An ALMA Survey of Submillimeter Galaxies in the Extended Chandra Deep Field South : The Redshift Distribution and Evolution of Submillimeter Galaxies

Accepted by ApJ. 45 pages, 16 figuresWe present the first photometric redshift distribution for a large unbiased sample of 870um selected submillimeter galaxies (SMGs) with robust identifications based on observations with the Atacama Large Millimeter Array (ALMA). In our analysis we consider 96 SMGs in the Extended Chandra Deep Field South, 77 of which have 4-19 band, optical-near-infrared, photometry. We model the Spectral Energy Distributions (SEDs) for these 77 SMGs, deriving a median photometric redshift of z=2.3+/-0.1. The remaining 19 SMGs have insufficient optical or near-infrared photometry to derive photometric redshifts, but a stacking analysis of IRAC and Herschel observations confirms they are not spurious. Assuming these sources have an absolute H-band magnitude distribution comparable to that of a complete sample of z~1-2 SMGs, we demonstrate that the undetected SMGs lie at higher redshifts, raising the median redshift for SMGs to z=2.5+/-0.2. More critically we show that the proportion of galaxies undergoing an SMG phase at z>3 is 35+/-5% of the total population. We derive a median stellar mass for SMGs of Mstar=(8+/-1)x10^10Mo, but caution that there are significant systematic uncertainties in our stellar mass estimate, up to x5 for individual sources. We compare our sample of SMGs to a volume-limited, morphologically classified sample of ellipticals in the local Universe. Assuming the star formation activity in SMGs has a timescale of ~100Myr we show that their descendants at z~0 would have a space density and M_H distribution which are in good agreement with those of local ellipticals. In addition the inferred mass-weighted ages of the local ellipticals broadly agree with the look-back times of the SMG events. Taken together, these results are consistent with a simple model that identifies SMGs as events that form most of the stars seen in the majority of luminous elliptical galaxies at the present day.Peer reviewe

An ALMA Survey of Submillimeter Galaxies in the Extended Chandra Deep Field South : The Redshift Distribution and Evolution of Submillimeter Galaxies

Accepted by ApJ. 45 pages, 16 figuresWe present the first photometric redshift distribution for a large unbiased sample of 870um selected submillimeter galaxies (SMGs) with robust identifications based on observations with the Atacama Large Millimeter Array (ALMA). In our analysis we consider 96 SMGs in the Extended Chandra Deep Field South, 77 of which have 4-19 band, optical-near-infrared, photometry. We model the Spectral Energy Distributions (SEDs) for these 77 SMGs, deriving a median photometric redshift of z=2.3+/-0.1. The remaining 19 SMGs have insufficient optical or near-infrared photometry to derive photometric redshifts, but a stacking analysis of IRAC and Herschel observations confirms they are not spurious. Assuming these sources have an absolute H-band magnitude distribution comparable to that of a complete sample of z~1-2 SMGs, we demonstrate that the undetected SMGs lie at higher redshifts, raising the median redshift for SMGs to z=2.5+/-0.2. More critically we show that the proportion of galaxies undergoing an SMG phase at z>3 is 35+/-5% of the total population. We derive a median stellar mass for SMGs of Mstar=(8+/-1)x10^10Mo, but caution that there are significant systematic uncertainties in our stellar mass estimate, up to x5 for individual sources. We compare our sample of SMGs to a volume-limited, morphologically classified sample of ellipticals in the local Universe. Assuming the star formation activity in SMGs has a timescale of ~100Myr we show that their descendants at z~0 would have a space density and M_H distribution which are in good agreement with those of local ellipticals. In addition the inferred mass-weighted ages of the local ellipticals broadly agree with the look-back times of the SMG events. Taken together, these results are consistent with a simple model that identifies SMGs as events that form most of the stars seen in the majority of luminous elliptical galaxies at the present day.Peer reviewe

Real-world use of once-weekly semaglutide in patients with type 2 diabetes: pooled analysis of data from four SURE studies by baseline characteristic subgroups

INTRODUCTION: This post hoc pooled analysis of four real-world studies (SURE Canada, Denmark/Sweden, Switzerland and UK) aimed to characterize the use of once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The Semaglutide Real-world Evidence (SURE) studies had a duration of ~30 weeks. Changes in glycated hemoglobin (HbA1c) and body weight (BW) were analyzed for the overall population and the following baseline subgroups: GLP-1RA-naïve/GLP-1RA switchers; body mass index 8-≤9%/>9%; T2D duration <5/≥5-<10/≥10 years. Data for patients achieving treatment targets were analyzed in the overall population and the baseline HbA1c ≥7% subgroup. RESULTS: Of 1212 patients, 960 were GLP-1RA-naïve and 252 had switched to semaglutide from another GLP-1RA. In the overall population, HbA1c was reduced from baseline to end of study (EOS) by -1.1% point and BW by -4.7 kg; changes were significant for all subgroups. There were significantly larger reductions of HbA1c and BW in GLP-1RA-naïve versus GLP-1RA switchers and larger reductions in HbA1c for patients with higher versus lower baseline HbA1c. At EOS, 52.6% of patients in the overall population achieved HbA1c <7%. No new safety concerns were identified in any of the completed SURE studies. CONCLUSIONS: In this pooled analysis, patients with T2D initiating OW semaglutide showed significant improvements from baseline to EOS in HbA1c and BW across various baseline subgroups, including patients previously treated with a GLP-1RA other than semaglutide, supporting OW semaglutide use in clinical practice. TRAIL REGISTRATION NUMBERS: NCT03457012; NCT03631186; NCT03648281; NCT03876015

