A Multi-dimensional visual history on the upper falls of the Genesee River, Rochester, NY

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Optical Spectroscopy of the Surface Population of the rho Ophiuchi Molecular Cloud: The First Wave of Star Formation

We present the results of optical spectroscopy of 139 stars obtained with the Hydra multi-object spectrograph. The objects extend over a 1.3 square degree area surrounding the main cloud of the rho Oph complex. The objects were selected from narrowband images to have H alpha in emission. Using the presence of strong H alpha emission, lithium absorption, location in the Hertzsprung-Russell diagram, or previously reported x-ray emission, we were able to identify 88 objects as young stars associated with the cloud. Strong H alpha emission was confirmed in 39 objects with line widths consistent with their origin in magnetospheric accretion columns. Two of the strongest emission-line objects are young, x-ray emitting brown dwarf candidates with M8 spectral types. Comparisons of the bolometric luminosities and effective temperatures with theoretical models suggest a medianage for this population of 2.1 Myr which is signifcantly older than the ages derived for objects in the cloud core. It appears that these stars formed contemporaneously with low mass stars in the Upper Scorpius subgroup, likely triggered by massive stars in the Upper-Centaurus subgroup.Comment: 35 pages of postscript which includes seven figures (some of which are multi-panel) and four postscript tables. Astronomical Journal (in press

Cabozantinib for previously treated radioiodine-refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC-311 trial

Cabozantinib; Differentiated thyroid cancer; Tyrosine kinase inhibitorCabozantinib; Cáncer de tiroides diferenciado; Inhibidor de la tirosina quinasaCabozantinib; Càncer de tiroides diferenciat; Inhibidor de la tirosina quinasaBackground At an interim analysis (median follow-up, 6.2 months; n = 187), the phase 3 COSMIC-311 trial met the primary end point of progression-free survival (PFS): cabozantinib improved PFS versus a placebo (median, not reached vs. 1.9 months; p < .0001) in patients with previously treated radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). The results from an exploratory analysis using an extended datacut are presented. Methods Patients 16 years old or older with RAIR-DTC who progressed on prior lenvatinib and/or sorafenib were randomized 2:1 to oral cabozantinib tablets (60 mg/day) or a placebo. Placebo patients could cross over to open-label cabozantinib upon radiographic disease progression. The objective response rate (ORR) in the first 100 randomized patients and the PFS in the intent-to-treat population, both according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded, independent review, were the primary end points. Results At the data cutoff (February 8, 2021), 258 patients had been randomized (cabozantinib, n = 170; placebo, n = 88); the median follow-up was 10.1 months. The median PFS was 11.0 months (96% confidence interval [CI], 7.4–13.8 months) for cabozantinib and 1.9 months (96% CI, 1.9–3.7 months) for the placebo (hazard ratio, 0.22; 96% CI, 0.15–0.32; p < .0001). The ORR was 11.0% (95% CI, 6.9%–16.9%) versus 0% (95% CI, 0.0%–4.1%) (p = .0003) with one complete response with cabozantinib. Forty placebo patients crossed over to open-label cabozantinib. Grade 3/4 treatment-emergent adverse events occurred in 62% and 28% of the cabozantinib- and placebo-treated patients, respectively; the most common were hypertension (12% vs. 2%), palmar–plantar erythrodysesthesia (10% vs. 0%), and fatigue (9% vs. 0%). There were no grade 5 treatment-related events. Conclusions At extended follow-up, cabozantinib maintained superior efficacy over a placebo in patients with previously treated RAIR-DTC with no new safety signals.This study was sponsored by Exelixis, Inc., (Alameda, California). We thank the patients and their families, the investigators, and the site staff. Writing and editorial assistance was provided by Alexus Rivas, PharmD, and Michael Raffin (Fishawack Communications, a part of Fishawack Health, Conshohocken, Pennsylvania) and was funded by Exelixis

Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy

Using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS), we determined incidence, prevalence, and outcomes among hemodialysis patients with atrial fibrillation. Cox proportional hazards models, to identify associations with newly diagnosed atrial fibrillation and clinical outcomes, were stratified by country and study phase and adjusted for descriptive characteristics and comorbidities. Of 17,513 randomly sampled patients, 2188 had preexisting atrial fibrillation, with wide variation in prevalence across countries. Advanced age, non-black race, higher facility mean dialysate calcium, prosthetic heart valves, and valvular heart disease were associated with higher risk of new atrial fibrillation. Atrial fibrillation at study enrollment was positively associated with all-cause mortality and stroke. The CHADS2 score identified approximately equal-size groups of hemodialysis patients with atrial fibrillation with low (less than 2) and higher risk (more than 4) for subsequent strokes on a per 100 patient-year basis. Among patients with atrial fibrillation, warfarin use was associated with a significantly higher stroke risk, particularly in those over 75 years of age. Our study shows that atrial fibrillation is common and associated with elevated risk of adverse clinical outcomes, and this risk is even higher among elderly patients prescribed warfarin. The effectiveness and safety of warfarin in hemodialysis patients require additional investigation

The Initial Mass Function and Disk Frequency of the Rho Ophiuchi Cloud: An Extinction-Limited Sample

