Placebo-controlled trial of an oral BTK inhibitor in multiple sclerosis

Evobrutinib; Multiple sclerosis; Receptors in B cells; Receptors in myeloid cellsEvobrutinib; Esclerosis múltiple; Receptores en células B; Receptores en células mieloidesEvobrutinib; Esclerosi múltiple; Receptors en cèl·lules B; Receptors en cèl·lules mieloidesBACKGROUND: Bruton's tyrosine kinase (BTK) regulates the functions of B cells and myeloid cells that are implicated in the pathogenesis of multiple sclerosis. Evobrutinib is a selective oral BTK inhibitor that has been shown to inhibit B-cell activation both in vitro and in vivo. METHODS: In this double-blind, randomized, phase 2 trial, we assigned patients with relapsing multiple sclerosis to one of five groups: placebo, evobrutinib (at a dose of 25 mg once daily, 75 mg once daily, or 75 mg twice daily), or open-label dimethyl fumarate (DMF) as a reference. The primary end point was the total (cumulative) number of gadolinium-enhancing lesions identified on T1-weighted magnetic resonance imaging at weeks 12, 16, 20, and 24. Key secondary end points included the annualized relapse rate and change from baseline in the score on the Expanded Disability Status Scale (EDSS). RESULTS: A total of 267 patients were randomly assigned to a trial group. The mean (±SD) total number of gadolinium-enhancing lesions during weeks 12 through 24 was 3.85±5.44 in the placebo group, 4.06±8.02 in the evobrutinib 25-mg group, 1.69±4.69 in the evobrutinib 75-mg once-daily group, 1.15±3.70 in the evobrutinib 75-mg twice-daily group, and 4.78±22.05 in the DMF group. The baseline adjusted rate ratios for the total number of lesions over time as compared with placebo were 1.45 in the evobrutinib 25-mg group (P = 0.32), 0.30 in the evobrutinib 75-mg once-daily group (P = 0.005), and 0.44 in the evobrutinib 75-mg twice-daily group (P = 0.06). The unadjusted annualized relapse rate at week 24 was 0.37 in the placebo group, 0.57 in the evobrutinib 25-mg group, 0.13 in the evobrutinib 75-mg once-daily group, 0.08 in the evobrutinib 75-mg twice-daily group, and 0.20 in the DMF group. There was no significant effect of trial group on the change from baseline in the EDSS score. Elevations in liver aminotransferase values were observed with evobrutinib. CONCLUSIONS: Patients with relapsing multiple sclerosis who received 75 mg of evobrutinib once daily had significantly fewer enhancing lesions during weeks 12 through 24 than those who received placebo. There was no significant difference with placebo for either the 25-mg once-daily or 75-mg twice-daily dose of evobrutinib, nor in the annualized relapse rate or disability progression at any dose. Longer and larger trials are required to determine the effect and risks of evobrutinib in patients with multiple sclerosis.Funded by EMD Serono; ClinicalTrials.gov number, NCT02975349

Stellar Mass--Gas-phase Metallicity Relation at 0.5≤z≤0.70.5\leq z\leq0.7: A Power Law with Increasing Scatter toward the Low-mass Regime

We present the stellar mass ($M_{*}$)--gas-phase metallicity relation (MZR) and its scatter at intermediate redshifts ($0.5\leq z\leq0.7$) for 1381 field galaxies collected from deep spectroscopic surveys. The star formation rate (SFR) and color at a given $M_{*}$ of this magnitude-limited ($R\lesssim24$ AB) sample are representative of normal star-forming galaxies. For masses below $10^9 M_\odot$, our sample of 237 galaxies is $\sim$10 times larger than those in previous studies beyond the local universe. This huge gain in sample size enables superior constraints on the MZR and its scatter in the low-mass regime. We find a power-law MZR at $10^{8} M_\odot < M_{*} < 10^{11} M_\odot$: ${12+log(O/H) = (5.83\pm0.19) + (0.30\pm0.02)log(M_{*}/M_\odot)}$. Our MZR shows good agreement with others measured at similar redshifts in the literature in the intermediate and massive regimes, but is shallower than the extrapolation of the MZRs of others to masses below $10^{9} M_\odot$. The SFR dependence of the MZR in our sample is weaker than that found for local galaxies (known as the Fundamental Metallicity Relation). Compared to a variety of theoretical models, the slope of our MZR for low-mass galaxies agrees well with predictions incorporating supernova energy-driven winds. Being robust against currently uncertain metallicity calibrations, the scatter of the MZR serves as a powerful diagnostic of the stochastic history of gas accretion, gas recycling, and star formation of low-mass galaxies. Our major result is that the scatter of our MZR increases as $M_{*}$ decreases. Our result implies that either the scatter of the baryonic accretion rate or the scatter of the $M_{*}$--$M_{halo}$ relation increases as $M_{*}$ decreases. Moreover, our measures of scatter at $z=0.7$ appears consistent with that found for local galaxies.Comment: 18 pages, 10 figures. Accepted by ApJ. Typos correcte