Protecting Human and Animal Health: The Road from Animal Models to New Approach Methods

Animals and animal models have been invaluable for our current understanding of human and animal biology, including physiology, pharmacology, biochemistry, and disease pathology. However, there are increasing concerns with continued use of animals in basic biomedical, pharmacological, and regulatory research to provide safety assessments for drugs and chemicals. There are concerns that animals do not provide sufficient information on toxicity and/or efficacy to protect the target population, so scientists are utilizing the principles of replacement, reduction, and refinement (the 3Rs) and increasing the development and application of new approach methods (NAMs). NAMs are any technology, methodology, approach, or assay used to understand the effects and mechanisms of drugs or chemicals, with specific focus on applying the 3Rs. Although progress has been made in several areas with NAMs, complete replacement of animal models with NAMs is not yet attainable. The road to NAMs requires additional development, increased use, and, for regulatory decision making, usually formal validation. Moreover, it is likely that replacement of animal models with NAMs will require multiple assays to ensure sufficient biologic coverage. The purpose of this manuscript is to provide a balanced view of the current state of the use of animal models and NAMs as approaches to development, safety, efficacy, and toxicity testing of drugs and chemicals. Animals do not provide all needed information nor do NAMs, but each can elucidate key pieces of the puzzle of human and animal biology and contribute to the goal of protecting human and animal health. SIGNIFICANCE STATEMENT: Data from traditional animal studies have predominantly been used to inform human health safety and efficacy. Although it is unlikely that all animal studies will be able to be replaced, with the continued advancement in new approach methods (NAMs), it is possible that sometime in the future, NAMs will likely be an important component by which the discovery, efficacy, and toxicity testing of drugs and chemicals is conducted and regulatory decisions are made

Time-of-Flight Three Dimensional Neutron Diffraction in Transmission Mode for Mapping Crystal Grain Structures

The physical properties of polycrystalline materials depend on their microstructure, which is the nano-to centimeter scale arrangement of phases and defects in their interior. Such microstructure depends on the shape, crystallographic phase and orientation, and interfacing of the grains constituting the material. This article presents a new non-destructive 3D technique to study centimeter-sized bulk samples with a spatial resolution of hundred micrometers: time-of-flight three-dimensional neutron diffraction (ToF 3DND). Compared to existing analogous X-ray diffraction techniques, ToF 3DND enables studies of samples that can be both larger in size and made of heavier elements. Moreover, ToF 3DND facilitates the use of complicated sample environments. The basic ToF 3DND setup, utilizing an imaging detector with high spatial and temporal resolution, can easily be implemented at a time-of-flight neutron beamline. The technique was developed and tested with data collected at the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Complex (J-PARC) for an iron sample. We successfully reconstructed the shape of 108 grains and developed an indexing procedure. The reconstruction algorithms have been validated by reconstructing two stacked Co-Ni-Ga single crystals, and by comparison with a grain map obtained by post-mortem electron backscatter diffraction (EBSD)

Publisher Correction: In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies

In the original version of this Article, the sixth sentence of the first paragraph of the Introduction incorrectly read ‘Particularly, elapid antivenoms often have an unbalanced antibody content with relatively low amounts of antibodies against small neurotoxic venom components that have low immunogenicity, which often leads to low immune cgqtns in production animals8–10’. The correct version states ‘responses’ instead of ‘cgqtns’. This has been corrected in both the PDF and HTML versions of the Article

Prisoners’ Families’ Research: Developments, Debates and Directions

After many years of relative obscurity, research on prisoners’ families has gained significant momentum. It has expanded from case-oriented descriptive analyses of family experiences to longitudinal studies of child and family development and even macro analyses of the effects on communities in societies of mass incarceration. Now the field engages multi-disciplinary and international interest although it arguably still remains on the periphery of mainstream criminological, psychological and sociological research agendas. This chapter discusses developments in prisoners’ families’ research and its positioning in academia and practice. It does not aim to provide an all-encompassing review of the literature rather it will offer some reflections on how and why the field has developed as it has and on its future directions. The chapter is divided into three parts. The first discusses reasons for the historically small body of research on prisoners’ families and for the growth in research interest over the past two decades. The second analyses patterns and shifts in the focus of research studies and considers how the field has been shaped by intersecting disciplinary interests of psychology, sociology, criminology and socio-legal studies. The final part reflects on substantive and ethical issues that are likely to shape the direction of prisoners’ families’ research in the future

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10−7) in SOX2OT and rs17030795 (P=5.84×10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10−6) between CUL3 and FAM124B and rs1886797 (P=8.05×10−6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4×10−6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field