We have completed an optical spectroscopic survey of an unbiased, extinction-limited sample of candidate young stars covering 1.3 square degrees of the Rho Ophiuchi star forming region. While infrared, X-ray, and optical surveys of the cloud have identified many young stellar objects (YSOs), these surveys are biased towards particular stages of stellar evolution and are not optimal for studies of the disk frequency and initial mass function.We have obtained over 300 optical spectra to help identify 135 association members based on the presence of H-alpha in emission, lithium absorption, X-ray emission, a mid-infrared excess, a common proper motion, reflection nebulosity, and/or extinction considerations. Spectral types along with R and I band photometry were used to derive effective temperatures and bolometric luminosities for association members to compare with theoretical tracks and isochrones for pre-main-sequence stars. An average age of 3.1 Myr is derived for this population which is intermediate between that of objects embedded in the cloud core of Rho Ophiuchi and low mass stars in the Upper Scorpius subgroup. Consistent with this age we find a circumstellar disk frequency of 27% plus or minus 5%. We also constructed an initial mass function for an extinction-limited sample of 123 YSOs (A_v less than or equal to 8 mag), which is consistent with the field star initial mass function for YSOs with masses > 0.2 M_sun. There may be a deficit of brown dwarfs but this result relies on completeness corrections and requires confirmation.Comment: 46 pages, 7 figures, 4 table

A Burgessian critique of nominalistic tendencies in contemporary mathematics and its historiography

We analyze the developments in mathematical rigor from the viewpoint of a Burgessian critique of nominalistic reconstructions. We apply such a critique to the reconstruction of infinitesimal analysis accomplished through the efforts of Cantor, Dedekind, and Weierstrass; to the reconstruction of Cauchy's foundational work associated with the work of Boyer and Grabiner; and to Bishop's constructivist reconstruction of classical analysis. We examine the effects of a nominalist disposition on historiography, teaching, and research.Comment: 57 pages; 3 figures. Corrected misprint

The MITRE trial protocol: a study to evaluate the microbiome as a biomarker of efficacy and toxicity in cancer patients receiving immune checkpoint inhibitor therapy.

BACKGROUND: The gut microbiome is implicated as a marker of response to  immune checkpoint inhibitors (ICI) based on preclinical mouse models and preliminary observations in limited patient series. Furthermore, early studies suggest faecal microbial transfer may have therapeutic potential, converting ICI non-responders into responders. So far, identification of specific responsible bacterial taxa has been inconsistent, which limits future application. The MITRE study will explore and validate a microbiome signature in a larger scale prospective study across several different cancer types. METHODS: Melanoma, renal cancer and non-small cell lung cancer patients who are planned to receive standard immune checkpoint inhibitors are being recruited to the MITRE study. Longitudinal stool samples are collected prior to treatment, then at 6 weeks, 3, 6 and 12 months during treatment, or at disease progression/recurrence (whichever is sooner), as well as after a severe (≥grade 3 CTCAE v5.0) immune-related adverse event. Additionally, whole blood, plasma, buffy coat, RNA and peripheral blood mononuclear cells (PBMCs) is collected at similar time points and will be used for exploratory analyses. Archival tumour tissue, tumour biopsies at progression/relapse, as well as any biopsies from body organs collected after a severe toxicity are collected. The primary outcome measure is the ability of the microbiome signature to predict 1 year progression-free survival (PFS) in patients with advanced disease. Secondary outcomes include microbiome correlations with toxicity and other efficacy end-points. Biosamples will be used to explore immunological and genomic correlates. A sub-study will evaluate both COVID-19 antigen and antibody associations with the microbiome. DISCUSSION: There is an urgent need to identify biomarkers that are predictive of treatment response, resistance and toxicity to immunotherapy. The data generated from this study will both help inform patient selection for these drugs and provide information that may allow therapeutic manipulation of the microbiome to improve future patient outcomes. TRIAL REGISTRATION: NCT04107168 , ClinicalTrials.gov, registered 09/27/2019. Protocol V3.2 (16/04/2021)

Geometrodynamics of Variable-Speed-of-Light Cosmologies

This paper is dedicated to the memory of Dennis Sciama. Variable-Speed-of-Light (VSL) cosmologies are currently attracting interest as an alternative to inflation. We investigate the fundamental geometrodynamic aspects of VSL cosmologies and provide several implementations which do not explicitly break Lorentz invariance (no "hard" breaking). These "soft" implementations of Lorentz symmetry breaking provide particularly clean answers to the question "VSL with respect to what?". The class of VSL cosmologies we consider are compatible with both classical Einstein gravity and low-energy particle physics. These models solve the "kinematic" puzzles of cosmology as well as inflation does, but cannot by themselves solve the flatness problem, since in their purest form no violation of the strong energy condition occurs. We also consider a heterotic model (VSL plus inflation) which provides a number of observational implications for the low-redshift universe if chi contributes to the "dark energy" either as CDM or quintessence. These implications include modified gravitational lensing, birefringence, variation of fundamental constants and rotation of the plane of polarization of light from distant sources.Comment: 19 pages, latex 209, revtex 3.1; To appear in Physical Review D; Numerous small changes of presentation and emphasis; new section on the entropy problem; references updated; central results unaffecte