping of their dark matter, which affects satellites in an outside-in fashion: The departure of the satellite SHMR from the centrals' relation diminishes for measurements of dynamical mass in progressively smaller apertures. Finally, we provide a family of fitting functions for the SHMR predicted by IllustrisTNG

Health-related quality of life in patients with β-thalassemia: Data from the phase 3 BELIEVE trial of luspatercept

BACKGROUND: Patients with transfusion-dependent (TD) β-thalassemia require long-term red blood cell transfusions (RBCTs) that lead to iron overload, impacting health-related quality of life (HRQoL). METHODS: The impact of luspatercept, a first-in-class erythroid maturation agent, versus placebo on HRQoL of patients with TD β-thalassemia was evaluated in the phase 3 BELIEVE trial. HRQoL was assessed at baseline and every 12 weeks using the 36-item Short Form Health Survey (SF-36) and Transfusion-dependent Quality of Life questionnaire (TranQol). Mean change in HRQoL was evaluated from baseline to week 48 for patients receiving luspatercept + best supportive care (BSC) and placebo + BSC and between luspatercept responders and non-responders. RESULTS: Through week 48, for both groups, mean scores on SF-36 and TranQol domains were stable over time and did not have a clinically meaningful change. At week 48, more patients who achieved clinical response (≥50% reduction in RBCT burden over 24 weeks) in the luspatercept + BSC group had improvement in SF-36 Physical Function compared with placebo + BSC (27.1% vs. 11.5%; p = .019). CONCLUSIONS: Luspatercept + BSC reduced transfusion burden while maintaining patients' HRQoL. HRQoL domain improvements from baseline through 48 weeks were also enhanced for luspatercept responders

Constructing Impactful Machine Learning Research for Astronomy: Best Practices for Researchers and Reviewers

Machine learning has rapidly become a tool of choice for the astronomical community. It is being applied across a wide range of wavelengths and problems, from the classification of transients to neural network emulators of cosmological simulations, and is shifting paradigms about how we generate and report scientific results. At the same time, this class of method comes with its own set of best practices, challenges, and drawbacks, which, at present, are often reported on incompletely in the astrophysical literature. With this paper, we aim to provide a primer to the astronomical community, including authors, reviewers, and editors, on how to implement machine learning models and report their results in a way that ensures the accuracy of the results, reproducibility of the findings, and usefulness of the method.Comment: 14 pages, 3 figures; submitted to the Bulletin of the American Astronomical Societ

Magnetic Field Amplification in Galaxy Clusters and its Simulation

We review the present theoretical and numerical understanding of magnetic field amplification in cosmic large-scale structure, on length scales of galaxy clusters and beyond. Structure formation drives compression and turbulence, which amplify tiny magnetic seed fields to the microGauss values that are observed in the intracluster medium. This process is intimately connected to the properties of turbulence and the microphysics of the intra-cluster medium. Additional roles are played by merger induced shocks that sweep through the intra-cluster medium and motions induced by sloshing cool cores. The accurate simulation of magnetic field amplification in clusters still poses a serious challenge for simulations of cosmological structure formation. We review the current literature on cosmological simulations that include magnetic fields and outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure

Taxa-area relationship of aquatic fungi on deciduous leaves

One of the fundamental patterns in macroecology is the increase in the number of observed taxa with size of sampled area. For microbes, the shape of this relationship remains less clear. The current study assessed the diversity of aquatic fungi, by the traditional approach based on conidial morphology (captures reproducing aquatic hyphomycetes) and next generation sequencing (NGS; captures other fungi as well), on graded sizes of alder leaves (0.6 to 13.6 cm2). Leaves were submerged in two streams in geographically distant locations: the Oliveira Stream in Portugal and the Boss Brook in Canada. Decay rates of alder leaves and fungal sporulation rates did not differ between streams. Fungal biomass was higher in Boss Brook than in Oliveira Stream, and in both streams almost 100% of the reads belonged to active fungal taxa. In general, larger leaf areas tended to harbour more fungi, but these findings were not consistent between techniques. Morphospecies-based diversity increased with leaf area in Boss Brook, but not in Oliveira Stream; metabarcoding data showed an opposite trend. The higher resolution of metabarcoding resulted in steeper taxa-accumulation curves than morphospecies-based assessments (fungal conidia morphology). Fungal communities assessed by metabarcoding were spatially structured by leaf area in both streams. Metabarcoding promises greater resolution to assess biodiversity patterns in aquatic fungi and may be more accurate for assessing taxa-area relationships and local to global diversity ratios.This work was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569), funded by national funds through the Portuguese Foundation for Science and Technology (FCT) I.P. (http://www.fct.pt/) and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI) and by the project PTDC/AAC-AMB/117068/2010, funded by national funds through FCT I.P. and the European Regional Development Funds through the Operational Competitiveness Program (FEDER-COMPETE). Support from FCT to SD (SFRH/BPD/47574/2008 and SFRH/BPD/109842/2015) and from NSERC Discovery grant program (http://www.nserc-crsng.gc.ca/index_eng.asp) to FB is also acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia

BACKGROUND: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 μg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS: The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.)