The Epoch of Disk Settling: Z Approximately Equal to 1 to Now

We present evidence from a sample of 544 galaxies from the DEEP2 Survey for evolution of the internal kinematics of blue galaxies over 0.2 < z < 1.2. DEEP2 provides a large sample of high resolution galaxy spectra and dual-band Hubble imaging from which we measure emission-line kinematics and galaxy inclinations, respectively. Our large sample allows us to overcome scatter intrinsic to galaxy properties, in order to examine trends. At a fixed stellar mass, galaxies systematically decrease in disturbed motions and increase in rotation velocity and potential well depth with time. The most massive galaxies are the most well-ordered at all times, with higher rotation velocities and less disturbed motions compared to less massive galaxies. We quantify disturbed motions with an integrated gas velocity dispersion (sigma(sub g)), which is unlike the typical pressure-supported velocity dispersion measured for early type galaxies and galaxy bulges. Due to finite slit width and seeing, sigma(sub g) integrates over unresolved velocity gradients which can correspond to non-ordered gas kinematics such as small-scale velocity gradients, gas motions due to star-formation, or super-imposed clumps along the line-of-sight. We compile surveys of galaxy kinematics over 1.2 < z < 3.8 and do not find any trends with redshift, likely because these studies are biased toward the most highly star-forming systems. In summary, over the last approx 8 billion years since z = 1.2, blue galaxies evolve from disturbed to ordered systems as they settle to become the rotation-dominated disk galaxies observed in the Universe today, with the most massive galaxies always being the most evolved at any time

The Epoch of Disk Settling: z~1 to Now

We present evidence from a sample of 544 galaxies from the DEEP2 Survey for evolution of the internal kinematics of blue galaxies with stellar masses ranging 8.0 < log M* (M_Sun) < 10.7 over 0.2<z<1.2. DEEP2 provides galaxy spectra and Hubble imaging from which we measure emission-line kinematics and galaxy inclinations, respectively. Our large sample allows us to overcome scatter intrinsic to galaxy properties in order to examine trends in kinematics. We find that at a fixed stellar mass galaxies systematically decrease in disordered motions and increase in rotation velocity and potential well depth with time. Massive galaxies are the most well-ordered at all times examined, with higher rotation velocities and less disordered motions than less massive galaxies. We quantify disordered motions with an integrated gas velocity dispersion corrected for beam smearing (sigma_g). It is unlike the typical pressure-supported velocity dispersion measured for early type galaxies and galaxy bulges. Because both seeing and the width of our spectral slits comprise a significant fraction of the galaxy sizes, sigma_g integrates over velocity gradients on large scales which can correspond to non-ordered gas kinematics. We compile measurements of galaxy kinematics from the literature over 1.2<z<3.8 and do not find any trends with redshift, likely for the most part because these datasets are biased toward the most highly star-forming systems. In summary, over the last ~8 billion years since z=1.2, blue galaxies evolve from disordered to ordered systems as they settle to become the rotation-dominated disk galaxies observed in the Universe today, with the most massive galaxies being the most evolved at any time.Comment: submitted to ApJ and responded to referee repor

FLORAL SCENT IN A WHOLE-PLANT CONTEXT Floral volatiles controlling ant behaviour

Summary 1. Ants show complex interactions with plants, both facultative and mutualistic, ranging from grazers through seed predators and dispersers to herders of some herbivores and guards against others. But ants are rarely pollinators, and their visits to flowers may be detrimental to plant fitness. 2. Plants therefore have various strategies to control ant distributions, and restrict them to foliage rather than flowers. These &apos;filters&apos; may involve physical barriers on or around flowers, or &apos;decoys and bribes&apos; sited on the foliage (usually extrafloral nectaries -EFNs). Alternatively, volatile organic compounds (VOCs) are used as signals to control ant behaviour, attracting ants to leaves and ⁄ or deterring them from functional flowers. Some of the past evidence that flowers repel ants by VOCs has been equivocal and we describe the shortcomings of some experimental approaches, which involve behavioural tests in artificial conditions. 3. We review our previous study of myrmecophytic acacias, which used in situ experiments to show that volatiles derived from pollen can specifically and transiently deter ants during dehiscence, the effects being stronger in ant-guarded species and more effective on resident ants, both in African and Neotropical species. In these plants, repellence involves at least some volatiles that are known components of ant alarm pheromones, but are not repellent to beneficial bee visitors. 4. We also present new evidence of ant repellence by VOCs in temperate flowers, which is usually pollen-based and active on common European ants. We use these data to indicate that across a wide range of plants there is an apparent trade-off in ant-controlling filter strategies between the use of defensive floral volatiles and the alternatives of decoying EFNs or physical barriers

