Sotatercept safety and effects on hemoglobin, bone, and vascular calcification

Introduction: Patients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD-MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1 fusion protein trap, on hemoglobin concentration; REN-001 also explored effects on bone mineral density (BMD) and abdominal aortic vascular calcification. Methods: Forty-three patients were treated in REN-001 (dose range: sotatercept 0.3‒0.7 mg/kg or placebo subcutaneously [s.c.] for 200 days) and 50 in REN-002 (dose range: 0.1‒0.4 mg/kg i.v. and 0.13‒0.5 mg/kg s.c. for 99 days). Results: In REN-001, frequency of achieving target hemoglobin response (\u3e10 g/dl [6.21 mmol/l]) with sotatercept was dose-related and greater than placebo (0.3 mg/kg: 33.3%; 0.5 mg/kg: 62.5%; 0.7 mg/kg: 77.8%; 0.7 mg/kg [doses 1 and 2]/0.4 mg/kg [doses 3‒15]: 33.3%; placebo: 27.3%). REN-002 hemoglobin findings were similar (i.v.: 16.7%-57.1%; s.c.: 11.1%‒42.9%). Dose-related achievement of ≥2% increase in femoral neck cortical BMD was seen among only REN-001 patients receiving sotatercept (0.3‒0.7 mg/kg: 20.0%‒57.1%; placebo: 0.0%). Abdominal aortic vascular calcification was slowed in a dose-related manner, with a ≤15% increase in Agatston score achieved by more REN-001 sotatercept versus placebo patients (60%‒100% vs. 16.7%). The most common adverse events during treatment were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza observed in both treatment and placebo groups. Conclusion: In patients with ESKD, sotatercept exhibited a favorable safety profile and was associated with trends in dose-related slowing of vascular calcification. Less-consistent trends in improved hemoglobin concentration and BMD were observed

A Response to Mooi, Williams and Gill

This is the publisher's version, which the author has permission to share. The original version may be found at the following link: http://www.mapress.com/zootaxa/list/2011/2946.htm

Will the Real Phylogeneticists Please Stand Up?

This is the publisher's version, also availalble electronically from http://www.mapress.com/zootaxa/list/2011/2946.html.In a recently published commentary, Mooi & Gill asserted that there is a crisis brewing in systematic ichthyology caused by a failure of investigators to apply the basic tenets of outgroup comparison to recover clades based solely on shared apomorphic characters. The result, they claim, is that many recent analyses disregard real synapomorphies and discover clades by phenetic rather than phylogenetic principles. We take the opportunity to refute this claim and assert that matrix-based analyses, whether parametric or nonparametric, satisfy the basic tenets of Hennig’s methods, resulting in monophyletic groups confirmed by synapomorphies

Towards More Precise Survey Photometry for PanSTARRS and LSST: Measuring Directly the Optical Transmission Spectrum of the Atmosphere

Motivated by the recognition that variation in the optical transmission of the atmosphere is probably the main limitation to the precision of ground-based CCD measurements of celestial fluxes, we review the physical processes that attenuate the passage of light through the Earth's atmosphere. The next generation of astronomical surveys, such as PanSTARRS and LSST, will greatly benefit from dedicated apparatus to obtain atmospheric transmission data that can be associated with each survey image. We review and compare various approaches to this measurement problem, including photometry, spectroscopy, and LIDAR. In conjunction with careful measurements of instrumental throughput, atmospheric transmission measurements should allow next-generation imaging surveys to produce photometry of unprecedented precision. Our primary concerns are the real-time determination of aerosol scattering and absorption by water along the line of sight, both of which can vary over the course of a night's observations.Comment: 41 pages, 14 figures. Accepted PAS

Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans

Ageing is associated with impaired hypertrophic responses to resistance exercise training (RET). Here we investigated the aetiology of ‘anabolic resistance’ in older humans. Twenty healthy male individuals, 10 younger (Y; 23 ± 1 years) and 10 older (O; 69 ± 3 years), performed 6 weeks unilateral RET (6 × 8 repetitions, 75% of one repetition maximum (1-RM), 3 times per week). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2O (70 atom%; thereafter 50 ml week−1), further bilateral VL muscle biopsies were taken at 3 and 6 weeks to quantify muscle protein synthesis (MPS) via gas chromatography–pyrolysis–isotope ratio mass spectrometry. After RET, 1-RM increased in Y (+35 ± 4%) and O (+25 ± 3%; P < 0.01), while MVC increased in Y (+21 ± 5%; P < 0.01) but not O (+6 ± 3%; not significant (NS)). In comparison to Y, O displayed blunted RET-induced increases in muscle thickness (at 3 and 6 weeks, respectively, Y: +8 ± 1% and +11 ± 2%, P < 0.01; O: +2.6 ± 1% and +3.5 ± 2%, NS). While ‘basal’ longer term MPS was identical between Y and O (∼1.35 ± 0.1% day−1), MPS increased in response to RET only in Y (3 weeks, Y: 1.61 ± 0.1% day−1; O: 1.49 ± 0.1% day−1). Consistent with this, O exhibited inferior ribosomal biogenesis (RNA:DNA ratio and c-MYC induction: Y: +4 ± 2 fold change; O: +1.9 ± 1 fold change), translational efficiency (S6K1 phosphorylation, Y: +10 ± 4 fold change; O: +4 ± 2 fold change) and anabolic hormone milieu (testosterone, Y: 367 ± 19; O: 274 ± 19 ng dl−1 (all P < 0.05). Anabolic resistance is thus multifactorial

Thermodynamic and cloud parameter retrieval using infrared spectral data

High-resolution infrared radiance spectra obtained from near nadir observations provide atmospheric, surface, and cloud property information. A fast radiative transfer model, including cloud effects, is used for atmospheric profile and cloud parameter retrieval. The retrieval algorithm is presented along with its application to recent field experiment data from the NPOESS Airborne Sounding Testbed - Interferometer (NAST-I). The retrieval accuracy dependence on cloud properties is discussed. It is shown that relatively accurate temperature and moisture retrievals can be achieved below optically thin clouds. For optically thick clouds, accurate temperature and moisture profiles down to cloud top level are obtained. For both optically thin and thick cloud situations, the cloud top height can be retrieved with an accuracy of approximately 1.0 km. Preliminary NAST-I retrieval results from the recent Atlantic-THORPEX Regional Campaign (ATReC) are presented and compared with coincident observations obtained from dropsondes and the nadir-pointing Cloud Physics Lidar (CPL)

The most luminous, merger-free AGN show only marginal correlation with bar presence

The role of large-scale bars in the fuelling of active galactic nuclei (AGN) is still debated, even as evidence mounts that black hole growth in the absence of galaxy mergers cumulatively dominated and may substantially influence disc (i.e., merger-free) galaxy evolution. We investigate whether large-scale galactic bars are a good candidate for merger-free AGN fuelling. Specifically, we combine slit spectroscopy and Hubble Space Telescope imagery to characterise star formation rates (SFRs) and stellar masses of the unambiguously disc-dominated host galaxies of a sample of luminous, Type-1 AGN with 0.02 < z 0.024. After carefully correcting for AGN signal, we find no clear difference in SFR between AGN hosts and a stellar mass-matched sample of galaxies lacking an AGN (0.013 < z < 0.19), although this could be due to a small sample size (n_AGN = 34). We correct for SFR and stellar mass to minimise selection biases, and compare the bar fraction in the two samples. We find that AGN are marginally (1.7$\sigma$) more likely to host a bar than inactive galaxies, with AGN hosts having a bar fraction, fbar = 0.59^{+0.08}_{-0.09} and inactive galaxies having a bar fraction fbar = 0.44^{+0.08}_{-0.09}. However, we find no further differences between SFR- and mass-matched AGN and inactive samples. While bars could potentially trigger AGN activity, they appear to have no further, unique effect on a galaxy's stellar mass or SFR.Comment: 15 pages (9 figures). Accepted for publication in MNRA

Architecture of Kepler's Multi-transiting Systems: II. New investigations with twice as many candidates

We report on the orbital architectures of Kepler systems having multiple planet candidates identified in the analysis of data from the first six quarters of Kepler data and reported by Batalha et al. (2013). These data show 899 transiting planet candidates in 365 multiple-planet systems and provide a powerful means to study the statistical properties of planetary systems. Using a generic mass-radius relationship, we find that only two pairs of planets in these candidate systems (out of 761 pairs total) appear to be on Hill-unstable orbits, indicating ~96% of the candidate planetary systems are correctly interpreted as true systems. We find that planet pairs show little statistical preference to be near mean-motion resonances. We identify an asymmetry in the distribution of period ratios near first-order resonances (e.g., 2:1, 3:2), with an excess of planet pairs lying wide of resonance and relatively few lying narrow of resonance. Finally, based upon the transit duration ratios of adjacent planets in each system, we find that the interior planet tends to have a smaller transit impact parameter than the exterior planet does. This finding suggests that the mode of the mutual inclinations of planetary orbital planes is in the range 1.0-2.2 degrees, for the packed systems of small planets probed by these observations.Comment: Accepted to Ap