A global alliance declaring war on cassava viruses in Africa

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Deep ugrizY imaging and DEEP2/3 spectroscopy: a photometric redshift testbed for LSST and public release of data from the DEEP3 Galaxy Redshift Survey

We present catalogues of calibrated photometry and spectroscopic redshifts in the Extended Groth Strip, intended for studies of photometric redshifts (photo-z’s). The data includes ugriz photometry from Canada–France–Hawaii Telescope Legacy Survey (CFHTLS) and Y-band photometry from the Subaru Suprime camera, as well as spectroscopic redshifts from the DEEP2, DEEP3, and 3D-HST surveys. These catalogues incorporate corrections to produce effectively matched-aperture photometry across all bands, based upon object size information available in the catalogue and Moffat profile point spread function fits. We test this catalogue with a simple machine learning-based photometric redshift algorithm based upon Random Forest regression, and find that the corrected aperture photometry leads to significant improvement in photo-z accuracy compared to the original SEXTRACTOR catalogues from CFHTLS and Subaru. The deep ugrizY photometry and spectroscopic redshifts are well suited for empirical tests of photometric redshift algorithms for LSST. The resulting catalogues are publicly available at http://d-scholarship.pitt.edu/36064/. We include a basic summary of the strategy of the DEEP3 Galaxy Redshift Survey to accompany the recent public release of DEEP3 data

Stellar Mass–Gas-Phase Metallicity Relation at 0.5 ≤ \u3cem\u3ez\u3c/em\u3e ≤ 0.7: A Power Law with Increasing Scatter Toward the Low-Mass Regime

We present the stellar mass (M*)–gas-phase metallicity relation (MZR) and its scatter at intermediate redshifts (0.5 ≤ z ≤ 0.7) for for 1381 field galaxies collected from deep spectroscopic surveys. The star formation rate (SFR) and color at a given M* of this magnitude-limited (R ≲ 24 AB) sample are representative of normal star-forming galaxies. For masses below 109 M☉ our sample of 237 galaxies is ~10 times larger than those in previous studies beyond the local universe. This huge gain in sample size enables superior constraints on the MZR and its scatter in the low-mass regime. We find a power-law MZR at 108 at M☉ \u3c M* \u3c 1011 M☉: 12 + log(O/H) = (5.83 ± 0.19) + (0.30 ± 0.02) log(M*/M☉). At 109 M☉ \u3c M* \u3c 1010.5 M☉, our MZR shows agreement with others measured at similar redshifts in the literature. Our power-law slope is, however, shallower than the extrapolation of the MZRs of others to masses below 109 M☉. The SFR dependence of the MZR in our sample is weaker than that found for local galaxies (known as the fundamental metallicity relation). Compared to a variety of theoretical models, the slope of our MZR for low-mass galaxies agrees well with predictions incorporating supernova energy-driven winds. Being robust against currently uncertain metallicity calibrations, the scatter of the MZR serves as a powerful diagnostic of the stochastic history of gas accretion, gas recycling, and star formation of low-mass galaxies. Our major result is that the scatter of our MZR increases as M* decreases. Our result implies that either the scatter of the baryonic accretion rate (σ Ṁ) or the scatter of the M* –Mhalo relation (σ SHMR) increases as M* decreases. Moreover, our measure of scatter at z = 0.7 appears consistent with that found for local galaxies. This lack of redshift evolution constrains models of galaxy evolution to have both σ Ṁ and σ SHMR remain unchanged from z = 0.7 to z = 0

CEERS Epoch 1 NIRCam Imaging: Reduction Methods and Simulations Enabling Early JWST Science Results

We present the data release and data reduction process for the Epoch 1 NIRCam observations for the Cosmic Evolution Early Release Science Survey (CEERS). These data consist of NIRCam imaging in six broadband filters (F115W, F150W, F200W, F277W, F356W and F444W) and one medium band filter (F410M) over four pointings, obtained in parallel with primary CEERS MIRI observations (Yang et al. in prep). We reduced the NIRCam imaging with the JWST Calibration Pipeline, with custom modifications and reduction steps designed to address additional features and challenges with the data. Here we provide a detailed description of each step in our reduction and a discussion of future expected improvements. Our reduction process includes corrections for known pre-launch issues such as 1/f noise, as well as in-flight issues including snowballs, wisps, and astrometric alignment. Many of our custom reduction processes were first developed with pre-launch simulated NIRCam imaging over the full 10 CEERS NIRCam pointings. We present a description of the creation and reduction of this simulated dataset in the Appendix. We provide mosaics of the real images in a public release, as well as our reduction scripts with detailed explanations to allow users to reproduce our final data products. These represent one of the first official public datasets released from the Directors Discretionary Early Release Science (DD-ERS) program.Comment: 27 pages, 14 figures, submitted to ApJ. Accompanying CEERS public Data Release 0.5 available at ceers.github.io/releases.htm